Journal

PLOS One

Papers (512)

Clinico-pathological and treatment characteristics of HIV and non-HIV related vulvar cancers: Analysis of a South African cohort

Objective The main objective of this study was to describe the clinical, pathological and treatment characteristics of patients with vulvar cancer who had surgery and or radiotherapy at Steve Biko Academic Hospital. The absolute and relative disease burden, trends over the time period were also analyzed. Materials and methods This was a retrospective study that described women with vulvar cancer who presented to the Gynaecology Oncology and Radiation Oncology departments of the hospital between January 2012 and December 2022. Their clinical, pathology and radiotherapy treatment records were reviewed for this study. Results 317 vulvar cancer cases between 2012 and 2022 were included in the analysis. The average age was 45.1±12.7. Forty percent of the participants were younger than 40 years. More than 75% of them were women living with HIV and were all on antiretroviral treatment. The average age of those who were HIV positive was 20 years lower than their HIV negative counterparts, p <0.0001. Their mean haemoglobin (Hb) at presentation was 10.7g/dL. Squamous cell carcinoma was the most common histological type in 96.5% of cases. Sixty four percent of the cases presented in advanced stage. About 48% of those who had primary radiation received curative doses. The median time to completion of radiotherapy treatment was higher among those who received primary radiotherapy as compared to those who received adjuvant treatment, 51.5 vs 46 days, p 0.039. The annual average age decreased from 56 years to as low as 40 years, a mean difference of 16 years, p 0.012. Conclusion It is striking that vulvar cancer is no longer a disease of elderly women. Its incidence is now high among women below 50 years. The study also showed an upward trend in the number of vulvar cancer cases in contrast to the declining average age at diagnosis. There is need for more vulvo-perineal surveillance of HIV positive women to detect early stage of vulvar cancers.

Inflammatory cytokines and a diverse cervicovaginal microbiota associate with cervical dysplasia in a cohort of Hispanics living in Puerto Rico

Cervical cancer (CC) is women’s fourth most common cancer worldwide. A worrying increase in CC rates in Hispanics suggests that besides Human papillomavirus infections, there may be other cofactors included in the epithelial microenvironment that could play a role in promoting the disease. We hypothesized that the cervical microbiome and the epithelial microenvironment favoring inflammation is conducive to disease progression in a group of Hispanics attending gynecology clinics in Puerto Rico. Few studies have focused on the joint microbiota and cytokine profile response in Hispanics outside the US, especially regarding the development of precancerous lesions. We aimed to investigate the relationship between the cervicovaginal microbiome and inflammation in Hispanic women living in PR while considering cervical dysplasia and HPV genotype risk. Cervical samples collected from 91 participants coming to gynecology clinics in San Juan, underwent 16S rRNA genes (V4 region) profiling, and cytokines were measured using Luminex MAGPIX technology. Cytokines were grouped as inflammatory (IL-1β, TNFα, IFNγ, IL-6), anti-inflammatory (IL- 4, IL-10, TGFβ1), and traffic-associated (IL-8, MIP1a, MCP1, IP10). They were related to microbes via an inflammation scoring index based on the quartile and tercile distribution of the cytokine’s concentration. We found significant differences in the diversity and composition of the microbiota according to HPV type according to carcinogenic risk, cervical disease, and cytokine abundance. Community State Types (CSTs) represents a profile of microbial communities observed within the vaginal microbiome ecological niche, and Lactobacillus-depleted CST IV had ~ 90% dominance in participants with high-grade squamous intraepithelial lesions and high-risk HPV. The increasing concentration of pro-inflammatory cytokines was associated with a decrease in L. crispatus. In contrast, dysbiosis-associated bacteria such as Gardnerella, Prevotella, Atopobium concomitantly increased with pro-inflammatory cytokines. Our study highlights that the cervical microbiota of Hispanics living in Puerto Rico is composed mostly of diverse CST profiles with decreased Lactobacillus and is associated with a higher pro-inflammatory environment. The joint host-microbe interaction analyses via cytokine and microbiota profiling have very good translational potential.

Identification of a novel chemotherapy benefit index for patients with advanced ovarian cancer based on Bayesian network analysis

Background This study aims to evaluate the efficacy of chemotherapy and optimize treatment strategies for patients with advanced ovarian cancer. Methods Based on The Cancer Genome Atlas (TCGA) transcriptome data, we conducted correlation and Bayesian network analyses to identify key genes strongly associated with chemotherapy prognosis. Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) was used to verify the expression of these key genes. The Chemotherapy Benefit Index (CBI) was developed using these genes via multivariable Cox regression analysis, and validated using both internal and external validation sets (GSE32062 and GSE30161) with a random forest model. Subsequently, we analyzed distinct molecular characteristics and explored additional immunotherapy in CBI-high and CBI-low subgroups. Results Based on the network and machine learning analyses, CBI was developed from the following ten genes: COL6A3, SPI1, HSF1, CD3E, PIK3R4, MZB1, FERMT3, GZMA, PSMB9 and RSF1. Significant differences in overall survival were observed among the CBI-high, medium, and low subgroups (P < 0.001), which were consistent with the two external validation sets (P < 0.001 and P = 0.003). The AUC of internal validation and two external validation cohorts were 0.87, 0.71 and 0.70, respectively. Molecular function analysis indicated that the CBI-low subgroup is characterized by the activation of cancer-related signaling pathways, immune-related biological processes, higher TP53 mutation rate, particularly with a better response to immune checkpoint blockade (ICB) treatment, while the CBI-high subgroup is characterized by inhibition of cell cycle, less response to ICB treatment, and potential therapeutic targets. Conclusions This study provided a novel CBI for patients with advanced ovarian cancer through network analyses and machine learning. CBI could serve as a prognostic prediction tool for patients with advanced ovarian cancer, and also as a potential indicator for immunotherapy.

Cervical cancer screening utilization and predictors among eligible women in Ethiopia: A systematic review and meta-analysis

BackgroundDespite a remarkable progress in the reduction of global rate of maternal mortality, cervical cancer has been identified as the leading cause of maternal morbidity and mortality, particularly in sub-Saharan African countries. The uptake of cervical cancer screening service has been consistently shown to be effective in reducing the incidence rate and mortality from cervical cancer. Despite this, there are limited studies in Ethiopia that were conducted to assess the uptake of cervical cancer screening and its predictors, and these studies showed inconsistent and inconclusive findings. Therefore, this systematic review and meta-analysis was conducted to estimate the pooled cervical cancer screening utilization and its predictors among eligible women in Ethiopia.Methods and findingsDatabases like PubMed, Web of Science, SCOPUS, CINAHL, Psychinfo, Google Scholar, Science Direct, and the Cochrane Library were systematically searched. All observational studies reporting cervical cancer screening utilization and/ or its predictors in Ethiopia were included. Two authors independently extracted all necessary data using a standardized data extraction format. Quality assessment criteria for prevalence studies were adapted from the Newcastle Ottawa quality assessment scale. The Cochrane Q test statistics andI2test were used to assess the heterogeneity of studies. A random effects model of analysis was used to estimate the pooled prevalence of cervical cancer screening utilization and factors associated with it with the 95% confidence intervals (CIs). From 850 potentially relevant articles, twenty-five studies with a total of 18,067 eligible women were included in this study. The pooled national cervical cancer screening utilization was 14.79% (95% CI: 11.75, 17.83). The highest utilization of cervical cancer screening (18.59%) was observed in Southern Nations Nationalities and Peoples’ region (SNNPR), and lowest was in Amhara region (13.62%). The sub-group analysis showed that the pooled cervical cancer screening was highest among HIV positive women (20.71%). This meta-analysis also showed that absence of women’s formal education reduces cervical cancer screening utilization by 67% [POR = 0.33, 95% CI: 0.23, 0.46]. Women who had good knowledge towards cervical screening [POR = 3.01, 95%CI: 2.2.6, 4.00], perceived susceptibility to cervical cancer [POR = 4.9, 95% CI: 3.67, 6.54], severity to cervical cancer [POR = 6.57, 95% CI: 3.99, 10.8] and those with a history of sexually transmitted infections (STIs) [POR = 5.39, 95% CI: 1.41, 20.58] were more likely to utilize cervical cancer screening. Additionally, the major barriers of cervical cancer screening utilization were considering oneself as healthy (48.97%) and lack of information on cervical cancer screening (34.34%).ConclusionsThis meta-analysis found that the percentage of cervical cancer screening among eligible women was much lower than the WHO recommendations. Only one in every seven women utilized cervical cancer screening in Ethiopia. There were significant variations in the cervical cancer screening based on geographical regions and characteristics of women. Educational status, knowledge towards cervical cancer screening, perceived susceptibility and severity to cervical cancer and history of STIs significantly increased the uptake of screening practice. Therefore, women empowerment, improving knowledge towards cervical cancer screening, enhancing perceived susceptibility and severity to cancer and identifying previous history of women are essential strategies to improve cervical cancer screening practice.

Efficacy and safety of pembrolizumab in cervical cancer: Protocol for systematic review and meta-analysis of randomized clinical trials

Purpose This paper reports a systematic review and meta-analysis protocol that will be used to evaluate the efficacy and safety of pembrolizumab, alone or combined with bevacizumab and other therapies, in adult women with cervical carcinoma from stage IB2 onwards. Methods The protocol follows PRISMA-P recommendations and was registered on PROSPERO (CRD42024531233). The search will be conducted without restrictions on language and year of publication in the following databases: Pubmed, Embase, Scopus, Web of Science, Cancerlit, The World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP) and Clinical Trials Registry Platform. Grey literature will be searched using the following sources: Clinicaltrials.gov, Google Scholar and Opengrey. Manual search will be carried out for the reference lists of eligible studies. The studies will be selected independently by two reviewers and all completed or ongoing randomized clinical trials that evaluated the efficacy and safety of pembrolizumab, used alone or combined with chemotherapy, radiotherapy, bevacizumab or surgery, in adult women diagnosed with cervical cancer, will be included. The data extraction will include population characteristics, type of treatment and main outcomes of studies. The methodological quality of the studies will be assessed using the Cochrane Risk of Bias 2.0. The certainty of the evidence will be rated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Conclusions The findings will be presented in narrative summary tables and a quantitative synthesis will be conducted using the ‘meta’ package of R software, version 4.3.1. This future systematic review may contribute with quality evidence for clinical decision-making on the use of pembrolizumab in women with cervical cancer.

Effect of human papillomavirus (HPV) vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment: A systematic review and meta-analysis

Background The prophylactic vaccines available to protect against infections by human papillomavirus (HPV) are well tolerated and highly immunogenic. This systematic review and meta-analysis aimed to explore the efficacy of HPV vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment. Methods A literature search was performed using PubMed/MEDLINE, Embase, the Cochrane Library, Scopus, Web of Science, and bioRxiv/medRxiv from inception to July 15, 2024. Randomized controlled trials (RCTs) reporting the effect of HPV vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment vs no HPV vaccination were included. The primary outcome measure was risk of recurrence cervical high-grade squamous intraepithelial lesion (HSIL) after local surgical treatment, with follow-up as reported by individual studies. Included studies were assessed for risk of bias using the Revised Cochrane risk-of-bias (RoB 2.0 tool). Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated. No restrictions were applied on language, the date of publication, age, sex, and country. All analyses were carried out using the Review Manager 5 software (version 5.4). Results Eight RCTs (n = 3068) met the inclusion criteria. The risk of cervical HSIL recurrence was not reduced in individuals who were vaccinated compared with those who were not vaccinated (RR 0.92, 95% CI: 0.66–1.27; I2 = 40%). However, HPV vaccination reduced the risk of recurrence of cervical HSIL related to the HPV types HPV16/18, but uncertainty was large (RR 0.57, 95% CI: 0.18–1.84; I2 = 29%). Conclusions Adjuvant HPV vaccination after surgical excision is not associated with a reduced risk of recurrent HSIL overall or a reduced risk of recurrent lesions caused by the most oncogenic strains (HPV16/18). Therefore, HPV vaccination should not be considered for adjuvant treatment in patients undergoing surgical excision.

Effect of ERCC1 polymorphisms on the response to platinum-based chemotherapy: A systematic review and meta-analysis based on Asian population

BackgroundPlatinum-based chemotherapy is one of the most common treatments for many cancers; however, the effect of chemotherapy varies from individual to individual. Excision repair cross complementation group 1 (ERCC1) is widely recognized as a key gene regulating nucleotide excision repair (NER) and is closely associated with platinum response. Many studies have yielded conflicting results regarding whether ERCC1 polymorphisms can affect the response to platinum and overall survival (OS). Therefore, it is necessary to perform a meta-analysis of patients with specific races and cancer types.MethodsEight databases (EMBASE, PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, Scopus, VIP, China Biology Medicine disc and Wanfang databases) were searched. Results were expressed in terms of odds ratios (ORs), hazard ratios (HRs) and 95% CIs.ResultsIn this study, rs11615, rs2298881 and rs3212986 SNPs were studied. In the comparison between CT and TT on the response to platinum, esophageal cancer [I2= 0%, OR = 6.18, 95% CI(1.89,20.23), P = 0.003] and ovarian cancer [I2= 0%, OR = 4.94, 95% CI(2.21,11.04), P<0.001] showed that the rs11615 CT genotype predicted a better response. In the comparison between CC and TT, ovarian cancer [I2= 48.0%, OR = 6.15, 95% CI (2.56,14.29), P<0.001] indicated that the CC genotype predicted a better response. In the meta-analysis of OS, the CC genotype was related to longer OS than TT in ovarian cancer [TT vs CC: I2= 57.7%, HR = 1.71, 95% CI (1.18, 2.49), P<0.001].ConclusionThe ERCC1 rs11615 polymorphism was related to the response to platinum and OS, but the correlation is based on specific cancer types in the Asian population.

A three protein signature fails to externally validate as a biomarker to predict surgical outcome in high-grade epithelial ovarian cancer

IntroductionFor patients with advanced epithelial ovarian cancer, complete surgical cytoreduction remains the strongest predictor of outcome. However, identifying patients who are likely to benefit from such surgery remains elusive and to date few surgical outcome prediction tools have been validated. Here we attempted to externally validate a promising three protein signature, which had previously shown strong association with suboptimal surgical debulking (AUC 0.89, accuracy 92.8%), (Riester, M., et al., (2014)).Methods238 high-grade epithelial ovarian cancer samples were collected from patients who participated in a large multicentre trial (ICON5). Samples were collected at the time of initial surgery and before randomisation. Surgical outcome data were collated from prospectively collected study records. Immunohistochemical scores were generated by two independent observers for the three proteins in the original signature (POSTN, CXCL14 and pSmad2/3). Predictive values were generated for individual and combination protein signatures.ResultsWhen assessed individually, none of the proteins showed any evidence of predictive affinity for suboptimal surgical outcome in our cohort (AUC POSTN 0.55, pSmad 2/3 0.53, CXCL 14 0.62). The combined signature again showed poor predictive ability with an AUC 0.58.ConclusionsDespite showing original promise, when this protein signature is applied to a large external cohort, it is unable to accurately predict surgical outcomes. This could be attributed to overfitting of the original model, or differences in surgical practice between cohorts.

The novel reversible LSD1 inhibitor SP-2577 promotes anti-tumor immunity in SWItch/Sucrose-NonFermentable (SWI/SNF) complex mutated ovarian cancer

Mutations of the SWI/SNF chromatin remodeling complex occur in 20% of all human cancers, including ovarian cancer. Approximately half of ovarian clear cell carcinomas (OCCC) carry mutations in the SWI/SNF subunit ARID1A, while small cell carcinoma of the ovary hypercalcemic type (SCCOHT) presents with inactivating mutations of the SWI/SNF ATPase SMARCA4 alongside epigenetic silencing of the ATPase SMARCA2. Loss of these ATPases disrupts SWI/SNF chromatin remodeling activity and may also interfere with the function of other histone-modifying enzymes that associate with or are dependent on SWI/SNF activity. One such enzyme is lysine-specific histone demethylase 1 (LSD1/KDM1A), which regulates the chromatin landscape and gene expression by demethylating proteins such as histone H3. Cross-cancer analysis of the TCGA database shows that LSD1 is highly expressed in SWI/SNF-mutated tumors. SCCOHT and OCCC cell lines have shown sensitivity to the reversible LSD1 inhibitor SP-2577 (Seclidemstat), suggesting that SWI/SNF-deficient ovarian cancers are dependent on LSD1 activity. Moreover, it has been shown that inhibition of LSD1 stimulates interferon (IFN)-dependent anti-tumor immunity through induction of endogenous retroviral elements and may thereby overcome resistance to checkpoint blockade. In this study, we investigated the ability of SP-2577 to promote anti-tumor immunity and T-cell infiltration in SCCOHT and OCCC cell lines. We found that SP-2577 stimulated IFN-dependent anti-tumor immunity in SCCOHT and promoted the expression of PD-L1 in both SCCOHT and OCCC. Together, these findings suggest that the combination therapy of SP-2577 with checkpoint inhibitors may induce or augment immunogenic responses of SWI/SNF-mutated ovarian cancers and warrants further investigation.

A Swedish genome-wide haplotype association analysis identifies novel candidate loci associated with endometrial cancer risk

Genome-wide association studies [GWAS] have identified a limited number of endometrial cancer risk loci by analyzing single nucleotide polymorphisms [SNPs]. We hypothesized that analyzing haplotypes rather than SNPs could provide novel and more detailed information on genetic cancer susceptibility loci. To examine the association of a SNP or haplotype with endometrial cancer risk we performed a two-stage haplotype GWAS. The discovery GWAS included a sub-cohort of 1,116 Swedish endometrial cancer cases and 5,021 controls from previously published GWAS data. A sliding window analysis was employed with window sizes of 1-25 SNPs using a logistic regression model. The Swedish haplotype analysis identified 15 novel candidate risk loci (2q31.1, 4p16.1, 4p15.31, 6q13, 7p21.1, 9p13.3, 10q26.3, 11q21, 12q13.11, 13q12.11, 15q13.3, 16q24.3, 19q13.32, 20p12.3 and 22q13.2) with OR ranging from 1.6 to 3.3 and p-values from 4.25 × 10−8 to 9.86 × 10−15. A second replication haplotype analysis of the Swedish novel loci was performed using two cohorts from Belgium and Germany. In spite of small sample sizes in the replication cohorts, there was still support for most loci with positive ORs. In addition, the findings in the two European cohorts motivates further studies to search for founder haplotypes. These novel findings suggested that endometrial cancer loci, identified through haplotype analysis, conferred a higher risk compared to previous single-variant GWAS.

Electrophysiological fingerprints of healthy cervical epithelial and HeLa cells: Membrane potential, zeta potential and passive electrical properties

There is a growing appreciation that cellular electrical mechanisms play an important role both in cell regulation, and in cell dysregulation in diseases such as cancer. These electrical mechanisms are measured using several different methods, which yield characteristics including the membrane potential, capacitance and conductance, the extracellular (ζ) potential and cytoplasm conductivity. However, since these are measured using different techniques, the combination of all of these (the cancer electrome ) has yet to be described. In this paper, we report on the difference between the electromes of cervical cancer cell line HeLa, with clinically-derived primary cervical epithelial cells. These were investigated using dielectrophoresis (DEP) and ζ-potential, with these data then being used to calculate the membrane potential V m . Results indicate significant differences in membrane conductance and capacitance, membrane potential, ζ-potential and cytoplasm conductivity between the two cell types. Furthermore, treatment with the K + blocker Tetraethylammonium caused distinct alterations in electrophysiology of the two lineages, pointing towards different roles for K + in cancer and normal cells. This work presents a novel and cost-effective approach, combining five distinct electrical properties to form a “fingerprint” to characterize and discriminate healthy and malignant cells in a label-free, rapid manner.

The Role of Interleukin 6 (IL6), Cancer Antigen—125 (CA-125), and Human Epididymis Protein 4 (HE4) to predict tumor resectability in the advanced epithelial ovarian cancer patients

Introduction A study of tumor resectability in pre-operative patients with advanced epithelial ovarian cancer is required to predict primary surgical benefits accurately. This study aims to investigate IL6, CA-125 and HE4 to predict tumor resectability in the pre-operative patients with advanced epithelial ovarian cancer. Methods This cross-sectional study was conducted in the polyclinic, oncology and gynecology inpatient room of Dr. M. Jamil Padang Hospital from June until December 2022. Advanced epithelial ovarian cancer stage based on histology result from FIGO stages IIIB–IVA. IL6, CA-125, and HE4 were measured using ECLIA (electrochemiluminescence immunoassay). Categorical data were assessed using Chi-square and Mann-Whitney tests. Numerical variable correlations were analyzed using Pearson Correlation tests. While the correlation between numerical and nominal variables was analyzed using the Eta correlation test. A p-value of <0,05 was considered a significant correlation. The cut-off value of serum IL6, CA-125, and HE4 was determined with a ROC curve. The sensitivity and specificity of each clinical parameter were calculated. Results There was a significant difference in IL-6 (1328 vs 752 pg/ml; p<0,001), CA-125 (1260,5 vs 819,5 U/ml; p<0,001), and HE4 levels (1320 vs 760 pmol/L; p<0,001) between patients with tumor resectability of > 1 cm (suboptimal) vs < 1 cm (optimal). There was a correlation between IL6 (r = 0,832), CA-125 (r = 0,716), and HE4 (r = 0,716) with tumor resectability. Conclusion Measuring IL6, CA-125, and HE4 levels is useful for clinicians to predict tumor resectability in pre-operative patients with advanced epithelial ovarian cancer.

PAXIP1-AS1 is associated with immune infiltration and predicts poor prognosis in ovarian cancer

The long non-coding RNA (LncRNA) PAXIP1 antisense RNA 1 (PAXIP1-AS1) was found to promote proliferation, migration, EMT, and apoptosis of ovarian cancer (OC) cells in OC cell lines, but the relationship between PAXIP1-AS1 expression and clinical characteristics, prognosis, and immune infiltration of OC patients and its regulatory network are unclear. 379 OC tissues were collected from The Cancer Genome Atlas (TCGA) database. 427 OC tissues and 88 normal ovarian tissues were collected from GTEx combined TCGA database. 130 OC samples were collected from GSE138866. Kruskal-Wallis test, Wilcoxon sign-rank test, logistic regression, Kaplan-Meier method, Cox regression analysis, Gene set enrichment analysis (GSEA), and immuno-infiltration analysis were used to evaluate the relationship between clinical characteristics and PAXIP1-AS1 expression, prognostic factors, and determine the significant involvement of PAXIP1-AS1 in function. QRT-PCR was used to validate the expression of PAXIP1-AS1 in OC cell lines. Low PAXIP1-AS1 expression in OC was associated with age (P = 0.045), histological grade (P = 0.011), and lymphatic invasion (P = 0.004). Low PAXIP1-AS1 expression predicted a poorer overall survival (OS) (HR: 0.71; 95% CI: 0.55–0.92; P = 0.009), progression free interval (PFS) (HR: 1.776; 95% CI: 1.067–2.955; P = 0.001) and disease specific survival (DSS) (HR: 0.67; 95% CI: 0.51–0.89; P = 0.006). PAXIP1-AS1 expression (HR: 0.711; 95% CI: 0.542–0.934; P = 0.014) was independently correlated with PFS in OC patients. GSEA demonstrated that neutrophil degranulation, signaling by Interleukins, GPCR-ligand binding, G alpha I signaling events, VEGFAVEGFR-2 signaling pathway, naba secreted factors, Class A 1 Rhodopsin-Like Receptors, PI3K-Akt signaling pathway, and Focal Adhesion-PI3K-Akt-mTOR-signaling pathway were differentially enriched in PAXIP1-AS1 high expression phenotype. PAXIP1-AS1 was significantly downregulated in OC cell lines compared with IOSE29 cell line. The expression of PAXIP1-AS1 was associated with immune infiltration. low expression of PAXIP1-AS1 was correlated with poor OS (HR: 0.52; 95% CI: 0.34–0.80; P = 0.003) from GSE138866. There were some genomic variations between the PAXIP1-AS1 high and low expression groups. Low expression of PAXIP1-AS1 was significantly associated with poor survival and immune infiltration in OC. PAXIP1-AS1 could be a promising prognosis biomarker and response to immunotherapy for OC.

Delineating Pixantrone Maleate’s adroit activity against cervical cancer proteins through multitargeted docking-based MM\GBSA, QM-DFT and MD simulation

Cervical cancer poses a substantial worldwide health challenge, especially in low- and middle-income nations, caused by high-risk types of human papillomavirus. It accounted for a significant percentage of cancer-related deaths among women, particularly in areas with limited healthcare resources, necessitating innovative therapeutic approaches, and single-targeted studies have produced significant results, with a considerable chance of developing resistance. Therefore, the multitargeted studies can work as a beacon of hope. This study is focused on performing the multitargeted molecular docking of FDA-approved drugs with the three crucial proteins TBK1, DNA polymerase epsilon, and integrin α-V β-8 of cervical cancer. The docking studies using multisampling algorithms HTVS, SP, and XP reveal Pixantrone Maleate (DB06193) as a multitargeted inhibitor with docking scores of -8.147, -8.206 and -7.31 Kcal/mol and pose filtration with MM\GBSA computations with scores -40.55, -33.67, and -37.64 Kcal/mol. We also have performed QM-based DFT and pharmacokinetics studies of the compound and compared it with the standard values, which results in the compound being entirely suitable against cervical cancer proteins. The interaction fingerprints have revealed that PHE, VAL, SER and ALA are the residues among most interactions. We also explore the stability of the multitargeted potential of Pixantrone Maleate through 100ns MD simulations and investigate the RMSD, RMSF and intermolecular interactions between all three proteins-ligand complexes. All computational studies favour Pixantrone Maleate as a multitargeted inhibitor of the TBK1, DNA polymerase epsilon, and integrin α-V β-8 and can be validated experimentally before use.

Assessing Knowledge, Uptake and Factors associated with cervical cancer screening among women in selected communities of Wakiso district in Uganda: A population-based study

Background Uganda has the highest prevalence and incidence of cervical cancer in the East African region, with 80% of women diagnosed at advanced stage when survival is minimal. Literature on uptake of cervical cancer screening is limited in Uganda and thus womens’ knowledge and uptake of cervical cancer screening in the general population remains unknown. This study examined this gap of knowledge among women aged 25–65 years, across rural, urban and semi urban communities in a Ugandan district to inform design of targeted future cervical cancer screening programs in the country. Methods This descriptive cross-sectional study was conducted in Wakiso district, Uganda in May 2024 among 783 eligible women. Face-to-face interviews were conducted. Uptake of cervical cancer screening (outcome of interest) was dichotomously (yes/no) assessed. Knowledge of cervical cancer disease was assessed using the AWACAN validated tool, knowledge of cervical cancer screening was assessed using a set of ten (10) questions adapted from previous studies elsewhere, and all were measured on a Likert scale. Univariate, bivariate, and multivariable Poisson regression models with robust variance were performed using Stata software version 17. Results Respondents’ median age was 31 years (IQR 27–39 years). Majority (89.5%, 701/783) had heard of cervical cancer, and 90.6% (635/701) were aware of screening. Median knowledge score on signs and symptoms, risk factors and cervical cancer screening was 8.0 (IQR = 5–10), 8.0 (IQR = 5–11) and 7.0 (IQR = 4–10) respectively, and 54.3% had high knowledge about cervical cancer screening. Uptake of cervical cancer screening was 33.4%. Living in urban areas (aPR = 1.41, 95% CI: 1.05–1.88), being the ages 40–49 years (aPR = 1.76, 95% CI: 1.36–2.27), 50 years and above (APR = 2.16, 95% CI: 1.53–3.04), smoking (aPR = 1.39, 95% CI: 1.05–1.86), partner involvement (aPR = 2.61, 95% CI: 2.12–3.21), high knowledge about cervical cancer screening (aPR = 3.29, 95% CI: 2.35–4.60), and living with HIV (aPR = 1.66, 95% CI: 1.66–2.13) were significantly associated with higher uptake of cervical cancer screening among women in this setting. Conclusion Knowledge of cervical cancer screening was high, but the uptake of cervical cancer screening was lower than the recommended population coverage by WHO and Uganda national guidelines. There is need to improve accessibility to cervical cancer screening, increase nationwide cervical cancer awareness campaigns focusing on high-risk age groups and design targeted, tailored, culturally and socially sensitive interventions for young women aged 25–39 years to improve cervical cancer screening in Uganda.

The prevalence of depressive disorder and its association in Thai cervical cancer patients

Purpose The purpose of this study is to examine the prevalence, associated factors and quality of life associated with depressive disorder in cervical cancer patients. Patients and methods This cross-sectional study was carried out in a gynecologic oncology clinic of a university hospital in Northern Thailand from October 2018 to August 2019. Two-hundred cervical cancer patients were screened for depressive disorder using the nine-item Patient Health Questionnaire (PHQ-9), and psychiatrists interviewed eligible patients to confirm diagnoses. We measured the quality of life using questionnaires from the European Organisation for the Research and Treatment of Cancer: Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and Cervical Cancer Module 24 (EORTC QLQ-Cx24). Associated factors, including comorbidity, fatigue, and pain, were collected using the Charlson Comorbidity Index (CCI), the eleven-item Chalder Fatigue Scale (CFQ 11), and the visual analog scale (VAS) for pain, respectively. Results Twenty-seven (13.5%) cervical cancer patients were diagnosed with depressive disorder by psychiatrists according to the DSM-5. Depressive disorder was related to a worse quality of life in these patients. A binary logistic regression analysis revealed that depressive disorder among these patients was linked with these factors: high fatigue score (aOR: 1.35; CI: 1.18–1.53), high pain score (aOR: 1.25; CI: 1.02–1.54), no perception of social support, (aOR: 3.12; CI: 1.11–8.81), and no previous surgical treatment for cervical cancer (aOR: 2.99; CI: 1.08–8.29). Conclusion The depressive disorder prevalence was 13.5% in Northern Thai cervical cancer patients. In this demographic, cervical cancer patients—who reported high fatigue or pain scores, did not perceive social support, or had no previous cervical cancer surgery- were more likely to have depressive disorder.

Epigenetic assessments of alcohol consumption predict mortality in smokers at risk for lung cancer in the prostate, lung, colorectal and ovarian cancer screening trial

DNA methylation at cg05575921, an established biomarker for smoking predicts risk for lung cancer (LC). Although heavy alcohol consumption (HAC) frequently accompanies smoking, the relationship of HAC to overall mortality in those at risk for LC is not well known. Determining the contribution of HAC to mortality in those who smoke is important because HAC is also a major driver of mortality and is potentially treatable. To help answer this question, we examined the relationship of epigenetic biomarkers of smoking (cg05575921) and chronic heavy alcohol consumption (Alcohol T Score, ATS) in a cohort of 92 LC cases and 402 age, sex, ethnicity and smoking history matched controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Screening Trial to all-cause mortality using proportional hazards survival analysis. We found that ATS values significantly predicted risk for all-cause mortality in those smokers who developed (p < 0.03) and did not develop lung cancer (p < 0.0001). When mortality data were analyzed using median splits, those who did and did not incur lung cancer with ATS values <3.6 lived 5.6 years and 3.2 years more, respectfully, than those with ATS values >3.6. Interestingly, in this group of 494 smokers or former smokers, after adjusting for the occurrence of lung cancer, cg05575921 methylation did not predict mortality. In summary, we found that excessive alcohol consumption is a significant risk factor for all-cause mortality in those at risk for LC and suggest that lung cancer screening efforts to address problem drinking could increase survival.

Synergistic celecoxib and dimethyl-celecoxib combinations block cervix cancer growth through multiple mechanisms

Objective The synergistic inhibitory effect of celecoxib (CXB) and dimethyl-celecoxib (DMC) plus paclitaxel (PA) or cisplatin (CP) on human cervix HeLa and SiHa cells was assessed at multiple cellular levels in order to elucidate the biochemical mechanisms triggered by the synergistic drug combinations. Methods The effect of CXB (5 μM)/CP (2 μM) or CXB (5 μM)/PA (15 μM) and DMC (15 μM)/CP (5 μM) or DMC (15 μM)/PA (20 μM) for 24 h was assayed on cancer cell proliferation, energy metabolism, mitophagy, ROS production, glycoprotein-P activity, DNA stability and apoptosis/necrosis. Results Drug combinations synergistically decreased HeLa and SiHa cell proliferation (>75%) and arrested cellular cycle by decreasing S and G2/M phases as well as the Ki67 content (HeLa) by 7.5–30 times. Cell viability was preserved (>90%) and no apparent effects on non-cancer cell growth were observed. Mitochondrial and glycolytic protein contents (44–95%) and ΔΨm (45–50%) in HeLa cells and oxidative phosphorylation and glycolysis fluxes (70–90%) in HeLa and SiHa cells were severely decreased, which in turn promoted a drastic fall in the ATP supply (85–88%). High levels of mitophagy proteins in HeLa cells and active mitochondrial digestion in HeLa and SiHa cells was observed. Mitochondrial fission and microtubule proteins were also affected. Intracellular ROS content (2–2.3-fold) and ROS production was stimulated (2.3–4 times), whereas content and activity of glycoprotein-P (45–85%) were diminished. DNA fragmentation was not observed and apoptosis/necrosis was not detected suggesting that cell death could be mainly associated to mitophagy induction. Conclusions CXB or DMC combination with canonical chemotherapy may be a promising chemotherapy strategy against cervical cancer growth, because it can selectively block multiple cell processes including inhibition of energy pathways and in consequence ATP-dependent processes such as cell proliferation, glycoprotein-P activity, ROS production and mitophagy, with no apparent effects on non-cancer cells.

Disparities and trends of the incidence and mortality of female-specific cancers in the United States

Background Female-specific cancers (FSCs) impose substantial burdens on healthcare systems and economies worldwide. The significant impact of these cancers in the United States warrants further investigation. Objective This study aimed to analyze trends in incidence and mortality rates of six female-specific cancers (breast, cervical, uterine, ovarian, vaginal, and vulvar cancers) among diverse racial and ethnic groups in the United States, and to evaluate the attributable contributions of major risk factors to the cancer death burden as well as their temporal changes. Methods Incidence and mortality data were obtained from the SEER (22 registry) database, to examine cross-sectional and temporal trends by race/ethnicity. The burden of FSCs attributable to specific risk factors was estimated based on the Global Burden of Disease 2021 database. Results Between 2017 and 2021, Breast cancer incidence increased across all racial groups, most notably among non-Hispanic White (White) women, while mortality declined. Cervical cancer incidence decreased in most groups but remained stable among American Indians and Alaska Native (AIAN) women. Uterine cancer incidence increased across all racial groups, except for Whites. Incidence and mortality rates for ovarian and vaginal cancers remained stable or decreased, whereas vulvar cancer mortality was highest among White and AIAN women and lowest among non-Hispanic Asian Americans and Pacific Islander (AAPI) women. From 2000 to 2021, risk-attributable deaths decreased for breast, cervical, and ovarian cancers but increased for uterine cancer. Conclusions Significant sociodemographic disparities and unfavorable trends persist in the incidence and mortality of all six major female-specific cancers, highlighting the importance for effective prevention and intervention strategies.

Current and future burden of gynecological cancers attributable to high body-mass index: A comprehensive global analysis and projection study

Background High body-mass index (BMI) is a major modifiable risk factor for gynecological cancers, yet its contribution to the global cancer burden remains incompletely characterized. This study provides a comprehensive analysis of the current burden of gynecological cancers attributable to high BMI and projects future trends through 2050. Methods We analyzed data from the Global Burden of Disease (GBD) 2021 study, examining uterine and ovarian cancers attributable to high BMI across 204 countries and territories. Burden was quantified using deaths and disability-adjusted life years (DALYs). Temporal trends were identified using joinpoint regression analysis, while future burden was projected using Bayesian Age-Period-Cohort (BAPC) models. We evaluated relationships between socio-demographic index (SDI) and cancer burden to identify development-associated patterns. Results Between 1990 and 2021, global deaths from gynecological cancers attributable to high BMI increased by 143.4% (from 20,743–50,479), with corresponding DALYs rising by 141.7% (from 561,515–1,357,395). Rising age-standardized rates indicated increasing individual-level risk. While burden was highest in high-SDI regions, the most rapid increases occurred in low- and middle-SDI settings. Cancer-specific patterns varied, with uterine cancer showing consistent increases across all SDI quintiles, while ovarian cancer exhibited decreasing trends in high-SDI regions after 2003. Projections indicate a 2.6-fold increase in deaths by 2050, with differential growth by cancer type: a 3.2-fold increase for ovarian cancer versus 2.3-fold for uterine cancer. Conclusions The global burden of gynecological cancers attributable to high BMI has increased substantially and is projected to accelerate through 2050, particularly in developing regions. These findings underscore the urgent need for targeted obesity prevention strategies within comprehensive cancer control programs to avert a substantial proportion of future gynecological cancer cases.

The rising burden of female cancer in Ethiopia (2000–2021) and projections to 2040: Insights from the global burden of disease study

Background Female cancers—breast, cervical, ovarian, and uterine—pose significant public health and socio-economic challenges, particularly in low- and middle-income countries like Ethiopia. However, detailed and geographically disaggregated data are limited, hindering effective policymaking. To address this gap, our study utilizes the Global Burden of Disease (GBD) methodology to analyze 21 years (2000–2021) of national and sub-national trends and risk factors for these cancers in Ethiopia, with projections to 2040, to support targeted cancer control and health system strengthening. Methods Using the 2021GBD data, we analyzed the national and sub-national prevalence, incidence, mortality, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for female specific cancer in Ethiopia. An Autoregressive Integrated Moving Average (ARIMA) model was employed for projecting epidemiological trajectories through 2040. All statistical analyses and data visualization were performed using Python. Results In 2021, the Ethiopian incidence of female breast, cervical, ovarian, and uterine cancer was 7,308 (95% uncertainty interval (UI): 5,794–9,199), 7,884 (95% UI: 5,759–11,765), 2,054 (95% UI: 1,034–2,929), and 669 (95% UI: 422–1,126), respectively. Cervical cancer accounts for the highest number of DALYs, 162,776 (95% UI: 119,900–239,116), followed by breast, ovarian, and uterine cancer at 155,931 (95% UI: 123,015–196,249), 40,430 (95% UI: 19,885–57,414), and 8,882 (95% UI: 5,579–15,240), respectively. Projections to 2040 indicate a continued rise in incidence for all female cancers. Conclusions Breast and ovarian cancers are emerging public health crises in Ethiopia, with significant increases in prevalence, incidence, and DALYs. While the cervical cancer burden is declining, rising YLDs indicate a growing need for long-term care. The projected rise in female cancer incidence calls for urgent, targeted interventions focused on early diagnosis, age-appropriate screening, and improved cancer care services to reduce the adverse impact on Ethiopian women's health.

STmiR: A Novel XGBoost-based framework for spatially resolved miRNA activity prediction in cancer transcriptomics

MicroRNAs (miRNAs) are critical regulators of gene expression in cancer biology, yet their spatial dynamics within tumor microenvironments (TMEs) remain underexplored due to technical limitations in current spatial transcriptomics (ST) technologies. To address this gap, we present STmiR, a novel XGBoost-based framework for spatially resolved miRNA activity prediction. STmiR integrates bulk RNA-seq data (TCGA and CCLE) with spatial transcriptomics profiles to model nonlinear miRNA-mRNA interactions, achieving high predictive accuracy (Spearman’s ρ > 0.8) across four major cancer types (breast, lung, ovarian, prostate), with performance further confirmed through direct comparison with experimentally measured miRNA expression in an independent spatial transcriptomics dataset. Applied to 10X Visium ST datasets from nine cancers, STmiR identifies six pan-cancer conserved miRNAs (e.g., hsa-miR-21, hsa-let-7a) consistently ranked in the top 40 across malignancies, and uncovers cell-type-specific regulatory networks in fibroblasts, B cells, and malignant cells. A breast cancer case study demonstrates STmiR’s utility in uncovering biologically relevant miRNA-target relationships and their association with key cancer pathways. By enabling spatial mapping of miRNA activity, STmiR provides a transformative tool to dissect miRNA-mediated regulatory mechanisms in cancer progression and TME remodeling, with implications for biomarker discovery and precision oncology.

Temporal trend in the national and sub-national burden of cancers attributable to risk factors in Iran from 1990 to 2021: Findings from the global burden of disease study 2021

Background Cancer is among leading causes of death globally and in Iran. However, studies exploring cancer risk factors trends in Iran are scarce. In this study, we provide estimations of risk-attributable cancer burden at the national and subnational levels in Iran from 1990 to 2021. Methods This study utilized data from the Global Burden of Disease (GBD) 2021 Study to estimate cancer-related years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life years (DALYs), and deaths attributable to behavioral, metabolic, and environmental/occupational risks in Iran nationally and subnationally, from 1990 to 2021. Summary exposure values (SEV) were given to assess the level of exposure. All estimations were reported along with 95% uncertainty intervals (UI). Results In 2021, 29.2% (95% UI: 22.9%–35.7%) of cancer deaths, equaling 16,893 (13,332–20,914) deaths and age-standardized rate of 22.66 (17.90–28.14), were attributable to risk factors in Iran. Since 1990, the number of risk-attributable cancer deaths increased by 192% (146% to 242%). Regarding attributable DALYs and deaths, the key risk factors were tobacco, dietary risks, and high body-mass index (BMI), with high BMI and high fasting plasma glucose increasing by two-fold in DALYs. Tracheal, bronchus, and lung cancer, followed by colorectal cancer and stomach cancer, had the highest risk-attributable number of DALYs and deaths in both sexes. The risk-attributable age-standardized DALY rates for ovarian cancer [207% (87%–382%)], thyroid cancer [198% (74%–294%)], and multiple myeloma [192% (98%–349%)] showed the most significant increases. Conclusions The all-age number of cancer deaths attributable to risk factors have increased in Iran. The age-standardized DALY rates attributable to high BMI and high FPG doubled from 1990 to 2021, indicating the emerging role of metabolic risk factors in cancer burden. These insights will guide effective cancer prevention strategies in Iran.

Histology-specific long-term oncologic outcomes in patients with epithelial ovarian cancer who underwent complete tumor resection: The implication of occult seeds after initial surgery

Objective Assessing the histology-specific prognosis of epithelial ovarian cancer (OvCa) is clinically challenging, especially in a patient population with a favorable prognosis. This study investigated the histology-specific long-term oncologic outcomes in OvCa patients who underwent complete tumor resection using a large-scale patient cohort form multiple institutions under a central pathological review system. Methods A regional multi-institutional study was conducted from 1986 to 2019. Of the 4,898 patients with ovarian tumors enrolled, 1,175 patients who underwent complete tumor resection were classified into three classes based on clinically important prognostic factors: stage, cytology, ascites volume. For each class category, the effect of histology types on recurrence-free survival, the site of recurrence, and post-recurrence survival was evaluated. Results Recurrence-free survival varied significantly across different histologies (P < 0.001). The risk of recurrence was higher in serous carcinoma compare to other histologies (P < 0.001). The site of tumor recurrence varied by the histology type. Multinominal logistic regression analysis revealed that mucinous histology had a significantly higher likelihood of developing recurrent tumors at distant sites from the peritoneum compared to other histologies (P = 0.002). Conversely, serous histology was associated with better post-recurrence survival (Log-rank P < 0.001). Conclusions Long-term oncologic outcomes significantly differ by histology type in OvCa patients who have undergone complete tumor resection at the initial surgery. A careful evaluation of the clinical background is necessary for these patients, and further clinical research into individualized treatment approaches is essential.

Precision-cut tumor tissue slices, a novel tool to study the tumor microenvironment interactions with chimeric antigen receptor (CAR) T cells

Up until present day, chimeric antigen receptor (CAR)-T cell therapy has only been approved for hematological malignancies, as CAR-T cells do not show comparable efficacy in solid tumors. Therefore, understanding the features of the tumor microenvironment (TME), is key to improve efficacy of adoptive cell therapies (ACTs) against solid tumors. In this context, robust workflows, which dissect the complex interactions between CAR-T cells and the TME are still lacking. To address this need, we have established an ex vivo workflow co-culturing tissue slices from patient tumor resections with CAR-T cells. The workflow is composed of assessing several complementary attributes, such as cytokine release via flow cytometry, quantification of cell infiltration into the tumor and assessment of the regions of the tissue slice the CAR-T cell infiltrate into by using the MACSima™ imaging cyclic staining technology. Using this workflow it is possible to observe the behavior of CAR-T cells within the tumor and its TME, their infiltration into distinct tumor compartments, as well as to dissect the underlying molecular mechanisms that drive T cell migration, thanks to MACSima™ multiplexing technology and its ability to image several markers at the same time. Assessment of ovarian carcinoma tissue slices revealed substantial release of specific cytokines and increased infiltration of T cells in the tumor areas when CAR-T cells were added to the tissue slices as compared to non-engineered T cells. The establishment of this novel approach will enable researchers to better characterize the interaction between CAR-T cells and the TME. Tissue slices present an intrinsic heterogeneity, which is indeed an advantage compared to other in vitro models but can turn itself into complex results interpretation. Therefore, we recommend that any conclusion derived from this assay should be verified with complementary models.

Characterization of small extracellular vesicles from ovarian cancer patients and pre-diagnostic patient samples: Evidence from the Danish blood donor study

Aim Ovarian cancer (OC) is the leading cause of gynecological cancer deaths. Current biomarkers of OC are not specific or sensitive enough. Extracellular vesicles (EVs), EV surface proteins and their cargo microRNA (miRNA) show potential as biomarkers. This study aimed to characterize the ability of EVs to identify early OC-biomarkers among blood donors six months before their diagnosis. Methods Study groups of OC patients, benign tumor patients (B), healthy blood donors (Control), and blood donors with incident OC diagnosis within six months of the last blood draw (Pre-diagnostic; PD) were established. Small EVs were enriched from plasma using ultracentrifugation. EVs were characterized by Dynamic Light Scattering (DLS), EV Array, NanoFlow Cytometry, Nanoparticle Tracking Analysis, and Western blots. RNA from EVs was isolated. A discovery study was performed on OC and B patients using the TaqMan Array Human MicroRNA A card. A validation study of 9 specific miRNAs was performed using RT-qPCR. Results With DLS, it was identified that the OC patients’ EVs were more heterogeneous in size compared to the other groups. Western blot identified CD63 and TSG101 in the EV enrichments. EV Array assessed 22 known protein biomarkers. TaqMan MicroRNA Array cards indicated a differential miRNA abundance between OC and B; however, technical replication and validation could not validate this pattern. Conclusion This study has analyzed EVs in OC, B, Control, and PD women. More extensive investigations of EV CD9, CD151, and CD81 in conjunction with other risk factors and well-known biomarkers like CA125 or HE4 should be the main objectives of future research.

Fabrication and appraisal of targeted axitinib loaded bilosomes for the enhanced breast and ovarian anticancer activity

The goal of this study was the formulation and optimization by statistical means of bilosomal formulations of axitinib (AXT) in order to improve its anticancer efficacy in a targeted manner. A central composite rotatable design was employed Using Design-Expert® software. The formulation factors were cholesterol, span 60, and sodium deoxy cholate (SDC) amounts (mg), whereas the dependent responses were Entrapment efficiency (EE%), Vesicles’ size (VS), and Zeta potential (ZP). The design expert software was utilized to perform the numerical optimization process. The optimized bilosomal formulation was assessed using differential scanning calorimetry (DSC), X-ray diffraction (XRD), transmission electron microscope (TEM), in-vitro release study, short-term stability study, and in-vitro cell proliferation assay and flow cytometry on MCF-7 breast and OV-2774 ovarian cancer cell lines. The optimized formulation was found to be composed of 19.999, 111.869 and 15 mgs of cholesterol, span 60, and SDC, respectively with a desirability of 0.753. EE%, VS, and ZP were predicted to be 88.4977%, 594.592 nm, and −44.2354 mV, respectively. The validation process on the optimized formula demonstrated that the variation from the predicted responses was less than 5%. The DSC and XRD studies revealed that AXT was entrapped within the bilosomal vesicles. The optimized AXT bilosomal formulation exhibited spherical non-aggregated nanovesicles in TEM images. Furthermore, it improved AXT release when compared to AXT suspension. According to stability experiments, the optimum bilosomal formulation was stable for thirty days. The cytotoxicity of the optimized bilosomal formulation was enhanced on the MCF-7 breast and OV-2774 ovarian cancer cell lines compared to AXT suspension even at lower concentrations. Flow cytometry showed that AXT loaded BSMs made a significant increase in the percentage of apoptotic cells in MCF-7 and OV-2774 cells, respectively. Molecular docking suggests that axitinib and SDC decreased the activation of the caspase-8 receptor on the surface of ovarian and breast cancer, which consequently led to an increase in anticancer activity. So, BSMs might be regarded a promising carrier of AXT to target ant treat breast and ovarian cancers.

KU60019 inhibits ovarian cancer progression by targeting DGAT1/has-miR-1273g-3p axis

Ataxia telangiectasia mutated (ATM) blockage can induce apoptosis in ovarian cancer. However, the molecular mechanisms underlying this process remain poorly understood. In this study, ovarian cancer cells (SKOV3) were treated with an ATM inhibitor (KU60019) for 24 hours, and the fold changes of DGAT1 and hsa-miR-1273g-3p were quantified by real-time quantitative polymerase chain reaction (RT-qPCR). Gene Ontology (GO) and pathway enrichment analyses of DGAT1-associated functions were performed. Hsa-miR-1273g-3p mimics were used to investigate the relationship between DGAT1 and hsa-miR-1273g-3p in ovarian cancer cells under ATM inhibitor treatment, and cell apoptosis rate, viability, and migration were detected. The DGAT1 inhibitor reversed KU60019-induced migration impairment in SKOV3 cells. Finally, Kaplan-Meier analysis showed the correlation between DGAT1 level and survival in ovarian cancer patients. We found that ATM blockage significantly suppressed hsa-miR-1273g-3p level and elevated DGAT1 level in SKOV3 cells. DGAT1 was enriched in cytokine receptor interaction, T cell receptor signaling pathway, and cell apoptosis. Hsa-miR-1273g-3p mimics reversed suppression of DGAT1 and impaired cell viability induced by KU60019. Higher levels of DGAT1 associated with worse survival in ovarian cancer patients. KU60019 induced ovarian cancer cell impairment by enhancing DGAT1 level and suppressing hsa-miR-1273g-3p level. Our results demonstrate the antitumor effect of KU60019 in ovarian cancer depended on miR1273g-3p/DGAT1 axis.

Fabrication and appraisal of axitinib loaded PEGylated spanlastics against MCF- 7 and OV- 2774 cell lines using molecular docking methods and in-vitro study

Axitinib is a second-generation tyrosine kinase inhibitor that works by selectively inhibiting vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3). Through this mechanism of action, axitinib blocks angiogenesis, tumor growth and metastases and therefor it shows significant promise as a chemotherapeutic agent for various types of cancer. Nevertheless, the clinical efficacy of this substance is hindered by its restricted solubility in water and inadequate stability. To address these challenges, we developed spanlastics with polyethylene glycol (PEG) to improve the efficacy and stability of axitinib against breast and ovarian tumor malignancies in a targeted manner. Moreover, the study conducts a thorough examination of the interactions between the ligand Axitinib alone or after coating with PEG and a diverse array of protein types in breast (Dopamine, VEGFR) and ovarian cancer (EGFR, BCL-xL). The fabrication of axitinib- spanlastics was achieved through a thin-film hydration method. The evaluation of the impact of formulation factors on the features of nanovesicles was conducted using the I- optimal design. Subsequently, the optimum formulation was calculated. The optimal formulation was coated with polyethylene glycol (axitinib-PEG-spanlastics). An in vitro assessment was computed to evaluate the efficiency of the optimized axitinib-PEG-spanlastics against the MCF-7 breast cancer cell line and the OV-2774 ovarian cancer cell line. The optimized axitinib-PEG-spanlastics formulation exhibited a diameter of 563.42 ± 8.63 nm, accompanied by a zeta potential of −46.44 ± 0.09 mV. The formulation demonstrated an 84.32 ± 3.64% entrapment percent and a cumulative release of 73.58 ± 3.37% during a 4-hour period. The results obtained from the WST-1 assay showed a significant decrease in the percentage of cell survival, reaching 50% at a concentration of 0.68 µM for the PEG-spanlastics. In contrast, the axitinib free drug suspension exhibited 50% cell survival at a concentration of 1.1 µM in the breast cancer (MCF-7) cell line. In MCF-7 cells, the percentage of apoptotic cells generated by axitinib-PEG-spanlastics compared to the free drug suspension was 70.76 ± 4.971% vs. 32.6 ± 1.803%, while in OV-2774 cells, it was 43.55 ± 4.243% vs. 24.44 ± 4.950%. These results propose that Axitinib-PEG-spanlastics have the potential to be a successful nanoplatform for targeting breast and ovarian cancer and effectively managing tumors.

DNA alterations in ovarian adult granulosa cell tumours: A scoping review protocol

Background Identifying and describing molecular alterations in tumors has become common with the development of high-throughput sequencing. However, DNA sequencing in rare tumors, such as ovarian adult granulosa cell tumor (aGCT), often lacks statistical power due to the limited number of cases in each study. Questions regarding personalized treatment or prognostic biomarkers for recurrence or other malignancies therefore still need to be elucidated. This scoping review protocol aims to systematically map the current evidence and identify knowledge gaps regarding DNA alterations, actionable variations and prognostic biomarkers in aGCT. Methods This scoping review will be conducted based on Arksey and O’Malley’s methodological framework and later modifications by JBI Evidence Synthesis. The protocol complies with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. All original publications describing molecular alterations of aGCT will be included. The search will be performed in May 2024 in the following databases: MEDLINE (Ovid), Embase (Ovid), Web of Science Core Collection and Google Scholar (100-top ranked). Discussion This scoping review will identify knowledge and gaps in the current understanding of the molecular landscape of aGCT, clinical trials on actionable variations and priorities for future research. As aGCT are rare, a possible limitation will be the small sample sizes and heterogenic study settings. Scoping review registration The review protocol is registered at Open Science Framework under https://doi.org/10.17605/OSF.IO/PX4MF.

Cyclophosphamide- and doxorubicin-induced impairment of high affinity choline uptake and spatial memory can be prevented by dietary choline supplementation in breast tumor bearing mice

AC chemotherapy (Adriamycin and Cytoxan, i.e., doxorubicin and cyclophosphamide, respectively), a common treatment for breast cancer, can lead to significant cognitive side effects, known as Chemotherapy-Related Cognitive Impairments (CRCIs). These cognitive impairments can persist over 20 years and significantly affect the quality of life for cancer patients and survivors. AC chemotherapy is known to impair ovarian function and reduce circulating estradiol (E2), an effect that can decrease high-affinity choline uptake (HACU) and reduce acetylcholine (ACh) availability. Because ACh is involved in attention, learning and memory function we hypothesized that the cognitive deficits observed during and after adjuvant chemotherapy (AC) are associated with compromised high affinity choline uptake (HACU) due to suppressed ovarian function. Increasing available choline has been demonstrated to enhance HACU under conditions of demand for ACh, therefore we propose that choline supplementation can mitigate CRCIs by maintaining cholinergic function throughout and following chemotherapy treatment. Our study demonstrates cognitive deficits in tumor-bearing but not non-tumor-bearing mice during and following AC chemotherapy, suggesting that tumors enhance vulnerability to CRCIs. We found that HACU was impaired in tumor-bearing mice administered AC chemotherapy and that a choline-enriched diet can mitigate both the reduction of HACU induced by chemotherapy and deficits in spatial memory, suggesting a protective role of dietary choline against disruptions in HACU and cognitive impairment caused by chemotherapy. This underscores the potential use of dietary choline supplementation as a part of chemotherapeutic interventions.

Matching plasma and tissue miRNA expression analysis to detect viable ovarian germ cell tumors

Purpose MicroRNAs (miRNAs) are emerging as circulating biomarkers in germ cell tumors (GCT) with potential to guide management. Their role and expression patterns are more established in testicular GCTs, while lesser data exist in ovarian GCTs (OGCT). Methods Patients diagnosed with OGCT with plasma and tumor tissue available in our provincial biobank were included. Total RNA was extracted, and RT-qPCR was performed to measure miR-371–3 and miR-302/367 levels. Healthy plasma and ovarian tissue served as controls. Statistical analyses were performed using ANOVA and the Mann-Whitney U test. Clinicopathologic data was collected by chart review. Results From 2007 to 2022, 23 patients with OGCT were identified: 13 with viable non-teratoma germ cell (VNTGC) and 10 with immature teratoma germ cell (ITGC) tumors. Compared to healthy controls, all patients with VNTGC but not ITGC tumors had significantly higher miRNA levels in preoperative plasma and tumor tissue. Plasma miRNA kinetics correlated with disease burden, decreasing to undetectable levels following treatment, and increasing significantly upon relapse. Conclusion MiR-371–3 and miR-302/367 are highly expressed in ovarian VNTGC but not ITGC tumors, and their plasma levels correlate with disease burden. Future studies validating these findings in a larger cohort are needed to develop miRNAs as circulating biomarkers for clinical use.

Reduced occludin expression is related to unfavorable tumor phenotype and poor prognosis in many different tumor types: A tissue microarray study on 16,870 tumors

Occludin is a key component of tight junctions. Reduced occludin expression has been linked to cancer progression in individual tumor types, but a comprehensive and standardized analysis across human tumor types is lacking. To study the prevalence and clinical relevance of occludin expression in cancer, a tissue microarray containing 16,870 samples from 148 different tumor types and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Occludin immunostaining was observed in 10,746 (76.6%) of 14,017 analyzable tumors, including 18.9% with weak, 16.2% with moderate, and 41.6% with strong staining intensity. Occludin positivity was found in 134 of 148 tumor categories and was most frequent in adenocarcinomas (37.5-100%) and neuroendocrine neoplasms (67.9-100%), less common in squamous cell carcinomas (23.8-93%) and in malignant mesotheliomas (up to 48.1%), and rare in Non-Hodgkin’s lymphomas (1-2%) and most mesenchymal tumors. Reduced occludin staining was linked to adverse tumor features in several tumor types, including colorectal adenocarcinoma (advanced pT stage, p < 0.0001; L1 status, p = 0.0384; absence of microsatellite instability, p < 0.0001), pancreatic adenocarcinoma (advanced pT stage, p = 0.005), clear cell renal cell carcinoma (high ISUP grade, p < 0.0001; advanced pT stage, p < 0.0001; high UICC stage, p < 0.0001; distant metastasis, p = 0.0422; shortened overall or recurrence-free survival, p ≤ 0.0116), papillary renal cell carcinoma (high pT stage, p < 0.0001; high UICC stage, p = 0.0228; distant metastasis, p = 0.0338; shortened recurrence-free survival, p = 0.006), and serous high-grade ovarian cancer (advanced pT stage, p = 0.0133). Occludin staining was unrelated to parameters of tumor aggressiveness in breast, gastric, endometrial, and thyroidal cancer. Our data demonstrate significant levels of occludin expression in many different tumor entities and identify reduced occludin expression as a potentially useful prognostic feature in several tumor entities.

The endometrial cancer A230V-ALK5 (TGFBR1) mutant attenuates TGF-β signaling and exhibits reduced in vitro sensitivity to ALK5 inhibitors

The ALK5 (TGFBR1) receptor serine/threonine kinase transduces TGF-β (Transforming Growth Factor beta) signaling to activate SMAD2/3-dependent and -independent pathways. Here, we aimed to determine the functional consequences of ALK5 mutations in human endometrial cancer (EC). Somatic mutation data were retrieved from publicly available databases. Using seven in silico algorithms, 78.5% (11 of 14) of ALK5 kinase domain mutations in EC, including A230V-ALK5, were predicted to impact protein function. For in vitro studies, we focused on A230V-ALK5 because it was the only mutated residue located within the ATP-binding pocket, which is an important region for both ATP-binding and binding of ATP-competitive inhibitors. Constructs expressing wildtype-, constitutively-active-, kinase-dead-, or mutant A230V-ALK5, were transfected into NIH/3T3 cells. Following TGF-β1 stimulation, transient exogenous expression of A230V-ALK5 resulted in attenuated SMAD2/3 signal transduction and reduced AKT activation. We further showed that the A230V-ALK5 mutant had reduced stability resulting from increased ubiquitin-dependent protein degradation. Our structural modeling predicted that SB-431542, a small molecule ATP-competitive inhibitor of ALK5, binds to the A230V-ALK5 mutant with reduced affinity compared to wildtype-ALK5. We therefore examined the inhibitory effect of SB-431542 and galunisertib on wildtype- and mutant-ALK5 activity using a Smad-binding element (SBE) luciferase reporter assay combined with TGF-β1 stimulation, in NIH/3T3 cells and HEC-265 EC cells. SBE luciferase activity in A230V-ALK5 transfected cells was inhibited less by SB-431542 and galunisertib than in wildtype-ALK5 transfected cells indicating that A230V-ALK5 is less sensitive to inhibition by these agents than wildtype-ALK5, potentially due to changes in SB-431542/A230V-ALK5 binding affinity. Our findings are novel and show that A230V-ALK5 is a partial loss-of-function mutant that attenuates TGF-β1 signal transduction and has reduced sensitivity to ALK5 small molecule inhibitors.

Curcumin induces mitochondrial dysfunction-associated oxidative DNA damage in ovarian cancer cells

Resistance to chemotherapeutic agents is a critical challenge for the clinical management of ovarian cancer. While curcumin has been reported to possess anti-cancer properties, how it exerts its anti-neoplastic effect on ovarian cancer cells remains to be explored. We here characterized the fate of human ovarian cancer cell lines HO8910 and OVCAR3 treated with curcumin. Cell proliferation, cell death, mitochondrial function, oxidative damage and tumor formation in nude mice were examined. Significant inhibition of proliferation and induction of apoptosis were observed in ovarian cells treated with curcumin. The cancer cells exhibit cell cycle arrest at G2/M phase, mitochondrial accumulation, mitochondrial oxidative stress and high level of DNA damage after curcumin treatment. This effect of curcumin is independent of the BRCA mutation status. Curcumin-induced proliferation inhibition and apoptosis were effectively attenuated by the application of antioxidant N-acetylcysteine (NAC), suggesting that curcumin exerts its anti-cancer effect by inflicting oxidative stress. Curcumin applied at 200 mg/kg intraperitoneal infusion daily also inhibited the growth, oxidative damage, and mitochondrial accumulation of tumor xenografts in vivo. Together, the results indicate that curcumin can exert its anti-tumor effect via inducing mitochondrial dysfunction-associated oxidative DNA damage and can be potentially used in combination with other DNA repair-interfering therapeutics, such as PARP inhibitor, in the treatment of ovarian cancer.

Prognostic impact of suspicious extraabdominal lymph nodes on patient survival in advanced ovarian cancer

Objective To evaluate the clinical impact of suspicious extra-abdominal lymph nodes (EALNs) identified preoperatively on CT and/or PET/CT images in advanced ovarian cancer. Methods A retrospective study was conducted with 122 patients diagnosed with stage III or IV ovarian cancer with preoperative CT and/or PET/CT images from 2006 to 2022. Imaging studies were evaluated for the presence, size and location of suspicious EALNs. Suspicious lymph node enlargement was defined by a cut-off ≥5mm short-axis dimension on CT and/or lesions with maximum standardized uptake values of ≥2.5 on PET/CT. This study only included patients who did not have their EALNs surgically removed. Results A total 109 patients met the inclusion criteria; 36 (33%) had suspicious EALNs and were categorized as “node-positive”. The median overall survival (OS) was 45.73 months for the “node-positive” and 46.50 months for the “node-negative” patients (HR 1.17, 95% CI 0.68–2.00, p = 0.579). In multivariate analysis, after adjusting for other variables selected by process of backward elimination using a significance level of p<0.20, suspicious EALNs still showed no clinical significance on OS (aHR 1.20, 95% CI 0.67–2.13, p = 0.537) as well as progression-free survival (aHR 1.43, 95% CI 0.85–2.41, p = 0.174). Old age (aHR 2.23, 95% CI 1.28–3.89, p = 0.005) and platinum resistance (aHR 1.92, 95% CI 1.10–3.36, p = 0.023) affects adversely on OS. Conclusion Suspicious EALNs did not worsen the prognosis of patients with advanced ovarian cancer. However, its impact on survival is not yet clarified. Further investigation is required to assess the clinical significance of suspicious EALNs on preoperative imaging studies.

Deciphering ovarian cancer heterogeneity through spatial transcriptomics, single-cell profiling, and copy number variations

High-grade serous ovarian carcinoma (HGSOC) poses a formidable clinical challenge due to multidrug resistance (MDR) caused by tumor heterogeneity. To elucidate the intricate mechanisms underlying HGSOC heterogeneity, we conducted a comprehensive analysis of five single-cell transcriptomes and eight spatial transcriptomes derived from eight HGSOC patients. This study provides a comprehensive view of tumor heterogeneity across the spectrum of gene expression, copy number variation (CNV), and single-cell profiles. Our CNV analysis revealed intratumor heterogeneity by identifying distinct tumor clones, illuminating their evolutionary trajectories and spatial relationships. We further explored the homogeneity and heterogeneity of CNV across tumors to pinpoint the origin of heterogeneity. At the cellular level, single-cell RNA sequencing (scRNA seq) analysis identified three meta-programs that delineate the functional profile of tumor cells. The communication networks between tumor cell clusters exhibited unique patterns associated with the meta-programs governing these clusters. Notably, the ligand-receptor pair MDK - NCL emerged as a highly enriched interaction in tumor cell communication. To probe the functional significance of this interaction, we induced NCL overexpression in the SOVK3 cell line and observed enhanced tumor cell proliferation. These findings indicate that the MDK - NCL interaction plays a crucial role in promoting HGSOC tumor growth and may represent a promising therapeutic target. In conclusion, this study comprehensively unravels the multifaceted nature of HGSOC heterogeneity, providing potential therapeutic strategies for this challenging malignancy.

Screening outcome of HPV-vaccinated women: Data from the Danish Trial23 cohort study

Background Danish women—who were HPV-vaccinated as girls—are now reaching an age where they are invited to cervical cancer screening. Because of their expected lower cervical cancer risk, we must reassess our screening strategies. We analyzed Danish HPV-vaccinated women’s outcomes after the first screening test at age 23. Methods and findings Our study was embedded in Danish routine cytology-based screening. We conducted an observational study and included women born in 1994, offered the 4-valent HPV vaccine at age 14, and subsequently invited to screening at age 23. Cervical cytology was used for diagnostics and clinical management. Residual material was HPV tested with Cobas® 4800/6800. The most severe histology diagnosis within 795 days of screening was found through linkage with the Danish National Pathology Register. We calculated the number of women undergoing follow-up (repeated testing and/or colposcopy) per detected cervical intraepithelial neoplasia (CIN2+). A total of 6021 women were screened; 92% were HPV-vaccinated; 12% had abnormal cytology; 35% were high-risk HPV-positive, including 0.9% HPV16/18 positive, and 20% had follow-up. In women that were cytology-abnormal and HPV-positive (Cyt+/HPV+), 610 (98.5%) had been followed up, and 138 CIN2+ cases were diagnosed, resulting in 4.4 (95% CI 3.9–5.2) women undergoing follow-up per detected CIN2+. In contrast to recommendations, 182 (12.2%) cytology-normal and HPV-positive (Cyt-/HPV+) women were followed up within 795 days, and 8 CIN2+ cases were found, resulting in 22.8 (95% CI 13.3–59.3) women undergoing follow-up per detected CIN2+. Conclusion Overall, HPV prevalence was high in HPV-vaccinated women, but HPV16/18 had largely disappeared. In the large group of cytology-normal and HPV-positive women, 23 had been followed up per detected CIN2+ case. Our data indicated that primary HPV screening of young HPV-vaccinated women would require very effective triage methods to avoid an excessive follow-up burden. Trial registration Trial registration number: NCT0304955.

Improving prediction of cervical cancer using KNN imputer and multi-model ensemble learning

Cervical cancer is a leading cause of women’s mortality, emphasizing the need for early diagnosis and effective treatment. In line with the imperative of early intervention, the automated identification of cervical cancer has emerged as a promising avenue, leveraging machine learning techniques to enhance both the speed and accuracy of diagnosis. However, an inherent challenge in the development of these automated systems is the presence of missing values in the datasets commonly used for cervical cancer detection. Missing data can significantly impact the performance of machine learning models, potentially leading to inaccurate or unreliable results. This study addresses a critical challenge in automated cervical cancer identification—handling missing data in datasets. The study present a novel approach that combines three machine learning models into a stacked ensemble voting classifier, complemented by the use of a KNN Imputer to manage missing values. The proposed model achieves remarkable results with an accuracy of 0.9941, precision of 0.98, recall of 0.96, and an F1 score of 0.97. This study examines three distinct scenarios: one involving the deletion of missing values, another utilizing KNN imputation, and a third employing PCA for imputing missing values. This research has significant implications for the medical field, offering medical experts a powerful tool for more accurate cervical cancer therapy and enhancing the overall effectiveness of testing procedures. By addressing missing data challenges and achieving high accuracy, this work represents a valuable contribution to cervical cancer detection, ultimately aiming to reduce the impact of this disease on women’s health and healthcare systems.

Probing the role of Coniferin and Tetrahydrocurcumin from Traditional Chinese medicine against PSAT1 in early-stage ovarian cancer: An in silico study

Ovarian cancer, a formidable gynaecological malignancy, poses a significant global health challenge, and it is characterised by late-stage diagnosis and a high mortality rate. Even in its early stages, when treatment choices are scarce, ovarian cancer is still a complicated cancer to treat. In this work, we used computational approaches to find putative Traditional Chinese Medicine (TCM) inhibitors that target Phosphoserine Aminotransferase 1 (PSAT1), a crucial enzyme linked to the development of early-stage ovarian cancer. Using a methodical screening approach, we chose a panel of TCM compounds and prepared them, expected to interact with PSAT1. We next evaluated the binding affinities using molecular docking, which helped to identify Coniferin and Tetrahydrocurcumin compounds as potent inhibitors with the docking score of -8.8 kcal/mol and -8.9 Kcal/mol, respectively, and compared to the native ligand. The inhibitory effects of Coniferin and Tetrahydrocurcumin compounds were evaluated with the Pharmacokinetic studies and compared with the standard values, which resulted in an utter performance against each descriptor of the QikProp and performed the Molecular Interaction Fingerprints that resulted in the most interaction residues with counts were 4GLY, 4ASN, 4HIE, 4SER, 4THR, 3ARG and many more. Further, 100ns MD Simulation was performed in neutralised water, resulting in entirely stable deviations, fluctuations, and many intermolecular interactions, and the MM\GBSA studies on all 1000 trajectories have supported the complex’s stability. The computational studies have shown a completely stable performance that supports Coniferin, and Tetrahydrocurcumin can be a potent inhibitor of PSAT1. However, further experimental works are needed to confirm this study.

Decisional conflict and knowledge in women with BRCA1/2 pathogenic variants: An exploratory age group analysis of a randomised controlled decision aid trial

Female BRCA1/2 pathogenic variant (PV) carriers face substantial risks for breast and ovarian cancer. Evidence-based decision aids (DAs) can facilitate these women in their decision-making process on an individually suitable preventive strategy. However, there is a gap in previous literature exploring whether DA effectiveness varies according to women’s age. This is an exploratory subanalysis with a descriptive approach from a randomised controlled study assessing the effectiveness of a German decision aid (DA) for women with BRCA1/2 PVs compared to no DA use. From the original sample, women aged 18–40 years and >40 years and the intervention and control groups (IG, CG) within each of the age groups were compared regarding decisional conflict (using the Decisional Conflict Scale DCS) and knowledge at baseline and after DA use three and six months post study inclusion. The subanalysis involved 236 women aged 18–40 and 181 women aged >40 years. At baseline, both age groups differed significantly in all socio-demographic variables, except BRCA1/2 PV distributions. The younger age group displayed higher scores in the DCS subscale informed (p = .002) and higher knowledge (p = .010). Among the 18-40-year-olds, DA use (versus no DA) led to improvements in the DCS subscale informed at three (p = .025) and six months (p = .000). In the >40-year-olds, DA use (versus no DA) led to improvements in the DCS subscales informed (p = .028), values clarity (p = .028) and support (p = .030) and increased knowledge at three months (p = .048). These results indicate that both age groups benefited from DA use, but the older ones did so to a greater extent. This suggests that it might be useful to tailor DAs more closely to age- or life stage-related needs to enable more personalised care and support for women with BRCA1/2 PVs.

Investigation of the trends and associated factors of ovarian cancer in Indonesia: A systematic analysis of the Global Burden of Disease study 1990–2021

Introduction Ovarian cancer is one of the most lethal gynecological cancers. Despite diagnosis and treatment advances, survival rates have not increased over the past 32 years. This study estimated and reported the global burden of ovarian cancer during the past 32 years to inform preventative and control strategies. Methods We examined ovarian cancer incidence, mortality, and disability-adjusted life years (DALYs) using age-standardized rates from the Global Burden of Disease, Injuries, and Risk Factors Study 2021. high body mass index and occupational asbestos exposure were linked with death and DALYs. Data are presented as averages with 95% uncertainty intervals (UIs). Results Indonesia had 13 250 (8 574–21 565) ovarian cancer cases in 2021, with 5 296 (3 520–8958) deaths and 186 917 (121 866–309 820) DALYs. The burden increased by 233.53% for new cases, 221.95% for mortalities, and 206.65% for DALYs. The age-standardized rate also increased from 1990 to 2021. Ovarian cancer burden increased with age but declined in the 50+ year age group. According to the sociodemographic index, the gross domestic product per capita and number of obstetricians and oncologic gynecologists in provinces showed different trends. Conclusions Indonesian ovarian cancer rates are rising despite gynecologic oncologists in 24 of 34 provinces. These findings will help policymakers and healthcare providers identify ovarian cancer prevention and control gaps.

Unlocking prognostic potential: A genomic signature of caloric restriction in patients with epithelial ovarian cancer

Objectives Epithelial ovarian cancer is a significant contributor to cancer-related mortality in women, frequently recurring post-treatment, often accompanied by chemotherapy resistance. Dietary interventions have demonstrated influence on cancer progression; for instance, caloric restriction has exhibited tumor growth reduction and enhanced survival in animal cancer models. In this study, we calculated a transcriptomic signature based on caloric-restriction for ovarian cancer patients and explored its correlation with ovarian cancer progression. Methods We conducted a literature search to identify proteins modulated by fasting, intermittent fasting or prolonged caloric restriction in human females. Based on the gene expression of these proteins, we calculated a Non-Fasting Genomic Signature score for each ovarian cancer sample sourced from the Cancer Genome Atlas (TCGA) database. Subsequently, we examined the association between this genomic profile and various clinical characteristics. Results The non-fasting genomic signature, comprising eight genes, demonstrated higher prevalence in primary ovarian tumors compared to normal tissue. Patients with elevated signature expression exhibited reduced overall survival and increased lymphatic invasion. The mesenchymal subtype, associated with chemotherapy resistance, displayed the highest signature expression. Multivariate analysis suggested the non-fasting genomic signature as a potential independent prognostic factor. Conclusions Ovarian cancer tumors expressing a “non-fasting” transcriptional profile correlate with poorer outcomes, emphasizing the potential impact of caloric restriction in improving patient survival and treatment response. Further investigations, including clinical trials, are warranted to validate these findings and explore the broader applicability of non-fasting genomic signatures in other cancer types.

Mirvetuximab Soravtansine in solid tumors: A systematic review and meta-analysis

Background Mirvetuximab Soravtansine (MIRV) is a promising antibody‒drug conjugate (ADC) that targets folate receptor alpha (FRα), which is overexpressed in several types of solid tumors. In November 2022, MIRV was approved in the USA for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who received 1–3 prior systemic treatment regimens. Therefore, high-quality evidence for its efficacy and safety in different cancers is urgently needed. Methods A systematic search (e.g., PubMed, Embase, Web Of Science, Cochrane Library) was conducted to identify all relevant clinical trials of MIRV alone or in combination with chemo- and/or target-therapies in solid tumors. The primary end-point was median progression-free survival (mPFS). The secondary endpoints were the Objective response rate (ORR) and adverse effects (AEs). A random-effects model was applied. Results The study included nine research studies with a total of 682 patients. The pooled mPFS and pooled ORR were 6.70 months (95% CI 4.54–8.86, I2 = 96.21%) and 36% (95% CI: 28% to 44%, I2 = 76.79%), respectively. Significant differences were observed among intervention regimens and response to platinum. The pooled mPFS of MIRV monotherapy and MIRV+ Bevacizumab (BEV) combined therapy was 4.28 (95% CI 3.90–4.65, I2 = 0.00%) and 7.78 (95% CI 6.62–8.95, I2 = 0.00%), respectively. The pooled ORRs of MIRV monotherapy and MIRV+BEV combined therapy were 25% (95% CI 21%–29%, I2 = 25.20%) and 43% (95% CI 36%–50%, I2 = 0.01%), respectively. The pooled ORRs of the platinum-sensitive, platinum-resistant groups were 59% (95% CI 36%–81%, I2 = 61.88%), 33% (95% CI 25%–40%, I2 = 69.73%), respectively. In addition, we conducted supplementary subgroup analyses to explore the influence of FRα receptor expression levels and the number of prior treatments on treatment outcomes. The most common adverse effects were blurred vision (45.20%), nausea (40.13%), diarrhea (39.52%), fatigue (33.84%) and keratopathy (31.20%). Conclusions MIRV has significant therapeutic effects in solid tumors, especially when combined with BEV. In platinum-tolerant tumors, the efficacy of MIRV is also considerable. Overall, MIRV is relatively safe in solid tumors, and adverse reactions are relatively rare and mild.

DFASGCNS: A prognostic model for ovarian cancer prediction based on dual fusion channels and stacked graph convolution

Ovarian cancer is a malignant tumor with different clinicopathological and molecular characteristics. Due to its nonspecific early symptoms, the majority of patients are diagnosed with local or extensive metastasis, severely affecting treatment and prognosis. The occurrence of ovarian cancer is influenced by multiple complex mechanisms including genomics, transcriptomics, and proteomics. Integrating multiple types of omics data aids in predicting the survival rate of ovarian cancer patients. However, existing methods only fuse multi-omics data at the feature level, neglecting the shared and complementary neighborhood information among samples of multi-omics data, and failing to consider the potential interactions between different omics data at the molecular level. In this paper, we propose a prognostic model for ovarian cancer prediction named Dual Fusion Channels and Stacked Graph Convolutional Neural Network (DFASGCNS). The DFASGCNS utilizes dual fusion channels to learn feature representations of different omics data and the associations between samples. Stacked graph convolutional network is used to comprehensively learn the deep and intricate correlation networks present in multi-omics data, enhancing the model’s ability to represent multi-omics data. An attention mechanism is introduced to allocate different weights to important features of different omics data, optimizing the feature representation of multi-omics data. Experimental results demonstrate that compared to existing methods, the DFASGCNS model exhibits significant advantages in ovarian cancer prognosis prediction and survival analysis. Kaplan-Meier curve analysis results indicate significant differences in the survival subgroups predicted by the DFASGCNS model, contributing to a deeper understanding of the pathogenesis of ovarian cancer and providing more reliable auxiliary diagnostic information for the prognosis assessment of ovarian cancer patients.

High-throughput viable circulating tumor cell isolation using tapered-slit membrane filter-based chipsets in the differential diagnosis of ovarian tumors

Objective To evaluate the diagnostic performance of circulating tumor cells (CTCs) using tapered-slit membrane filter (TSF)-based chipsets for the differential diagnosis of adnexal tumors. Methods A total of 230 women with indeterminate adnexal tumors were prospectively enrolled. The sensitivity, specificity, and accuracy of the CTC-detecting chipsets were analyzed according to postoperative pathological results and compared with those of cancer antigen (CA)-125 and imaging tests. Results Eighty-one (40.3%) benign tumors, 31 (15.4%) borderline tumors, and 89 (44.3%) ovarian cancers were pathologically confirmed. The sensitivity, specificity, and accuracy of CTC-detecting chipsets (75.3%, 58.0%, and 67.1%) for differentiating ovarian cancer from benign tumors were similar to CA-125 (78.7%, 53.1%, and 66.5%), but lower than CT/MRI (94.2%, 77.9%, and 86.5%). “CTC or CA125” showed increased sensitivity (91.0%) and “CTC and CA-125” revealed increased specificity (77.8%), comparable to CT/MRI. CTC detection rates in stage I/II and stage III/IV ovarian cancers were 69.6% and 81.4%, respectively. The sensitivity to detect high-grade serous (HGS) cancer from benign tumors (84.6%) was higher than that to detect non-HGS cancers (68.0%). Conclusion Although the diagnostic performance of the TSF platform to differentiate between ovarian cancer and benign tumors did not yield significant results, the combination of CTC and CA-125 showed promising potential in the diagnostic accuracy of ovarian cancer.

From symptoms to surgery—A pathway through uncertainty and hope: An interview study of women facing ovarian surgery

Background Diagnosis of an adnexal mass might be a sign of ovarian cancer, with an overall poor prognosis. This study aimed to explore women’s experiences and perceptions of facing ovarian surgery due to an adnexal mass, and expectations on life after surgery. Methods Individual in-depth interviews with 15 women facing ovarian surgery due to an adnexal mass. Interviews were analysed using qualitative content analysis. Results An overarching theme, From symptoms to surgery–a pathway through uncertainty and hope, was identified. The theme was made up of three categories; I. The road to diagnosis, II. Striving for information and guidance, and III. Balancing emotions of hope and fear. The period between discovering the adnexal mass and surgery was often described as chaotic and difficult to manage. However, the diagnostic procedures were mostly described as timely and efficient, and participants felt safe and cared for. Person-centred care was considered crucial when being in this vulnerable situation, and the nurse navigator was described as a key person to approach for any queries. While participants expressed overall satisfaction with the information provided by health professionals, some reported a lack of information regarding the surgery’s potential impact on hormonal production and sexuality. Restrictions during the COVID-19 pandemic forced participants to attend healthcare visits alone, and some wished that health professionals had taken more responsibility for informing their relatives. Many participants focused on the positive aspects of the information gained about the adnexal mass, and that the entire situation gave perspective of what was important in life. Conclusions Waiting for surgery on a possibly malignant adnexal mass can be very stressful, however person-centred care and the guidance of a nurse navigator can make the process more manageable. To improve women’s experience, health professionals may involve relatives more often and make sure to inform of potential hormonal loss and sexuality after ovarian surgery.

Platelet and epithelial cell interations can be modeled in cell culture, and are not affected by dihomo-gamma-linolenic acid

Increasing evidence is implicating roles for platelets in the development and progression of ovarian cancer, a highly lethal disease that can arise from the fallopian tubes, and has no current method of early detection or prevention. Thrombosis is a major cause of mortality of ovarian cancer patients suggesting that the cancer alters platelet behavior. The objective of this study was to develop a cell culture model of the pathological interactions of human platelets and ovarian cancer cells, using normal FT epithelial cells as a healthy control, and to test effects of the anti-platelet dihomo-gamma-linolenic acid (DGLA) in the model. Both healthy and cancer cells caused platelet aggregation, however platelets only affected spheroid formation by cancer cells and had no effect on healthy cell spheroid formation. When naturally-formed spheroids of epithelial cells were exposed to platelets in transwell inserts that did not allow direct interactions of the two cell types, platelets caused increased size of the spheroids formed by cancer cells, but not healthy cells. When cancer cell spheroids formed using magnetic nanoshuttle technology were put in direct physical contact with platelets, the platelets caused spheroid condensation. In ovarian cancer cells, DGLA promoted epithelial-to-mesenchymal (EMT) transition at doses as low as 100 μM, and inhibited metabolic viability and induced apoptosis at doses ≥150 μM. DGLA doses ≤150 μM used to avoid direct DGLA effects on cancer cells, had no effect on the pathological interactions of platelets and ovarian cancer cells in our models. These results demonstrate that the pathological interactions of platelets with ovarian cancer cells can be modeled in cell culture, and that DGLA has no effect on these interactions, suggesting that targeting platelets is a rational approach for reducing cancer aggressiveness and thrombosis risk in ovarian cancer patients, however DGLA is not an appropriate candidate for this strategy.

Glyoxalase 1: Emerging biomarker and therapeutic target in cervical cancer progression

Introduction Cervical cancer presents a significant global health challenge, disproportionately impacting underserved populations with limited access to healthcare. Early detection and effective management are vital in addressing this public health concern. This study focuses on Glyoxalase-1 (GLO1), an enzyme crucial for methylglyoxal detoxification, in the context of cervical cancer. Methods We assessed GLO1 expression in cervical cancer patient samples using immunohistochemistry. In vitro experiments using HeLa cells were conducted to evaluate the impact of GLO1 inhibition on cell viability and migration. Single-cell RNA sequencing (scRNA-seq) and gene set variation analysis were utilized to investigate the role of GLO1 in the metabolism of cervical cancer. Additionally, public microarray data were analyzed to determine GLO1 expression across various stages of cervical cancer. Results Our analysis included 58 cervical cancer patients, and showed that GLO1 is significantly upregulated in cervical cancer tissues compared to normal cervical tissues, independent of pathological findings and disease stage. In vitro experiments indicated that GLO1 inhibition by S-p-bromobenzylglutathione cyclopentyl diester decreased cell viability and migration in cervical cancer cell lines. Analyses of scRNA-seq data and public gene expression datasets corroborated the overexpression of GLO1 and its involvement in cancer metabolism, particularly glycolysis. An examination of expression data from precancerous lesions revealed a progressive increase in GLO1 expression from normal tissue to invasive cervical cancer. Conclusions This study highlights the critical role of GLO1 in the progression of cervical cancer, presenting it as a potential biomarker and therapeutic target. These findings contribute valuable insights towards personalized treatment approaches and augment the ongoing efforts to combat cervical cancer. Further research is necessary to comprehensively explore GLO1’s potential in clinical applications.

Anti-Müllerian hormone and fertility in women after childhood cancer treatment: Association with current infertility risk classifications

Background To identify childhood cancer survivors (CCSs) at risk of premature ovarian insufficiency (POI) and impaired fertility is important given its impact on quality of life. The aim of this study was to assess ovarian markers and fertility outcomes in adult female CCSs. We used the Swedish and the PanCareLIFE classifications for infertility risk grouping. Methods 167 CCSs, at median age 34.6 years (19.3–57.8) with a median follow-up time of 25.4 years (11.6–41.3), and 164 healthy matched controls were included in this cross-sectional study. We assessed anti-Müllerian hormone (AMH) levels, antral follicle count (AFC), ovarian volume (OV), and fertility outcomes. Based on gonadotoxic treatments given, CCSs were categorized into infertility risk groups. Results The median levels of AMH, AFC and OV were lower in CCSs (1.9 vs. 2.1 ng/ml, 12.0 vs. 13.0, 6.8 vs. 8.0 cm3) compared with controls, although statistically significant only for OV (p = 0.021). AMH levels in CCSs <40 years were lower for those classified as high-risk (p = 0.034) and very high-risk (p<0.001) for infertility, based on the Swedish risk classification. Similarly, AFC was reduced in the high-risk (p<0.001) and the very high-risk groups (p = 0.003). CCSs of all ages showed a trend towards impaired fertility, especially in the very high-risk group. POI was diagnosed in 22/167 CCSs, of whom 14 were in the high- and very high-risk groups. The results according to the PanCareLIFE classification were similar. Conclusion Both the Swedish and the PanCareLIFE infertility risk classifications are reliable tools for identifying those at risk of reduced ovarian markers and fertility, as well as POI. We recommend fertility preservation counselling for patients receiving highly gonadotoxic treatments (i.e., Cyclophosphamide Equivalent Dose ≥6 g/m2, radiotherapy exposure to ovaries or stem cell transplantation) with follow-up at a young reproductive age due to the risk of a shortened reproductive window.

Prevalence of BRCA mutation in breast and ovarian cancer among women in India: A systematic review and meta-analysis protocol

Purpose We present a methodically devised protocol for conducting a systematic review and meta-analysis aimed at ascertaining the prevalence of BReast CAncer gene (BRCA) mutations in breast and ovarian cancer (BOC) among women in India. The review will include cross-sectional, cohort, case-series, and registry-based studies focusing on females clinically diagnosed with any stage of BOC, tested for BRCA germline mutation and undergone any form of treatment. Methods A Cochrane literature search will be carried out to identify all the published and unpublished articles available in English from 2010 till date across various electronic databases including PubMed, Psych Info, SCI, Cochrane Central, Embase, Scopus, IND Med and Google Scholar. A step-by-step process will be followed to select all the relevant studies for final inclusion using Rayyan software. The selection process of the review will be reported based on Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA) checklist. The protocol has been registered in PROSPERO (ID: CRD42023463452). Joanna Briggs Institute Critical Appraisal Checklist will be used to evaluate the methodological quality of the included studies. The outcome measure will be the prevalence of BRCA1/2 gene mutation in this population. Meta-analysis will be performed to report the pooled prevalence along with 95% confidence interval. Discussion The results of this review study will provide valuable insights for clinicians, and policy makers, enabling them to formulate guidelines that underscore the importance of screening for BRCA mutations in cases of BOC.

Polyploid giant cancer cells induced by Docetaxel exhibit a senescence phenotype with the expression of stem cell markers in ovarian cancer cells

Docetaxel (Doc) plays a crucial role in clinical antineoplastic practice. However, it is continuously documented that tumors frequently develop chemoresistance and relapse, which may be related to polyploid giant cancer cells (PGCCs). The aim of this study was investigate the formation mechanism and biological behavior of PGCCs induced by Doc. Ovarian cancer cells were treated with Doc, and then the effect of Doc on cellular viability was evaluated by MTT assay and microscopic imaging analysis. The biological properties of PGCCs were further evaluated by Hoechst 33342 staining, cell cycle and DNA content assay, DNA damage response (DDR) signaling detection, β-galactosidase staining, mitochondrial membrane potential detection, and reverse transcription-quantitative polymerase chain reaction. The results indicated that Doc reduced cellular viability; however, many cells were still alive, and were giant and polyploid. Doc increased the proportion of cells stayed in the G2/M phase and reduced the number of cells. In addition, the expression of γ-H2A.X was constantly increased after Doc treatment. PGCCs showed senescence-associated β-galactosidase activity and an increase in the monomeric form of JC-1. The mRNA level of octamer-binding transcription factor 4 (OCT4) and krüppel-like factor 4 (KLF4) was significantly increased in PGCCs. Taken together, our results suggest that Doc induces G2/M cell cycle arrest, inhibits the proliferation and activates persistent DDR signaling to promote the formation of PGCCs. Importantly, PGCCs exhibit a senescence phenotype and express stem cell markers.

Prediction of final pathology depending on preoperative myometrial invasion and grade assessment in low-risk endometrial cancer patients: A Korean Gynecologic Oncology Group ancillary study

Objectives Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST. Methods/Materials This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1–4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed. Results Among 251 eligible patients, Groups 1–4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4). Conclusions In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.

Construction and analysis of competitive endogenous RNA networks and prognostic models associated with ovarian cancer based on the exoRBase database

Objective To construct a competitive endogenous RNA (ceRNA) regulatory network in blood exosomes of patients with ovarian cancer (OC) using bioinformatics and explore its pathogenesis. Methods The exoRbase2.0 database was used to download blood exosome gene sequencing data from patients OC and normal controls and the expression profiles of exosomal mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) were detected independently using R language for differential expression analysis. TargetScan and miRanda databases were combined for the prediction and differential expression of mRNA-binding microRNAs (miRNA). The miRcode and starBase databases were used to predict miRNAs that bind to differentially expressed lncRNAs and circRNAs repectively. The relevant mRNA, circRNA, lncRNA and their corresponding miRNA prediction data were imported into Cytoscape software for visualization of the ceRNA network. The R language and KEGG Orthology-based Annotation System (KOBAS) were used to execute and illustrate the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Hub genes were identified using The CytoHubba plugin. Results Thirty-one differentially expressed mRNAs, 17 differentially expressed lncRNAs, and 24 differentially expressed circRNAs were screened. Cytoscape software was used to construct the ceRNA network with nine mRNA nodes, two lncRNA nodes, eight circRNA nodes, and 51 miRNA nodes. Both GO and KEGG were focused on the Spliceosome pathway, indicating that spliceosomes are closely linked with the development of OC, while heterogenous nuclear ribonucleoprotein K and RNA binding motif protein X-linked genes were the top 10 score Hub genes screened by Cytoscape software, including two lncRNAs, four mRNAs, and four circRNAs. In patients with OC, the expression of eukaryotic translation initiation factor 4 gamma 2 (EIF4G2), SERPINE 1 mRNA binding protein 1 (SERBP1), ribosomal protein L15 (RPL15) and human leukocyte antigen complex P5 (HCP5) was significantly higher whereas that of testis expressed transcript, Y-linked 15 and DEAD-box helicase 3 Y-linked genes was lower compared to normal controls Immunocorrelation scores revealed that SERBP1 was significantly and negatively correlated with endothelial cells and CD4+ T cells and positively correlated with natural killer (NK) cells and macrophages, respectively; RPL15 was significantly positively correlated with macrophages and endothelial cells and negatively correlated with CD8+ T cells and uncharacterized cells, respectively. EIF4G2 was significantly and negatively correlated with endothelial cells and CD4+ T cells, and positively correlated with uncharacterized cells, respectively. Based on the survival data and the significant correlation characteristics derived from the multifactorial Cox analysis (P < 0.05), the survival prediction curves demonstrated that the prognostic factors associated with 3-year survival in patients with OC were The prognostic factors associated with survival were Macrophage, RPL15. Conclusion This study successfully constructs a ceRNA regulatory network in blood exosomes of OV patients, which provides the specific targets for diagnosis and treatment of OC.

Detecting the impact of diagnostic procedures in Pap-positive women on anxiety using artificial neural networks

Introduction Women who receive a result of an abnormal Papanicolaou (Pap) smear can fail to participate in follow up procedures, and this is often due to anxiety. This study aimed to apply artificial neural networks (ANN) in prediction of anxiety in women with an abnormal Pap smear test, prior to and following diagnostic procedures. Methods One hundred-seventy two women who received an abnormal Pap screening result took part in this study, completing a questionnaire about socio-demographic characteristics and Hospital Anxiety and Depression Scale (HADS), right before and two to four weeks after diagnostics (i.e. colposcopy/biopsy/endocervical curettage). A feedforward back-propagation multilayer perceptron model was applied in analysis. Results Prior to diagnostic procedures 50.0% of women experienced anxiety, while after diagnostics anxiety was present in 61.6% of women. The correlation-based feature selection showed that anxiety prior to diagnostic procedures was associated with the use of sedatives, worry score, depression score, and score for concern about health consequences. For anxiety following diagnostics, predictors included rural place of residence, depression score, history of spontaneous abortion, and score for tension and discomfort during colposcopy. The ANN models yielded highly accurate anxiety prediction both prior and after diagnostics, 76.47% and 85.30%, respectively. Conclusion The presented findings can aid in identification of those women with a positive Pap screening test who could develop anxiety and thus represent the target group for psychological support, which would consequently improve adherence to follow-up diagnostics and enable timely treatment, finally reducing complications and fatal outcome.

PMFFNet: A hybrid network based on feature pyramid for ovarian tumor segmentation

Ovarian cancer is a highly lethal malignancy in the field of oncology. Generally speaking, the segmentation of ovarian medical images is a necessary prerequisite for the diagnosis and treatment planning. Therefore, accurately segmenting ovarian tumors is of utmost importance. In this work, we propose a hybrid network called PMFFNet to improve the segmentation accuracy of ovarian tumors. The PMFFNet utilizes an encoder-decoder architecture. Specifically, the encoder incorporates the ViTAEv2 model to extract inter-layer multi-scale features from the feature pyramid. To address the limitation of fixed window size that hinders sufficient interaction of information, we introduce Varied-Size Window Attention (VSA) to the ViTAEv2 model to capture rich contextual information. Additionally, recognizing the significance of multi-scale features, we introduce the Multi-scale Feature Fusion Block (MFB) module. The MFB module enhances the network’s capacity to learn intricate features by capturing both local and multi-scale information, thereby enabling more precise segmentation of ovarian tumors. Finally, in conjunction with our designed decoder, our model achieves outstanding performance on the MMOTU dataset. The results are highly promising, with the model achieving scores of 97.24%, 91.15%, and 87.25% in mACC, mIoU, and mDice metrics, respectively. When compared to several Unet-based and advanced models, our approach demonstrates the best segmentation performance.

Prediction of homologous recombination deficiency from Oncomine Comprehensive Assay Plus correlating with SOPHiA DDM HRD Solution

Objective Poly(ADP-ribose) polymerase (PARP) inhibitors are used for targeted therapy for ovarian cancer with homologous recombination deficiency (HRD). In this study, we aimed to develop a homologous recombination deficiency prediction model to predict the genomic integrity (GI) index of the SOPHiA DDM HRD Solution from the Oncomine Comprehensive Assay (OCA) Plus. We also tried to a find cut-off value of the genomic instability metric (GIM) of the OCA Plus that correlates with the GI index of the SOPHiA DDM HRD Solution. Methods We included 87 cases with high-grade ovarian serous carcinoma from five tertiary referral hospitals in Republic of Korea. We developed an HRD prediction model to predict the GI index of the SOPHiA DDM HRD Solution. As predictor variables in the model, we used the HRD score, which included percent loss of heterozygosity (%LOH), percent telomeric allelic imbalance (%TAI), percent large-scale state transitions (%LST), and the genomic instability metric (GIM). To build the model, we employed a penalized logistic regression technique. Results The final model equation is -21.77 + 0.200 × GIM + 0.102 × %LOH + 0.037 × %TAI + 0.261 × %LST. To improve the performance of the prediction model, we added a borderline result category to the GI results. The accuracy of our HRD status prediction model was 0.958 for the test set. The accuracy of HRD status using GIM with a cut-off value of 16 was 0.911. Conclusion The Oncomine Comprehensive Assay Plus provides a reliable biomarker for homologous recombination deficiency.

Evaluating synergistic effects of metformin and simvastatin on ovarian cancer cells

Background Ovarian Cancer (OC) stands as the most lethal gynecological malignancy, presenting an urgent clinical challenge in the quest to improve response rates. One approach to address this challenge is through drug repurposing, exemplified by the investigation of metabolic-modulating drugs such as Metformin (MTF) and Simvastatin (SIM). This study aims to explore the molecular mechanisms contributing to the potential synergistic anti-cancer effects between MTF and SIM on ovarian cancer cells. Methods We assessed the effects of the combination on the proliferation and viability of two cell lines OVCAR-3 and SKOV-3. IC50 concentrations of MTF and SIM were determined using a proliferation assay, followed by subtoxic concentrations to explore the potential synergistic effects on the viability of both cell lines. Transcriptomic analysis was conducted on OVCAR-3 treated cells, and the findings were validated by assessing the expression levels of differentially expressed genes (DEGs) through real-time PCR in both cell lines SK-OV-3 and OVCAR-3. Results Cytotoxicity analysis guided the selection of treatment concentrations as such MTF 10 mM and SIM 5 μM. The combined treatment of MTF and SIM demonstrated a synergistic inhibition of proliferation and viability in both cell lines. In OVCAR-3, exclusive identification of 507 DEGs was seen in the combination arm. Upregulation of FOXO3, RhoA, and TNFα, along with downregulation of PIK3R1, SKP2, and ATP6V1D levels, was observed in OVCAR-3 treated cells. Real-time PCR validation confirmed the consistency of expression levels for the mentioned DEGs. Conclusion Our data strongly supports the presence of synergy between MTF and SIM in OC cells. The combination’s effect is associated with the dysregulation of genes in the key regulators AMPK and mTOR alongside other interconnected pathways.

A deep learning framework for predicting endometrial cancer from cytopathologic images with different staining styles

Endometrial cancer screening is crucial for clinical treatment. Currently, cytopathologists analyze cytopathology images is considered a popular screening method, but manual diagnosis is time-consuming and laborious. Deep learning can provide objective guidance efficiency. But endometrial cytopathology images often come from different medical centers with different staining styles. It decreases the generalization ability of deep learning models in cytopathology images analysis, leading to poor performance. This study presents a robust automated screening framework for endometrial cancer that can be applied to cytopathology images with different staining styles, and provide an objective diagnostic reference for cytopathologists, thus contributing to clinical treatment. We collected and built the XJTU-EC dataset, the first cytopathology dataset that includes segmentation and classification labels. And we propose an efficient two-stage framework for adapting different staining style images, and screening endometrial cancer at the cellular level. Specifically, in the first stage, a novel CM-UNet is utilized to segment cell clumps, with a channel attention (CA) module and a multi-level semantic supervision (MSS) module. It can ignore staining variance and focus on extracting semantic information for segmentation. In the second stage, we propose a robust and effective classification algorithm based on contrastive learning, ECRNet. By momentum-based updating and adding labeled memory banks, it can reduce most of the false negative results. On the XJTU-EC dataset, CM-UNet achieves an excellent segmentation performance, and ECRNet obtains an accuracy of 98.50%, a precision of 99.32% and a sensitivity of 97.67% on the test set, which outperforms other competitive classical models. Our method robustly predicts endometrial cancer on cytopathologic images with different staining styles, which will further advance research in endometrial cancer screening and provide early diagnosis for patients. The code will be available on GitHub.

Protocol for a systematic review and meta-analysis of the impact of cervical cancer prevention initiatives in Ghana

Background Cervical cancer, though preventable, remains the second most diagnosed cancer and the primary cause of cancer-related deaths among females in Sub-Saharan Africa. The significance of coordinated screening programmes for reducing the burden of cervical cancer in Africa is not well documented. This systematic review will summarize published reports from key databases, grey literature and programme reports to assess the performance of cervical cancer prevention programmes in Ghana. Methods To be eligible for inclusion, interventions must target Ghanaian women with cervical cancer screening and prevention strategies using methods such as visual inspection with acetic acid (VIA), mobile colposcopy, HPV DNA testing, cytology (Pap smear), and treatment approaches such as cryotherapy, thermal ablation, loop electrosurgical excision procedure (LEEP). A comprehensive electronic search strategy will be used to identify studies published since database inception, and indexed in MEDLINE, EMBASE, CINAHL and Web of Science. The search strategy will include MeSH terms (and synonyms) relevant to cervical cancer, screening/treatment methods, geographic focus and implementing institution. We will include searches for grey literature, recognizing the value of programmatic and governmental reports that might not appear in traditional databases. Search results will be summarized in line with PRISMA guidelines. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to evaluate and document evidence certainty for all outcomes, internal validity of included reports, inconsistency, indirectness, imprecision, and publication bias. Where sufficient homogeneity exists among included studies in terms of interventions, study designs, populations, and outcome measures, we will perform a meta-analysis to calculate pooled effect estimates and their corresponding 95% confidence intervals. Significance This systematic review will assess the performance and impact of cervical cancer screening and prevention programmes conducted in Ghana to date and identify what contextual strategies have delivered the most impact as well as highlight what gaps remain in our understanding of how a nationwide screening programme can be properly construed for maximum impact.

Comprehensive analysis of single cell and bulk data develops a promising prognostic signature for improving immunotherapy responses in ovarian cancer

The tumor heterogeneity is an important cause of clinical therapy failure and yields distinct prognosis in ovarian cancer (OV). Using the advantages of integrated single cell RNA sequencing (scRNA-seq) and bulk data to decode tumor heterogeneity remains largely unexplored. Four public datasets were enrolled in this study, including E-MTAB-8107, TCGA-OV, GSE63885, and GSE26193 cohorts. Random forest algorithm was employed to construct a multi-gene prognostic panel and further evaluated by receiver operator characteristic (ROC), calibration curve, and Cox regression. Subsequently, molecular characteristics were deciphered, and treatments strategies were explored to deliver precise therapy. The landscape of cell subpopulations and functional characteristics, as well as the dynamic of macrophage cells were detailly depicted at single cell level, and then screened prognostic candidate genes. Based on the expression of candidate genes, a stable and robust cell characterized gene associated prognosis signature (CCIS) was developed, which harbored excellent performance at prognosis assessment and patient stratification. The ROC and calibration curves, and Cox regression analysis elucidated CCIS could serve as serve as an independent factor for predicting prognosis. Moreover, a promising clinical tool nomogram was also constructed according to stage and CCIS. Through comprehensive investigations, patients in low-risk group were charactered by favorable prognosis, elevated genomic variations, higher immune cell infiltrations, and superior antigen presentation. For individualized treatment, patients in low-risk group were inclined to better immunotherapy responses. This study dissected tumor heterogeneity and afforded a promising prognostic signature, which was conducive to facilitating clinical outcomes for patients with OV.

Cost-effectiveness analysis of olaparib maintenance therapy for BRCA mutation ovarian cancer in the public sector in Malaysia

Introduction Ovarian cancer is one of the most common cancer among women in Malaysia. Patients with ovarian cancer are often diagnosed at an advanced stage. Despite initial response to surgery and chemotherapy, most patients will experience a relapse. Olaparib has been reported have promising effects among BRCA mutated ovarian cancer patients. This study aimed to evaluate the cost–effectiveness of olaparib as a maintenance therapy for BRCA ovarian cancer in Malaysia. Methods We developed a four-state partitioned survival model which compared treatment with olaparib versus routine surveillance (RS) from a Malaysian healthcare perspective. Mature overall survival (OS) data from the SOLO-1 study were used and extrapolated using parametric models. Medication costs and healthcare resource usage costs were derived from local inputs and publications. Deterministic and probabilistic sensitivity analyses (PSA) were performed to explore uncertainties. Results In Malaysia, treating patients with olaparib was found to be more costly compared to RS, with an incremental cost of RM149,858 (USD 33,213). Patients treated with olaparib increased life years by 3.05 years and increased quality adjusted life years (QALY) by 2.76 (9.45 years vs 6.40 years; 7.62 vs 4.86 QALY). This translated to an incremental cost-effectiveness ratio (ICER) of RM 49,159 (USD10,895) per life year gained and RM54,357 (USD 12,047) per QALY gained, respectively. ICERs were most sensitive to time horizon of treatment, discount rate for outcomes, cost of treatment and health state costs, but was above the RM53,770/QALY threshold. Conclusion The use of olaparib is currently not a cost-effective strategy compared to routine surveillance based upon the current price in Malaysia for people with ovarian cancer with BRCA mutation, despite the improvement in overall survival.

CXC chemokines: Potential biomarker and immunotherapeutic target for uterine corpus endometrial carcinoma

Uterine corpus endometrial carcinoma (UCEC) is one of the most common type of gynecological malignancies. Multiple lines of evidence indicated that CXC chemokines exerted an anti-tumor immunological role in the tumor microenvironment which were critical regulators of cancer immunity. However, the relevance of CXC chemokines in the evaluation of prognosis and immune infiltration of UCEC remains to be explored. This study utilized various online databases, including TCGA, UALCAN, Kaplan-Meier Plotter, cBioPortal, TIMER2.0, TISIDB, and MethSurv to perform the analysis. Gene expression data from the TCGA-UCEC dataset indicated decreased expression of CXCL2/12 and increased expression of CXCL14/17. CXCL2/12 expression was negatively whereas CXCL14/17 expression was positively correlated with clinicopathological features of UCEC patients, including cancer stage, patients’ age, weight and menopause status. Patients with higher CXCL12/14 expression corresponded with better clinical outcomes, which were not influenced by the genetic alterations. The differential expression of CXCL2/12/14/17 was not only significantly correlated with immune infiltration levels, but also the abundance of immune checkpoint inhibitors. Heatmaps of DNA methylation of CXCL2/12/14/17 were investigated, and 4 CpGs of CXCL2, 16 CpGs of CXCL12, 3 CpGs of CXCL14/17 were identified where altered methylation affected the prognosis of UCEC patients. These findings provided novel insights into the immunologic features of UCEC and might pave the way toward the prognostic evaluation and immunotherapy selection based on CXCL2/12/14/17 expression status.

Efficacy of preoperative lymphoscintigraphy in predicting surgical outcomes of lymphaticovenous anastomosis in lower extremity lymphedema: Clinical correlations in gynecological cancer-related lymphedema

Background Lymphaticovenous anastomosis (LVA) is a promising microsurgical treatment for lower extremity lymphedema (LEL). Lymphoscintigraphy effectively assesses lower limb lymphatic systems before LVA, but its role in predicting the therapeutic outcomes of LVA is indeterminate. In this study we investigate the efficacy of preoperative lymphoscintigraphy using clinical findings to predict outcomes in gynecological cancer-related LEL patients who underwent LVA. Methods A retrospective review was conducted on consecutive gynecological cancer patients with LEL who had undergone LVA between June 2018 and June 2021. The therapeutic efficacy was assessed by measuring the change rate of the lower extremity lymphedema index (LELi) six months after surgery. Clinical data and lymphoscintigraphic findings were analyzed to assess therapeutic efficacy of LVA. Results Out of the 60 evaluated legs, 83.3% of the legs showed improved results after LVA. Univariable linear regression analysis revealed that higher preoperative LELi, and ovarian cancer were associated with superior LELi change rate (LC rate). Absence of dermal backflow (DBF) on lymphoscintigraphy was associated with inferior LC rate. Multivariable linear regression analysis identified ovarian cancer and higher preoperative LELi were independently correlated with favorable outcomes, while the absence of DBF was independently correlated with inferior outcomes. Conclusion The results of this study emphasizes the effectiveness of preoperative lymphoscintigraphy, preoperative LELi, and primary malignancy as predictors of LVA outcomes in gynecological cancer-related LEL patients.

The KRAS, ATR and CHEK1 expression levels in endometrial cancer are the risk factors predicting recurrence

Endometrial cancer is the most prevalent gynecologic malignancy with a high risk of recurrence. Local recurrence occurs in 7–20% of patients with treated stage I cancer within 3 years after primary treatment. In this study, we found significantly elevated mRNA expression levels of the oncoprotein KRAS, along with two replicative stress markers, ATR and CHEK1, in samples of endometrial carcinomas of endometrium (ECE) from patients with relapse. In contrast, mRNA expression levels of the studied genes were low and uniform in samples from patients without relapse. Elevated levels of KRAS protein and the phosphorylated form of ATR/CHEK1 were distinguishing features of recurrent ECE. A strong positive correlation was found between elevated mRNA and protein levels of the studied molecules. Elevated KRAS protein levels are characteristic of poorly differentiated (G3) endometrial carcinomas with deep myometrial invasion in patients without recurrence. In contrast, in patients with recurrence, higher protein levels of KRAS, pATR and pCHEK1 were observed in samples of G1-2 endometrial carcinomas, with statistically significant differences confirmed for pATR. High pCHEK1 protein levels are associated with deep tumor invasion in the myometrium among patients with recurrence. ROC analysis confirmed that evaluating the specificity and sensitivity of KRAS, pATR and pCHEK1 predicts recurrence development in patients with ECE. Our findings indicate that markers of replicative stress may play a significant role in ECE pathogenesis. Determining their levels in tumor samples after primary treatment could help define patients at high risk of recurrence and guide consequent courses of treatment.

Sociodemographic, clinical characteristics, and treatment patterns of endometrial cancer cases in Puerto Rico during the period 2009 to 2015: A retrospective study

Background Over the past decades, the rising incidence rates of endometrial cancer have made it a significant public health concern for women worldwide. Treatment strategies for endometrial cancer vary based on several factors such as stage, histology, the patient’s overall health, and preferences. However, limited amount of research on treatment patterns and potential correlations with sociodemographic characteristics among Hispanics is available. This study analyzes the treatment patterns for patients diagnosed with endometrial cancer in Puerto Rico. Methods A secondary database analysis was performed on endometrial cancer cases reported to the Puerto Rico Central Cancer Registry-Health Insurance Linkage Database from 2009 to 2015 (n = 2,488). The study population’s sociodemographic and clinical characteristics were described, along with an overview of the therapy options provided to patients receiving care on the island. Logistic regression models were used to evaluate the association of sociodemographic/clinical characteristics with treatment patterns stratified by risk of recurrence. Results In our cohort, most patients were insured through Medicaid and had a median age of 60 years. Almost 90% of patients received surgery as the first course of treatment. Surgery alone was the most common treatment for low-risk patients (80.2%). High-risk patients were more likely to receive surgery with radiotherapy and chemotherapy (24.4%). Patients with Medicare insurance were five times (HR: 4.84; 95% CI: 2.45–9.58; p < 0.001) more likely to receive surgery when compared with patients insured with Medicaid. In contrast, those with private insurance were twice as likely to receive surgery (HR: 2.38; 95% CI: 1.40–4.04; p = 0.001) when compared to those with Medicaid. Conclusion These findings provide insight into the treatment patterns for endometrial cancer in Puerto Rico and highlight the importance of considering factors such as disease risk when making treatment decisions. Addressing these gaps in treatment patterns can contribute to effective management of endometrial cancer.

Development of a long term, ex vivo, patient-derived explant model of endometrial cancer

Incidence of endometrial cancer (EC) is rising in the developed world. The current standard of care, hysterectomy, is often infeasible for younger patients and those with high body mass index. There are limited non-surgical treatment options and a lack of biologically relevant research models to investigate novel alternatives to surgery for EC. The aim of the present study was to develop a long-term, patient-derived explant (PDE) model of early-stage EC and demonstrate its use for investigating predictive biomarkers for a current non-surgical treatment option, the levonorgestrel intra-uterine system (LNG-IUS). Fresh tumour specimens were obtained from patients with early-stage endometrioid EC. Tumours were cut into explants, cultured on media-soaked gelatin sponges for up to 21 days and treated with LNG. Formalin-fixed, paraffin embedded (FFPE) blocks were generated for each explant after 21 days in culture. Tumour architecture and integrity were assessed by haematoxylin and eosin (H&E) and immunohistochemistry (IHC). IHC was additionally performed for the expression of five candidate biomarkers of LNG resistance. The developed ex vivo PDE model is capable of culturing explants from early-stage EC tumours long-term (21 Days). This model can complement existing models and may serve as a tool to validate results obtained in higher-throughput in vitro studies. Our study provides the foundation to validate the extent to which EC PDEs reflect patient response in future research.

Single-cell analysis reveals landscape of endometrial cancer response to estrogen and identification of early diagnostic markers

Background The development of endometrial cancer (EC) is closely related to the abnormal activation of the estrogen signaling pathway. Effective diagnostic markers are important for the early detection and treatment of EC. Method We downloaded single-cell RNA sequencing (scRNA-seq) and spatial transcriptome (ST) data of EC from public databases. Enrichment scores were calculated for EC cell subpopulations using the “AddModuleScore” function and the AUCell package, respectively. Six predictive models were constructed, including logistic regression (LR), Gaussian naive Bayes (GaussianNB), k-nearest neighbor (KNN), support vector machine (SVM), extreme gradient boosting (XGB), and neural network (NK). Subsequently, receiver-operating characteristics with areas under the curves (AUCs) were used to assess the robustness of the predictive model. Result We classified EC cell coaggregation into six cell clusters, of which the epithelial, fibroblast and endothelial cell clusters had higher estrogen signaling pathway activity. We founded the epithelial cell subtype Epi cluster1, the fibroblast cell subtype Fib cluster3, and the endothelial cell subtype Endo cluster3 all showed early activation levels of estrogen response. Based on EC cell subtypes, estrogen-responsive early genes, and genes encoding Stage I and para-cancer differentially expressed proteins in EC patients, a total of 24 early diagnostic markers were identified. The AUCs values of all six classifiers were higher than 0.95, which indicates that the early diagnostic markers we screened have superior robustness across different classification algorithms. Conclusion Our study elucidates the potential biological mechanism of EC response to estrogen at single-cell resolution, which provides a new direction for early diagnosis of EC.

COX7A1-mediated mitochondrial dysfunction can induce ferroptosis in endometrial cancer cells

In endometrial cancer, research on ferroptosis is still in its nascent stages, yet its potential therapeutic value is becoming increasingly evident. We explore the impact of COX7A1 on mitochondrial dysfunction and ferroptosis in endometrial cancer. In this study, through comprehensive bioinformatics analysis, differentially expressed genes related to ferroptosis in endometrial cancer were identified. In vitro experiments were conducted using cytochrome c oxidase subunit 7A1 (COX7A1) overexpression and knockdown cell lines, followed by ferroptosis-related phenotypic assays to validate the effect of COX7A1 on the inhibition of endometrial cancer cell growth. Mechanistically, mitochondrial function-related parameters were assessed to explore the potential mechanisms by which COX7A1 induces ferroptosis. Online data analysis revealed that COX7A1 acts as a ferroptosis driver and is significantly downregulated in endometrial cancer tissues. In vitro experiments have demonstrated that overexpression of COX7A1 inhibits the proliferation of endometrial cancer cells and induces ferroptosis by regulating intracellular iron metabolism and mitochondrial function. The specific mechanisms include increasing intracellular Fe 2+ and malondialdehyde (MDA) levels, decreasing the GSH/GSSG ratio, and disrupting mitochondrial membrane potential, thereby leading to mitochondrial dysfunction. Furthermore, COX7A1 overexpression significantly reduces the expression of glutathione peroxidase 4 (GPX4) and SLC7A11, while upregulating acyl-coenzyme A synthetase long-chain family member 4 (ACSL4). In contrast, knockdown of COX7A1 promotes the proliferation of endometrial cancer cells and inhibits ferroptosis, exhibiting the opposite effects. These findings provide new insights into the molecular mechanisms of endometrial cancer.

Multi-cancer analysis of histopathologic MSI screening based on digital histology image

Microsatellite instability, a genetic indication of DNA mismatch impairment, provides promising treatment options. Our study aimed to detect the mutation with whole-slide image (WSI) and discover the most effective pre-trained deep-learning model to sort diagnostic slides between high microsatellite instability (MSI-H) and microsatellite stable (MSS). WSI data retrieved from public dataset were processed for training and evaluating MSI categorization model. We detected MSI in slide levels for colorectal cancer (CRC), stomach adenocarcinoma (STAD), uterine corpus, and endometrial adenocarcinoma (UCEC). Models trained with a single tissue type were evaluated with the test dataset of corresponding tissue and subsequently with the test dataset of other types of tissue (cross-tissue evaluation). Finally, another model trained with multi-tissue types was built to predict the test dataset of individual tissue. Our models achieved AUC values of 0.93, 0.84, and 0.79 in TCGA-CRC, TCGA-STAD and TCGA-UCEC, respectively. We observed that a model trained on a corresponding tumor tissue demonstrates higher accuracy, particularly compared to those trained on other tumor tissues. In the combined model trained on multi-tissue, we observed diverse outcomes regarding which model was prioritized depending on the cancer type. These results demonstrate that models trained on multiple tissues have the potential to discern features that are generalizable across different types of cancer.

DDIAS promotes endometrial cancer progression via β-catenin signaling

Background DDIAS has been recognized as an oncogene in various cancers, but its role in endometrial cancer remains unexplored. Methods The expression of DDIAS in normal endometrium and endometrial cancer samples was analysed via the The Cancer Genome Atlas (TCGA) database, and prognostic analysis was performed. The differential expression of DDIAS between endometrial cancer and normal endometrium tissues was analyzed using quantitative polymerase chain reaction (qPCR). To study the expression of DDIAS in endometrial cancer, immunohistochemistry was performed on endometrial cancer, atypical endometrial hyperplasia and normal endometrial tissue. The association between DDIAS expression and clinicopathology was analysed. The expression of DDIAS in endometrial cancer cell lines was studied via Western blot (WB) analysis. DDIAS was knocked down in endometrial cancer cell lines via small interfering RNA (siRNA), and the effects of DDIAS knockdown on endometrial cancer cell biology and its related regulatory mechanisms were investigated via Cell Counting Kit-8(CCK8), Colony formation assay, scratch test, Transwell, and WB assays. Finally, the relevant regulatory mechanisms were verified using rescue experiments. Results According to the public database analysis, High DDIAS expression correlates with endometrial cancer and predicts unfavorable prognosis..The qPCR confirmed higher expression of DDIAS in tumor samples.We found that DDIAS was highly expressed in endometrial cancer and atypical endometrial hyperplasia, and that the upregulation of DDIAS expression predicted poor prognosis. In endometrial cancer, higher DDIAS expression was associated with increased tumor grade and advanced FIGO stage. In terms of cellular function, knocking down DDIAS suppressed the proliferation, migration and invasion capabilities of endometrial cancer cells. In the mechanistic pathway, reducing DDIAS expression led to the inhibition of β-catenin and its downstream targets, including c-Myc, cyclin D1, and survivin, while also suppressing epithelial-mesenchymal transition (EMT).However, these changes were rescued by the upregulation of β-catenin. Conclusion DDIAS regulated EMT in endometrial cancer cell migration and invasion through the β-catenin pathway, demonstrating that DDIAS is a potential target for the treatment of endometrial cancer.

Analysis of cervical and breast cancer screening behavior and its influencing factors among urban and rural women in Beijing

Objective To clarify the screening behavior and influencing factors of females with breast cancer and cervical cancer in suburban areas and to provide a scientific basis for the subsequent implementation of targeted health education, intervention measures and the formulation of relevant policies. Methods This study used a multi-stage stratified random sampling method to select 4, 000 women in urban and rural areas of Beijing to analyze their behavior, basic situation, and influencing factors regarding cervical and breast cancer screening. Results The sample size of the final included valid analysis was 3861 people, and the screening rate was 27.25% for cervical cancer, 20.64% for breast cancer, 30.46% for at least one screening and 17.43% for both cervical cancer and breast cancer screening. The rate of four screening conditions was greater in urban areas (PCervical cancer screening = 31.1%, PBreast cancer screening = 22.0%, PAt least one = 33.9%, PBoth cancers were screened = 19.1%) than in rural areas (PCervical cancer screening = 22.6%, PBreast cancer screening = 19.0%, PAt least one = 26.2%, PBoth cancers were screened = 15.4%) and was greater with medical insurance (PCervical cancer screening = 28.7%, PBreast cancer screening = 21.7%, PAt least one = 32.0%, PBoth cancers were screened = 18.5%) than without medical insurance (PCervical cancer screening = 12.8%, PBreast cancer screening = 10.3%, PAt least one = 15.6%, PBoth cancers were screened = 7.5%). The highest percentage of the four screening conditions was found in the 45–59-year-old group (PCervical cancer screening = 36.0%, PBreast cancer screening = 29.8%, PAt least one = 39.5%, PBoth cancers were screened = 26.4%). The rate of cervical cancer screening behavior increased with increasing education level and family per capita monthly income, and the highest percentage of respondents had a college education or above (PCervical cancer screening = 35.2%, PBreast cancer screening = 23.6%, PAt least one = 38.2%, PBoth cancers were screened = 20.6%), as did the percentage of families whose per capita monthly income was above 15, 000 yuan (PCervical cancer screening = 34.7%, PBreast cancer screening = 27.3%, PAt least one = 38.3%, PBoth cancers were screened = 23.6%). Multivariate analysis revealed that an age range of 45 to 59 years (PAll four screening conditions were obtained<0.001), an education level of junior high school, a high school (PAll four screening conditions were obtained<0.001), a college education or above (PAll four screening conditions were obtained<0.001), a marital status of a spouse (PAll four screening conditions were obtained<0.001), a divorce status (PAll four screening conditions were obtained<0.001) or a widowhood status (PAll four screening conditions were obtained<0.001), and a medical insurance status (PAll four screening conditions were obtained<0.001) were positively correlated with the percentages of the four screening behaviors. Conclusion The level of "two- cancer" screening behavior of suburban residents in Beijing still warrants improvement, and precision nutrition and health communication and intervention should be carried out continuously for rural residents, individuals under age 45, unmarried individuals, individuals with a primary school education and below, and people without medical insurance.

Time since last birth and the risk of endometrial cancer: A meta-analysis of observational studies

Introduction Endometrial cancer, an adenocarcinoma originating from the uterine lining, is the most prevalent cancer of the female genital tract globally.Identifying early risk factors for endometrial cancer is crucial for prevention.Prior research suggests that pregnancy may lower endometrial cancer risk by reducing estrogen exposure.This meta-analysis aims to delve into the existing population-based longitudinal studies to evaluate the association between the time elapsed since the last birth and the risk of endometrial cancer. Methods and analysis We searched PubMed, Cochrane Library, Embase, and Web of Science for cohort studies published up to June 21, 2024, using relevant medical subject headings (MeSH) and keywords. Statistical analyses were conducted using Stata version 14.0. A fixed-effects model was applied if P > 0.1 and I 2  ≤ 50%; otherwise, a random-effects model was used to account for significant heterogeneity Publication bias was assessed using funnel plots and Egger’s test. Our meta-analysis included 3 cohort studies and 5 case-control studies with a total of 3,310,734 participants, published between 1994 and 2024. The analysis revealed that time since last birth is associated with endometrial cancer risk. Specifically, a period of 0–10 years since the last birth was linked to a reduced risk of endometrial cancer (OR= 0.431; 95% CI: 0.351–0.530). A period of 10–20 years since the last birth also showed a decreased risk (OR=0.867; 95% CI:0.747–1.007), whereas more than 20 years since the last birth was associated with an increased risk (OR = 1.304; 95% CI: 1.111–1.530). Conclusions Our meta-analysis indicates that a shorter time since the last birth is protective against endometrial cancer, whereas a longer interval increases risk. Further research is needed to clarify the underlying mechanisms of this association. These findings are crucial for developing new strategies for endometrial cancer prevention and treatment.

Mitochondria-related genes as prognostic signature of endometrial cancer and the effect of MACC1 on tumor cells

Mitochondria are essential organelles involved in cell metabolism and are closely linked to various metabolic disorders. In this study, we aimed to develop a prognostic model for endometrial cancer (EC) patients based on mitochondria-related genes (MRGs), and to investigate the role of MACC1 in EC. As shown in the graphic summary, we retrieved gene expression and clinical data from open-access databases. To construct a predictive signature, we applied the Lasso Cox regression algorithm to MRGs. The predictive performance, immune features, and anti-tumor response of the mitochondrial signature were evaluated through multiple algorithms. Additionally, expression levels of key genes were validated using quantitative Real-Time PCR and Western Blot. A total of 2030 MRGs were retrieved, and 267 were found to be prognostically relevant. Eight MRGs—MACC1, CMPK2, NDUFAF6, DUSP18, TOMM40L, MT-TP, SAMM50, and MAIP1—were identified to construct a prognostic signature for EC. The MRG signature demonstrated significant associations with drug sensitivity, immune therapy, and immune cell infiltration. Based on comprehensive bioinformatic analysis, MACC1 was identified as the most promising MRG candidate in EC. Systematic experimental validation, including both in vitro and in vivo approaches, demonstrated that MACC1 down-regulation significantly suppressed EC progression, highlighting its potential as a therapeutic target.

Pan-cancer analysis and validation show GTF2E2’s diagnostic, prognostic, and immunological roles in regulating ferroptosis in endometrial cancer

Background Transcription initiation factor IIE subunit beta (GTF2E2) is a crucial component of the RNA polymerase II transcription initiation complex. There is a lack of more detailed research on the biological function of GTF2E2 in pan-cancer. Methods We conducted a comprehensive pan-cancer analysis using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) project. Employing a multi-pronged approach with tools including R, Cytoscape, TISIDB, cBioPortal, STRING, GSCALite, and CancerSEA, we investigated GTF2E2’s expression patterns, prognostic value, mutational landscape, functional enrichment, and immunological associations across 33 cancer types. Besides, we further validated the bioinformatic results through in vitro experiments in Uterine corpus endometrial carcinoma (UCEC), including western blotting (WB), cell proliferation assays and transwell. DCFH-DA, C11-BODIPY 581/591 and FeRhoNox-1 probes were performed to identify ferroptosis levels in vitro. Results GTF2E2 expression was significantly elevated in most cancers compared to normal tissues, with notable diagnostic potential (AUC > 0.7) in 20 cancer types. GTF2E2 expression varied across molecular and immune subtypes and correlated with tumor stage and patient age in several cancers. Functional enrichment analyses highlighted GTF2E2’s involvement in key cancer-related and immunological pathways. Notably, GTF2E2 promoted UCEC progression in vitro, and knockdown of GTF2E2 significantly inhibited the proliferation, migration and invasion of UCEC cells. Compared with the control group, GPX4 expression was down-regulated and ACSL4 expression was up-regulated in the GTF2E2-knockdown group. Knockdown of GTF2E2 also increased the intracellular levels of Fe2+, lipid peroxides (LPOs) and reactive oxygen species (ROS). Conclusions Our findings underscore GTF2E2’s multifaceted roles in cancer biology, highlighting its potential as a diagnostic biomarker, prognostic indicator, and immunotherapeutic target across various malignancies. This investigation has the potential to contribute significantly to a deeper understanding of the substantial involvement of GTF2E2 in human malignancies, particularly UCEC.

Identifying risk factors for cancer-specific early death in patients with advanced endometrial cancer: A preliminary predictive model based on SEER data

Objective To identify risk factors associated with cancer-specific early death in patients with advanced endometrial cancer and to develop a preliminary nomogram prediction model based on these factors, with an emphasis on the potential implications for clinical practice. Methods Patients from the Surveillance, Epidemiology, and End Results (SEER) database in the United States from 2018 to 2021 were included in the study. The study data was randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Multivariate logistic regression analysis was performed in the training cohort to screen for risk factors for cancer-specific early mortality in advanced endometrial cancer patients, and a preliminary nomogram prediction model was further constructed. The results of the Receiver Operating Characteristic (ROC) curve, calibration analysis, and clinical decision curve analysis (DCA) were presented for transparency. Results Significant risk factors for cancer-specific early death were identified, including tumor size (≥101 mm, OR = 2.11, P < 0.001), non-endometrioid histology (OR = 3.11, P < 0.001), high tumor grade (G3, OR = 2.68, P = 0.007), advanced tumor stages (T3-T4, OR = 1.84, P = 0.004), and metastatic stage (M1, OR = 2.05, P < 0.001), as well as the presence of liver metastases (OR = 2.21, P = 0.005) and brain metastases (OR = 8.08, P < 0.001). Protective factors that were significantly associated with a reduced risk of early death included hysterectomy (OR = 0.13, P = 0.012), radical surgery (OR = 0.21, P < 0.001), radiation therapy (OR = 0.40, P < 0.001), and chemotherapy (OR = 0.31, P < 0.001). A preliminary nomogram model was demonstrated adequate predictive performance with AUC values of 0.89 (95% CI 0.87 to 0.91) in the training cohort and 0.88 (95% CI 0.84 to 0.91) in the validation cohort. The model’s predictive performance was further supported by the calibration and DCA analyses, suggesting its potential clinical utility. Conclusion This study identified key risk factors for early cancer-specific mortality in patients with advanced endometrial cancer. The preliminary nomogram model holds promise for predicting early death risk and could be valuable in clinical practice. Future work may explore its performance with additional data to ensure broad applicability.

Comprehensive analysis of ceRNA Networks in UCEC: Prognostic and therapeutic implications

Endometrial cancer (UCEC) is the most prevalent gynecological malignancy in high-income countries, and its incidence is rising globally. Although early-stage UCEC can be treated with surgery, advanced cases have a poor prognosis, highlighting the need for effective molecular biomarkers to improve diagnosis and prognosis. In this study, we analyzed mRNA and miRNA sequencing data from UCEC tissues and adjacent non-cancerous tissues from the TCGA database. Differential expression analysis was conducted using the DESeq2 package, identifying differentially expressed lncRNAs, miRNAs, and mRNAs (DElncRNAs, DEmiRNAs, and DEmRNAs). Key molecules were screened using LASSO regression, and a ceRNA network was constructed by predicting lncRNA-miRNA and miRNA-mRNA interaction, which were visualized with Cytoscape. Functional enrichment analysis elucidated the roles and mechanisms of the network. The prognostic potential of the identified RNAs was assessed through survival and Cox regression analyses, while methylation and immune infiltration analyses explored regulatory mechanisms and immune interactions. We identified a prognostic lncRNA-miRNA-mRNA ceRNA network in UCEC, centered on the CDKN2B-AS1-hsa-miR-497-5p-IGF2BP3 axis. Survival analyses confirmed the prognostic significance of this network, with univariate Cox regression demonstrating a strong association between its aberrant expression and overall prognosis in UCEC. However, multivariate Cox regression suggested that other clinical factors may modulate this relationship. Methylation analysis revealed low methylation levels of IGF2BP3, possibly contributing to its overexpression. Furthermore, immune infiltration studies highlighted significant correlations between CDKN2B-AS1, IGF2BP3, and multiple immune cell types, suggesting that this axis regulates the tumor immune microenvironment. These findings suggest that the CDKN2B-AS1-hsa-miR-497-5p-IGF2BP3 axis is a key regulatory element in UCEC and a potential therapeutic target.

Synergistic cytotoxicity of olive leaf extract-loaded lipid nanocarriers combined with Newcastle disease virus against cervical cancer cells

Despite recent medical progress, cervical cancer remains a major global health concern for women. Current standard treatments have limitations such as non-specific toxicity that necessitate development of safer and more effective therapeutic strategies. This research evaluated the combinatorial effects of olive leaf extract (OLE), rich in anti-cancer polyphenols, and the oncolytic Newcastle disease virus (NDV) against human cervical cancer cells. OLE was efficiently encapsulated (>94% loading) within MF59 lipid nanoparticles and nanostructured lipid carriers (NLCs; contains Precirol as NLC-P, contains Lecithin as NLC-L) to enhance stability, bioavailability, and targeted delivery. Physicochemical analysis confirmed successful encapsulation of OLE within nanoparticles smaller than 150 nm. In vitro cytotoxicity assays demonstrated significantly higher toxicity of the OLE-loaded nanoparticle formulations on HeLa cancer cells versus HDF normal cells (P<0.05). MF59 achieved the highest encapsulation efficiency, while NLC-P had the best drug release profile. NDV selectively infected and killed HeLa cells versus HDF cells. Notably, combining NDV with OLE-loaded nanoparticles led to significantly enhanced synergistic cytotoxicity against cancer cells (P<0.05), with NLC-P (OLE) and NDV producing the strongest effects. Apoptosis and cell cycle analyses confirmed the increased anti-cancer activity of the combinatorial treatment, which induced cell cycle arrest. This study provides evidence that co-delivery of OLE-loaded lipid nanoparticles and NDV potentiates anti-cancer activity against cervical cancer cells in vitro through a synergistic mechanism, warranting further development as a promising alternative cervical cancer therapy.

The effectiveness of HPV16 and HPV18 genotyping and cytology with different thresholds for the triage of human papillomavirus-based screening on self-collected samples

Human papillomavirus (HPV) genotyping and cytology have been recommended for colposcopy triage, but it is unclear which combinations of high-risk HPV (hrHPV) types and cytology with various thresholds provide clinically useful information for the triage after primary HPV screening on self-collected samples. Chinese Multi-site Screening Trial (CHIMUST) database focused on self-collected samples was reviewed using the results of Cobas4800 HPV assay. Absolute risks of each genotype for cervical intraepithelial neoplasia 2 or worse/ 3 or worse (CIN2+/CIN3+) were calculated. Triage of atypical squamous cells of undetermined significance (ASCUS) or worse cytology was used as the comparator, and diagnostic accuracy for paired comparisons between algorithms was obtained using McNemar's test. A total of 10, 498 women were included, the overall prevalence of hrHPV, HPV16, HPV18, and Other hrHPV genotypes were 13.7%, 2.4%, 0.8%, and 10.5%, respectively. HPV16-positive women had the highest absolute risk among various genotypes for CIN2+/CIN3+ whether in normal or abnormal cytology (ASCUS or worse) and among all age groups. When compared with the comparator, combining HPV16 positivity and/or high-grade squamous intraepithelial lesion (HSIL) or worse yielded higher specificity (97.7% vs. 97.0%, p<0.0001), similar sensitivity (90.7% vs. 96.3%, p = 0.256) for detection of CIN3+, and a decrease in colposcopy referral rate from 3.5% to 2.7%, similar results were found for CIN2+. Positivity for HPV16 and/or (ASCUS or worse), and positivity for (HPV16 and/or HPV18) and/or (ASCUS or worse) achieved favorable sensitivity compared with the comparator (80.6% and 81.3% vs. 70.1% respectively for CIN2+, p<0.0001; both 96.3% vs. 96.3% for CIN3+, p = 1.000), these algorithms would reduce the colposcopy referral rate to 5.0% and 5.6% respectively, compared with 13.7% of that for HPV alone. Triage of HPV-positive women on self-collected samples by combining HPV16 or HPV16/18 genotyping with different thresholds of cytology could provide tradeoffs in sensitivity for detecting cervical lesions and colposcopy referral rates, and tailor management in various circumstances of clinical practice.

Personal and workplace factors influencing the resilience of nurses caring for women with cervical cancer in a resource-constrained setting in Ghana

Introduction Cervical cancer has been identified as the fourth most common form of malignancy affecting and killing women globally. Nurses caring for cervical cancer patients are exposed to emotional and psychological distress due to late presentation and the burden of care. Resilience has been identified as one of the effective ways of helping nurses to cope well with the stress of oncology nursing, but this remains undetermined in Ghana Aim This study explored personal and workplace factors influencing the resilience of nurses caring for women diagnosed with advanced cervical cancer (stage III and IV) in a resource-constrained setting in Ghana Method Using a qualitative approach, we recruited twenty nurses and midwives who had worked for a year and above caring for advanced-stage cervical cancer patients at the national referral hospital in Ghana. We conducted in-depth interviews between July, 2022 to September, 2022 which were audio-taped with participants’ consent. Transcription was done verbatim, and analysis conducted using thematic analysis approach with the aid of NVivo 10.0. Results The results revealed experience as a safety toolkit, inherent desire to help/care for the patient, emotional numbness and maintaining professional outlook as personal factors influencing resilience among the participants. Regarding the workplace factors influencing resilience, we identified the main theme of demands of caregiving for advanced cervical cancer patients with the following sub-themes; severity of cases managed, nature of care rendered, activities of care given, reshuffling, schedules and gender mirroring as an exacerbator of psychological suffering. Conclusion Resilience among nurses and midwives caring for terminally ill cervical cancer patients is influenced by longer years of service, intrinsic motivation to work as a nurse, and the defense strategy of emotional numbness and professionalism at the individual level. Also, the huge demand of caregiving serves as a major workplace factor affecting the resilience of nurses and midwives. We recommend strategies such as regular ward conferences and in-service trainings aimed at enhancing job-experience, inherent desire to render care and professionalism be adopted in resource-constrained settings to improve nurses’ resilience. In addition, political actors and management of hospitals must prioritize allocation of resources for advanced cervical cancer care with particular focus on providing more specialized nurses and midwives.

Mapping evidence on the distribution of uterine fibroids in sub-Saharan Africa: A scoping review protocol

Background Uterine fibroids are the most common pelvic benign tumours found in reproductive-aged women and may affect up to 70% of all women by menopause. Uterine fibroids place a heavy burden on women and society resulting in poor quality of life, impaired self-image, and impaired social, sexual, emotional, and physical well-being of affected individuals. Aim This study aims to map the evidence on the burden of uterine fibroids in Sub-Saharan Africa; uterine fibroids’ burden by age, uterine fibroids’ geographic burden, uterine fibroids’ cost estimation and reported experiences among women diagnosed with uterine fibroids. Setting Articles will be selected from countries within Sub-Saharan Africa Methods and analysis This scoping review will be guided by the Arksey &amp; O’Malley framework, enhanced by Levac et al (2010). The following electronic databases will be searched; PubMed, EBSCOhost (Cumulated Index to Nursing and Allied Health Literature and Health Source), Medical Literature Analysis and Retrieval System Online, Cochrane Library, Scopus, Web of Science, Africa Journal Online, and Google Scholar. The Population Concept and Context (PCC) framework will be used and the PRISMA flow diagram will also be used to show the literature search and selection of studies. Descriptive data analysis will be used; results will be presented in themes, narrative summaries, tables, and charts. Discussion The study anticipates finding relevant literature on the distribution of uterine fibroids, the burden of uterine fibroids in terms of geographic distribution, age distribution, and cost approximation related to the disease. This will assist in identifying research gaps to guide future research contribute to the body of scientific knowledge and develop preventative strategies for the disease.

Surgical outcomes of single-port vs multi-port laparoscopic hysterectomy for endometrial cancer: A systematic review and meta-analysis

Objective This study aimed to compare the surgical outcomes in patients with endometrial cancer who underwent either single-port laparoscopic hysterectomy (SPLH) or multi-port laparoscopic hysterectomy (MPLH). Methods We conducted a systematic literature search from the earliest records available up to May 2023. The databases searched included PubMed, Embase, ClinicalTrials.gov, and the Cochrane Library. Results A total of 12 studies were included in the analysis. Both the SPLH and MPLH groups had similar operative times (MD = -4.27, 95% CI [-35.75, 27.22], p = 0.98), conversion rates (odds ratio [OR] = 1.43, 95% CI [0.57, 3.59], p = 0.44), blood transfusion rates, intraoperative complications (bladder injury, bowel injury, and vascular injury), and postoperative complications (umbilical hernia, fever, fistula, lymphocyst, and wound-related issues). However, the SPLH group showed significant advantages in certain areas. There was a notable reduction in estimated intraoperative blood loss (EBL) compared to the MPLH group (mean difference [MD] = -23.80, 95% CI [-42.99, -4.62], p = 0.02) and a shorter hospital stay duration (MD = -0.33, 95% CI [-0.46, -0.20], p &lt; 0.00001). Although there was some debate about postoperative pain, SPLH tended to have more favorable outcomes. Despite these advantages, the SPLH group was less efficient in para-aortic lymph node clearance compared to the MPLH group (MD = -0.96, 95% CI [-1.57, -0.35], p = 0.002). No significant differences were observed in overall lymph node dissection (MD = -0.91, 95% CI [-2.52, 0.70], p = 0.27) and pelvic lymph node dissection (MD = -1.22, 95% CI [-3.82, 1.27], p = 0.36) between the two groups. Additionally, both groups showed similar therapeutic results, with no significant differences in overall survival (OS) and progression-free survival (PFS). Conclusion SPLH and MPLH techniques are equally effective in treating endometrial cancer, with both showing low rates of surgical complications with similar rates of surgical complications and therapeutic outcomes. However, SPLH offers additional benefits, including smaller incisions, reduced estimated intraoperative blood loss, and shorter hospital stays, making it an increasingly popular option for treating endometrial cancer.

Preserving circumflex iliac lymph nodes to reduce the incidence of lower limb lymphedema following lymphadenectomy in cervical and endometrial cancers: A prospective randomized controlled trial

Lower limb lymphedema (LLL) is a common postoperative complication following lymphadenectomy in cervical and endometrial cancers. Removal of the circumflex iliac nodes distal to the external iliac node (CINDEIN) is associated with LLL. Here, we sought to evaluate whether preserving the CINDEIN is helpful in reducing the incidence of LLL in women with cervical and endometrial cancers and to evaluate the safety of preserving CINDEIN. In this prospective randomized controlled trial, patients with clinical stage I A2 to II A cervical cancer and stage I to III endometrial carcinoma undergoing surgery were randomly assigned (1:1) to undergo pelvic lymphadenectomy with CINDEIN removal or preservation. The primary endpoint was the incidence of LLL at 24 months post-surgery. Eligible patients underwent sentinel lymph node (SLN) mapping with carbon nanoparticles (CNP). The study was registered with ClinicalTrials.gov, number ChiCTR2300071911. Between Jun 1, 2017, and Dec 31, 2018, 328 participants were randomly assigned to the two groups. Thirteen patients were excluded from the lymphedema analysis. A total of 158 patients in the CINDEIN preservation group and 157 in the CINDEIN removal group completed the follow-up examination. At baseline, no significant differences were observed between the two groups. The 3-year overall survival rate was 96.9% in the preservation group and 95.7% in the resection group. For cervical cancer and endometrial carcinoma, the incidence of LLL were significantly lower in the preservation group than in the removal group both at 24 months. No differences in the occurrence time of LLL were observed between the two groups. The LLL stages also showed no significant difference between the two groups. In the removal group, no CINDEIN metastases were identified in any patient. A total of 125 evaluable patients received the injection of CNP. None of the patients had CINDEIN detected as SLNs. CINDEIN removal is an important risk factor for LLL following lymphadenectomy in cervical and endometrial cancers. The metastasis rate of CINDEIN in cervical cancer and early endometrial cancer is relatively low, and preserving CINDEIN might be safe and helpful in reducing the occurrence of LLL.

Effect of ultrasound-guided transverse abdominal plane block on neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune inflammation index in patients undergoing radical resection of endometrial carcinoma

Objective The purpose of this trial was to explore the effects of the ultrasound-guided transverse abdominal plane block (TAPB) on the systemic immune-inflammatory index (SII), peripheral blood neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) in patients undergoing radical resection of endometrial carcinoma. Methods This trail was registered in the Chinese Clinical Trial Registry (ChiCTR2300072186, www.chictr.org/; approval date: 2023-06-06). In the study, a total of 90 patients who were scheduled for radical resection of endometrial carcinoma were selected, and they were randomized to receive ultrasound-guided TAPB combined with general anesthesia (GA) or either GA. The primary outcomes were the values of NLR、PLR and SII which were obtained at postoperative 24 hours and 72 hours. Other observational indicators included: the counts of neutrophil, lymphocyte, and platelet; the numbers of effective press of the analgesic pump; postoperative pain intensity; remifentanil consumption; and adverse reactions. Results The values of preoperative peripheral blood neutrophil, platelet, lymphocyte, NLR, PLR, and SII did not differ between the two groups (P&gt;0.05). The TAP+GA group exhibited significantly reduced levels of neutrophil, NLR, and SII at 24 and 72 hours post-surgery than the GA group (P&lt;0.05). However, there were no significant differences in the values of PLR between the two groups (P&gt;0.05). Compared with the GA group, the VAS scores at 6 hours, 12 hours, and 24 hours after surgery in the TAP+GA group were significantly decreased, and the intraoperative consumption of remifentanil and the numbers of postoperative analgesic pump presses were significantly reduced (P&lt;0.05). Moreover, the incidence of postoperative nausea and vomiting was reduced considerably in the TAP+GA group (P&lt;0.05). Conclusions Ultrasound-guided TAPB can effectively lower the values of postoperative neutrophil, NLR, and SII, improve postoperative pain intensity, decrease opioid consumption, and reduce the incidence of postoperative nausea and vomiting.

TMEM41A overexpression correlates with poor prognosis and immune alterations in patients with endometrial carcinoma

Background Expression levels of transmembrane protein 41A (TMEM41A) are related to the progression of malignant tumors. However, the association between TMEM41A expression and endometrial carcinoma (EC) remains unclear. This study aims to identify the roles of TMEM41A expression in the prognosis of patients with EC and its correlation with EC progression. Methods The TMEM41A expression and its correlation with the survival of patients with EC were assessed. Cox regression analysis was used to identify the prognostic factors, while nomograms were used to examine the association between the prognostic factors and the survival of patients with EC. Finally, the link between TMEM41A level and immune microenvironment and RNA modifications was investigated in EC. Results TMEM41A was overexpressed in EC. TMEM41A overexpression could diagnose the EC and evaluate the poor prognosis of patients. Overexpression of TMEM41A was associated with clinical stage, age, weight, histological subtype, tumor grade, and survival status of patients with EC. Clinical stage, age, tumor grade, radiotherapy, and TMEM41A overexpression were factors of poor prognosis in patients with EC. The nomograms revealed the correlation between the TMEM41A level and survival time of patients with EC at 1, 3, and 5 years. Furthermore, TMEM41A overexpression was significantly correlated with the level of the stromal score, immune score, estimate score, NK CD56 bright cells, iDC, NK cells, eosinophils, pDC, T cells, TReg, cytotoxic cells, mast cells, Th17 cells, neutrophils, aDC, NK CD56 dim cells, TFH, Th2 cells, CD8 T cells, macrophages, immune cell markers, and RNA modifications. Conclusions TMEM41A is overexpressed in EC tissues and is associated with the prognosis, immune microenvironment, and RNA modification. Our preliminary studies indicate that overexpression of TMEM41A can potentially serve as a biomarker for EC treatment.

Validation and usability of SeDAR e-health video for enhancing cervical cancer screening

Background The cervical cancer (CC) incidence rate is increasing among young women aged &lt;50 years despite early screening is proven effective. Electronic health (e-health) has great potential for disseminating health education. Methods This study validated a newly developed e-health tool “SeDAR®” and assessed its usability via evaluations by health experts (HE), media experts (ME), and women. The SeDAR® content was developed based on protection motivation theory (PMT) using the nominal group technique and in-depth interviews that involved HE and women, respectively. Content validation was performed among the HE (n = 12) and ME (n = 5) using the content validation index (CVI) to identify their agreement. Subsequently, the Video Engagement Scale (VES®) was used to validate SeDAR® among women of different ethnicities (n = 11) to achieve ecological validity. The experts and women also commented on the presentation of the video. Results The validation yielded a good CVI among the HE (scale-level CVI-average [SCVI/Ave] = 0.986; scale-level CVI-universal agreement [SCVI/UA] = 0.900) and ME (SCVI/Ave = 0.979, SCVI/UA = 0.897). The highest VES® score [mean (±SD) = 92.90(±3.46)] proved the ecological validity of SeDAR®. The experts’ feedback established that SeDAR® conveyed a clear message about awareness of performing CC screening and was suitable for public viewing. The women considered SeDAR® easy to understand, and it advised early exposure for early CC screening. Conclusions SeDAR® was valid and could constitute an important e-health tool to improve motivation and uptake of CC screening.

Impact of pre-treatment prognostic nutritional index and the haemoglobin, albumin, lymphocyte and platelet (HALP) score on endometrial cancer survival: A prospective database analysis

Purpose The Onodera’s prognostic nutritional index (PNI) and the haemoglobin, albumin, lymphocyte and platelet (HALP) score are immune-nutritional indices that correlate with survival outcomes in several adult solid malignancies. The aim of this study was to investigate whether PNI and HALP are associated with survival outcomes in endometrial cancer. Patients and methods Women undergoing management for endometrial cancer were recruited to a single centre prospective cohort study. Pre-treatment PNI and HALP scores were computed for study participants and analysed as continuous variables and by selecting cut-off values based on previous publications. Both parameters were analysed in relation to overall, endometrial cancer-specific and recurrence-free survival using Kaplan-Meier estimation and multivariable Cox proportional regression. Results A total of 439 women, with a median age of 67 years (interquartile range (IQR), 58, 74) and BMI of 31kg/m2 (IQR 26, 37) were included in the analysis. Most had low-grade (63.3%), early-stage (84.4% stage I/II) endometrial cancer of endometrioid histological subtype (72.7%). Primary treatment was surgery in 98.2% of cases. Adjusted overall mortality hazard ratios for PNI and HALP as continuous variables were 0.97(95%CI 0.94–1.00, p = 0.136) and 0.99(95%CI 0.98–1.01, p = 0.368), respectively. Women with pre-treatment PNI ≥45 had a 45% decrease in both overall (adjusted HR = 0.55, 95% CI 0.33–0.92, p = 0.022) and cancer-specific mortality risk (adjusted HR = 0.55, 95%CI 0.30–0.99, p = 0.048) compared to those with PNI &lt;45. There was no evidence for an effect of PNI on recurrence free survival. HALP scores were associated with adverse clinico-pathologic factors, but not overall, cancer-specific or recurrence-free survival in the multivariable analysis. Conclusion PNI is an independent prognostic factor in endometrial cancer and has the potential to refine pre-operative risk assessment.

MPA alters metabolic phenotype of endometrial cancer-associated fibroblasts from obese women via IRS2 signaling

Obese women have a higher risk of developing endometrial cancer (EC) than lean women. Besides affecting EC progression, obesity also affects sensitivity of patients to treatment including medroxprogesterone acetate (MPA). Obese women have a lower response to MPA with an increased risk for tumor recurrence. While MPA inhibits the growth of normal fibroblasts, human endometrial cancer-associated fibroblasts (CAFs) were reported to be less responsive to MPA. However, it is still unknown how CAFs from obese women respond to progesterone. CAFs from the EC tissues of obese (CO) and non-obese (CN) women were established as primary cell models. MPA increased cell proliferation and downregulated stromal differentiation genes, including BMP2 in CO than in CN. Induction of IRS2 (a BMP2 regulator) mRNA expression by MPA led to activation of glucose metabolism in CO, with evidence of greater mRNA levels of GLUT6, GAPDH, PKM2, LDHA, and increased in GAPDH enzymatic activity. Concomitantly, MPA increased the mRNA expression of a fatty acid transporter, CD36 and lipid droplet formation in CO. MPA-mediated increase in glucose metabolism genes in CO was reversed with a progesterone receptor inhibitor, mifepristone (RU486), leading to a decreased proliferation. Our data suggests that PR signaling is aberrantly activated by MPA in CAFs isolated from endometrial tissues of obese women, leading to activation of IRS2 and glucose metabolism, which may lead to lower response and sensitivity to progesterone in obese women.

The clinicopathology and survival characteristics of patients with POLE proofreading mutations in endometrial carcinoma: A systematic review and meta-analysis

Background Endometrial carcinoma (EC) is classified into four distinct molecular subgroups. Patients with polymerase epsilon exonuclease domain mutated (POLE-EDM) tumors have the best prognosis of all. This meta-analysis consolidated the clinicopathology variations reported in the POLE-mutant subtype and survival parameters in patients with EC. Methods The following internet data bases were searched: PubMed, Web of science, Embase and Scimage directory. Data was extracted from eligible studies including sample size, number of positive POLE-mutant cases, EDM sequencing information, clinicopathologic, and survival data. Meta-analysis and a random-effects model produced pooled estimates of POLE prognostic parameters using 95% confidence intervals (CI), hazard ratios (HR), and odds ratios (OR). Results The meta-analysis included 11 cohort studies comprising 5508 EC patients (442 POLE EDM tumors). Patients with POLE mutant EC were associated with improved disease specific survival (HR = 0.408, 95% CI: 0.306 to 0.543) and progression-free survival (HR = 0.231, 95% CI: 0.117 to 0.456). POLE-mutated tumors were mostly endometrioid histology (84.480%; 95% CI: 77.237 to 90.548), although not significantly more than wild type tumors (OR = 1.386; p = 0.073). The POLE mutant tumors significantly present (p&lt;0.001) at Federation of International of Gynecologists and Obstetricians (FIGO) lower stages I-II (OR = 2.955, p&lt;0.001) and highest grade III (OR = 1.717, P = 0.003). The tumors are significantly associated with invasion less than half (&lt;50%) of the myometrium (OR = 1.765, p = 0.001), but not deeply invasive EC (MI&gt;50%, OR = 0.83, p = 0.34). POLE mutations significantly protected against lymph node metastases (OR = 0.202, p = 0.001), and have no clear association with lymph-vascular space invasion (OR = 0.967, 95% 0.713–1.310, p = 0.826). The tumors are predominantly of low ESMO risk stratification distribution (40.356%; 95% CI: 27.577 to 53.838). Conclusions POLE mutations serve as an important biomarker of favorable prognosis in EC. The tumors are characteristically high grade, early stage, and remain localized in the endometrium with reduced likelihood of lymph node metastasis for improved survival prospects and the lowest risk classification. These findings have implications for medical management of EC.

Expression of epigenetic pathway related genes in association with PD-L1, ER/PgR and MLH1 in endometrial carcinoma

The distribution of Endometrial Cancer (EC)-related deaths is uneven among the morphologic subtypes of EC. Serous Cancer (SC) makes 10% of all EC and accounts for 40% of EC-related deaths. We investigated expression of selected genes involved in epigenetic pathways by immunohistochemistry in a cohort of 106 EC patients and analyzed mRNA-based expression levels for the same set of genes in EC samples from The Cancer Genome Atlas (TCGA) dataset. A tissue microarray was constructed using low-grade (n = 30) and high-grade (n = 28) endometrioid, serous (n = 31) and clear cell carcinoma (n = 17) samples. Epigenetic marker levels were associated with PD-L1, ER/PgR, and MLH1 expression. Epigenetic markers were evaluated by H-score and PD-L1 expression was recorded by using Combined Positive Score. Results were correlated with disease stage and survival outcome. BRD4, KAT6a and HDAC9 levels were higher in SC compared to other histologic subtypes (p&lt;0.001–0.038). After adjusting for multiple comparisons, DNMT3b expression was higher in SC compared to endometrioid-type but not between SC and CCC. The expression levels of BRD4 (p = 0.021) and KAT6a (p = 0.0027) were positively associated with PD-L abundance, while PgR (p = 0.029) and PD-L1 expression were negatively associated. In addition, BRD4 expression was low in specimens with loss of MLH1 expression (p = 0.02). More importantly, BRD4 abundance had a negative impact on disease outcome (p = 0.02). Transcriptionally, BRD4, KAT6a and DNMT3b expression levels were higher in SC in TCGA dataset. The median PD-L1 expression was marginally associated with BRD4, a transcriptional activator of CD274/PD-L1 (p = 0.069) and positively with KAT6a (p = 0.0095). In conclusion, the protein expression levels of epigenetic markers involved in cancer pathogenesis are increased by immunohistochemistry in SC. PD-L1 levels are associated with BRD4 and KAT6a in EC samples. A combination therapy with BRD4/PD-L1 or KAT6a/PD-L1 inhibitors might have a potential use in EC, in particular serous-type carcinoma.

Clinical factors as prognostic variables among molecular subgroups of endometrial cancer

Background Clinical factors may influence endometrial cancer survival outcomes. We examined the prognostic significance of age, body mass index (BMI), and type 2 diabetes among molecular subgroups of endometrial cancer. Methods This was a single institution retrospective study of patients who underwent surgery for endometrial carcinoma between January 2007 and December 2012. Tumors were classified into four molecular subgroups by immunohistochemistry of mismatch repair (MMR) proteins and p53, and sequencing of polymerase-ϵ (POLE). Overall, cancer-related, and non-cancer-related mortality were estimated using univariable and multivariable survival analyses. Results Age &gt;65 years was associated with increased mortality rates in the whole cohort (n = 515) and in the “no specific molecular profile” (NSMP) (n = 218) and MMR deficient (MMR-D) (n = 191) subgroups during a median follow-up time of 81 months (range 1‒136). However, hazard ratios for cancer-related mortality were non-significant for NSMP and MMR-D. Diabetes was associated with increased overall and non-cancer-related mortality in the whole cohort and MMR-D subgroup. Overweight/obesity had no effect on outcomes in the whole cohort, but was associated with decreased overall and cancer-related mortality in the NSMP subgroup, and increased overall and non-cancer-related mortality in the MMR-D subgroup. Overweight/obesity effect on cancer-related mortality in the NSMP subgroup remained unchanged after controlling for confounders. High-risk uterine factors were more common, and estrogen and progesterone receptor expression less common in NSMP subtype cancers of normal-weight patients compared with overweight/obese patients. No clinical factors were associated with outcomes in p53 aberrant (n = 69) and POLE mutant (n = 37) subgroups. No cancer-related deaths occurred in the POLE mutant subgroup. Conclusions The prognostic effects of age, BMI, and type 2 diabetes do not appear to be uniform for the molecular subgroups of endometrial cancer. Our data support further evaluation of BMI combined with genomics-based risk-assessment.

CKMT1A is a novel potential prognostic biomarker in patients with endometrial cancer

Purpose The International Federation of Gynecology and Obstetrics (FIGO) stage remains the standard staging system for the assessment of endometrial cancer (EC) prognosis. Thus, we aim to identify the significant genes or biomarkers associated with the stage of endometrial cancer, which may also help reveal the mechanism of EC progression and assess the prognosis of patients with EC. Materials and methods We compared the mRNA expression levels of EC patients with stages I and II as well as stages III and IV in the Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) of EC patients at different stages were selected by volcano plot and Venn analysis. Gene Ontology (GO) and Pathways were applied to analyze the identified genes. Protein protein interaction (PPI) network was employed to identify the correlation. The survival analyses based on TCGA database were conducted for further screening. The Human Protein Atlas, quantitative PCR and immunohistochemistry were utilized to confirm the differences in expression of DEGs in endometrial cancer samples at different FIGO stages. Results CKMT1A was identified as a candidate gene. Through survival analyses, we found that CKMT1A may be a poor prognostic factor in the overall survival of endometrial cancer patients. GO and Pathways revealed that CKMT1A is closely associated with the metabolic process. More importantly, Human Protein Atlas and quantitative PCR confirmed the differences in expression of CKMT1A in endometrial cancer samples at different FIGO stages. Conclusion In summary, this study shows that CKMT1A is a newly identified essential tumor progression regulator of endometrial cancer, which may give rise to novel therapeutic strategies in the management of endometrial cancer patients to prolong its prognosis and prevent tumor progression.

Characterization of the endometrial, cervicovaginal and anorectal microbiota in post-menopausal women with endometrioid and serous endometrial cancers

Objective To characterize the microbiota of postmenopausal women undergoing hysterectomy for endometrioid (EAC) or uterine serous cancers (USC) compared to controls with non-malignant conditions. Methods Endometrial, cervicovaginal and anorectal microbial swabs were obtained from 35 postmenopausal women (10 controls, 14 EAC and 11 USC) undergoing hysterectomy. Extracted DNA was PCR amplified using barcoded 16S rRNA gene V4 primers. Sequenced libraries were processed using QIIME2. Phyloseq was used to calculate α- and β- diversity measures. Biomarkers associated with case status were identified using ANCOM after adjustment for patient age, race and BMI. PICRUSt was used to identify microbial pathways associated with case status. Results Beta-diversity of microbial communities across each niche was significantly different (R2 = 0.25, p &lt; 0.001). Alpha-diversity of the uterine microbiome was reduced in USC (Chao1, p = 0.004 and Fisher, p = 0.007) compared to EAC. Biomarkers from the three anatomical sites allowed samples to be clustered into two distinct clades that distinguished controls from USC cases (p = 0.042). The USC group was defined by 13 bacterial taxa across the three sites (W-stat&gt;10, FDR&lt;0.05) including depletion of cervicovaginal Lactobacillus and elevation of uterine Pseudomonas. PICRUSTt analysis revealed highly significant differences between the USC-associated clades within the cervicovaginal and uterine microbiota. Conclusions The microbial diversity of anatomic niches in postmenopausal women with EAC and USC is different compared to controls. Multiple bacteria are associated with USC case status including elevated levels of cervicovaginal Lactobacillus, depletion of uterine Pseudomonas, and substantially different functional potentials identified within cervicovaginal and uterine niches.

Loss of ten-eleven translocation 1 (TET1) expression as a diagnostic and prognostic biomarker of endometrial carcinoma

Endometrial carcinoma (EC) is the most common gynecological cancer. However, there is currently no routinely used biomarker for differential diagnosis of malignant and premalignant endometrial lesions. Ten-eleven translocation (TET) proteins, especially TET1, were found to play a significant role in DNA demethylation, via conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1, 5-mC, and 5-hmC expression profiles in endometrial carcinogenesis are currently unclear. We conducted a hospital-based retrospective review of the immunohistochemical expression of TET1, 5-mC, and 5-hmC in 181 endometrial samples. A “high” TET1 and 5-hmC expression score was observed in all cases of normal endometrium (100.0% and 100.0%, respectively) and in most samples of endometrial hyperplasia without atypia (90.9% and 78.8%, respectively) and atypical hyperplasia (90.6% and 93.8%, respectively), but a “high” score was found in only less than half of the EC samples (48.8% and 46.5%, respectively). The TET1 and 5-hmC expression scores were significantly higher in normal endometrium and premalignant endometrial lesions than in ECs (p &lt; 0.001). A “high” 5-mC expression score was observed more frequently for ECs (81.4%) than for normal endometrium (40.0%), endometrial hyperplasia without atypia (51.5%), and atypical hyperplasia (53.1%) (p &lt; 0.001). We also found that TET1 mRNA expression was lower in ECs compared to normal tissues (p = 0.0037). TET1 immunohistochemistry (IHC) scores were highly proportional to the TET1 mRNA levels and we summarize that the TET1 IHC scoring can be used for biomarker determinations. Most importantly, a higher TET1 score in EC cases was associated with a good overall survival (OS) rate, with a hazard ratio (HR) of 0.31 for death (95% confidence interval: 0.11–0.84). Our findings suggest that TET1, 5-mC, and 5-hmC expression is a potential histopathology biomarker for the differential diagnosis of malignant and premalignant endometrial lesions. TET1 is also a potential prognostic marker for EC.

Differential impact of clinicopathological risk factors within the 2 largest ProMisE molecular subgroups of endometrial carcinoma

Objective To assess whether the prognostic impact of conventional risk factors and ancillary biomarkers differs across the 2 largest ProMisE molecular subgroups of endometrial carcinoma (EC). Methods Direct sequencing of POLE exonuclease domain hot spots and immunohistochemistry for MLH1, PMS2, MSH2, MSH6 and p53 were performed on 745 unselected endometrioid ECs to identify mismatch repair deficient (MMR-D, n = 264) and no specific molecular profile (NSMP, n = 206) ECs. Molecular group-specific survival analyses and interaction analyses were performed to determine the prognostic relevance of clinicopathological factors and various biomarkers (L1 cell adhesion molecule, estrogen and progesterone receptor, beta-catenin, p16, E-cadherin, KRAS) within the subgroups. Results Molecular subgroup did not have an independent effect on disease-specific survival after adjustment for conventional risk factors (P = 0.101). High grade (G3) and p16 hyperexpression remained significant predictors of survival in NSMP. Stage II-IV, ≥50% myometrial invasion, lymphovascular space invasion and loss of E-cadherin were independent predictors in the MMR-D group. In the interaction analysis, molecular subclass significantly modified the prognostic effect of high grade and p16 hyperexpression, which showed a stronger negative effect on survival in NSMP as compared to MMR-D (P for interaction = 0.016 for grade and 0.033 for p16). Conclusions Grade of differentiation and p16 hyperexpression appear to have a stronger prognostic impact in NSMP as compared to MMR-D EC. While these results need to be confirmed in a larger study population, they indicate that differential impact of risk factors needs to be taken into account when developing new molecular class-integrated risk stratification algorithms for EC.

Integrated microRNA and mRNA signatures associated with overall survival in epithelial ovarian cancer

Ovarian cancer (OC), the eighth-leading cause of cancer-related death among females worldwide, is mainly represented by epithelial OC (EOC) that can be further subdivided into four subtypes: serous (75%), endometrioid (10%), clear cell (10%), and mucinous (3%). Major reasons for high mortality are the poor biological understanding of the OC mechanisms and a lack of reliable markers defining each EOC subtype. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression primarily by targeting messenger RNA (mRNA) transcripts. Their aberrant expression patterns have been associated with cancer development, including OC. However, the role of miRNAs in tumorigenesis is still to be determined, mainly due to the lack of consensus regarding optimal methodologies for identification and validation of miRNAs and their targets. Several tools for computational target prediction exist, but false interpretations remain a problem. The experimental validation of every potential miRNA-mRNA pair is not feasible, as it is laborious and expensive. In this study, we analyzed the correlation between global miRNA and mRNA expression patterns derived from microarray profiling of 197 EOC patients to identify the signatures of miRNA-mRNA interactions associated with overall survival (OS). The aim was to investigate whether these miRNA-mRNA signatures might have a prognostic value for OS in different subtypes of EOC. The content of our cohort (162 serous carcinomas, 15 endometrioid carcinomas, 11 mucinous carcinomas, and 9 clear cell carcinomas) reflects a real-world scenario of EOC. Several interaction pairs between 6 miRNAs (hsa-miR-126-3p, hsa-miR-223-3p, hsa-miR-23a-5p, hsa-miR-27a-5p, hsa-miR-486-5p, and hsa-miR-506-3p) and 8 mRNAs ( ATF3 , CH25H , EMP1 , HBB , HBEGF , NAMPT , POSTN , and PROCR ) were identified and the findings appear to be well supported by the literature. This indicates that our study has a potential to reveal miRNA-mRNA signatures relevant for EOC. Thus, the evaluation on independent cohorts will further evaluate the performance of such findings.

Personalized tumor-specific DNA junctions to detect circulating tumor in patients with endometrial cancer

Introduction There are no reliable blood biomarkers for monitoring endometrial cancer patients in the current clinical practice. Circulating tumor DNA (ctDNA) is emerging as a promising non-invasive method to measure tumor burden, define prognosis and monitor disease status in many solid cancers. In this pilot study, we investigated if unique tumor-specific DNA junctions can be used to detect ctDNA levels in patients with endometrial cancer. Methods Chromosomal rearrangements in primary tumors of eleven patients with high-grade or advanced stage endometrial cancer were determined by whole-genome Mate-Pair sequencing. Identified unique tumor-specific junctions were evaluated in pre- and six-week post-surgery patient plasma using individualized quantitative polymerase chain reaction (qPCR) assays. The relationship between clinicopathological features and detection of ctDNA was investigated. Results CtDNA was detected in 60% (6/10) of cases pre-surgery and in 27% (3/11) post-surgery. The detection of ctDNA pre-surgery was consistent with clinical indicators of aggressive disease such as advanced stage (80% - 4/5), lymphatic spread of disease (100% - 3/3), serous histology (80% - 4/5), deep myometrial invasion (100% - 3/3), lympho-vascular space invasion (75% - 3/4). All patients in which ctDNA was detected post-surgically had type II endometrial cancer. Discussion This pilot study demonstrates the feasibility of using personalized tumor-specific junction panels for detecting ctDNA in the plasma of endometrial cancer patients. Larger studies and longer follow-up are needed to validate the potential association between pre-surgical ctDNA detection and the presence of cancers with aggressive pathologic tumor characteristics or advanced stage observed in this study.

Non-invasive host transcriptome and HPV oncogene expression map the molecular landscape of HPV-driven cervical lesions

Cervical cancer remains a significant global health burden. Current screening methods are not yet capable of detecting molecular alterations preceding cytological abnormalities. In this study, we performed integrative transcriptomic profiling of 132 HPV-positive cervical Pap Smear specimens (NILM, ASCUS, LSIL, HSIL), combining HPV genotyping, and E6/E7 mRNA quantification to map molecular progression. Our analysis revealed stage-specific signatures: NILM displayed a “stealth infection” profile marked by upregulated protein synthesis and growth signaling (EGFR/ERBB2) alongside immune suppression. ASCUS presented a critical tipping point with introduction of early oncogenic drivers (CCND1, SHH), while LSIL prioritized viral productivity with suppressed antimicrobial defenses (MPO, DEFA1). HSIL was distinct from earlier stages and defined by cell cycle hyperactivation (CDK1, PLK1), replication licensing (MCMs), and epithelial dedifferentiation. Pathway crosstalk analysis demonstrated minimal overlap between HSIL and earlier stages (OC &lt; 0.07), highlighting molecular discontinuity during malignant transformation. Additionally, E6/E7 mRNA Ct levels were significantly associated with lesion severity (X 2  = 24.407, df = 9, p  = 0.003), indicating higher viral mRNA expression are associated with more severe cytological abnormalities. These findings highlight the transformative potential of transcriptomic profiling in cervical cancer prevention, offering stage-specific biomarkers to refine risk stratification. By integrating transcriptomics profiling with current clinical testing, clinicians can distinguish transient infections from high-risks lesions likely to progress. This combined approach addresses the critical limitations of morphology and DNA-based methods, enabling more precise therapeutic interventions and reducing unnecessary overtreatment, and the risk of undertreatment or dismissal of high-risk cases.

Establishment and characterization of VOA1066 cells: An undifferentiated endometrial carcinoma cell line

Dedifferentiated endometrial carcinoma (DDEC) is a rare but highly aggressive type of endometrial cancer, in which an undifferentiated carcinoma arises from a low-grade endometrioid endometrial carcinoma. The low-grade component is often eclipsed, likely due to an outgrowth of the undifferentiated component, and the tumor may appear as a pure undifferentiated endometrial carcinoma (UEC). We and others have recently identified inactivating mutations of SMARCA4, SMARCB1 or ARID1B, subunits of the SWI/SNF chromatin-remodeling complex, that are unique to the undifferentiated component and are present in a large portion of DDEC and UEC. However, the understanding of whether and how these mutations drive cancer progression and histologic dedifferentiation is hindered by lack of cell line models of DDEC or UEC. Here, we established the first UEC cell line, VOA1066, which is highly tumorigenic in vivo. This cell line has a stable genome with very few somatic mutations, which do include inactivating mutations of ARID1A and ARID1B (2 mutations each), and a heterozygous hotspot DICER1 mutation in its RNase IIIb domain. Immunohistochemistry staining confirmed the loss of ARID1B, but ARID1A staining was retained due to the presence of a truncating non-functional ARID1A protein. The heterozygous DICER1 hotspot mutation has little effect on microRNA biogenesis. No additional DICER1 hotspot mutations have been identified in a cohort of 33 primary tumors. Therefore, we have established the first UEC cell line with dual inactivation of both ARID1A and ARID1B as the main genomic feature. This cell line will be useful for studying the roles of ARID1A and ARID1B mutations in the development of UEC.

Establishment of a rabbit uterine cancer model using VX2 tumor fragments

Background Preclinical uterine cancer models using the rabbit VX2 system have been described in previous studies; however, they often involve complex procedures such as cell culture, uterine suturing, or imaging validation. This study aimed to establish a technically simple and reproducible rabbit model of uterine cancer using VX2 tumor fragments. Methods We established a rabbit uterine cancer model by injecting minced VX2 tumor tissue into the endometrium of New Zealand White rabbits. We first generated VX2 tumors in donor rabbits via subcutaneous thigh injection and harvested them after three weeks. Recipient rabbits were assigned to two cohorts with scheduled assessments at 14 days or 4 weeks post-implantation. Tumor formation was assessed at each time point by intraoperative inspection and histopathological analysis. Results In the initial 14-day cohort (n = 8), all rabbits developed well-defined uterine tumors without perioperative complications. Histological analysis confirmed viable tumor growth. No lymph node metastasis or distant spread was observed at the 14-day endpoint. In a separate, extended 4-week cohort (n = 8), all rabbits also developed uterine tumors. This cohort demonstrated tumor progression, with 75% exhibiting retroperitoneal lymph node metastasis, and 37.5% showing peritoneal metastasis. Conclusion This study demonstrates the feasibility and reproducibility of a simplified VX2 uterine cancer model using tumor fragments. Furthermore, the model replicates metastatic progression, including retroperitoneal lymph node and peritoneal metastasis, by 4 weeks. The model may serve as a reliable platform for future preclinical studies involving uterine tumor biology and metastatic progression.

Targeted sequencing of genes associated with the mismatch repair pathway in patients with endometrial cancer

Germline variants inactivating the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 cause Lynch syndrome that implies an increased cancer risk, where colon and endometrial cancer are the most frequent. Identification of these pathogenic variants is important to identify endometrial cancer patients with inherited increased risk of new cancers, in order to offer them lifesaving surveillance. However, several other genes are also part of the MMR pathway. It is therefore relevant to search for variants in additional genes that may be associated with cancer risk by including all known genes involved in the MMR pathway. Next-generation sequencing was used to screen 22 genes involved in the MMR pathway in constitutional DNA extracted from full blood from 199 unselected endometrial cancer patients. Bioinformatic pipelines were developed for identification and functional annotation of variants, using several different software tools and custom programs. This facilitated identification of 22 exonic, 4 UTR and 9 intronic variants that could be classified according to pathogenicity. This study has identified several germline variants in genes of the MMR pathway that potentially may be associated with an increased risk for cancer, in particular endometrial cancer, and therefore are relevant for further investigation. We have also developed bioinformatics strategies to analyse targeted sequencing data, including low quality data and genomic regions outside of the protein coding exons of the relevant genes.

Global trends and forecasts of cervical cancer and a real-world safety assessment of human papillomavirus vaccines in women: A systematic analysis of the Global Burden of Disease study 2021 and the Vaccine Adverse Event Reporting System database

Background Cervical cancer (CCA) remains a major cause of morbidity and mortality among women globally, particularly in low- and middle-income countries. Although human papillomavirus (HPV) vaccination is central to prevention, safety concerns may affect vaccine acceptance. We integrated global disease-burden trends with real-world post-marketing safety data to provide complementary public health evidence for CCA prevention. Methods Using Global Burden of Disease (GBD) 2021 data, we assessed global prevalence, incidence, death, and disability-adjusted life years (DALYs) for women with CCA from 1990–2021, and applied age–period–cohort (APC) models to characterize temporal patterns. Bayesian APC models were used to project future incidence and death, with retrospective validation. For vaccine safety, adverse event (AE) reports following HPV vaccination in females (Cervarix, Gardasil, Gardasil 9; 2006–2025) were extracted from the Vaccine Adverse Event Reporting System (VAERS). We performed disproportionality analyses using four algorithms to identify reporting signals, with designated medical event (DME) screening and subgroup analyses by age and vaccine type. Results Globally, the age-standardized incidence rate of CCA decreased from 18.1 to 15.3 cases per 100,000 women from 1990 to 2021, while new cases increased from 0.41 million to 0.67 million. The highest incidence and death rates were observed in sub-Saharan Africa and selected Pacific Island countries. Projections suggest continued declines in age-standardized incidence and death through 2050, although the absolute burden will likely remain substantial. In VAERS, 41,731 HPV vaccine-related reports were identified; most were non-serious (80.9%). Syncope (ROR = 5.81, 95%CI:5.64–5.99), loss of consciousness (ROR = 5.26, 95%CI: 5.06–5.47) and pallor (ROR = 6.39, 95%CI: 6.10–6.70) were the most frequently reported events, and six potential DME-related signals were detected. Conclusions Despite declining age-standardized rates, CCA continues to impose a substantial global burden with marked regional disparities. Sustained HPV vaccine prevention efforts should be supported by epidemiological evidence and transparent, evidence-based safety communication.

Concurrent and future risk of endometrial cancer in women with endometrial hyperplasia: A systematic review and meta-analysis

To inform treatment decisions in women diagnosed with endometrial hyperplasia, quantification of the potential for concurrent endometrial cancer and the future risk of progression to cancer is required. We identified studies up to September 2018 that reported on the prevalence of concurrent cancer (within three months of endometrial hyperplasia diagnosis), or the incidence of cancer, identified at least three months after hyperplasia diagnosis. Random-effects meta-analyses produced pooled estimates and 95% confidence intervals (CIs). A total of 36 articles were identified; 15 investigating concurrent and 21 progression to cancer. In pooled analysis of 11 studies of atypical hyperplasia, the pooled prevalence of concurrent endometrial cancer was 32.6% (95% CI: 24.1%, 42.4%) while no studies evaluated concurrent cancer in non-atypical hyperplasia. The risk of progression to cancer was high in atypical hyperplasia (n = 5 studies, annual incidence rate = 8.2%, 95% CI 3.9%, 17.3%) and only one study reported on non-atypical hyperplasia (annual incidence rate = 2.6%, 95% CI: 0.6%, 10.6%). Overall, a third of women with atypical hyperplasia had concurrent endometrial cancer, although the number of studies, especially population-based, is small. Progression to cancer in atypical hyperplasia was high, but few studies were identified. Population-based estimates are required, in both atypical and non-atypical hyperplasia patients to better inform treatment strategies.

Concurrent depression and anxiety in women undergoing additional diagnostic procedures due to positive screening for cervical cancer

Introduction Undergoing additional diagnostic procedures due to a positive cervical cancer screening in women can lead to psychosocial burden. This study investigated the co-occurrence of depression and anxiety in women both before and after additional diagnostic procedures for cervical cancer. Methods This prospective observational study with repeated measures was conducted in a cohort consisting of all consecutive women (N = 172) who received an abnormal Pap screening test result and therefore presented to a gynecologist for additional diagnostic examinations. Multivariate logistic regression was used to identify the independent predictors of the concurrent depression and anxiety occurrence among women while undergoing additional diagnostic procedures due to positive screening for cervical cancer. Results The prevalence of concurrent depression/anxiety among women while undergoing additional diagnostic procedures due to positive screening for cervical cancer was elevated from 34.3% before diagnostics to 46.5% after diagnostics (P &lt; 0.05). Also, the prevalence of more severe concurrent depression/anxiety was higher after diagnostics than before diagnostics. Multivariate logistic regression presented that worry (regarding cervical cancer, general health, the result of the next cytology test, and having sex) was an independent significant predictive factor for concurrent depression/anxiety in women before undergoing additional diagnostic procedures due to positive screening for cervical cancer. Multivariate logistic regression presented that urban place of residence, history of induced abortion, and sedative use were predictive factors for concurrent depression and anxiety in women after undergoing additional diagnostic procedures due to positive screening for cervical cancer. Conclusion Concurrent depression and anxiety occurrence was highly prevalent among women while undergoing additional diagnostic procedures due to positive screening for cervical cancer. This prospective observational study showed a correlation between certain risk factors and concurrent depression/anxiety, although it is difficult to determine causality of this association due to the limitations of the study design. Only evidence that establishes causality can definitively guide the implementation of specific procedures and interventions during cervical cancer screening aimed at reducing concurrent depression/anxiety.

Limonin induces ferroptosis in cervical squamous cell carcinoma by activating the expression of soluble epoxide hydrolase 2 protein

Natural products are a rich sources for developing anti-cancer drugs with low toxicity and high efficiency. Limonin has anti-cancer activity; however, its effect on cervical squamous cell carcinoma remains unreported. The aim of this study was to explore how Limonin affects ferroptosis in cervical squamous cell carcinoma (CESC) and its underlying mechanism. Based on differential gene analysis of the Gene Expression Omnibus database and drug target prediction of the Comparative Toxicogenomics Database, combined with molecular docking technology, potential anti-cancer targets of Limonin were identified. In vitro experiments were conducted to create epoxide hydrolase 2 ( EPHX2) knockdown and overexpression cell lines. Relevant phenotypic experiments were conducted to verify how Limonin targeting EPHX2 affects cell proliferation and ferroptosis. Integrated bioinformatic analysis revealed EPHX2 as a key target of Limonin. Functional experiments showed that EPHX2 overexpression inhibited the proliferation of CESC and induced ferroptosis, while Limonin treatment could enhance EPHX2 expression in a concentration-dependent manner. Furthermore, EPHX2 knockdown could reverse the inhibitory effect of Limonin on CESC proliferation and alterations in ferroptosis-related indicators. This study results reveals a new mechanism by which Limonin induces ferroptosis in CESC by activating EPHX2, providing a new strategy for natural compound-based ferroptosis-targeted therapy.

The relational association between multiple sexual partners and HIV testing on cervical cancer screening among women of reproductive age in Ghana: A national population-based study

Background Cervical cancer screening remains vital in the early detection of precancerous lesions and promotes better treatment outcomes. Though evidence suggested multiple sexual partners and HIV infection as risk factors for cervical cancer, limited studies have investigated how multiple sexual partners and HIV infection impact cervical cancer screening in Ghana. Therefore, this study assessed the association of multiple sexual partnership and HIV testing on cervical cancer screening among Ghanaian women of reproductive age. Methods The study utilized data from the 2022 Ghana Demographic and Health Survey. A weighted representative sample of 15,014 women from the 16 regions of Ghana was used for the analysis. Descriptive statistics, Pearson’s Chi-square and multivariable logistic regressions were used to analyze the data. Adjusted odds ratios (aORs) at 95% Confidence Intervals were presented from the multivariable logistic regression. Results The prevalence of cervical cancer screening was 5.0%. We found lower odds of cervical cancer screening with multiple sexual partners at the bivariate level [aOR=0.69, 95% CI: 0.52–0.90], but no association was found in the multivariable model. On the other hand, women who had ever tested for HIV [aOR=4.73, 95% CI:3.39–6.59] were more likely to screen for cervical cancer than those who had never tested. This was still significant after adjusting for covariates [aOR=2.47, 95% CI:1.61–3.80]. Conclusions The study highlights the influence of multiple sexual partners and HIV testing on cervical cancer screening uptake among women of reproductive age in Ghana. Though the study found no significant association between multiple sexual partners and cervical screening uptake, HIV testing was a predictor of cervical cancer screening among women in Ghana. We recommend continued creation of awareness of cervical cancer screening among women of reproductive age.

Computational analysis for identification of the extracellular matrix molecules involved in endometrial cancer progression

Recurrence and poorly differentiated (grade 3 and above) and atypical cell type endometrial cancer (EC) have poor prognosis outcome. The mechanisms and characteristics of recurrence and distal metastasis of EC remain unclear. The extracellular matrix (ECM) of the reproductive tract in women undergoes extensive structural remodelling changes every month. Altered ECMs surrounding cells were believed to play crucial roles in a cancer progression. To decipher the associations between ECM and EC development, we generated a PAN-ECM Data list of 1516 genes including ECM molecules (ECMs), synthetic and degradation enzymes for ECMs, ECM receptors, and soluble molecules that regulate ECM and used RNA-Seq data from The Cancer Genome Atlas (TCGA) for the studies. The alterations of PAN-ECM genes by comparing the RNA-Seq expressions profiles of EC samples which have been grouped as tumorigenesis and metastasis group based on their pathological grading were identified. Differential analyses including functional enrichment, co-expression network, and molecular network analysis were carried out to identify the specific PAN-ECM genes that may involve in the progression of EC. Eight hundred and thirty-one and 241 PAN-ECM genes were significantly involved in tumorigenesis (p-value <1.571e-15) and metastasis (p-value <2.2e-16), respectively, whereas 140 genes were in the intersection of tumorigenesis and metastasis. Interestingly, 92 of the 140 intersecting PAN-ECM genes showed contrasting fold changes between the tumorigenesis and metastasis datasets. Enrichment analysis for the contrast PAN-ECM genes indicated pathways such as GP6 signaling, ILK signaling, and interleukin (IL)-8 signaling pathways were activated in metastasis but inhibited in tumorigenesis. The significantly activated ECM and ECM associated genes in GP6 signaling, ILK signaling, and interleukin (IL)-8 signaling pathways may play crucial roles in metastasis of EC. Our study provides a better understanding of the etiology and the progression of EC.

Ten years of experience with endometrial cancer treatment in a single Brazilian institution: Patient characteristics and outcomes

Few reports have described the clinical and prognostic characteristics of endometrial cancer, which is increasing worldwide, in large patient series in Brazil. Our objective was to analyze the clinicopathological characteristics, prognostic factors, and outcomes of patients with endometrial cancer treated and followed at a tertiary Brazilian institution over a 10-year period.This retrospective study included 703 patients diagnosed with endometrial cancer who were treated at a public academic tertiary hospital between 2008 and 2018. The following parameters were analyzed: age at diagnosis, race, body mass index, serum CA125 level before treatment; histological type and grade, and surgical stage. Outcomes were reported relative to histological type, surgical staging, serum CA125, lymph-vascular space involvement (LVSI), and lymph-node metastasis. The median patient age at diagnosis was 63 (range, 27-93) years (6.4% were <50 years). Minimally invasive surgeries were performed in 523 patients (74.4%). Regarding histological grade, 468 patients (66.5%) had low-grade endometrioid histology and 449 patients (63.9%) had stage I tumors. Tumors exceeded 2.0 cm in 601 patients (85.5%). Lymphadenectomy was performed in 551 cases (78.4%). LVSI was present in 208 of the patients' tumors (29.5%). Ninety-three patients (13.2%) had recurrent tumors and 97 (13.7%) died from their malignant disease. The robust prognostic value of FIGO stage and lymph node status were confirmed. Other important survival predictors were histological grade and LVSI [overall survival: hazard ratio (HR) = 3.75, p < 0.001 and HR = 2.01, p = 0.001; recurrence: HR = 2.49, p = 0.004 and HR = 3.22, p = 0.001, respectively). Disease-free (p = 0.087) and overall survival (p = 0.368) did not differ significantly between patients with stage II and III disease. These results indicate that prognostic role of cervical involvement should be explored further. This study reports the characteristics and outcomes of endometrial cancer in a large population from a single institution, with systematic surgical staging, a predominance of minimally invasive procedures, and well-documented outcomes. Prognostic factors in the present study population were generally similar to those in other countries, though our patients' tumors were larger than in studies elsewhere due to later diagnosis. Our unexpected finding of similar prognoses of stage II and III patients raises questions about the prognostic value of cervical involvement and possible differences between carcinomas originating in the lower uterine segment versus those originating in the body and fundus. The present findings can be used to guide public policies aimed at improving the diagnosis and treatment of endometrial cancer in Brazil and other similar countries.

Screening attendance of breast or cervical cancers and its associated factors among 30–49 year old women in Gedeo zone, South Ethiopia: Cross-sectional study

Introduction Breast and cervical cancers are the most frequent and fatal cancers among women. Thus, early detection is necessary to improve the prognosis of affected women. However, in Ethiopia, the rates of screening remain alarmingly low. Objective To assess the magnitude of screening attendance for breast or cervical cancer, as well as the factors that predict it, among women aged 30–49 years old in Gedeo Zone, South Ethiopia, in 2023. Method A community-based cross-sectional study was conducted using a multi-stage cluster sampling technique. Data were collected using pretested, structured questionnaires by trained interviewers. Univariate and multivariate logistic regression models were employed to identify factors associated with screening attendance. Results A total of 554 women participated in the study. Of them, 132 (23.8%) were screened for breast or cervical cancer. Higher age of 40–44 versus 45–49 years (adjusted odds ratio [AOR] 4.18 [95% CI 1.59, 10.9]), higher education status ([AOR] 5.49 [95% CI 2.01, 13.1]), having family or a friend with history of breast or cervical cancer ([AOR] 5.55 [95% CI 2.47, 12.5]), short anticipated time to seek help ([AOR] 4.66 [1.31, 11.7]), adequate health literacy ([AOR] 6.98 [95% CI 2.82,13.3]) and high self-efficacy ([AOR] 2.32 [95% CI 1.08, 4.96]) were positive factors with higher screening attendance. High response cost ([AOR] 0.19 95% CI [0.08, 0.50]) was a negative factor and associated with lower screening attendance. Conclusion and recommendation The study found that only one in four women attended breast or cervical cancer screening. Screening uptake was better in women with higher education, health literacy, self-efficacy, and older age–similar to factors associated with other health seeking behavior. Interestingly, history of breast or cervical cancer in a friend or relative was also associated with higher uptake. This indicates that in addition to awareness campaigns, personal testimonials of survivors could encourage women to visit screening facilities.

Cost analysis of hospital-based symptomatic uterine fibroids in the kingdom of Eswatini: A prevalence-based cost-of-illness study

Background Uterine fibroids are common benign tumours of uterine smooth muscle. It has been established that uterine fibroids cause a marked global financial burden on healthcare systems and society; however, significant gaps exist in the knowledge of costs related to uterine fibroids. This study aimed to estimate costs associated with the diagnosis, care, and management of uterine fibroids in Eswatini. Methods The study employed the Cost of Illness (COI) method, a retrospective prevalence cost model. The provider’s perspective was used to estimate all identifiable direct medical costs of UFs. Data was collected from participants’ charge and claims records from the hospitals between 21 August 2021 and 21 August 2022. The study employed a bottom-up approach to estimate all patient costs related to uterine fibroids care and treatment. The costs were calculated at the 2022 price level and converted to United States dollars (USD) using private-payer prices. Results The total annual direct medical cost of uterine fibroids in Eswatini was estimated at USD 837894.60. This includes the total estimated costs of outpatient treatment and care, surgical treatment and care, and inpatient treatment and care. The key cost drivers were surgical and inpatient costs, USD 421583.18 and USD 110716.59, respectively. Conclusion The total annual cost estimation of uterine fibroids care is significantly high, with the majority of the cost related to theatre and hospitalisation charges. Understanding these financial implications can help guide healthcare policies and resource management.

Social inequities and clinical outcomes in young women with cervical cancer: Real-world evidence

Objective To assess the influence of social inequities and clinicopathological factors on survival outcomes in young women with cervical cancer treated at a comprehensive public cancer center in Brazil. Methods This retrospective analysis reviewed the medical records of women aged 18–39 diagnosed with cervical cancer at the Brazilian National Cancer Institute between January 2017 and December 2021, assessing demographic characteristics and survival outcomes. Results This analysis included 475 patients with a mean age of 33.6 years, with the majority being non-white (67.7%), never married women (68.0%), and having a low education level (&lt; 8 years) (86.1%). Multivariate analysis indicated that a lower education level was associated with advanced stage (p = 0.001). Recurrence or progression occurred in 224 patients (47.2%), mainly as distant metastases (56.7%). The median progression-free survival (PFS) was 19.8 months, with two-year rates of 81.6%, 45.7%, 28.2%, and 6.2% for stages I, II, III, and IV, respectively. Shorter PFS was correlated with lower education level (p = 0.009), alcohol consumption (p = 0.026), undifferentiated carcinoma (p = 0.007), and advanced disease stage (p &lt; 0.001). The median overall survival (OS) was 35.1 months, with five-year rates of 82.9%, 42.7%, 23.7%, and 9.7% for stages I, II, III, and IV, respectively. Factors associated with shorter OS included lower education level (p = 0.005), undifferentiated carcinoma (p = 0.006), and advanced stage (p &lt; 0.001). Conclusion Undifferentiated carcinomas and advanced stages negatively influence the prognosis of young women with cervical cancer. Social factors may also be correlated with poorer outcomes, especially alcohol consumption and lower education levels.

MRI differentiation of usual type endocervical adenocarcinoma and cervical squamous cell carcinoma

Objectives To evaluate the magnetic resonance imaging (MRI) features that may help differentiate usual-type endocervical adenocarcinoma (UEA) from cervical squamous cell carcinoma (SCC), with particular emphasis on diffusion-weighted imaging–derived apparent diffusion coefficient (ADC) values and tumor growth patterns. Methods This retrospective study included 26 patients with histopathologically confirmed UEA and 50 patients with SCC who underwent preoperative pelvic MRI. Quantitative MRI parameters—including tumor size, tumor-to-muscle signal intensity ratios (SIRs) on T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), contrast-enhanced T1-weighted imaging (CE-T1WI), and mean ADC values—were analyzed. Qualitative imaging features such as tumor growth pattern, location, uterine corpus invasion, intratumoral cyst formation, hydrometra/hematometra, and lymphadenopathy were also assessed. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of ADC values. Multivariable logistic regression analysis was used to identify independent predictors of UEA. Interobserver agreement was assessed using intraclass correlation coefficients (ICC) and Cohen’s kappa statistics. Results Mean ADC values were significantly higher in the UEA group than in the SCC group (0.901 × 10 ⁻ ³ mm²/s vs. 0.825 × 10 ⁻ ³ mm²/s, p = 0.008). ROC analysis showed a statistically significant but moderate discriminatory performance of mean ADC for differentiating UEA from SCC (AUC = 0.659; 95% CI: 0.527–0.790; p = 0.024). Using the Youden index, an optimal ADC cut-off value of 0.837 × 10 ⁻ ³ mm²/s yielded a sensitivity of 65.4% and a specificity of 62.0% for identifying UEA. Endophytic growth was more frequently observed in UEA, whereas mixed growth was more common in SCC (p = 0.023). Intratumoral cyst formation was observed exclusively in UEA (p = 0.004). In multivariable analysis, mean ADC value and tumor growth pattern were independent predictors of UEA. Interobserver agreement for quantitative and qualitative MRI assessments was excellent. Conclusion Higher ADC values, an endophytic growth pattern, and the presence of intratumoral cysts are useful MRI features for differentiating usual-type endocervical adenocarcinoma from cervical squamous cell carcinoma. These imaging characteristics may contribute to improved preoperative diagnostic accuracy and treatment planning.

Analysis of the correlation between vaginal microbiota and high-risk human papillomavirus infection and cervical lesions

The aim of this study was to evaluate changes in the vaginal microbiota and biomarkers among high-risk human papillomavirus (hrHPV)-positive women, those with hrHPV accompanied by mucositis, and patients with cervical intraepithelial neoplasia (CIN) and to establish a novel predictive model. Vaginal samples from 102 women were categorized into four groups: control group (n = 26), hrHPV-positive group (n = 22), hrHPV-positive with mucositis group (n = 26), and CIN group (n = 28). Microbiota analysis was performed using the PacBio platform with full-length 16S rDNA gene sequencing. The vaginal microbiota in the hrHPV-positive, hrHPV-positive with mucositis, and CIN groups showed significant differences compared with the healthy control group. The microbial richness in the hrHPV-positive group was significantly different from both the CIN group and healthy controls. Compared with the control group, the hrHPV-positive group exhibited significantly increased relative abundances of Bifidobacterium , Escherichia-Shigella , Hoylesella and nominally increased abundances of Gardnerella , Prevotella , along with a significant decrease in Lactobacillus . No statistically significant differences were retained between the hrHPV-positive group and the hrHPV-positive with mucositis group after FDR correction for the top 10 genera. Compared with the hrHPV-positive with mucositis group, the CIN group demonstrated significantly reduced levels of Pseudomonas, nominally decreased levels of Bifidobacterium and Faecalibacterium , whereas Glutamicibacter and Sporosarcina were nominally enriched. A random forest model was constructed to predict risk across groups and demonstrated good predictive performance, suggesting that vaginal microbiota may serve as valuable indicators for predicting cervical lesion risk. During hrHPV infection, significant alterations occur in the vaginal microecology, primarily characterized by an increase in pathogenic bacteria and a reduction in beneficial bacterial populations.

Development of a blood test for uterine sarcoma—Diagnosis and monitoring (DOORS-D and DOORS-M) studies

Uterine sarcomas can be difficult to differentiate from uterine fibroids due to many shared symptoms and imaging features, which can result in delayed or missed diagnosis, or over treatment. The ‘Development of a blood test for uterine Sarcoma – Diagnosis’ (DOORS-D) (ISRCTN14800787) and ‘Development of a blood test for uterine Sarcoma – Monitoring’ (DOORS-M) (ISRCTN14174468) studies aim to explore the role for circulating tumour DNA (ctDNA) to diagnose and to monitor uterine sarcomas. DOORS-D will recruit patients who have a suspected uterine sarcoma or large fibroid and are due to undergo surgery (hysterectomy or myomectomy) for a blood sample prior to surgery whereas DOORS-M will recruit patients who have been diagnosed with a uterine sarcoma in the previous 10 years for longitudinal blood sampling every 3–6 months over the course of the study. Information will be collated on patient characteristics and symptoms, tumour characteristics and diagnostic imaging, with representative images selected and analysed using large language models. Analysis of genomic/methylation profile of ctDNA samples collected from DOORS-M will be used to design a ctDNA-based ‘test’. Analysis of the samples collected from the participants recruited to the DOORS-D study will enable the accuracy of the ‘test’ to differentiate uterine sarcomas from fibroids to be determined. In addition, the opinions of patients with a suspected or confirmed sarcoma will be explored through semi-structured qualitative interviews. Purposeful recruitment strategy will ensure that the experiences of women from diverse socioeconomic, cultural and ethnic backgrounds are included. The results of the studies will be shared through conference presentations and peer-reviewed publications.

Iran is falling behind WHO cervical cancer elimination targets: HPV vaccination coverage and cervical cancer screening participation in 2021

Objective This study aimed to assess HPV vaccination coverage and cervical cancer screening participation among Iranian females under 46 years old, comparing Iran’s situation to he Cervical Cancer Elimination Initiative (CCEI) targets. Methods This nationally and sub-nationally representative cross-sectional study analyzed data from the STEPS 2021 survey. Female participants aged 18–45 years without missing data on HPV vaccination or cervical cancer screening were included. Categorical data were presented as weighted percentages with 95% confidence intervals (95% CI). Logistic regression assessed associations between demographic and female cancer screening variables with the outcomes. Results A total of 8,158 females were included. Only 0.85% (95% CI: 0.69–1.02) of women received the HPV vaccine, while cervical cancer screening participation was 39.4% (95% CI: 38.21–40.6). No significant differences in HPV vaccination coverage were observed across age groups. However, screening rates were significantly higher in older women, rising from 27.99% (18–35 years) to 54.07% (36–45 years). HPV vaccination was not significantly associated with demographic variables. In contrast, cervical cancer screening participation was higher among unemployed women (40.58%), married women (49.6%), and those in the highest wealth quintile (42.47% compared to 28.29% in the lowest quintile). Conclusion HPV vaccination coverage in Iran is critically low, falling far short of the CCEI target of 90%. Cervical cancer screening participation is comparatively better but still lags approximately 30% behind the target. Strategic interventions are critical to bridge the gap between Iran’s current status and the CCEI targets.

Assessing the influence of the health system on access to cervical cancer prevention, screening, and treatment services at public health centers in Addis Ababa, Ethiopia

Background Cervical cancer is the second leading cause of cancer death among Ethiopian women. This study aimed to assess the influence of the health system on access to cervical cancer prevention, screening, and treatment services at public health centers in Addis Ababa, Ethiopia. Methods This study used a cross-sectional survey design and collected data from 51 randomly selected public health centers in Addis Ababa. Open Data Kit was used to administer a semi-structured questionnaire on Android tablets, and SPSS version 26 was used to analyze the descriptive data. Results In the study conducted at 51 health centers, cervical cancer prevention and control services achieved 61% HPV vaccination for girls, 79% for cervical cancer awareness messages, 80% for precancer lesion treatment, and 71% for cervical screening of women. All health centers were performing cervical screening mostly through visual inspection with acetic acid due to the inconsistent availability of HPV DNA tests and the lack of Pap smear tests. In 94% of health centers, adequate human resources were available. However, only 78% of nurses, 75% of midwives, 35% of health officers, and 49% of health extension workers received cervical cancer training in the 24 months preceding the study. Women had provider choices in only 65% of health centers, and 86% of the centers lacked electronic health records. In 41% of the health centers, the waiting time was 30 minutes or longer. About 88% and 90% of the facilities lacked audio and video cervical cancer messages, respectively. Conclusion This study revealed that the annual cervical cancer screening achievement was on track to fulfill the WHO’s 90-70-90 targets by 2030. We recommend that decision-makers prioritize increasing HPV vaccination rates, enhancing messaging, reducing wait times, and implementing electronic health records to improve access to cervical cancer services in Addis Ababa.

Uptake of cervical cancer screening and its associated factors among women of reproductive age in Kericho County

Cervical cancer is a public health issue among reproductive-aged women worldwide. It is the second most common cancer among females and contributes to 12.9% of new cancer cases and 11.84% of all cancer deaths annually. Early detection and treatment can prevent and cure the disease. Screening among women has gained global attention since it’s a crucial step in early detection. This study investigated the level of uptake of cervical cancer screening and factors associated with the cervical cancer screening among women aged 18–49 years in Bureti Constituency, Kericho County. The study adopted an institution-based cross-sectional study design. The study used systematic random sampling technique to select 328 women aged 18–49 who attended maternal and child health clinic at Kapkatet Sub-County Hospital during study period. Data was collected using structured questionnaires, including sociodemographic, awareness and knowledge and screening uptake sections. The data was analyzed using SPSS version 26.0. Descriptive analyses were performed to all the variables. Binary logistic regression analyses were conducted to assess factors associated with cervical cancer screening. The uptake of cervical cancer screening was 16.2% (n = 53, 95% CI: 10.5–23.4). We found that being 34 years and above (aOR = 1.43, 95% CI: 1.11–2.52, p &lt; 0.001), having a primary education (aOR = 3.20, 95% CI: 1.50–7.00, p = 0.003), being self-employed (aOR = 5.20, 95% CI: 2.40–10.70, p &lt; 0.001), or unemployed (aOR =7.50, 95% CI: 2.45–25.00, p &lt; 0.001), and having a family history of cervical cancer (aOR = 2.10, 95% CI: 0.80–6.00, p = 0.015) significantly increased the odds of screening uptake. In contrast, earning an income of Ksh. 2,001–5,000 (aOR = 0.38, 95% CI: 0.10–0.90, p = 0.016) or&gt; Ksh. 10,000 (aOR = 0.15, 95% CI: 0.06–0.33, p &lt; 0.001) significantly decreased the odds of screening. Additionally, poor knowledge on risk factors (aOR = 0.50, 95% CI: 0.28–0.65, p &lt; 0.001), signs and symptoms (aOR = 0.40, 95% CI: 0.10–0.70, p &lt; 0.001), and groups at risk (aOR = 0.35, 95% CI: 0.15–0.60, p &lt; 0.001) were all associated with lower odds of screening. Uptake of cervical cancer screening was influenced by multiple factors including socio-demographics and economic factors, awareness, and knowledge related factors. Thus, there is urgent need for intensified health education to enhance awareness and knowledge of women on cervical cancer and its screening.

A pilot multimodal study of cervical cancer: Raman spectroscopy as a molecular fingerprint tool

Cervical cancer remains a significant global health burden, highlighting the need for more effective tools for early detection and tissue characterization. In this study, we propose a multimodal strategy that combines Raman spectroscopy, Atomic Force Microscopy (AFM), and Scanning Electron Microscopy (SEM) to investigate the molecular and morphological features of cervical squamous cell carcinoma (SCC). Raman spectroscopy was used to analyze biochemical signatures across different tissue regions tumor, necrotic, stromal, and glandular within the 813–1668 cm -1 range, identifying distinct molecular profiles between malignant and healthy areas. Specific vibrational peaks associated with DNA, proteins, and lipids were examined to track molecular changes related to tumor progression. AFM enabled nanoscale mapping of surface morphology, revealing structural irregularities associated with malignancy, while SEM provided detailed imaging of cellular and extracellular architecture, enhancing the visualization of cancer-induced morphological alterations. Although Raman spectroscopy has been studied for decades in cancer research, it has not yet replaced Pap smears and biopsies in clinical practice due to challenges in standardization, reproducibility, and clinical validation. This pilot study aims to serve as a stepping stone toward that goal, providing proof-of-concept data that may support the gradual translation of Raman spectroscopy into clinically relevant diagnostic workflows and underscores the potential of the technique, supported by complementary high-resolution imaging techniques, in the characterization of cervical cancer tissues. The integration of Raman, AFM, and SEM was used here as a pilot approach on paraffin-embedded samples, with AFM and SEM providing supportive morphological information while the long-term aim is to transfer Raman spectroscopy to fresh, untreated tissues, where its non-destructive and label-free nature could enable minimally invasive diagnostic applications.

Gene expression and soluble protein level of PD-1 and its ligands (PD-L1 and PD-L2) in endometrial cancer

Checkpoint programmed death-1 (PD-1) and programmed cell death ligands (PD-Ls) are negative immunoregulatory molecules that assist tumour cells in evading the immune system. The interaction of PD-1 and PD-Ls inhibits T cells and tumour-infiltrating lymphocytes (TILs) while increasing the function of immunosuppressive regulatory T cells (Tregs). This leads to the evasion of the immune response by tumour cells. The roles of PD-1, PD-L1, and PD-L2 in endometrial cancer (EC) have not been fully elucidated. This study investigates the mRNA gene expression and soluble protein levels of these molecules in EC compared to controls, with detailed analysis of clinical profiles. The results showed that EC had significantly higher mRNA gene expression and soluble protein levels of PD-L1 and PD-L2, but not PD-1. Specifically, PD-1 mRNA gene expression was significantly higher in cases with less than 50% myometrial invasion. Additionally, the soluble protein level of PD-1 was substantially higher in patients under the age of 60. Higher gene expression of PD-L1 was observed only in advanced stages of EC. However, the soluble PD-L1 protein level was significantly elevated in type II EC, advanced stage, higher grade, lympho-vascular space invasion (LVSI), and in cases with myometrial invasion of 50% or more. PD-L2 mRNA gene expression and soluble protein levels significantly differed across all clinical profiles except for LVSI. These findings suggest that PD-1, PD-L1, and PD-L2 may serve as potential predictive biomarkers, which could be beneficial for the management of endometrial cancer patients through immunotherapy.

Association between serum γ-Glutamyltransferase and the risk of cervical cancer: Evidence from the national health and nutrition examination survey

Background The principal cause of cervical cancer is sustained high-risk human papillomavirus (HPV) infection. However, some cases remain unrelated to HPV infections. Current HPV screening methods have difficulties identifying HPV-negative patients and implementing them in low-resource settings. Therefore, it is important to explore easily accessible and low-cost biomarkers to optimize the current cervical cancer screening strategies. Methods This cross-sectional study included 6998 women from the US National Health and Nutrition Examination Survey (NHANES), among whom 147 had self-reported cervical cancer. Serum γ – Glutamyltransferase (GGT) was employed as a continuous variable (naturally logarithmically transformed) and a categorical variable (≥50 U/L versus &lt;50 U/L), and multivariate logistic regression models were utilized to progressively adjust for demographic features, sexual history, and clinical behaviors. The restricted cubic spline approach was adopted to further explore the dose-response relationship between GGT levels and cervical cancer to depict the potential nonlinear trends between them in a more elaborate manner. We also conducted subgroup and sensitivity analyses to ensure reliability of our results. This included multiple imputation of missing data and adjustment for crucial covariates, such as body mass index (BMI) and tobacco exposure, to comprehensively evaluate the impact of different factors on the outcomes. Ultimately, through mediation analysis, we probed the mediating function of tobacco exposure in the association between GGT levels and cervical cancer, aiming to obtain a more profound understanding of the underlying mechanisms of this health-related relationship. Results Serum GGT levels are positively correlated with cervical cancer risk. For each log unit increase in GGT levels, there was a 31% increased risk of cervical cancer (OR = 1.31, 95%CI: 1.01–1.70, P = 0.041) in the model adjusted for multiple risk factors. When the GGT level reached or exceeded 50 U/L, the risk increased by 76% (OR = 1.76, 95%CI: 1.04–2.98, P = 0.034). This tendency was consistent across several crucial subgroups, particularly among HPV-negative women (OR = 1.36, 95%CI: 1.01–1.84), suggesting that GGT may have some significance in different populations. The results of the sensitivity analyses demonstrated that the main findings remained robust, even when multiple imputations were employed to handle missing data. Nevertheless, the significant association between GGT and cervical cancer weakened when tobacco exposure was further adjusted, indicating that tobacco use might be involved. Mediation analysis further showed that the overall impact of GGT on cervical cancer was statistically significant (β = 0.0014; 95%CI: 0.0001–0.0020; P = 0.046), and approximately 18.15% of the impact was accounted for by tobacco exposure (ACME: β = 0.0003, 95%CI: 0.0001–0.0004, P &lt; 0.001), suggesting a partial mediating role. Conclusion Elevated serum GGT levels are associated with a heightened risk of cervical cancer even in HPV-negative patients. Although this association is partly mediated by tobacco exposure, GGT may still play a role in cervical cancer via nontobacco routes. The potential application of GGT as an auxiliary biomarker requires further validation in prospective studies.

Impact of MED12 mutation and CDK8 activity on uterine leiomyoma growth and response to gonadotropin-releasing hormone agonist treatment

MED12 exon 2 mutation is the most frequent mutation associated with uterine leiomyomas. MED12 wild-type leiomyomas have a higher growth potential than mutant leiomyomas, suggesting that the mutation limits leiomyoma growth. MED12 forms a complex with CDK8 and is involved in the phosphorylation of RNA polymerase II, playing a role in transcriptional regulation. However, its mechanism of action in leiomyoma growth is not clear. We aimed to clarify the relationship between MED12 mutation status, response to gonadotropin-releasing hormone (GnRH) agonist treatment, and CDK8 activity in leiomyomas. We also examined the effects of CDK8 inhibitors on primary cultured uterine leiomyoma cells. We classified 44 surgically removed uterine leiomyomas into four groups according to GnRH agonist use and MED12 mutation status. CDK8 was co-immunoprecipitated from leiomyoma tissue extracts using MED12 antibody to test its kinase activity in vitro , and the amount of phosphorylated substrate was measured. Cell proliferation and apoptosis of primary cultured MED12 wild-type leiomyoma cells were evaluated in the presence of a CDK8 inhibitor and sex steroid hormones. Of the 44 leiomyomas tested, 11 MED12 wild-type leiomyomas without preoperative GnRH agonist treatment had significantly higher CDK8 activity than nine GnRH agonist-treated MED12 wild-type leiomyomas and 15 leiomyomas with MED12 mutations without GnRH agonist treatment. Treatment of primary cultured MED12 wild-type cells with CDK8 inhibitors significantly inhibited cell growth and increased apoptosis. MED12 wild-type leiomyoma cells without GnRH agonist treatment showed high CDK8 activity, and inhibition of CDK8 activity suppressed cell growth in vitro .

A Comparison of neoadjuvant chemotherapy and concurrent chemoradiotherapy for for FIGO 2018 stage IB3/IIA2 Cervical squamous cell carcinoma: Long-term efficacy and safety in a resource-limited setting

Purpose The purpose of this research was to evaluate the effectiveness and safety of neoadjuvant chemotherapy plus radical surgery (NCRS) and concurrent chemoradiotherapy (CCRT) based on three-dimensional conformal radiation therapy (3DCRT) for FIGO 2018 stage IB3/IIA2 patients with cervical squamous cell carcinoma in a resource-limited setting. Methods The clinical outcomes and incidence of complications in 137 patients who underwent NCRS with those of 163 patients who CCRT based on 3DCRT were compared. Propensity score matching (PSM) analysis was used to match the two groups to enable further statistical comparisons. Survival analysis was performed utilizing Cox proportional hazards regression analyses, Kaplan-Meier curves, and log-rank tests. Furthermore, the incidence of complications between the two groups was also compared using chi-squared tests. Results PSM analysis identified 103 matched pairs of patients. The NCRS and CCRT groups exhibited 5-year overall survival (OS) rates of 85.4% and 91.2%, respectively (p=0.19). Additionally, the NCRS and CCRT groups exhibited 5-year disease-free survival (DFS) rates of 76.7% and 89.3% (p=0.02), and the recurrence rates were 20.4% and 9.7% (p=0.03), respectively. However, the CCRT group exhibited a higher incidence of early any-grade complications (79.6% vs 35.9%, p&lt;0.001) and early grade 3 complications (15.5% vs 2.9%, p=0.002) compared to the NCRS group. In terms of overall late complications, there was no significant difference in the incidence between the two groups. Multivariate analysis revealed that stage IIA2 emerged as an independent risk factor for OS (aHR 8.89; p=0.033). Moreover, histologic grade 2–3 (aHR 5.3; p=0.022), stage IIA2 (aHR 2.95; p=0.043), NCRS treatment (aHR 2.41; p=0.012) were identified as independent risk factors for DFS. Conclusion In resource-limited settings, for patients with FIGO 2018 stage IB3/IIA2 cervical squamous cell carcinoma, 3DCRT-based CCRT offers superior disease-free survival and reduced recurrence rates compared to NCRS, despite increased early complication rates.

Prevalence and determinants of precancerous cervical lesions among women screened for cervical cancer in Africa: A systematic review and meta-analysis

Background Precancerous cervical lesions, or cervical intraepithelial neoplasia (CIN), represent a significant precursor to cervical cancer, posing a considerable threat to women’s health globally, particularly in developing countries. In Africa, the burden of premalignant cervical lesions is not well studied. Therefore, the main purpose of this systematic review and meta-analysis was to determine the overall prevalence of precancerous cervical lesions and identifying determinants among women who underwent cervical cancer screening in Africa. Methods This study followed the Preferred Reporting Item Review and Meta-analysis (PRISMA) guidelines. The protocol for this systematic review and meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42025645427). We carried out a systematic and comprehensive search on electronic databases such as PubMed and Hinari. In addition, Google Scholar and ScienceDirect were utilized to find relevant studies related to precancerous cervical lesions. Data from the included studies were extracted using an Excel spreadsheet and analyzed using STATA version 17. The methodological quality of the eligible studies was examined using the Joanna Briggs Institute (JBI) assessment tool. Publication bias was checked by using the funnel plot and Egger’s tests. A random-effects model using the Der Simonian Laird method was used to estimate the pooled prevalence of pre-cancerous cervical lesions in Africa. The I-squared and Cochrane Q statistics were used to assess the level of statistical heterogeneity among the included studies. Results A total of 112 eligible articles conducted in Africa, encompassing 212,984 study participants, were included in the quantitative meta-analysis. Thus, the pooled prevalence of pre-cancerous cervical lesions in Africa was 17.06% (95% confidence interval: 15.47%−18.68%). In this review, having no formal education (AOR = 4.07, 95% CI: 1.74, 9.53), being rural dweller(AOR = 2.38, 95% CI: 1.64, 3.46), history of STIs (AOR = 3.94, 95% CI: 2.97, 5.23), history of having multiple partners (AOR = 2.73, 95% CI: 2.28, 3.28), early initiation of coitus (AOR = 2.77, 95% CI: 2.11, 3.62), being HIV-seropositive women (AOR = 3.33, 95% CI: 2.32, 4.78), a CD4 count &lt;200 cells/mm³ (AOR = 5.17, 95% CI: 1.70, 15.71), not being on ART (AOR = 2.58, 95% CI: 1.45, 4.58), smoking (AOR = 3.91, 95% CI: 1.43, 10.67) and prolonged use of oral contraceptive pills (AOR = 4.39, 95% CI: 2.77, 6.96) were significantly associated with precancerous cervical lesions. Conclusions In Africa, the overall prevalence of pre-cancerous cervical lesions is high (17%). The findings of this review highlight that health professionals, health administrators, and all other concerned bodies need to work in collaboration to expand comprehensive cervical cancer screening methods in healthcare facilities for early detection and treatment of cervical lesions. In addition, increasing community awareness and health education, expanding visual inspection of the cervix with acetic acid in rural areas, offering special attention to high-risk groups (HIV-positive women), encouraging adherence to antiretroviral therapy for HIV-positive women, overcoming risky sexual behaviors and practices, and advocating early detection and treatment of precancerous cervical lesions.

High-risk human papillomavirus genotypes among women of hill districts in Bangladesh

Knowledge on the distribution of type specific HPV (Human papillomavirus) genotypes in female cervix is crucial to identify women who are at a higher risk of developing cancer. This study aimed to find out the prevalence of High-risk HPV genotypes among women of three Hill districts of Bangladesh. This cross-sectional study was conducted between 1st January and 30th June 2024 among 1602 selected married asymptomatic tribal and nontribal women (30–60 years of age) at three Hill districts. Partial genotyping of HPV DNA specimens which detects the presence of 14 high-risk genotypes (including individual HPV-16, HPV-18, and others as a pooled group) was performed at Bangladesh Medical University (BMU). Women with previous treatment of cervical precancer and cancer, hysterectomy, cervical amputation and pregnancy were excluded. Statistical analysis utilized SPSS version 25.0, employing Chi-square and Fisher’s Exact tests and P value &lt;0.05 were considered significant. HR-HPV prevalence’s were expressed as proportions. The influence of HR-HPV infection and socio-demographic factors was assessed using multinomial logistic regression analysis. The overall HR-HPV prevalence was 2.7% (n = 44) and 0.8% (n = 13) were tested positive for HPV16, 0.2% (n = 4) for HPV18 and 1.6% (n = 26) for ‘Other HR-HPV’ types. No significant difference of HR-HPV prevalence was observed among the three districts (p-value = 0.352) and among tribal (2.4%) and non-tribal/Bengali (3.2%) women (p-value&gt;0.05). Higher number of marriages of the husbands have independent association with HR-HPV positivity showing an odds ratio of 2.02 (95% CI: 1.07–3.82, p = 0.030). The HR-HPV prevalence in hill districts of Bangladesh is low with independent association of higher number of marriages of the husbands with HR-HPV positivity. These findings may guide policymakers to initiate HR-HPV DNA-based screening and reconsider vaccination strategies in the hill areas, including the introduction of gender-neutral vaccination.

From cervix to multisite: Detection of lower genital tract lesions in a 10-year cross-sectional colposcopy clinic study

Objective To evaluate detection rates of multisite lesions (cervical, vaginal, vulvar) among women attending colposcopy clinics. Methods Our cross-sectional study included 20,486 patients between 2014 and 2023 in Shanxi China. Detection rates for cervical, vaginal, and vulvar lesions were retrospectively analyzed across strata by HPV status, cytological diagnosis, and clinical manifestations (vaginal bleeding/discharge). Multinomial logistic regression was applied to calculate odds ratios for high-grade lesions and squamous cell carcinoma (SCC). Results High-risk HPV (hr-HPV) infection was detected in 16,636 of 20,486 women (81.2%), and 9,137 (44.6%) had ASC-US+ cytology. Following cervical lesion detection on histopathology among hr-HPV-positive women (CIN2/3: 19.9%; SCC: 5.3%; AIS/ADC: 0.4%), additional lesions were identified at other anatomical sites: vaginal lesions (VaIN2/3: 3.6%; SCC: 1.1%; AIS/ADC: 0.04%) and vulvar lesions (VIN2/3: 0.4%; SCC: 0.1%) were further identified. Overall, 21.6% of hr-HPV-positive women exhibited high-grade lesions (CIN/VaIN/VIN2/3), with 5.6% demonstrating multi-focal SCC and 0.4% showing AIS/ADC. Stratified analysis revealed that patients even with negative HPV or cytology result still had relative high detection rate of high-grade lesions. Among these HPV-negative women, those reporting vaginal bleeding/discharge carried an elevated risk, with 3.2% having high-grade lesions and 10.5% having SCC. The integrative examination combining hr-HPV, cytology, and vaginal bleeding/discharge identified 3,753 high-grade lesions and 1,154 cancers. Conclusion Integrating the assessment of hr-HPV testing, cytology, and clinical symptoms (e.g., vaginal bleeding or discharge) could help finding more cases of multisite lesions (cervical, vaginal, vulvar). This is especially important for some high-risk women, including those who visit the colposcopy clinics, and more attention should be paid to the multisite examination.

Prevalence and genotype distribution of Human Papillomavirus (HPV) among 14,110 women in Anqing urban area: A population-based cross-sectional survey

Human papillomavirus (HPV), particularly persistent infection with high-risk types, is one of the major etiological factors for cervical cancer, posing significan health risks to women. This study aims to analyze the epidemiology of HPV infection among women in the Anqing region, and provide a valuable reference for the prevention and control strategies of cervical cancer in this region. Between 2022 and 2024, a total of 14,110 women attending the First People’s Hospital of Anqing were enrolled in this study. All participants underwent both HPV testing and ThinPrep cytology test (TCT). The overall prevalence of HPV infection in the study population was 18.97%. The predominant pattern of HPV infection identified was single infection, followed by double infection. The top five HPV genotypes detected were HPV 52 (2.78%), HPV 81 (1.55%), HPV 58 (1.42%), HPV 16 (1.20%) and HPV 53 (1.16%). The highest HPV positivity rate was observed in women aged &lt; 20 years (79.17%), followed by those aged 50–59 (84.88%), and then those aged &gt; 59 years (42.53%). Among all HPV-positive women, analysis of TCT results revealed that HPV 52, 53, 16, 58 and 81 were frequently detected in ASC-US, HPV 52, 16 and 58 in ASC-H, HPV 52, 58 and 81 in LSIL, and HPV 16, 58 and 18 were the most common genotypes in HSIL. HPV 52, 81, 58, 16 and 53 are the common genotypes among women in Anqing region. The highest prevalence rates of HPV infection were observed in women aged &lt;20 years and those aged 50–59 years. Based on these findings, the 9-valent HPV vaccine is strongly recommended as a primary prevention strategy for this population.

Knowledge, attitude and practices towards cervical cancer control among University students in Kilimanjaro region, Tanzania

Background Cervical cancer (CC) is a major public health issue in the sub-Saharan Africa region, partly due to limited public awareness among women at risk. University students are part of the age group that is at risk. Assessing their knowledge, attitude, and practices (KAP) about CC, its causes, and prevention methods can reveal gaps that need to be addressed through education. We aimed to assess KAP towards CC control and their determinants among University students in Tanzania. Methods A cross-sectional survey was conducted among 708 undergraduate students in three Universities, using a pre-tested questionnaire. Descriptive statistics and binary logistic regression were used to describe variables and identify associations between variables; a p-value of &lt;0.5 determined the association. Results The majority of students (75.7%) were not knowledgeable, and 82.5% had a negative attitudes regarding CC. Only 25.4% had ever been screened against CC. Being female and a medical student in ≥4th year of studying were significantly associated with good knowledge and attitude of CC (p &lt; 0.000), while other socio-demographic characteristics didn’t show any association. Conclusion The findings indicate that Tanzanian University students’ lack the basic knowledge and attitudes towards CC prevention and control, highlighting the need for comprehensive strategies to ensure no woman is left behind.

The economic burden of cervical cancer from diagnosis to one year after final discharge in Henan Province, China: A retrospective case series study

In China, the disease burden of cervical cancer remains substantial. Human papillomavirus (HPV) vaccines are expensive and not yet centrally funded. To inform immunization policy, understanding the economic burden of the disease is necessary. This study adopted a societal perspective and investigated costs and quality of life changes associated with cervical cancer from diagnosis to one year after final discharge in Henan province, China. Inpatient records of cervical cancer patients admitted to the largest cancer hospital in Henan province between Jan. 2017 and Dec. 2018 were extracted. A telephone interview with four modules was conducted in Jun.-Jul. 2019 with a 40% random draw of patients to obtain direct non-medical costs and indirect costs associated with inpatients, costs associated with outpatient visits, and changes in quality of life status using the EQ-5D-5L instrument. Direct medical expenditures were converted to opportunity costs of care using cost-to-charge ratios obtained from hospital financial reports. For each clinical stage (IA-IV), total costs per case from diagnosis to one year after final discharge were extrapolated based on inpatient records, responses to the telephone interview, and recommendation on outpatient follow-ups by Chinese cervical cancer treatment guidelines. Loss in quality-adjusted life years was obtained using the 'under the curve' method and regression predictions. A total of 3,506 inpatient records from 1,323 patients were obtained. Among 541 randomly selected patients, 309 completed at least one module of the telephone interview. The average total costs per case associated with cervical cancer from diagnosis to one year after final discharge ranged from $8,066-$22,888 (in 2018 US Dollar) and the quality-adjusted life years loss varied from 0.05-0.26 for IA-IV patients. The economic burden associated with cervical cancer is substantial in Henan province. Our study provided important baseline information for cost-effectiveness analysis of HPV immunization program in China.

Dosimetric divergence in ICBT vs. IC/ISBT configurations: Comparative analysis of three optimization algorithms for cervical cancer brachytherapy

Objective To compare dosimetric differences among graphical-based manual planning (MA), simulated annealing inverse optimization (IPSA), and hybrid inverse optimization (HIPO) for cervical cancer in both intra-cavitary brachytherapy (ICBT) and interstitial brachytherapy combined with ICBT (IC/ISBT) settings, providing evidence for clinical optimization method selection. Methods This study consisted of 60 cervical cancer patients undergoing CT-guided three-dimensional brachytherapy, including 30 ICBT patients and 30 IC/ISBT patients. Plans were generated using MA, IPSA, and HIPO. The dosimetric parameters for the high-risk clinical target volume (HRCTV) including D 100% , V 150% , V 200% , conformity index (CI), homogeneity index (HI) were compared. Meanwhile, the dosimetric parameters D 1cc , D 2cc for the bladder, rectum, sigmoid, and total treatment time were evaluated. Results Compared with MA, both IPSA and HIPO delivered lower doses to organs at risk (OARs). The total treatment time was significantly shorter for HIPO compared to IPSA and MA (P &lt; 0.05). In ICBT patients, the D 1cc and D 2cc of OARs were lower for IPSA compared to HIPO (P &gt; 0.05), while the CI was significantly better for HIPO (P &lt; 0.05). Nevertheless, in IC/ISBT patients, D 2cc of rectum for HIPO was significantly lower compared to IPSA (P &lt; 0.05), with better CI. Conclusion Inverse optimization effectively reduces doses to OARs while maintaining target coverage. HIPO appears to be the preferred choice for IC/ISBT, due to shortened treatment time, superior CI and rectal protection compared with IPSA.

HPV vaccine uptake among adolescent girls in Nigeria: The complex role of caregivers’ education

Introduction Cervical cancer remains a leading cause of cancer-related deaths among women in low- and middle-income countries (LMICs), with sub-Saharan Africa (SSA) bearing a disproportionate burden of the disease. Human papillomavirus (HPV) vaccination offers a critical intervention, yet uptake remains suboptimal due to vaccine hesitancy, misinformation, and socio-economic disparities. This study examines factors associated with HPV vaccine uptake among adolescent girls whose caregivers use social media. Methods We conducted a cross-sectional survey in October and November 2024 among 4,830 caregivers of adolescent girls 9–17 in Abuja, Nasarawa, and Adamawa states. Participants were recruited via advertisements on Facebook and Instagram. Data on adolescents’ HPV vaccination was collected from caregivers. Caregiver also provided data on their own education, motivation, ability, and exposure to HPV vaccine messaging. Multivariate logistic regression was used to identify predictors of vaccine uptake, adjusting for socio-demographic factors, motivation, and ability. Results The HPV vaccination rate among adolescent girls 9–17 was 53.9%. Caregivers with no formal education had higher exposure to HPV campaign messaging than caregivers with Higher National Diploma (HND) or Bachelor’s (BSc) education (95.3% vs 53.8%, p &lt; 0.001). The least educated caregivers were also more likely to report a three times higher odds ratio of HPV vaccination compared to caregivers with Higher National Diploma (adjusted odds ratio [aOR] = 3.01, 95% CI: 1.52–5.93). Exposure to HPV vaccine messaging was associated with a seven times higher odds ratio of HPV vaccine uptake (aOR = 6.87, 95% CI: 6.20–7.61). Motivation and ability were positively associated with HPV vaccination. Regional differences were observed, with Nasarawa demonstrating higher a vaccination rate than Abuja and Adamawa. Conclusion Exposure to HPV vaccine messages is higher among less educated compared to more educated caregivers. Moreover, the impact of advertising exposure on vaccine uptake is stronger among less educated caregivers. Educational disparities in campaign exposure and campaign effects highlight the need for strategies to increase campaign reach to more educated caregivers and to ensure that HPV messages resonate with them. Our findings suggest that existing campaigns may need to be restructured to more effectively reach educated and skeptical audiences.

Construction of a prognostic prediction model for concurrent radiotherapy in cervical cancer using GEO and TCGA databases with preliminary validation analysis

Introduction Radiotherapy is a primary treatment for intermediate and advanced cervical cancer (CC). Resistance to radiotherapy is a principal reason for treatment failure in synchronous applications, yet the molecular mechanisms remain poorly understood. Identifying reliable prognostic markers to predict and evaluate patient outcomes is essential for advancing therapeutic strategies. This study aims to address this need by developing a prognostic prediction model for concurrent radiotherapy in CC, utilizing both single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data. Methods The research began by screening for co-expressed genes using samples from two GEO datasets (GSE236738 and GSE56363). To pinpoint target genes that exhibit significant co-expression, both univariate and multivariate Cox regression analyses were conducted, facilitating the development of prognostic prediction models. The clinical significance of these models was confirmed through the analysis of 144 CC samples sourced from the TCGA database, utilizing Kaplan-Meier survival curves, ROC curve analyses, and Spearman’s correlation tests to investigate the relationships between gene expression and the levels of immune cell infiltration. IHC assays were conducted to further validate the prognostic potential of the identified target genes in CC patients. Results Prognostic models for four target genes—MPP5, SNX7, LSM12, and GALNT3—showed significant predictive value for the outcomes of CC patients undergoing radiotherapy, as demonstrated using the GSE236738 and GSE56363 datasets. The prognostic efficacy of the model was illustrated through scatter plots and calibration curves. Additionally, the model exhibited significant associations with tumor immune infiltration, immune checkpoints, and chemotherapeutic drug sensitivity. Immunohistochemistry (IHC) on clinical tumor samples confirmed that the protein expression levels of MPP5, SNX7, LSM12, and GALNT3 were distinctively predictive for CC patients. Conclusion The results indicate that MPP5, SNX7, LSM12, and GALNT3 are significantly associated with radiotherapy sensitivity in CC cells. A prognostic risk model based on these genes demonstrated strong predictive capabilities for patient outcomes in radiotherapy, suggesting these genes as effective predictors and potential therapeutic targets for treating CC.

Patient perspectives on cervical cancer screening interventions among underscreened women

Background Cervical cancer is highly preventable with regular screening, yet over 4,000 women die from it annually in the United States. Over half of new cervical cancer cases in the U.S. are attributable to insufficient screening. Methods Participants were 23 low-income, uninsured or Medicaid-insured women in North Carolina who were overdue for cervical cancer screening according to national guidelines. Semi-structured interviews examined perspectives on barriers to cervical cancer screening and on interventions to reduce these barriers. We also elicited feedback on three proposed evidence-based interventions: one-on-one education, coupons to reduce out-of-pocket costs, and self-collection of samples for detection of high-risk human papillomavirus (HPV) infection, the primary cause of cervical cancer. Results Reported barriers included high cost, inconvenient clinic hours, lack of provider recommendation, poor transportation, difficulty finding a provider, fear of pain, and low perceived need. Participants suggested interventions including reducing cost, improving convenience through community-based screening or extended clinic hours, strengthening provider recommendations, and providing one-on-one counseling and education outreach. HPV self-collection was most frequently selected as the “most helpful” of 3 proposed interventions (n = 11), followed by reducing out-of-pocket costs (n = 7) and one-on-one education (n = 5). Conclusion Cost was the most reported barrier to cervical cancer screening, although women experience multiple simultaneous barriers. Novel interventions such as HPV self-collection promise to reduce some, but not all, barriers to primary screening. Interventions that work on reducing multiple barriers, including obstacles to receiving follow-up care, may be most effective to prevent cervical cancer among these high-risk women.

Identification of novel therapeutic inhibitors against E6 and E7 oncogenes of HPV-16 associated with cervical cancer

Human Papilloma Virus type 16 (HPV-16) is highly oncogenic with the E6 and E7 oncogenes playing crucial roles in the pathogenesis of HPV-related cervical carcinogenesis. Targeting these oncoproteins with specific inhibitors offers a promising approach for therapeutic intervention. This study aimed to identify potential inhibitors of the HPV-16 E6 and E7 oncoproteins through an in silico approach, providing a foundation for the development of targeted therapies against HPV associated malignancies. We performed virtual screening on a library of 1000 compounds to identify promising candidates. Subsequent molecular docking studies were conducted to assess the binding affinities of the promising candidates. The top-scoring compounds for oncoproteins were then subjected to molecular dynamics simulations to evaluate their stability and interaction profiles. The virtual screening identified 14 promising candidates followed by docking studies. Among these Galangin was identified as a promising inhibitor for the E6 oncogene, while Neoechinulin showed potential as an inhibitor of the E7 oncogene. Our findings suggest Galangin and Neoechinulin with high potential as therapeutic inhibitors of HPV-16 E6 and E7 oncogenes respectively. These inhibitors could contribute significantly to the development of targeted therapies against HPV associated malignancies. However, further in vitro and in vivo investigations are required to use these phytochemicals as antiviral agents against HPV-16.

HPV testing in cervical cancer formalin-fixed paraffin embedded tissues: Reliability of the Xpert HPV test and high-risk HPV genotypes distribution in Tunisia

Objectives This study aims to assess the performance of the Xpert HPV test for the detection and genotyping of high-risk HPVs (HR-HPV) on FFPE cervical cancer (CC) tissues and to determine the distribution of HR-HPV genotypes in a CC Tunisian series. Methods The Xpert HPV test was conducted on purified DNA from 134 FFPE CC tissues. A single-tube multiplex polymerase chain reaction (PCR) served as a comparator assay to evaluate Xpert HPV performance in detecting and genotyping HR-HPVs. Discordant cases were tested using uniplex PCR. Results The Xpert HPV test generated valid results in 131/134 (97.8%) samples. Sensitivity, specificity, positive and negative predictive values of Xpert HPV for HR-HPV detection among valid samples were 99.16%, 100%, 100%, and 92.31%, respectively. Agreement between Xpert HPV and multiplex PCR for HPV detection was observed in 131/134 cases (97.8%), with a kappa value of 0.892. Agreement between Xpert HPV and Multiplex PCR for HR-HPV genotyping was 96.6%. Combining assays results and after confirmation with uniplex PCR, HR-HPVs were detected in 119/134 (88.8%) samples and 11 HR-HPV genotypes were detected with a predominance of HPV 16 (71%), followed by HPV 31 (8%) and HPV 18 (5%). Conclusion This study demonstrated a high accuracy of the Xpert-HPV test for HR-HPVs detection and genotyping in FFPE CC tissues and revealed a distinct distribution of HR-HPVs in Tunisia.

Molecular triage on HPV-positive samples in a cervical screening setting

Objective To improve human papilloma virus (HPV) screening, more effective triage methods for HPV-positive samples need development and validation. Cytology, the most common triage method today, is subjective and can only be applied to professionally collected samples. Methylation status has been shown to be informative, as genes are highly methylated in HPV-induced cervical dysplasia and cancer. This study aimed to assess whether triaging HPV-positive samples using molecular methods, such as methylation and genotyping for high-risk HPV types, could be as effective as cytology in cervical screening. Methods A retrospective biobank study was conducted on HPV-positive samples collected in 2017–2018, analyzing FAM19A4/MiR-124-2 hypermethylation and HPV genotyping for types 16, 18, 31, 33, 45, 52, and/or 59, comparing these results to cytology triage for detecting histologically confirmed high-grade squamous intraepithelial lesions (HSIL) and cancer. Results Results from 1915 positive screening samples were analyzed, including 1052 follow-up biopsies with 402 HSIL or cancer cases. Genotyping showed slightly higher sensitivity than cytology but lower specificity, while methylation had higher specificity but much lower sensitivity. Cytology’s positive predictive value (PPV) was 36%, with lower PPVs for the molecular methods. Combining molecular methods increased the PPV but significantly reduced sensitivity. Conclusions Based on these findings with molecular methods reducing sensitivity, we do not recommend adopting the molecular triage methods evaluated in this study in the Swedish setting. The trade-off between sensitivity and specificity does not support a change from the current cytology-based triage approach.

MVT-Net: A novel cervical tumour segmentation using multi-view feature transfer learning

Cervical cancer is one of the most aggressive malignant tumours of the reproductive system, posing a significant global threat to women’s health. Accurately segmenting cervical tumours in MR images remains a challenging task due to the complex characteristics of tumours and the limitations of traditional methods. To address these challenges, this study proposes a novel cervical tumour segmentation model based on multi-view feature transfer learning, named MVT-Net. The model integrates a 2D global axial plane encoder-decoder network and a 3D multi-scale segmentation network as source and target domains, respectively. A transfer learning strategy is employed to extract diverse tumour-related information from multiple perspectives. In addition, a multi-scale residual blocks and a multi-scale residual attention blocks are embedded in the 3D network to effectively capture feature correlations across channels and spatial positions. Experiments on a cervical MR dataset of 160 images show that our proposed MVT-Net outperforms state-of-the-art methods, achieving a DICE score of 75.9±7.43%, an ASD of 2.69±0.58 mm and superior performance in tumour localisation, shape delineation and edge segmentation. Ablation studies further validate the effectiveness of the proposed multi-view feature transfer strategy. These results demonstrate that our proposed MVT-Net represents a significant advance in cervical tumour segmentation, offering improved accuracy and reliability in clinical applications.

Determinants of cervical cancer screening utilisation among women in the least developed countries: A systematic review and meta-analysis

Background and aims Globally, cervical cancer is the fourth most common cancer among women, and more than 90% of all cervical cancer-related deaths worldwide are recorded in resource-limited countries. The present review investigated the uptake rate of cervical cancer screening and identified the factors associated with screening service utilisation in the female populations of least developed countries (LDCs). Methods Five electronic databases (EMBASE, Ovid MEDLINE, CINAHL, Cochrane Library, and PubMed) and grey literature were searched for relevant literature using the keywords of the included studies. Both qualitative and quantitative studies were included. Three reviewers performed critical appraisals using the Mixed Methods Appraisal Tool. Meta-analysis was performed to pool the quantitative results from comparable studies. Results A total of twenty-five studies were included in the review. The cervical cancer screening uptake rate in LDCs ranged from 4% to 21%. Multiple factors were associated with screening service utilisation among women in the LDCs, namely socio-demographic characteristics, including employment status (odds ratio (OR): 2.72; 95% CI: 1.97–3.76; p &lt; 0.001); knowledge of cervical cancer and its screening (OR: 3.39; 95% CI: 2.00–5.75; p &lt; 0.001); sexual and reproductive health-related factors such as parity status (OR: 2.73; 95% CI: 1.61–4.64; p = 0.002); healthcare providers’ recommendations (OR: 5.32; 95% CI: 2.44–11.58; p &lt; 0.001); perceived risk of developing cervical cancer (OR: 3.76; 95% CI: 2.62–5.38; p &lt; 0.001); use of media for cervical cancer screening promotion, including radio; cultural factors; and myths and misconceptions about cervical cancer and its screening. Conclusions The uptake of cervical cancer screening among eligible women in the LDCs was notably low. The governments of these countries are advised to invest and allocate additional resources to advance policies and develop cervical cancer prevention programmes that are accessible, affordable, and acceptable.

Exploring the roles of male partners in the transmission, prevention and control of cervical cancer in Central Kenya: A qualitative study

Background Cervical cancer (CC), primarily caused by persistent infection with high-risk human papillomavirus (HPV) types, remains a major global public health issue. While it primarily affects women, male partners significantly influence HPV transmission, as well as women’s access to prevention and treatment through decision-making and social support. However, their role in prevention and treatment engagement remains underexplored. Aim The study aimed to explore the perceptions of couples’, healthcare workers’, and policymakers’ regarding the role of male partners in the transmission, prevention, and control of cervical cancer. Setting The study was carried out in three public county hospitals and community settings in Nyeri, Murang’a and Kirinyaga counties in Central Kenya. Methods We used qualitative research approaches for a comprehensive exploration of the roles of male partners in CC transmission, prevention and control. We conducted in-depth interviews and focus group discussions with 73 participants including 20 couples, 20 Nurses, 2 Clinical officers 2 Gynecologists, 6 Community health workers and 3 County directors of health. All the participants were purposefully sampled. We analyzed data thematically using inductive qualitative analysis approaches. Results Overall, we found key organizing themes including financial and logistical support, moral and emotional support, HPV transmission and prevention, gender norms and beliefs and practices. First male partners were perceived to offer financial support to facilitate cervical cancer treatment services as well as logistical support escorting their partners to the clinic or arranging for transport services. Additionally, men’s role in HPV prevention and transmission included supporting their children in vaccination as well as prevention by limiting number of sexual partners. However, Key barriers to male involvement in cervical cancer prevention and treatment reported by participants included limited knowledge about the disease, prevailing cultural beliefs and practices that favor traditional medicine over conventional healthcare, and entrenched gender norms that restrict male participation in reproductive health matters. Conclusion Cervical cancer awareness is limited, and male partners support is shaped by financial, cultural, social, and health system factors. Addressing these issues is key to improving prevention and control efforts. Contribution Identifying the potential barriers and male partners influence in access, screening and treatment of cervical cancer services.

Practice of opportunistic cervical cancer screening and health education among health workers in Ogun State, Nigeria: A qualitative study of barriers and facilitators

Background The burden of cervical cancer is highest in low- and middle-income countries. In Nigeria, where organized cervical cancer screening programs are lacking, opportunistic screening during maternal healthcare visits may enhance screening uptake. This study is aimed at understanding the practice of opportunistic cervical cancer screening and health education, and the barriers and facilitators experienced by health workers practicing in antenatal and postnatal clinics in Ogun State, Nigeria. Methods This is a qualitative cross-sectional study. In-depth interviews were conducted among 43 health workers – doctors, nurses and community health extension workers, working in antenatal and postnatal clinics in public primary, secondary and tertiary health facilities selected by quota sampling. A hybrid thematic data analysis approach, combining deductive and inductive methods was employed. Results Health education on cervical cancer prevention was not done in most health facilities. Where cervical cancer health education was practiced, it was done mostly prior to family planning provision, and sometimes at antenatal, postnatal/infant immunization clinics. Facilities for cervical cancer screening was not available in most of the health facilities and patients had to travel long distances to tertiary facilities to have a Pap smear done. Barriers to cervical cancer screening and health education include, high cost of screening, manpower shortage, fear of positive result among patients, poor awareness among patients, and religious and cultural beliefs. The major facilitators to screening and health education mentioned were passion for their work and the desire that no woman should die from preventable cancers. Conclusion To address identified barriers, the government should enhance health worker training, ensure adequate staffing, improve the availability of screening equipment and reagents and make screening free/affordable. Community mobilization efforts should be intensified to increase awareness and promote accessibility. Integrating cervical cancer health education and screening into routine antenatal and postnatal care is essential for improving uptake.

Prognostic follow-up of high-grade squamous intraepithelial lesions of the cervix near the conization margin: A retrospective cohort study

Objective This study explored the prognosis of high-grade squamous intraepithelial lesion (HSIL) patients with negative margins, investigating the impact of different distances between lesions and incisal margins in conization specimens. Methods This retrospective cohort study included 240 HSIL patients. Patients with negative incisal margins were divided into 3 groups according to the distance between the lesion and the incisal margin in the conization tissue. Group 1 consisted of a distance of &lt;1 mm (n = 23), Group 2 of 1–3 mm (n = 15), and Group 3 of &gt;3 mm (n = 202). For patients with lesions close to the incisal margin (≤3 cm), the decision between total hysterectomy and clinical observation was made based on patient preference following detailed counseling of disease characteristics and prognosis. Thinprep cytologic test (TCT) and HPV testing were performed during follow-up at 6 and 12 months after the operation. Results No significant difference in HPV and TCT positive rate was observed among the three groups at 6 months and 12 months after the operation (P = 0.561, 0.561 and P = 0.324, 0.268). In the group with a distance shorter than 3 mm, no difference in HPV positive rate was found between the total hysterectomy and observation groups (P = 0.480, 0.737). Additionally, no difference in HPV positive rate was observed between patients who underwent total hysterectomy compared to clinical observation in groups 1 and 2 (P = 0.565, 0.692; P = 0.758, 0.593). Stratified analysis revealed that HPV positive rates at 6 months and 12 months had no statistical significance with any factor. Conclusion Different distances between conization tissue lesions and incisal edges have no direct impact on the prognosis of HSIL patients with negative conization biopsy tissues; excessive hysterectomy is not recommended in patients (≤3 mm) close to incisal edges.

Enhanced cervical cancer and HIV interventions reduce the disproportionate burden of cervical cancer cases among women living with HIV: A modeling analysis

Introduction Women living with HIV experience heightened risk of cervical cancer, and over 50% of cases in Southern Africa are attributed to HIV co-infection. Cervical cancer interventions tailored by HIV status delivered with HIV antiretroviral therapy (ART) for treatment can decrease cancer incidence, but impact on HIV-related disparities remains understudied. Methods Using a dynamic model calibrated to KwaZulu-Natal, South Africa, we projected HIV prevalence, cervical cancer incidence, and proportion of cancer cases among women living with HIV between 2021–2071. Relative to the status quo of moderate intervention coverage, we modeled three additive scenarios: 1) ART scale-up only; 2) expanded human papillomavirus (HPV) vaccination, screening, and treatment; and 3) catch-up HPV vaccination and enhanced screening for women living with HIV. Results Under the status quo, HIV prevalence among women aged 15+ decreased from a median of 35% [Uncertainty Range (UR): 26–42%] in 2021 to 25% [19–34%] in 2071. The proportion of cervical cancer cases that were women living with HIV declined from 73% [63–86%] to 58% [47–74%], but incidence remained 4.3-fold [3.3–5.7] that of women without HIV. ART scale-up reduced HIV prevalence in 2071, but increased the incidence rate ratio to 5.2 [3.7–7.3]. Disparities remained after expanding cancer interventions for all women (incidence rate ratio: 4.8 [3.6–7.6]), while additional catch-up HPV vaccination and screening for women living with HIV decreased the incidence rate ratio to 2.7 [1.9–3.4] in 2071. Conclusions Tailored cervical cancer interventions for women living with HIV can counteract rising cancer incidence incurred by extended life expectancy on ART and reduce disparate cancer burden.

Parents’ acceptance of human papilloma virus vaccination for their daughters in adet town, North Gojjam zone, Northwest Ethiopia: A mixed method study

Human papilloma virus vaccination is an effective way to reduce cervical cancer. Although the health of adolescents is the priority goal across the globe, including Ethiopia, parent s’ acceptance of Human papilloma virus vaccination for their daughters becomes a big challenge in Ethiopia. This study aimed to assess parent’s acceptance of human papilloma virus vaccination for their daughters and associated factors in Adet town, northwest Ethiopia, 2024. Community based mixed method study was employed from May 24 to June 27, 2024. For quantitative data, the sample size was 319 and systematic random sampling technique was used to select study participants. Structured questionnaires were administered for quantitative data, and interview guides were used for qualitative data. The quantitative data was coded, entered and cleaned using Epi info software and exported to SPSS version 25 for analysis. Descriptive statistics, bivariable and multivariable logistic regression analysis were used. Variables with p-value of &lt;0.05 with 95% confidence interval and adjusted odds ratio in multivariable analysis were considered as statistically significant factor for the outcome variable. Thematic analysis approached was employed to analyse qualitative data. Results were presented in tables, texts, charts and graphs. In this study, 249(78.1%) with 95%CI: 73.0–82.4) of parents accept HPV vaccination for their daughters. Knowledge (AOR = 2.96, 95% CI: 1.43–6.10), attitude (AOR = 3.47, 95%CI: 1.71–7.04), subjective norms (AOR = 3.20, 95% CI: 1.56–6.51) and safety concern (AOR = 8.20, 95%CI: 3.45–19.49) were significantly associated factors with parents’ acceptance of HPV vaccine. Qualitative results identified barriers to parental acceptance of the HPV vaccine for daughters, including fear of side effects like infertility, perceiving it as contraceptive method, lack of HPV knowledge, and absence of institutional accountability. Facilitators included influential stakeholder engagement, positive perceptions of the vaccine’s benefits, and confidence in its safety and efficacy. The result of this study seems promising as a more than two thirds of women accept to vaccinate their daughters against HPV though there are still misconceptions, safety and efficacy concerns. To foster cervical cancer prevention efforts, parents’ health education should address vaccination safety concerns, improve HPV knowledge, and foster positive attitudes towards vaccinating daughters.

Patient-derived and artificial ascites have minor effects on MeT-5A mesothelial cells and do not facilitate ovarian cancer cell adhesion

The presence of ascites in the peritoneal cavity leads to morphological and functional changes of the peritoneal mesothelial cell layer. Cells loose cell-cell interactions, rearrange their cytoskeleton, activate the production of fibronectin, and change their cell surface morphology in a proinflammatory environment. Moreover, ovarian cancer cell adhesion has been shown to be facilitated by these changes due to increased integrin- and CD44-mediated binding sites. In this study, the biological responsiveness of the human pleural mesothelial cell line MeT-5A to patient-derived and artificial ascites was studiedin vitroand adhesion of ovarian cancer cells, i.e. SKOV-3 cells, investigated. Changes were mainly observed in cells exposed to artificial ascites containing higher cytokine concentrations than patient-derived ascites. Interestingly, reduced cell-cell interactions were already observed in untreated MeT-5A cells and effects on tight junction protein expression and permeability upon exposure to ascites were minor. Ascites induced upregulation of CDC42 effector protein 2 expression, which affects stress fiber formation, however significant F-actin reorganization was not observed. Moreover, fibronectin production remained unchanged. Analysis of mesothelial cell surface characteristics showed upregulated expression of intercellular adhesion molecule 1, slightly increased hyaluronic acid secretion and decreased microvillus expression upon exposure to ascites. Nevertheless, the observed changes were not sufficient to facilitate adhesion of SKOV-3 cells on MeT-5A cell layer. This study revealed that MeT-5A cells show a reduced biological responsiveness to the presence of ascites, in contrast to published studies on primary human peritoneal mesothelial cells.

Effectiveness of integrating cervical cancer prevention strategies into HIV care programmes: A mixed-methods systematic review protocol

Introduction Cervical cancer, which is the fourth most frequently diagnosed cancer among women globally, remains a significant health burden despite being preventable and treatable, exposing gaps in accessing prevention and control services. Adolescent girls and young women (AGYW) living with HIV face heightened risk of persistent HPV infection, a primary cause of cervical cancer, making this population the ideal target for preventing cervical cancer before HPV exposure or disease progression. The overlap of cervical cancer and HIV exacerbates public health challenges, urging intensified efforts in bolstering prevention and control measures. Integration of cervical cancer prevention strategies into HIV care programs shows promise in effectively addressing this dual burden. Methods To evaluate the effectiveness of integrating cervical cancer prevention strategies within HIV care programs, a mixed-methods systematic review will be conducted. A comprehensive Boolean search for literature published and indexed in PubMed, Cochrane Library, EBSCO Host, Web of Science, Scopus, and Google Scholar will be conducted, without imposing any language restrictions. This review will be conducted in alignment with the Joanna Briggs guidelines on systematic reviews together with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data from eligible studies will be extracted and synthesized, and their quality assessed. Discussion There is limited understanding of the effectiveness of integrating cervical cancer prevention and HIV care in the real-world setting. While some studies touch on integration, focus tends to be on cervical cancer screening alone, neglecting vaccination, treatment of precancerous lesions, and education programs. Previous reviews on this focus are outdated, surpassing six years. This systematic review aims to fill these evidence gaps by thoroughly evaluating the challenges and opportunities associated with integrating the full complement of HPV prevention strategies and HIV care programs. The anticipated findings could enhance service delivery models aimed at reducing cervical cancer incidence and mortality among AGYW living with HIV. Trial registration Systematic review registration: PROSPERO registration number: CRD42024535821.

Factors affecting caregivers’ HPV vaccination decisions for adolescent girls: A secondary analysis of a Chinese RCT

Background Despite the HPV vaccine’s effectiveness against cervical cancer, uptake among adolescent girls in China remains low, with caregivers playing a crucial role in vaccination decisions. This study investigates factors influencing caregivers’ action to vaccinate their adolescent daughters. Methods Pay-it-forward is a novel model that motivates participants in adopting healthy behaviors and making community contributions. In this study, it offers an individual a free shot of HPV vaccine and then asks whether they would like to donate to support another person to get the same vaccination. This study was embedded in a two-arm randomized controlled trial in China. Potential associated factors were identified based on Anderson’s Health Service Utilization Behavioral Model and analyzed through univariate and multivariate binary logistic regression. Caregivers’ information, knowledge, attitudes, vaccine confidence, hesitancy, and willingness to vaccinate were collected through online questionnaires. The endpoint was the receipt of the first dose HPV vaccine following an intervention or no intervention (pay-it-forward vs. standard-of-care), which was obtained from an electronic vaccination registry system. Results Among 321 caregivers, 25.9% of their daughters received the HPV vaccine, with 34.2% in the pay-it-forward group and 17.5% in the standard-of-care group. Daughters of caregivers who were previously unaware of the HPV vaccine were three times more likely to be vaccinated (OR=3.01,95%CI:1.27–7.14). Caregivers who did not intend to delay vaccination had daughters with eight times higher vaccination uptake (OR=8.26,95%CI:4.36–15.67). Participation in the “pay-it-forward” intervention increased vaccination rates by more than twofold (OR=2.22,95%CI:1.19–4.15). Daughters of unemployed or retired caregivers had nearly four times higher vaccination rates compared to those whose caregivers were employed (OR=3.97,95%CI:1.81–8.72). Prior refusal of the vaccine by caregivers was associated with an 80% reduction in vaccination uptake among daughters (OR=0.23,95%CI:0.06–0.81). Conclusion The pay-it-forward intervention, caregivers’ knowledge, intention to delay vaccination, occupation, and prior vaccine refusal significantly influence HPV vaccine uptake among adolescent girls in China. Tailored health education, financial support, and community involvement are essential to encourage HPV vaccination among adolescent girls in China.

Human Papillomavirus Vaccination uptake and associated factors among schools girls aged between 9–14 years in Ethiopia: Performance Monitoring for Action (PMA-ET) 2023, multilevel analysis

Background Human papillomavirus (HPV) is one of the sexually transmitted diseases infections that causes cervical cancer, and it is the second-leading cause of infection-related cancer globally. HPV infection causes around 604,000 cervical cancer cases (342,000 deaths) globally each year. Therefore, this study aimed to assess Human Papillomavirus Vaccination uptake and associated factors among schools girls in Ethiopia. Method Performance Monitoring for Action Ethiopia (PMA Ethiopia) is a survey project designed to generate data on various reproductive, maternal, and newborn health (RMNH) indicators that can inform national and regional governments. The prevalence of HPV vaccine uptake with a 95% Confidence Interval (CI) was reported and presented in a forest plot for East Africa Countries using STATA version 14.1. Intra-class Correlation Coefficient (ICC), Likelihood Ratio (LR) test, Median Odds Ratio (MOR), and deviance (−2LLR) values were used for model comparison and fitness. Adjusted Odds Ratios (AOR) with a 95% Confidence Interval (CI) and p-value ≤0.05 in the multilevel logistic model were used to declare significant factors associated with HPV vaccine uptake. Result In Ethiopia, the prevalence of HPV vaccine uptake among schools girls was 30.82% (95% CI: 29.21, 32.45). In the multilevel logistic regression model, girls in age groups of 12–14 years were 2.44 [AOR = 2.44, 95% CI: 1.86–3.16] times more likely to take HPV vaccine as compared to girls aged 9–11 years. Similarly, girls who had received any health service and received sexual and reproductive health services had 7.75 [AOR = 7.75, 95% CI: 5.65–10.62], and 3.24 [AOR = 3.24, 95% CI: 2.33–4.51] were more likely to take HPV vaccine compared to their counterparts respectively. Conclusion The study findings indicate that the proportion of girls reporting receipt of the HPV vaccine in this nationally representative survey is an alarmingly low 30.8%. The following critical factors have influenced this rate: age, access to sexual and reproductive health services, general health service utilization, and regional health disparity.

Risk factors associated with adverse outcomes after cervical conization in patients with cervical adenocarcinoma in situ

Background Identifying high-risk groups for adverse outcomes after conization is crucial for developing targeted treatment plans for patients with cervical adenocarcinoma in situ (ACIS). This study aimed to analyze the clinical characteristics of patients with ACIS and identify risk factors associated with adverse outcomes. Methods Patients diagnosed with ACIS through colposcopic biopsy at the Affiliated Hospital of Qingdao University and Qilu Hospital between January 2012 and December 2022 were selected. After meeting the inclusion and exclusion criteria, we collected their clinical data. Chi-square (χ2) tests and logistic regression models were employed to determine independent risk factors. Results A total of 379 patients with ACIS were included in this analysis. About 26.1% of these patients tested positive on preoperative endocervical curettage (ECC), while 79.4% had a single lesion. Among the 334 patients who underwent cervical conization, 17.1% had positive surgical margins. Additionally, residual lesions were present in 53.6% of cases, and pathological upgrading occurred in 7.8% of patients. Multivariate analysis indicated that age (p &lt; 0.001), preoperative histopathological results from ECC (p = 0.033), and the number of ACIS lesions (p &lt; 0.001) were associated with positive surgical margins. Number of births (p = 0.011), preoperative histopathological results from ECC (p = 0.030), and surgical margin statuses at cervical conization (p &lt; 0.001) were independent risk factors for residual lesions. Preoperative histopathological result of ECC (p = 0.035) was confirmed as a predictor of postoperative pathological upgrading. Conclusions Older, multiparous patients with ACIS and abnormal preoperative ECC results require deeper diagnostic excision. Patients with positive conization margins necessitate further treatment, particularly when accompanied by abnormal ECC results. For women who wish to preserve their fertility, a repeat conization may be appropriate; however, in older and multiparous women, a hysterectomy would be recommended.

Prevalence and risk factors associated with high-risk human papillomavirus infection among women living with HIV (WLWH) at a tertiary health facility in Accra, Ghana

Background Women living with HIV (WLWH) have high risk of developing cervical cancer. High- risk Human papillomavirus (hrHPV) is the single most important cause of cervical cancer. Vaccination for and early detection of pre-malignant cervical changes, through cervical cancer screening contributes to prevention of cervical cancer. This study sought to determine the prevalence of HPV among WLWH, genotypes present and the risk factors associated with cervical cancer development. Methods and findings An analytical cross-sectional study of 250 sexually active women aged 18 years and above, attending HIV clinic at a tertiary health facility in Accra. Demographic data collection and risk factor assessments were done using interviewer-administered questionnaire, and patient records. Cervical swabs were collected and tested for HPV using real-time PCR assays. Genotype analysis was performed on 92 samples. Descriptive statistics and logistic regression analysis were used to establish associations between hrHPV and risk factors among WLWH. Approximately 60% of study participants tested positive for HPV. The prevalence of hr-HPV among WLH was 44.4%. Factors identified to be protective of hrHPV were employment (AOR = 0.19, 95% CI = 0.06, 0.56, p = 0.003) and highly active antiretroviral therapy (HAART) Tenofovir-Lamivudine-Ritonavir-Lopinavir (TLRL) (AOR = 0.30, 95% CI = 0.09, 0.95, p = 0.04). Women with HIV diagnosis within 6 to10 years (AOR = 4.89, 95% CI = 1.05, 22.70, p = 0.043) and diagnosis &gt;10 years (AOR = 8.25, 95% CI = 1.24, 54.84, p = 0.029) had higher odds of hrHPV. Approximately 25% of samples analysed tested positive for hr-HPV group 1 (genotypes 16, 18, 31, 33, 35, 39, 45,51, 52, 56, 58, 69) and 46.8% for multiple HPV genotypes. Conclusion A high prevalence of genotypes that include high risk genotypes 16 and 18 and multiple HPV infections was found among WLWH. Almost half of the women screened had high-risk HPV and were prone to cervical cancer without their knowledge. Regular HPV screening is recommended for high-risk patient groups.

A cross-sectional study of factors influencing sexual health among spouses of patients with cervical cancer

Background After treatment, cervical cancer patients commonly experience sexual health problems that lead to marital conflict. However, the sexual health cognition, distress and needs of patients’ spouses remain unclear. This study examined the factors influencing sexual health among spouses of patients with cervical cancer and provided a reference for targeted nursing interventions. Methods This cross-sectional study was conducted in Chongqing, China. A total of 202 spouses of patients with cervical cancer were selected via convenience sampling. All participants completed the questionnaire via WeChat from September 27 to October 5, 2022. The questionnaire assessed demographic information, clinical information, and information about sexual health cognition, sexual distress and sexual needs. Multiple linear regression analysis was used to identify the factors associated with sexual health cognition. Pearson’s correlation analysis was used to analyse the correlations among sexual cognition, distress and needs. Results The cognitive scores of the spouses of cervical cancer patients with respect to sexual health ranged from 6 to 25 (13.79 ± 6.74). The distress scores ranged from 8 to 35 (27.24 ± 7.88). The need scores ranged from 3 to 12 (8.68 ± 3.64). Age, education level, place of residence and other factors affected sexual health cognition. Age (β, -0.178; 95% CI, 0.099–1.060), education level (β, 0.152; 95% CI, 0.021–0.663), place of residence (β, 0.665; 95% CI, 0.102–5.789), occupation type (β, 0.507; 95% CI, 0.485–4.982), and monthly family income (β, 0.229; 95% CI, 0.311–1.344) were associated with higher levels of sexual health cognition. The results of Pearson’s correlation analysis revealed that there was a negative correlation between sexual health cognition and distress (r = - 0.6165, 95% CI: -0.69 to -0.52, P &lt; 0.001), that cognition was positively correlated with needs (r = 0.6757,95% CI 95% CI: 0.59 to 0.74, P &lt; 0.001), and that distress was positively correlated with needs (r = 0.6860, 95% CI: 0.60 to 0.75, P &lt; 0.001). Conclusions Our study revealed that sexual health cognition among spouses of patients with cervical cancer is affected by multiple factors. The degree of sexual distress among these individuals is high. There was a negative correlation between sexual cognition and distress, a positive correlation between sexual cognition and demand, and a positive correlation between sexual distress and demand. These results suggest that nurses should also include the patient’s spouse in the care process and provide targeted sexual health guidance, thereby improving the overall quality of life of patients and spouses.

Public Health Implications of Introducing Human Papillomavirus (HPV) Vaccination in Pakistan: A protocol for a mixed-method study to explore community perceptions and health system preparedness

Introduction Cervical cancer is a preventable illness, and early vaccination can serve as a primary prevention strategy. Currently, HPV vaccination has not been introduced at the national level in Pakistan, and the vaccine remains unavailable in most regions. However, efforts are underway to launch the HPV vaccination program soon. For a successful roll-out, it is essential to address circumstantial challenges and mitigate vaccine hesitancy, which stems from a complex interplay of sociocultural and contextual factors. Therefore, this study aims to comprehensively evaluate the multifaceted sociocultural, contextual, and demographic factors influencing the uptake of HPV vaccination at the community level. Objectives 1.To assess the current level of knowledge, belief, and factors associated with the acceptability of HPV vaccination among potential vaccine recipients and their parents/caregivers 2. To explore stakeholders’ perspectives on the launch of HPV vaccination, considering the dynamics of the local population in the resource-constrained country, Pakistan (OBJ 2). 3.To identify the social and behavioral factors that influence HPV vaccination acceptance and hesitancy within a local community (Punjab) (OBJ 3). Method The ethical approval of the study has been already obtained from the ethical review board of Rawalpindi Medical University (843 IREF/RMU/2024). Data will be collected after obtaining informed written consent from parents and assent from daughters. Data collection will start from April 2025 and will be completed in six months. Data compilation and results are expected by December 2025. A convergent mixed methods design will be used as it will enable the merging of qualitative and quantitative data. Data collection will involve a quantitative phase in which data will be collected from potential vaccine recipients (girls between 9–16 years) and their parents/caregivers to assess the current level of knowledge, belief, and HPV vaccine hesitancy. The qualitative phase aims to explore key stakeholders’ perspective on the health system’s preparedness and capacity for launch and uptake of HPV vaccination. The quantitative findings will be integrated with the qualitative data via the merging and expanding integration techniques to generate confirmed, expanded, and discordant meta-inferences. Discussion This study will comprehensively identify the multilevel contextual and health system factors that influence HPV vaccine uptake. This study will significantly contribute in field of Public Health by providing a foundational basis of first step of cultural adaptation and validation of BeSD tool specifically for HPV Vaccination.

Sexual function outcomes in prostate and cervical cancer patients treated with radiotherapy in sub-Saharan Africa: A cross-sectional study

Radiotherapy is indispensable for the successful treatment of many pelvic malignancies, but it is often associated with significant adverse effects on sexual function, including vaginal stenosis, decreased lubrication, erectile dysfunction, and loss of libido. Sexuality and sexual function are important aspects of quality of life for cancer survivors, yet sexual dysfunction remains an underreported complication among patients, particularly those treated for prostate and cervical cancers in limited-resource settings. This quantitative cross-sectional study aimed to evaluate sexual function outcomes among 144 prostate and 160 cervical cancer patients treated with pelvic radiotherapy at a major cancer treatment centre in sub-Saharan Africa. Data were collected using questionnaires based on the Female Sexual Function Index and the International Index of Erectile Function. Data were coded, cleaned, and analyzed using STATA statistical software package (version 17). The mean age of the patients with cervical cancer was 53.5 years (SD 9.6) ranging from 37 to 69 years whereas the mean age of patients with prostate cancer was 67.1 years (SD 7.7) ranging from 56 to 79 years. Among female participants, 79.9%, had moderate to severe sexual dissatisfaction, 94.4% had poor or no satisfactory orgasm whereas 97.2% had difficulty with lubrication. Only 5.6%, 5.6%, 2.8%, and 20.1% of the female participants achieved sexual desire, orgasm, lubrication, and overall satisfaction respectively. In all, 94.4% of the female participants had a total FSFI score less than 26 whereas 5.6% had a score greater than 26. Most patients did not indulge in sexual activity. There was a high prevalence of sexual dysfunction across multiple domains, with cervical cancer patients experiencing diminished desire, poor arousal, lubrication difficulties, and impaired orgasmic function, leading to low relationship satisfaction and avoidance of sexual activity. Similarly, prostate cancer patients demonstrated severe erectile dysfunction, low sexual desire, and dissatisfaction with intercourse and overall sexual experience.

Boosting immune response against cervical cancer: A combined approach using oncolytic virus and targeted therapies

Background Cervical cancer remains a primary reason for cancer malignancy among women worldwide, primarily due to human papillomavirus (HPV) strains HPV16 and HPV18. Despite having access to vaccines, there are few treatment options for advanced or recurring cases. This research investigates the possibility of using Newcastle disease virus (NDV) along with Everolimus (EVE) and Beclin-1 (BEC) to improve immune reactions and decrease tumor development in an experimental model of HPV-related cervical cancer. Methods A mouse model for cervical cancer was created by utilizing HPV16 E6/E7-expressing TC-1 cells in C57BL/6 mice. The mice underwent treatment with NDV, EVE, BEC, or various combinations of these therapies. Tumor progression was monitored, evaluated immune responses by measuring cytokine levels (including IL-4, IFN-γ, and IL-12), and investigated the presence of CD8 + T cells within the tumors. Additionally, survival rates were monitored throughout the study. Results The synergy of NDV, EVE, and BEC led to a remarkable decrease in tumor growth, achieving reductions of as much as 70% when compared to monotherapies. Additionally, our combination therapy elicited strong immune reactions, evidenced by increased concentrations of IL-4, IFN-γ, and IL-12, along with enhanced infiltration of CD8 + T cells into the tumors. Mice that were subjected to this Triple therapy exhibited better survival rates than those in other treatment categories. Conclusions Our findings highlight the potential to improve outcomes in cervical cancer associated with HPV through a multi-faceted approach incorporating NDV, Everolimus, and Beclin-1. This therapeutic strategy not only hinders tumor growth but also strengthens the immune system’s ability to fight against cancer. These results prompt further exploration of this combination in clinical trials, with the goal of offering new treatment avenues for patients who have limited choices.

Green synthesized Polyscias fulva silver nanoparticles ameliorate uterine fibroids in female Wistar Albino rats

Uterine fibroids affect a substantial proportion of women in their reproductive age. Despite their effectiveness, surgical options such as hysterectomy are invasive, costly, and associated with recurrences. Pharmacological treatments are non-curative, only alleviate symptoms, and associated with adverse effects. Polyscias fulva (Araliaceae) is traditionally used to manage uterine fibroids in East Africa. In this study we synthesized Polyscias fulva silver nanoparticles (PFAgNPs), evaluated their toxicity and activity against monosodium glutamate (MSG)-induced uterine fibroids in Wistar albino rats. The UV-visible spectroscopy showed maximal absorbance at 425 nm with adequate stability at varying temperatures, pH and storage conditions. Dynamic light scattering (DLS) analysis revealed an average hydrodynamic size of 107.4 d.nm, polydispersity index of 0.264, and zeta potential of -18.3 mV. X-ray diffraction (XRD) confirmed the crystalline nature of PFAgNPs with an average size of 25 nm while scanning electron microscopy (SEM) showed a spherical shape with an average size of 35 nm. The PFAgNPs caused lethargy, hyperventilation, and hyperactivity at a dose of 300 mg/kg BW, whereas 2000 mg/kg caused severe toxicity, resulting in death in acute toxicity testing. The no observed adverse effect level was 50 mg/kgBW, the lowest observed adverse effect level was 100 mg/kgBW, and median lethal dose (LD50) was 1000 mg/kg. The PFAgNPs significantly decreased (P &lt; 0.05) serum proteins, cholesterol, estrogen and progesterone alongside preservation of the histoarchitecture of the uterus. Further research is needed to investigate the clinical safety of PFAgNPs in managing uterine fibroids.

Cervical intraepithelial neoplasia grade 1 and long-term risk of progression and treatment

Background Cervical intraepithelial neoplasia grade 1 (CIN1) is often managed by active surveillance, as the risk of progression to high grade lesions is reported to be low, but long-term data is sparse. To inform management of CIN1, we estimated risk of progression and occurrence of treatment in women attending a cervical cancer screening program. Methods We used nationwide, registry data on all women aged 25–69 years attending the Norwegian Cervical Cancer Screening Program in 2002–2019. The eligible source population was women with at least one cytology registration (n = 1,771,876). Women with a histologically confirmed, first CIN1 diagnosis were included (n = 26,130) and followed for detection of CIN2+, defined as histologically confirmed CIN2, CIN3, adenocarcinoma in situ (AIS), or cervical cancer. CIN3+ was defined as CIN3, AIS, or cervical cancer. Treatment included both excision and ablation. Results Overall, the cumulative incidence of CIN2+ increased to 9.5% (95% confidence interval (CI), 8.8 to 9.5) during the first year and to 19.0% (95% CI, 18.4–19.5) during the first five years. For women with high-grade cytology, 5-year cumulative incidence reached 26.0% (95% CI, 25.0–27.0), whereas for women with normal or low-grade cytology, but HPV16 and/or HPV18 positive status, the corresponding estimate was 25.0% (95% CI, 23.3–26.8). Other high-risk HPV genotypes and HPV negative status were associated with lower risks (5-year cumulative incidence 15.5% (95% CI, 14.5–16.6) and 8.2% (95% CI, 7.1–9.5), respectively). Detection of CIN3+ was substantial (cumulative incidence 5.7% (95% CI, 5.4–6.0) and 12.7% (95% CI, 12.2–13.1) after 1 and 5 years, respectively), and overall, cumulative incidence of treatment was 15.2% (95% CI, 14.7–15.7) after 5 years, following similar patterns as observed for CIN2+. Conclusions A differentiation of follow-up guidelines by index cytology and HPV16/18 status for women diagnosed with CIN1, might be warranted.

Utilization of screening services on cervical cancer and associated factors among female health workers in Addis Ababa, Ethiopia

Background Cervical cancer is the fourth most common cancer among women worldwide and the second most common cancer in women in Ethiopia with the disease claiming the lives of more than 340, 000 women globally in 2020. A well organized and arranged screening is one of the key intervention strategies in the reduction of the incidence and mortality from the disease. Healthcare workers, being the front line in health delivery system, are expected to play a critical role in cervical cancer screening. This being the fact on the ground, the gap on the cervical cancer screening service utilization and the factors influencing it among female health workers in Ethiopia is not well elucidated. We aim to explore the magnitude of the screening uptake and associated factors among female healthcare providers in Addis Ababa, Ethiopia. Methods Institution-based cross-sectional study using stratified multi-stage sampling technique was done from June 05 to July 05, 2023 among female health workers in Addis Ababa. The data was collected using a structured self-administered questionnaire. Descriptive statistics like mean, median, and proportion were used to summarize the data. Bivariable regression analysis was used to measure the association between the dependent and independent variables, while multivariable regression analysis was used to determine the independent associations. Variables with P-value≤ 0.25 on bivariable model were entered into a multivariable logistic regression model. Odds ratios with 95% confidence intervals (CIs) were computed to measure the strength of association, and statistical significance was declared at P&lt; 0.05. Results A total of 432 study participants were enrolled in the final analysis with the response rate of 100%. Out of the total participants, 243 (56.3%) were nurses, and 183 (42.4%) were of age 30 years and above. In this study, only 19.4% (84/432) and 31.2% (57/183) among all participants and the targeted groups (age ≥30 years), respectively, have utilized the screening services. The lack of attention was the main reason identified hindering the screening service utilization (32.5%) while the promoter factors being awareness about screening methods (48.8%) and physician recommendation (26.2%). On Multivariable model; participant age ≥30 years (AOR=1.6, 95%CI1.15–3.37), being married (AOR=6.1, 95%CI 2.42–15.06), and working in cervical cancer screening units (AOR=3.7, 95%CI1.01–12.12), respectively had an independent association with the screening service utilization. Similarly, the study participants knowledge of the etiology, knowledge of cigarette smoking as risk factor, and visual inspection with acetic acid as screening method had shown an independent association with screening service utilization, (AOR=1.6, 95%CI=1.01–12.12), (AOR=4.1, 95%CI1.68–9.76), (AOR=14.2, 95%CI3.77–53.32), respectively. Conclusion The low screening services utilization among the targeted age group of female health workers is alarming. The lack of attention and feeling of healthy were hindering factors among those not yet screened, while those screened were motivated by the awareness created and physician recommendation. Continual awareness creation and training of female healthcare providers on cervical cancer and its screening is recommended to improve the screening service uptake by the women in the population.

Towards 90-70-90 targets: Individual and community level factors associated with cervical cancer screening among women of reproductive age in Tanzania: A multi-level analysis based on 2022 Tanzania demographic and health survey

Introduction Cervical cancer is a major public health problem worldwide, and is mainly caused by human papillomaviruses. More than 90% of cervical cancer cases can be prevented by using a human papilloma vaccine and screening. Despite the ongoing global cervical cancer screening target, uptake remains unacceptably low in sub-Saharan Africa such as Tanzania. Although cervical cancer is the leading cause of mortality in Tanzania, evidence on the individual- and community-level factors associated with cervical cancer screening among women of reproductive age is scarce. Therefore, this study aimed to determine the individual- and community-level factors associated with cervical cancer screening among women of reproductive age in Tanzania. Methods This study used data from the 2022 Tanzania Demographic and Health Survey (TDHS). A weighted sample of 15,140 women of reproductive age was included in this study. Given the effect of clustering and binary nature of the outcome variable, we used a multilevel binary logistic regression model. The adjusted odds ratio (AOR) with 95% Confidence Interval (CI) was statistically significant. Moreover, the model with the lowest deviance best suited the data. Results The overall uptake of cervical cancer screening among Tanzanian women was 7.28% (95% confidence interval [CI]: 6.87%, 7.70%). Women’s age (25–34, 35–49), women with primary, secondary, and higher educational levels, being employed, a high household wealth index, visiting health facilities in the last 12 months, owning mobile phones, urban residence, and southern highlands, Southern, and Zanzibar administrative zones, were significantly associated with cervical cancer screening. Conclusion Cervical cancer screening among women in Tanzania was low. Low uptake underscores the need for increased focus on addressing the coverage of the 2030 Sustainable Development Goals (SDGs). The study would help policymakers create programs that consider education, employment, visiting health facilities, mobile phones, wealth, residence, and administrative zones, which would make women undergo cervical cancer screening. Pointing to women living with low cervical cancer screening could help increase their uptake and achieve the targets of the national and World Health Organization.

Evaluation of Onco E6 point of care rapid diagnostic test for human papilloma virus in Bahir Dar, Amhara Regional State, Ethiopia

Introduction Cervical cancer is a malignant tumor arising from the cells of the uterine cervix. The oncogenic human papillomavirus (HPV) infection is the main causative agent of cervical cancer. Effective HPV screening program can lead to a significant reduction in the morbidity and mortality associated with this cancer. Objective The aim of the study was to evaluate the diagnostic performance of OncoE6™ cervical test kit for cervical precancer and cancer in Amhara Regional State, northwest Ethiopia. Methods An institute-based cross-sectional study was conducted at Felege Hiwot Compressive Specialized Hospital which is found in Bahir Dar, Amhara Regional state. A total of 297 samples were collected. A sterile, disposable speculum was inserted, without lubricant, and two swabs were taken using the “Tipped Polyester” (Dacron) swab provided with the Onco E6™ kit. Swabs taken were tested for onco E6 proteins testing as per the manufacturer’s protocol and pap smear for cytology test. A punch of biopsy was also taken for histopathological diagnosis. Data for all samples were collected using pre-prepared excel database for onco E6 test, pap cytology and punch histopathology. All the data were coded and entered into Epi-info and transported to SPSS version 26.0 software package for analysis. Results Out of 56 (18.86%) participants who tested positive on the histo-pathological diagnosis, Onco E6 was positive in 32 (57.14%), negative in 24 (42.85%). Of 241 participants who tested negative on the histo-pathological diagnosis, Onco E6 was positive in 5 (2.07%) and negative in 236 (97.9%). OncoE6™ cervical test kit had a sensitivity of 57.14% (95% CI: 43.22%–70.29%) and specificity of 98% (95% CI: 95.23%–99.32%) with positive predictive value of 86.6% (95% CI: 71.36%–95.53%), negative predictive value of 90.76% (95% CI: 86.49%–93.93%), and accuracy of 90.18% (95% CI: 86.21%–93.31%). Conclusion The HPV 16/18 OncoE6™ Cervical test kit test had sub-optimum sensitivity and high specificity for detection of cervical precancer and cancer cases. The sensitivity of the kit could be increased by incorporating other more prevalent genotypes like genotype 52, 58, 31 and 35. The HPV16/18-E6 test could be used either as primary screening tool or in conjunction with other diagnostic methods.

Findings from a qualitative analysis: Social media influencers of color as trusted messengers of HPV vaccination messages

Background Despite HPV vaccination reducing the prevalence of cervical cancer by 90%, vaccination rates remain lower among communities of color due to vaccine hesitancy and mistrust in traditional public health messengers. The emergence of social media influencers, a newer kind of messenger, presents a unique opportunity to share immunization messages in new ways with a variety of communities. This paper reviews the qualitative findings from a study aimed at assessing influencers’ perceptions of and approaches to sharing messaging about the HPV vaccine. Methods Guided by several theories (Theory of Planned Behavior, Narrative Theory, and Opinion Leader Theory), the study team designed an intervention-based study consisting of qualitative interviews and social media influencer-designed and disseminated messaging. We worked closely with an influencer marketing firm to recruit 10 influencers of color who had children aged 9-14 – to write about the vaccine with their followers. Influencers used a provided factsheet to draft social media posts about vaccinating their children against HPV. Influencers were interviewed about their post and posts and interview transcripts were analyzed for key themes. Results Most influencers were hesitant to talk about vaccinations for fear of backlash. Most committed to writing, however, because they were compelled to support important health topics. All used the power of storytelling to convey the messages and highlighted their personal journeys of vaccine decision making. Influencers also highlighted the struggles of parenting and talked emotionally about how making decisions about this vaccine prompted feelings about their child growing up. Influencers also believed that they could help people make the decision to vaccinate. Conclusions The findings from this study elucidates the emotional context within which parents are being asked to vaccinate their children and thus, how personal the decision to vaccinate is. Most influencers noted that they had received a doctor’s recommendation but were taking the time to do their own research. Insights from this study can help inform current and future public health communication programs aimed at supporting immunization efforts. It also can provide lessons for other health topics.

Comparative evaluation of Allplex HPV28 and Anyplex II HPV28 assays for high-risk HPV genotyping in cervical samples

Background/Objectives Human papillomavirus (HPV) genotyping is essential for cervical cancer screening and prevention. The AllplexTM HPV28 real-time PCR kit, using different chemistry and results analysis compared with its predecessor, the AnyplexTM II HPV28 kit, has recently been launched. This study aims to compare the AllplexTM HPV28 and AnyplexTM II HPV28 assays in detecting and genotyping the 13 high-risk (HR)-HPV types. Study design Between 2022 and 2023, 459 cervical samples from women undergoing cervical cancer screening were selected. These samples were analysed by liquid-based cytology and tested by both kits concurrently. Results AllplexTM HPV28 Ct values correlated well with AnyplexTM II HPV28 signal intensity scores. No significant differences between assays were observed in overall and genotype-specific HR-HPV prevalence determined in all samples and according to cytological results. In addition, no significant differences were identified between assays in the detection of single and multiple HR-HPV infections. Most of the discordant results corresponded to samples showing weak HR-HPV signals and multiple HR-HPV types. Conclusions Our results demonstrate that the AllplexTM HPV28 kit can be used for HPV genotyping, with results overall similar to those obtained with the AnyplexTM II HPV28 kit and the addition of Ct values for patient follow-up. The clinical implications of the potentially reduced sensitivity of the AllplexTM HPV28 kit in detecting HPV31 (p =  0.07) and HPV39 (p =  0.08) warrant further investigation in subsequent studies.

Healthcare-seeking behaviors and factors influencing non-adherence among cervical cancer patients attending Bugando Oncology Clinic in Mwanza, Tanzania: A qualitative Phenomenological study

Background In low- and middle-income countries, particularly in Tanzania, most patients with cervical cancer present with advanced-stage disease and exhibit non-adherence which results in increased numbers of patients with cancer-related deaths. The current study explores the health-seeking behavior of cervical cancer patients and the factors that influence their non-adherence to cancer care. Objective To explore the healthcare-seeking behaviors and identify factors influencing non-adherence among cervical cancer patients attending Bugando Medical Center’s Oncology Clinic in Mwanza, Tanzania. Methods A qualitative phenomenological design was adopted to explore the lived experiences of 15 households with non-adherent cervical cancer patients, after obtaining patients’ information from the chemo radiation treatment registries of Bugando Oncology Clinic in Mwanza, Tanzania. Data were generated through in-depth interviews with patients, and NVivo 12 qualitative computer software was used to aid analysis. Thematic content analysis was conducted to uncover underlying meanings and patterns in the data, providing valuable insights into the phenomena under investigation. Findings The study revealed poor adherence to treatment-seeking by most of the study informants in the form of delayed health-seeking at nearby health facilities. The limited capacity for correct cervical cancer diagnosis also pushed some of the informants to turn to self-medication including traditional remedies. The findings revealed delayed healthcare-seeking behavior and poor adherence to most of the study participants seeking medical care at nearby health facilities with limited capacity for correct cervical cancer diagnosis. Some turned to self-medications including traditional remedies. Financial constraints emerged as a major obstacle, affecting the affordability of treatments, transportation, and accommodation. Moreover, the malfunctioning radiotherapy machine posed a significant barrier to effective treatment. Limited comprehensive information on their condition, treatment options, and schedules further hindered adherence. Conclusion There is a need for improved access to an appropriate healthcare system and interventions to improve non-adherence to treatment of cervical cancer services, as well as increase public awareness, initiation of tools for good adherence of chemotherapy treatment and mass screening of cervical cancer risk factors and earlier diagnosis for better survival from the disease in Tanzania.

Transcriptomic profile induced by calcitriol in CaSki human cervical cancer cell line

The vitamin D endocrine system, primarily mediated by its main metabolite calcitriol and the vitamin D receptor (VDR), plays a critical role in numerous human physiological processes, ranging from calcium metabolism to the prevention of various tumors, including cervical cancer. In this study, we comprehensively investigated the genomic regulatory effects of calcitriol in a cervical cancer model. We examined the transcriptional changes induced by calcitriol in CaSki cells, a cervical cell line harboring multiple copies of HPV16, the primary causal agent of cervical cancer. Our microarray findings, revealed that calcitriol regulated over 1000 protein-coding genes, exhibiting a predominantly repressive effect on the CaSki cell transcriptome by suppressing twice as many genes as it induced. Calcitriol decreased EPHA2 and RARA expression while inducing KLK6 and CYP4F3 expression in CaSki cells, as validated by qPCR and Western blot. Functional analysis demonstrated that calcitriol effectively inhibited key processes involved in cancer progression, including cell proliferation and migration. This was further supported by the significant downregulation of MMP7 and MMP13 mRNA levels. Our microarray results also showed that, in addition to its effects on protein-coding genes, calcitriol significantly regulates non-coding RNAs, altering the expression of approximately 400 non-coding RNAs, including 111 microRNA precursors and 29 mature microRNAs, of which 17 were upregulated and 12 downregulated. Notably, among these calcitriol-regulated microRNAs are some involved in cervical cancer biology, such as miR-6129, miR-382, miR-655, miR-211, miR-590, miR-130a, miR-301a, and miR-1252. Collectively, these findings suggest that calcitriol exhibits a significant antitumor effect in this advanced cervical cancer model by blocking critical processes for tumor progression, underscoring the importance of maintaining adequate vitamin D nutritional status.

Gynecologic health of women with multiple sclerosis: An overview on the current status and findings of Pap tests in a low-income setting

Background Women with MS (wwMS), particularly ones in low-income settings, and exposed to disease-modifying therapy (DMT), could have specific gynecological health-related issues. Aim To assist policy making and lead further research by describing the current status of gynecological health and Pap test results in wwMS. Methods Cross-sectional study on wwMS living in Isfahan, Iran. Participants were surveyed and referred for a Pap test, results of which were compared with 1:2 age- and socioeconomic status-matched healthy controls (HC). Primary outcome was the degree of non-benign squamous/glandular cell abnormalities. Secondary outcomes were presence of evidence of infection, and the degree of benign inflammatory/reactive changes. Logistic regression models were utilized for analyses. Results 197 wwMS were included (mean age [SD], 41.2 [8.3]; median EDSS (IQR) 1.5 [0.5]). 74.1% reported having sexual activity more than once per week in the past year. For contraception, 21.6% and 16.8% used calendar-based methods and male condoms, respectively. 7% had contracted a gynecological infection in the past. Only 1% had received HPV vaccination. Compared to HC, benign reactive/inflammatory changes in Pap tests were less frequently seen in the wwMS (OR: 0.3; 95% CI: 0.2, 0.4; p &lt;  0.001), while evidence of infection was seen more frequently (OR: 11.5, 95% CI: 3.3, 40; p &lt;  0.001). Results were consistent across DMT groups except anti-CD20 therapies. Additionally, the frequency of non-benign changes in wwMS was two times of that in the HC, but the study lacked adequate power to confirm statistical significance (1.5% vs. 0.8%, OR: 2; 95% CI: 0.4, 10.1; p =  0.39). Conclusion There is room for improvement of the gynecological health status of wwMS who live in low-income settings. Also, findings support an immune dysfunction in the cervices of DMT-exposed wwMS. Additionally, further research is merited to determine the risk of changes of malignant potential in cervices of wwMS.

Evaluation of the cervical liquid-based cytology sample as a microbiome resource for dual diagnosis

Cervical cancer, which is mainly caused by oncogenic human papillomavirus subtypes, remains a significant global health challenge. Recent studies have indicated a connection between cervical cancer and the uterine microbiome, underscoring its importance. This study explored the potential of liquid-based cytology (LBC) samples, which are typically used for cytological analysis, in investigating the cervical microbiome. Thirty women participated in the study and provided clinical information. Three samples were obtained from each participant: one for clinical purposes using LBC, another for microbiome sampling using LBC, and a third using the SWAB Microbiome kit. The LBC and traditional swab (SWAB) samples were subjected to high-throughput 16S rRNA gene sequencing for microbiome analysis. The results revealed a consistent dominance of key taxa, particularly Lactobacillus spp. The analysis of differential abundance highlighted variations in microbial abundance among individuals, which were more prominent than those resulting from the sampling methods. Functional analysis identified arachidonic acid and alpha-linolenic acid metabolism, along with a cautionary note regarding the low mean proportion values. The network analysis revealed positive correlations between indicators of structure among the networks, highlighting the robustness of microbiome similarities despite the diversity of sampling methods. Supervised machine learning has revealed challenges in distinguishing LBC and SWAB samples based on their microbiome features. Weighted co-expression network analysis revealed that the correlation between microbial clusters and the sampling method with clinical data was not significant. This study emphasizes the similarity in microbial communities observed using the LBC and SWAB methods, highlighting the potential of using dual diagnostic approaches. Additionally, the use of residual LBC samples in large-scale microbiological studies can provide comprehensive insights into cervical health and disease.

Factors associated with uptake of human papilloma virus vaccine among adolescent girls: A cross sectional survey on insights into HPV Infection Prevention in Kabarole District, Western Uganda

Background Human papilloma virus (HPV) infection imposes a substantial global disease burden and represents a critical public health concern. The persistently low uptake of HPV vaccination poses a significant obstacle to reducing cervical cancer incidence, particularly in remote rural areas of developing nations. Objective This study aims to assess the extent of Human papilloma virus vaccine coverage among adolescents and explore the associated determinants to facilitate enhanced planning strategies within the Kabarole district. Methodology Employing a cross-sectional survey approach, data were gathered from 240 adolescent girls residing in the Kabarole district between 01/09/2022 and 18/10/2022. Simple and multiple logistic regression analyses were employed to investigate the relationships between HPV vaccination uptake and various independent variables, including demographics, HPV knowledge, and health system factors. Results Of the 240 adolescents enrolled, the overall prevalence of uptake of HPV vaccination was 63%. The uptake of human papilloma was associated with demographics knowledge about HPV and health systems factors. The multivariate analysis showed that parents who completed secondary level of education were 4.1 times more likely to take their children for HPV vaccination compared to parents whose education level was primary or had no formal education (AOR = 4.06; 95%CI (1.69 - 6.87); p = 0.004). Distance from home to facility was associated with uptake HPV vaccination. Participants who came from the distance of more than 5 km were 60% less likely to uptake HPV vaccination compared to those who come from 5km or less (OR = 0.4; 95%CI (0.34 – 0.89); p = 0.006). Results further revealed that parents whose knowledge about HPV vaccination was moderate were three times more likely to take up HPV vaccine compared to those whose knowledge was low (OR =  2.99; 95%CI(1.14 – 7.87); p = 0.026). Conclusion HPV vaccination uptake was at 63% and relatively lower than national average. Education of parents, Knowledge of HPV vaccination and distance to facility were factors significantly associated with uptake of human papilloma virus vaccine.

Navigating the risks: Stakeholder views on risk-based cervical cancer screening

Background The development of risk-based cancer screening programs requires a paradigm shift in existing practices and healthcare policies. Therefore, it is crucial to not only assess the effectiveness of new technologies and risk prediction models but also to analyze the acceptability of such programs among healthcare stakeholders. This study aims to assess the acceptability of risk-based cervical cancer screening (RB CCS) in Estonia from the perspectives of relevant stakeholders. Methods and materials This qualitative study employed semi-structured interviews with healthcare policy and service level stakeholders in Estonia. The Theoretical Framework of Acceptability guided the interview design, and the findings were charted using framework analysis based on the Consolidated Framework for Implementation Research. Results 17 interviews were conducted with stakeholders, including healthcare professionals, cancer registry representatives, technology specialists, policymakers, and health insurance providers. While stakeholders generally supported the concept and potential benefits of RB CCS, recognizing its capacity to improve screening outcomes and resource allocation, they raised significant concerns about feasibility, complexity, and ethical challenges. Doubts were expressed about the readiness of the healthcare system and population, particularly the current health information system’s capacity to support risk-based approaches. The need for evidence-based and internationally validated screening models, comprehensive public communication, provider training, and collaborative discussions involving all relevant parties, including the public, was emphasized. Conclusion The favorable attitude towards RB CCS among stakeholders provides a strong foundation for advancing its development. However, a comprehensive strategy emphasizing the generation of robust evidence, strengthening healthcare infrastructure, prioritizing patient empowerment, and cultivating a collaborative environment built on trust is crucial.

Locally advanced cervical cancer: Neoadjuvant chemotherapy plus radical surgery an alternative approach to chemo-radiation in a low-income setting: A descriptive study

Objective To describe the treatment outcomes of locally advanced cervical cancer managed with neoadjuvant chemotherapy (NACT) plus radical surgery at a gynecology oncology center in Ethiopia. Methods This was a retrospective descriptive study of management of locally advanced cervical cancer (LACC) at St. Paul’s Hospital Millennium Medical College (Ethiopia) over 5 years. Data were collected by reviewing patient records. Data were analyzed using SPSS version 23. Simple descriptive analysis was employed to analyze clinical, histologic, and treatment outcomes of LACC managed with NACT+ radical surgery. Frequency and proportions were used to present the results’ significance. Results A total of 98 patients were analyzed. One-third (31.6%) of cervical cancer patients with locally advanced disease were operable after neoadjuvant chemotherapy. Out of this, nodal metastasis was found in 2 patients (all pelvic lymph node metastasis). Disease recurrence within 2 years was 3% (1 recurrence within 6–12 months and 2 recurrences at 12–24 months). Conclusion This study supports utilization of NACT plus radical surgery for locally advanced cervical cancer, where chemoradiation is not readily available. Our findings imply that this treatment modality is a life-saving alternative treatment in a low-income setting, which is often married by shortage or unavailability of radiotherapy at the needed time before disease progression ensues.

Breast and cervical cancer screening among women at reproductive age in Cambodia: A secondary analysis of Cambodia Demographic and Health Survey 2022

Breast and cervical cancers are the most prevalent diagnosed in women worldwide, significantly contributing to maternal morbidity and mortality. We examined socio-demographic and behavioral factors associated with breast and cervical cancer screening among Cambodian women aged 15–49 years old. We analyzed women’s data from the 2022 Cambodia Demographic and Health Survey (CDHS). In total, 19,496 women were interviewed. Multiple logistic regression was performed using STATA V17 to examine factors associated with breast and cervical cancer screening. The proportion of breast and cervical cancer screenings was 10.6% and 15.3%, respectively. After being adjusted, factors independently associated with breast cancer screening included age group 20–29 years [AOR = 2.51; 95% CI: 1.55–4.06], 30–39 years [AOR = 4.34; 95% CI: 2.66–7.09], and 40–49 years [AOR = 4.66; 95% CI: 2.81–7.71], higher education [AOR = 1.92; 95% CI: 1.26–2.93], exposure media [AOR = 1.66; 95% CI: 1.32–2.10], and rich wealth quintile [AOR = 1.50; 95% CI: 1.25–1.80]. Similarly, the odds of having cervical cancer screening were age group 20–29 years [AOR = 2.88; 95% CI: 1.76–4.71], 30–39 years [AOR = 5.94; 95% CI: 3.58–9.83], and 40–49 years [AOR = 7.61; 95% CI: 4.55–12.73], higher education [AOR = 1.55; 95% CI: 1.55–2.73], exposure media [AOR = 1.62; 95% CI: 1.35,1.95], and rich wealth quintile [AOR = 2.14; 95% CI: 1.78–2.5f8]. In conclusion, this study shows the low screening proportion for both breast and cervical cancers, and it also highlights that socio-economic factors are significantly important in determining the health care seeking for these two main cancer screening services among women aged 15–49 years in Cambodia. Therefore, increase of exposure media with health education focusing on these cancer screenings should be made better accessible to women, particularly those of low socio-economic status.

Current evidence and future direction on evaluating the anticancer effects of curcumin, gingerols, and shogaols in cervical cancer: A systematic review

Cervical cancer ranked fourth most common malignancy among women worldwide despite the establishment of vaccination programmes. This systematic review evaluates the anti-cancer properties of turmeric and ginger bioactive compounds, specifically curcumin, 6/10-gingerol, and 6/10-shogaol, and their combination in cervical cancer through in-vitro and in-vivo models. A comprehensive electronic search was performed using Science Direct, PubMed, and Scopus from inception until the second week of June 2024 for studies published in English. Only studies investigating the effects of curcumin, gingerol, shogaol, and/or their combination in human cervical cancer cell lines and/or rodent animal models implanted with cervical cancer xenografts were included. Altogether, 27 studies were included in this review. The evidence gathered indicated that curcumin, 6/10-gingerol and 6-shogaol exert their anticancer action through modulation of cell signalling pathways, including AMPK, WNT, PI3K/AKT, and NF‐κB pathway, and mediators including Bax/Bcl2, TNF‐α, EGFR, COX‐2, caspases‐3, ‐9, p53, and pRb. However, the synergistic effect of these bioactive compounds is not known due to lack of evidence. In conclusion, curcumin, 6/10-gingerols, and 6-shogaols hold promise as therapeutic agents for cervical cancer. Yet, further research is essential to understand their combined efficacy, emphasising the need for additional studies exploring the synergistic anticancer effects of these bioactive compounds. Additional factors to explore include long-term effects and susceptibility of chemoresistant cervical cancer cells towards curcumin, shogaols, and gingerols.

Modeling the health and economic implications of adopting a 1-dose 9-valent human papillomavirus vaccination program in adolescents in low/middle-income countries: An analysis of Indonesia

Background Recent evidence suggests that 1 dose of the human papillomavirus (HPV) vaccine may have similar effectiveness in reducing HPV infection risk compared to 2 or 3 doses. Objective To evaluate the public health impact and cost-effectiveness of implementing a 1-dose or a 2-dose program of the 9-valent HPV vaccine in a low- and middle-income country (LMIC). Methods We adapted a dynamic transmission model to the Indonesia setting, and conducted a probabilistic sensitivity analysis using distributions reflecting the uncertainty in levels and durability of protection of a 1-dose that were estimated under a Bayesian framework incorporating 3-year vaccine efficacy data from the KEN SHE trial (base-case) and 10 year effectiveness data from the India IARC study (alternative analysis). Scenarios included different coverage levels targeted at girls-only, or girls and boys. Costs and benefits were computed over 100 years from a national single-payer perspective. Results Depending on the coverage and target population, the median number of cancer cases avoided in 2-dose programs ranged between 600,000–2,100,000, compared to 200,000–600,000 in 1-dose programs. The 1-dose programs are unlikely to be cost-effective compared to 2-dose programs even at low willingness-to-pay (WTP) thresholds. The girls-only 2-dose program tends to be cost-effective at lower WTP thresholds, particularly in scenarios with high coverage, dose price and discount rate, while the girls and boys 2-dose program is cost-effective at higher WTP thresholds. In the alternative analysis, 1-dose programs have higher probability of being cost-effective compared to the base-case, particularly for low WTP thresholds (less than 0.5 GDP) and for high coverage, dose price and discount rate. Conclusion Adoption of 1-dose programs with 9-valent vaccine in an LMIC resulted in more vaccine-preventable HPV-related cancer cases than 2-dose programs. The 2-dose programs were more likely to be cost-effective than 1-dose programs for a wide range of WTP thresholds and scenarios.

Effects of different educational interventions on cervical cancer knowledge and human papillomavirus vaccination uptake among young women in Japan: Preliminary results of a cluster randomized controlled trial

The incidence and mortality rates of cervical cancer are increasing among young Japanese women. In November 2021, the Japanese Ministry of Health, Labour, and Welfare reinstated the active recommendation of the human papillomavirus (HPV) vaccine, after it had been suspended in June 2013 due to reports of adverse reactions. However, vaccine hesitancy is prevalent in the younger generation in Japan. To identify obstacles to vaccine uptake, we conducted a randomized study using different methods to provide educational content to improve health literacy regarding cervical cancer and HPV vaccination among Japanese female students. We surveyed 188 Japanese female students, divided into three groups according to the intervention: no intervention, print-based intervention, and social networking service-based intervention. Twenty questionnaires and the Communicative and Critical Health Literacy scales were used as health literacy scales. Participants’ knowledge and health literacy improved regardless of the method of education. In fact, participants acquired proper knowledge when given the opportunity to learn about the importance of the disease and its prevention. Therefore, medical professionals in Japan must provide accurate scientific knowledge regarding routine HPV vaccination and the risk of cervical cancer in young women to improve their health literacy and subsequently increase HPV vaccination rates in Japan, which may lead to cervical cancer elimination. Trial registration number: UMIN000036636.

Problems of magnetic resonance diagnosis for gastric-type mucin-positive cervical lesions of the uterus and its solutions using artificial intelligence

Purpose To reveal problems of magnetic resonance imaging (MRI) for diagnosing gastric-type mucin-positive (GMPLs) and gastric-type mucin-negative (GMNLs) cervical lesions. Methods We selected 172 patients suspected to have lobular endocervical glandular hyperplasia; their pelvic MR images were categorised into the training (n = 132) and validation (n = 40) groups. The images of the validation group were read twice by three pairs of six readers to reveal the accuracy, area under the curve (AUC), and intraclass correlation coefficient (ICC). The readers evaluated three images (sagittal T2-weighted image [T2WI], axial T2WI, and axial T1-weighted image [T1WI]) in every patient. The pre-trained convolutional neural network (pCNN) was used to differentiate between GMPLs and GMNLs and perform four-fold cross-validation using cases in the training group. The accuracy and AUC were obtained using the MR images in the validation group. For each case, three images (sagittal T2WI and axial T2WI/T1WI) were entered into the CNN. Calculations were performed twice independently. ICC (2,1) between first- and second-time CNN was evaluated, and these results were compared with those of readers. Results The highest accuracy of readers was 77.50%. The highest ICC (1,1) between a pair of readers was 0.750. All ICC (2,1) values were &lt;0.7, indicating poor agreement; the highest accuracy of CNN was 82.50%. The AUC did not differ significantly between the CNN and readers. The ICC (2,1) of CNN was 0.965. Conclusions Variation in the inter-reader or intra-reader accuracy in MRI diagnosis limits differentiation between GMPL and GMNL. CNN is nearly as accurate as readers but improves the reproducibility of diagnosis.

TPP1 is associated with risk of advanced precursors and cervical cancer survival

It is unclear how telomere-binding protein TPP1 interacts with human telomerase reverse transcriptase (hTERT) and influences cervical cancer development and progression. This study included all eligible 156 cervical cancers diagnosed during 2003–2008 and followed up through 2014, 102 cervical intraepithelial neoplasia (CIN) patients, and 16 participants with normal cervix identified at the same period. Correlation of expression of TPP1 and hTERT in these lesions was assessed using Kappa statistics. TPP1 was knocked down by siRNA in three cervical cancer cell lines. We assessed mRNA expression using quantitative real-time polymerase chain reaction and protein expression using tissue microarray-based immunohistochemical staining. We further analyzed the impact of TPP1 expression on the overall survival of cervical cancer patients by calculating the hazard ratio (HR) with 95% confidence intervals (CIs) using the multivariable-adjusted Cox regression model. Compared to the normal cervix, high TPP1expression was significantly associated with CIN 3 and cervical cancers (P&lt;0.001 for both). Expressions of TPP1 and hTERT were highly correlated in CIN 3 (Kappa statistics = 0.50, P = 0.005), squamous cell carcinoma (Kappa statistics = 0.22, P = 0.011), and adenocarcinoma/adenosquamous carcinoma (Kappa statistics = 0.77, P = 0.001). Mechanistically, knockdown of TPP1 inhibited the expression of hTERT in both mRNA and protein levels. High expression of TPP1 (HR = 2.61, 95% CI 1.23–5.51) and co-high expression of TPP1 and hTERT (HR = 2.38, 95% CI 1.28–4.43) were independently associated with worse survival in cervical cancer patients. TPP1 and hTERT expression was correlated and high expression of TPP1 was associated with high risk of CIN 3 and cervical cancer and could predict a worse survival in cervical cancer.

Impact of financial literacy and education on breast and cervical cancer screening participation in Japan

Despite government efforts, the uptake of screening for breast and cervical cancers among Japanese women remains low. This study employs financial literacy and financial education as proxies for rational decision-making to explore their potential to enhance cancer screening practices in Japan. Using data from Osaka University’s Preference Parameters Study, mean comparison tests and probit regression models are utilized to examine the association between breast and cervical cancer screening and financial literacy and financial education. The results of probit regression show that individuals with higher levels of financial education tend to participate in both breast and cervical cancer screening. In contrast, individuals with higher financial literacy are likely to participate in breast cancer screening, whereas no significant impact is observed for cervical cancer screening. Furthermore, our findings reveal that financial education positively influences both breast and cervical cancer screening. Factors such as employment, marriage, higher education, increased household income, and greater assets demonstrate robust positive relationships with breast and cervical cancer screening. Meanwhile, psychological factors including happiness, a myopic view of the future, anxiety about later life, and perceived health status have no significant associations, except for a positive association between anxiety about life and cervical cancer screening. Our study suggests the development of targeted educational programs that leverage financial literacy and financial education to raise awareness about the importance of breast and cervical cancer screening.

Prediction of high-grade cervical precancerous abnormalities: The role of personal factors, vaginal microflora, sexually transmitted infections, and high-risk human papillomavirus

High-risk human papillomavirus infection (HR-HPV) is necessary but not the only factor needed to develop cervical cancer. It is essential to estimate cervical cancer development risk in the population of high-risk HPV-positive women and to avoid unnecessary examinations and treatment in low-risk individuals. The study aimed to identify associations between different personal factors, vaginal microflora, sexually transmitted, high-risk HPV infection, and various degrees of cervical precancerous lesions. A study was performed in 2016–2020. The study group consisted of 112 patients with abnormal cervical cytology results referred for colposcopic examination. 120 women who came for a routine gynecological check-up were included in the control group. Material from the cervix and upper vaginal fornix was taken for pH measurement, wet mount microscopy, testing the six most common high-risk HPV DNA types (16/18, 31, 33, 45, 58), HPV E6/E7 mRNA, and 7 genital infections–C. trachomatis, N. gonorrhea, T. vaginalis, M. hominis, M. genitalium, U. urealyticum, U. parvum. Results showed that women with all grades of cervical intraepithelial neoplasia (CIN) more often were smokers, had increased vaginal pH levels, and had positive HR-HPV DNA and HR HPV E6/E7 mRNA expression. Abnormal vaginal microflora, especially types associated with aerobic vaginitis, and M. hominis were significantly more often found in women with CIN2+. The presence of C.trachomatis, U. parvum, and U.urealyticum did not differ between the groups. The most important factors independently associated with CIN2+ were positive high-risk HPV E6/E7 mRNA expression (OR 59.4, 95% CI 14.84–237.51), and positive high-risk HPV DNA (OR 3.9, 95% CI 1.16–13.23). Higher education level was associated with reduced risk of CIN2+ (OR 0.2, 95% CI 0.07–0.71). In conclusion, this study reports HR-HPV DNA of the most common six types and E6/E7 mRNA positivity as the most significant factors associated with CIN2+ lesions and higher education related to lower risk of high-grade cervical lesions.

Genital infections in high-risk human papillomavirus positive Paraguayan women aged 30–64 with and without cervical lesions

Objective To determine the prevalence of genital infections (GIs), including sexual transmitted STIs: Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, and opportunistic pathogens that generally do not cause STIs, non-classic STI: Ureaplasma urealyticum, Ureaplasma parvum and Mycoplasma hominis, in women with high-risk oncogenic human papillomavirus (hr-HPV) infection and their association with cervical lesions. Methods A cross-sectional study was carried out including 231 hr-HPV positive women. Of these, 46 has histologically confirmed cervical intraepithelial neoplasia 3 (CIN3) or more (including CIN3 and cervical cancer lesions-CIN3+). GIs were detected by multiplex real time PCR. Odds ratios (OR) were estimated to explore possible associations between GIs and the presence or absence of CIN3+ lesions. Additionally, we examined associations between sociodemographic, sexual, and clinical characteristics and the presence of GIs. Results In total, there were 174/231 cases of GIs corresponding to an overall prevalence of 75.3% (95%CI: 69.4–80.4), being non-classic STIs the most common (72.3%) compared to STIs (12.6%). The most prevalent non-classic STI and STI were U. parvum (49.8%) and C. trachomatis (7.4%), respectively. The odds of presenting GIs were 3 times higher in women under 46 years compared to older counterparts (OR: 3.32, 95%CI: 1.74–6.16), and in women with a normal Pap smear with inflammation compared to those without inflammation (OR: 3.31, 95%CI: 1.15–9.77). GIs were equally present in women with and without CIN3+ lesions. Conclusion We observed an association of GIs with inflammation in the Pap smear, but no association with CIN3+, as some of them are very common and likely part of the normal vaginal flora, suggesting that such infections do not appear to be cofactors in cervical carcinogenesis, although larger prospective studies are needed.

Pain scores reduction with the use of ultrasound-guided paracervical nerve block in patients with cervical cancer undergoing intracavitary brachytherapy: A randomized controlled trial

Study objective To determine the safety and effectiveness of ultrasound-guided paracervical nerve blocks for the painless treatment of patients with cervical cancer post-implantation. Design Single-center randomized controlled trial. Setting Fourth Hospital of Hebei Medical University (July 2023 to October 2023). Trial number ChiCTR2300071580 [https://clin.larvol.com/trial-detail/ChiCTR2300071580]. Patients Eighty patients with cervical cancer underwent post-implantation treatment. Interventions Patients receiving and not receiving paracervical nerve blocks (Groups T and C, respectively) were randomly allocated. Measurements Primary measures included visual analog scale (VAS) scores and patient body movement scores at various stages, including vaginal speculum placement (T1), applicator/needle insertion (T2), treatment administration following connection of the treatment tube (T3), needle withdrawal and hemostasis (T4), and willingness to receive further treatment. The secondary observation indices in this study included the operation time, incidence of hypoxemia, occurrence of nausea and vomiting, adverse events related to the circulatory system, patient satisfaction score, operator satisfaction score, and operation duration required by patients with an Alderte score of ≥ 9. Main results Forty patients each were randomly allocated into Groups T and C. The VAS scores did not differ significantly between the two groups at T1. However, at T3 and T4, the VAS scores of Group T was significantly lower than that of Group C. No significant difference was observed in the body movement scores between the two groups at T1 and T3. However, the body movement score of Group T was significantly lower than that of Group C (P &lt; 0.001) at T2 and T4. Group T showed higher postoperative satisfaction and willingness to receive further treatment compared to that of Group C. Conclusions Ultrasound-guided paracervical nerve block effectively reduced the pain scores in patients with cervical cancer undergoing post-implantation treatment and enhanced their inclination to undergo further treatment.

Achieving cervical cancer elimination: The simulated impacts of HPV vaccination and transitioning from liquid-based cytology to HPV-based screening test

The Ministry of Health Malaysia aims to fully replace liquid-based cytology (LBC) with Human Papillomavirus (HPV) tests and increase the screening coverage from a baseline of 25% to 40% by 2023, followed by a 10% yearly increment until 70% coverage. This transition requires proper planning, including the number of tests needed and budget allocation. This study aims to simulate different transition strategies involving the shift from LBC to HPV testing with expanded screening coverage to predict their impact on cervical cancer elimination in Malaysia. A system dynamics model was developed to simulate the transition from LBC to HPV testing and HPV vaccination coverage in Malaysia. The dynamic model utilised local epidemiological data, published research, and expert opinion when data was unavailable. The simulation showed that a combination of high HPV vaccination coverage and transitioning fully to five-yearly HPV testing by 2030, coupled with a 70% screening uptake by 2040, would accelerate cancer elimination in Malaysia by 18 years with an estimated screening cost of MYR1.81 billion equivalent to USD 411 millions compared to the baseline of using LBC as the primary screening method (MYR1.39 billion, USD 315 millions). Sustained, it would lead to averting 6,000 new cancer cases by 2070. Alternatively, conducting HPV screenings twice before age 50 would advance cervical cancer elimination by 14 years and prevent approximately 1000 new cases by 2070, with an estimated cost of MYR1.13 billion equivalent to USD 257 millions. A delay in achieving the full transition prolonged the elimination more than a delay in increasing the screening coverage. In all scenarios, yearly vaccination of 90% of girls age 13 is crucial to achieving elimination. In the Malaysian context, where HPV vaccination coverage has reached considerable levels, the evidence advocates for a full transition from LBC to HPV testing, ideally by 2030. While expanding screening coverage remains a critical factor in this endeavour, the findings unequivocally endorse prioritising the transition process. Trial registration: Trial registration number: NMRR ID-22-00187-DJU.

Evaluation of the anti-cancer efficacy of lipid nanoparticles containing siRNA against HPV16 E6/E7 combined with cisplatin in a xenograft model of cervical cancer

Objective To investigate the anti-cancer efficacy of ENB101-LNP, an ionizable lipid nanoparticles (LNPs) encapsulating siRNA against E6/E7 of HPV 16, in combination therapy with cisplatin in cervical cancer in vitro and in vivo. Methods CaSki cells were treated with ENB101-LNP, cisplatin, or combination. Cell viability assessed the cytotoxicity of the treatment. HPV16 E6/E7 gene knockdown was verified with RT-PCR both in vitro and in vivo. HLA class I and PD-L1 were checked by flow cytometry. A xenograft model was made using CaSki cells in BALB/c nude mice. To evaluate anticancer efficacy, mice were grouped. ENB101-LNP was given three times weekly for 3 weeks intravenously, and cisplatin was given once weekly intraperitoneally. Tumor growth was monitored. On day 25, mice were euthanized; tumors were collected, weighed, and imaged. Tumor samples were analyzed through histopathology, immunostaining, and western blot. Results ENB101-LNP and cisplatin synergistically inhibit CaSki cell growth. The combination reduces HPV 16 E6/E7 mRNA and boosts p21 mRNA, p53, p21, and HLA class I proteins. In mice, the treatment significantly blocked tumor growth and promoted apoptosis. Tumor inhibition rates were 29.7% (1 mpk ENB101-LNP), 29.6% (3 mpk), 34.0% (cisplatin), 47.0% (1 mpk ENB101-LNP-cisplatin), and 68.8% (3 mpk ENB101-LNP-cisplatin). RT-PCR confirmed up to 80% knockdown of HPV16 E6/E7 in the ENB101-LNP groups. Immunohistochemistry revealed increased p53, p21, and HLA-A expression with ENB101-LNP treatments, alone or combined. Conclusion The combination of ENB101-LNP, which inhibits E6/E7 of HPV 16, with cisplatin, demonstrated significant anticancer activity in the xenograft mouse model of cervical cancer.

Validation of the Amharic version of perceived access to healthcare services for patients with cervical cancer in Ethiopia: A second-order confirmatory factor analysis

BackgroundAccessing healthcare services is a multifaceted phenomenon involving various elements, encompassing the demand, identification, reach, and utilization of healthcare needs. The literature offers methods for capturing patients’ perceptions of healthcare access. However, to accurately measure patient perceptions, it is imperative to ensure the validity and reliability of such instruments by designing and implementing localized language versions.AimThe primary aim of this study was to validate the Amharic version of the perceived access to health-care services among patients diagnosed with cervical cancer in Ethiopia.MethodA cross-sectional study was conducted among cervical cancer patients at oncology centers in Addis Ababa, Ethiopia. A consecutive sampling approach was used and data collection took place from January 1 to March 30, 2023. Following initial validation and pretesting, a KoboCollect mobile phone application was employed for data collection. Subsequently, the collected data underwent cleaning in Microsoft Excel and analysis through Amos software v.26 and R programming. Various validity and reliability tests, such as content validity, convergent validity, face validity, divergent validity, known-group validity, and reliability tests, were executed. A second-order confirmatory factor analysis was developed to calculate incremental model fit indices, including CFI and TLI, along with absolute measures, namely SRMR and RMSEA.ResultsA total of 308 participants were involved in the study, with 202 (65.6%) being patients referred from outside Addis Ababa. The initial evaluation of content validity by expert panels indicated that all criteria were met, with a CVR range of 0.5 to 1, I-CVI values ranging from 0.75 to 1, an S-CVI value of 0.91, and face validity values ranging from 2.4 to 4.8. The internal consistency of items within the final constructs varied from 0.76 to 0.93. Convergent, known-group, and most divergent validity tests fell within acceptable fit ranges. Common incremental fit measures for CFI and TLI were achieved with corresponding values of 0.95 and 0.94, respectively. The absolute fit measures of SRMR and RMSEA were 0.04 and 0.07, indicating good and moderate fit, respectively.ConclusionThe study indicated a high internal consistency and validity of items with good fit to the data, suggesting potential accuracy of the domains. A five-domain structure was developed which enables adequate assessment of perceived access to health-care services of patients with cervical cancer in Ethiopia. We suggest that the tool can be utilized in other patient populations with a consideration of additional constructs, such as geographic accessibility.

Cost-utility analysis of primary HPV testing through home-based self-sampling in comparison to visual inspection using acetic acid for cervical cancer screening in East district, Sikkim, India, 2023

Introduction Primary Human Papilloma Virus (HPV) testing offers higher sensitivity and specificity over Visual Inspection using Acetic acid (VIA) in cervical cancer screening. Self-sampling is a promising strategy to boost participation and reduce disparities. However, concerns about the initial costs hinder HPV testing adoption in low and middle-income countries. This study assesses the cost-utility of home-based HPV self-sampling versus VIA for cervical cancer screening in India. Methods A cross-sectional study was conducted in East district, Sikkim, India, comparing the costs and utility outcomes of population-based cervical cancer screening through VIA and primary HPV screening through self-sampling. Cost-related data were collected from April 2021 to March 2022 using the bottom-up micro-costing method, while utility measures were collected prospectively using the EuroQoL-5D-5L questionnaire. The utility values were converted into quality-adjusted life days (QALDs) for an 8-day period. The willingness to pay threshold (WTP) was based on per capita GDP for 2022. If the calculated Incremental Cost-Effectiveness Ratio (ICER) value is lower than the WTP threshold, it signifies that the intervention is cost-effective. Results The study included 95 women in each group of cervical cancer screening with VIA &amp; HPV self-sampling. For eight days, the QALD was found to be 7.977 for the VIA group and 8.0 for the HPV group. The unit cost per woman screened by VIA and HPV self-testing was ₹1,597 (US$ 19.2) and ₹1,271(US$ 15.3), respectively. The ICER was ₹-14,459 (US$ -173.6), which was much below the WTP threshold for eight QALDs, i.e. ₹ 4,193 (US$ 50.4). Conclusion The findings support HPV self-sampling as a cost-effective alternative to VIA. This informs policymakers and healthcare providers for better resource allocation in cervical cancer screening in Sikkim.

Awareness about cervical cancer and its socio-economic determinants among adults in Bangladesh: Results from a nationwide cross-sectional study

Cervical cancer is a major global health issue now and is the second leading cancer among women in Bangladesh, caused primarily by Human papillomavirus (HPV). Despite effective vaccination and screening methods, awareness and access to preventive methods are limited in developing regions. This nationwide study aims to explore socio-economic and cultural factors affecting cervical cancer awareness in Bangladesh and generate evidence-based recommendations for tailoring suitable health promotion strategies for the country. This cross-sectional study was conducted in Bangladesh to evaluate cervical cancer awareness among adults aged 18 years and above. A semi-structured questionnaire was designed for this research, keeping in mind the local sociocultural contexts. Face-to-face interviews were conducted after getting the participants’ consent and making sure they understood all the questions. After checking for data quality and consistency, responses of 2,151 participants were finally retained. The collected data was analyzed using STATA (Version 17) statistical software. The majority (80.15%) of the participants were aware of cervical cancer, with healthcare workers being the primary source of information. Higher awareness rates were noted among married individuals (80.88%), urban dwellers (83.24%), those with more education (average 11.96 ± 4.36 years), individuals with higher income (88.17%), and those belonging to nuclear families (82.86%). Healthcare professionals had significantly greater awareness (98.91%) compared to other occupations. Participants undergoing regular health checkups were more informed and the association was statistically significant (87.03%, p &lt; 0.001). Univariate and multiple logistic regression models revealed that each additional year of education increased the probability of being aware by 16−20%. Men had significantly lower odds of being aware compared to women (Adjusted Odds Ratio AOR = 0.41, β = −0.895, 95% CI: 0.23 to 0.70, p = 0.001 in the multiple logistic regression analysis). Similarly, respondents not cohabitating with their spouse were less aware than those who were living with partners (AOR = 0.47, β = −0.750, 95% CI: 0.28 to 0.81, p = 0.006). Income levels conversely influenced awareness level, participants from the highest income group (earning 35,001−50,000 BDT) had 47% lower odds (AOR = 0.53, β = −0.629, 95% CI: 0.36 to 0.80, p = 0.002) of awareness compared to the lowest income group (earning ≤20,000 BDT). Despite the widespread awareness of cervical cancer among most Bangladeshi adults, there remains a notable gap, particularly among certain demographics. Since the study identified healthcare workers, social media, and mass media as major sources of information, targeted educational campaigns through media channels and outreach activities by healthcare workers might effectively enhance nationwide awareness of cervical cancer.

Strategies for primary HPV test-based cervical cancer screening programme in resource-limited settings in India: Results from a quasi-experimental pragmatic implementation trial

BackgroundIn order for low and middle income countries (LMIC) to transition to Human Papilloma Virus (HPV) test based cervical cancer screening, a greater understanding of how to implement these evidence based interventions (EBI) among vulnerable populations is needed. This paper documents outcomes of an implementation research on HPV screening among women from tribal, rural, urban slum settings in India.MethodsA mixed-method, pragmatic, quasi-experimental trial design was used. HPV screening on self-collected cervical samples was offered to women aged 30–60 years. Implementation strategies were 1) Assessment of contextual factors using both qualitative and quantitative methods like key informant interviews (KII), focus group discussions (FGDs), pre-post population sample surveys, capacity assessment of participating departments 2) enhancing provider capacity through training workshops, access to HPV testing facility, colposcopy, thermal ablation/cryotherapy at the primary health care centers 3) community engagement, counselling for self-sampling and triage process by frontline health care workers (HCWs). Outcomes were assessed using the RE-AIM (Reach, Effectiveness, adoption, implementation, maintenance) framework.ResultsScreening rate in 8 months’ of study was 31.0%, 26.7%, 32.9%, prevalence of oncogenic HPV was 12.1%, 3.1%, 5.5%, compliance to triage was 53.6%, 45.5%, 84.6% in tribal, urban slum, rural sites respectively. Pre-cancer among triage compliant HPV positive women was 13.6% in tribal, 4% in rural and 0% among urban slum women. Unique challenges faced in the tribal setting led to programme adaptations like increasing honoraria of community health workers for late-evening work and recalling HPV positive women for colposcopy by nurses, thermal ablation by gynaecologist at the outreach camp site.ConclusionsSelf-collection of samples combined with HCW led community engagement activities, flexible triage processes and strengthening of health system showed an acceptable screening rate and better compliance to triage, highlighting the importance of identifying the barriers and developing strategies suitable for the setting.Trial registrationCTRI/2021/09/036130.

Health disparities in cervical cancer: Estimating geographic variations of disease burden and association with key socioeconomic and demographic factors in the US

Background Despite advances in cervical cancer (CC) prevention, detection, and treatment in the US, health disparities persist, disproportionately affecting underserved populations or regions. This study analyzes the geographical distribution of both CC and recurrent/metastatic CC (r/mCC) in the US and explores potential risk factors of higher disease burden to inform potential strategies to address disparities in CC and r/mCC. Methods We estimated CC screening rates, as well as CC burden (number of patients with CC diagnosis per 100,000 eligible enrollees) and r/mCC burden (proportion of CC patients receiving systemic therapy not in conjunction with surgery or radiation), at the geographic level between 2017–2022 using administrative claims. Data on income and race/ethnicity were obtained from US Census Bureau’s American Community Survey. Brachytherapy centers were proxies for guideline-conforming care for locally advanced CC. Associations among demographic, socioeconomic, and healthcare resource variables, with CC and r/mCC disease burden were assessed. Results Between 2017–2022, approximately 48,000 CC-diagnosed patients were identified, and approximately 10,000 initiated systemic therapy treatment. Both CC and r/mCC burden varied considerably across the US. Higher screening was significantly associated with lower CC burden only in the South. Lower income level was significantly associated with lower screening rates, higher CC and r/mCC burden. Higher proportion of Hispanic population was also associated with higher CC burden. The presence of ≥1 brachytherapy center in a region was significantly associated with a reduction in r/mCC burden (2.7%). Conclusion CC and r/mCC disparities are an interplay of certain social determinants of health, behavior, and race/ethnicity. Our findings may inform targeted interventions for a geographic area, and further highlight the importance of guideline-conforming care to reduce disease burden.

Novel candidates of pathogenic variants of the BRCA1 and BRCA2 genes from a dataset of 3,552 Japanese whole genomes (3.5KJPNv2)

Identification of the population frequencies of definitely pathogenic germline variants in two major hereditary breast and ovarian cancer syndrome (HBOC) genes, BRCA1/2 , is essential to estimate the number of HBOC patients. In addition, the identification of moderately penetrant HBOC gene variants that contribute to increasing the risk of breast and ovarian cancers in a population is critical to establish personalized health care. A prospective cohort subjected to genome analysis can provide both sets of information. Computational scoring and prospective cohort studies may help to identify such likely pathogenic variants in the general population. We annotated the variants in the BRCA1 and BRCA2 genes from a dataset of 3,552 whole-genome sequences obtained from members of a prospective cohorts with genome data in the Tohoku Medical Megabank Project (TMM) with InterVar software. Computational impact scores (CADD_phred and Eigen_raw) and minor allele frequencies (MAFs) of pathogenic (P) and likely pathogenic (LP) variants in ClinVar were used for filtration criteria. Familial predispositions to cancers among the 35,000 TMM genome cohort participants were analyzed to verify the identified pathogenicity. Seven potentially pathogenic variants were newly identified. The sisters of carriers of these moderately deleterious variants and definite P and LP variants among members of the TMM prospective cohort showed a statistically significant preponderance for cancer onset, from the self-reported cancer history. Filtering by computational scoring and MAF is useful to identify potentially pathogenic variants in BRCA genes in the Japanese population. These results should help to follow up the carriers of variants of uncertain significance in the HBOC genes in the longitudinal prospective cohort study.

A fraction of Pueraria tuberosa extract, rich in antioxidant compounds, alleviates ovariectomized-induced osteoporosis in rats and inhibits growth of breast and ovarian cancer cells

Pueraria tuberosa (Roxb. ex Willd.) DC., known as Indian Kudzu belongs to family Fabaceae and it is solicited as “Rasayana” drugs in Ayurveda. In the present study, we analyzed the efficacy of an ethyl acetate fraction from the tuber extract of Pueraria tuberosa (fraction rich in antioxidant compounds, FRAC) against menopausal osteoporosis, and breast and ovarian cancer cells. The FRAC from Pueraria tuberosa was characterized for its phenolic composition (total phenolic and flavonoid amount). Antioxidant property ( in vitro assays) of the FRAC was also carried out followed by the analysis of the FRAC for its antiosteoporotic and anticancer potentials. The antiosteoporotic activity of FRAC was investigated in ovariectomy-induced osteoporosis in rats. The cytotoxicity effect was determined in breast and ovarian cancer cells. Gas chromatography/mass spectrometry (GC/MS) analysis of the FRAC was performed to determine its various phytoconstituents. Docking analysis was performed to verify the interaction of bioactive molecules with estrogen receptors (ERs). The FRAC significantly improved various biomechanical and biochemical parameters in a dose-dependent manner in the ovariectomized rats. FRAC also controlled the increased body weight and decreased uterus weight following ovariectomy in rats. Histopathology of the femur demonstrated the restoration of typical bone structure and trabecular width in ovariectomized animals after treatment with FRAC and raloxifene. The FRAC also exhibited in vitro cytotoxicity in the breast (MCF-7 and MDA-MB-231) and ovarian (SKOV-3) cancer cells. Furthermore, genistein and daidzein exhibited a high affinity towards both estrogen receptors (α and β) in the docking study revealing the probable mechanism of the antiosteoporotic activity. GC/MS analysis confirmed the presence of other bioactive molecules such as stigmasterol, β-sitosterol, and stigmasta-3,5-dien-7-one. The FRAC from Pueraria tuberosa has potential for treatment of menopausal osteoporosis. Also, the FRAC possesses anticancer activity.

The Adler grade by Doppler ultrasound is associated with clinical pathology of cervical cancer: Implication for clinical management

To analyze the relationship of Adler grade by transvaginal color Doppler flow imaging (TV-CDFI) and the clinical pathological parameters of patients with cervical cancer, and to identify the value of Adler grade in the diagnosis and treatment of cervical cancer. Patients with cervical cancer diagnosed pathologically in our hospital from January 1, 2019 to December 31, 2019 were included, All patients underwent TV-CDFI examination, and the images were divided into 0 to III grades according to the Adler grades, and the correlations between the Adler classification and clinical pathological parameters (clinical stage, mass size, pathological type, squamous cell carcinoma subtype, CA125, CA199) were analyzed. A total of 162 patients with cervical cancer were included. With the increase of Adler severity, the clinical stage of cervical cancer increased accordingly. the cancer size differed significantly in patients with different Adler grade (p = 0.004); There were significant differences in the level of CA125, CA199 between the squamous cell carcinoma and adenocarcinoma (all p0.05). The area under ROC curve of the cervical squamous cell carcinoma predicted by Adler grade based on FIGO results and pathological results was 0.811and 0.762 respectively (all p<0.05). Adler grades are closely associated with the clinical pathology of cervical cancer, which may be a convenient and effective approach for the assisting assessment of cervical cancer.

Spatial distribution and characteristics of women reporting cervical cancer screening in Malawi: An analysis of the 2020 to 2021 Malawi Population-based HIV Impact Assessment survey data

Background Malawi has one of the highest incidence and mortality rates of cervical cancer in the world. Despite a national strategic plan and the roll-out of VIA and screen-and-treat services, cervical cancer screening coverage in Malawi remains far below the national target.Using a nationally representative sample of women enumerated in the Malawi Population-based Impact Assessment (MPHIA) survey we estimated the prevalence and spatial distribution of self-reported cervical cancer screening as a proxy for uptake in Malawi. Methods MPHIA was a nationally representative household survey in Malawi, targeting adults aged 15 and above, that employed a cross-sectional, two-stage, cluster design. The primary aim of MPHIA was to assess the regional prevalence of viral load suppression and the progress towards achieving the UNAIDS 95-95-95 goals among adults aged 15 and above. The survey was carried out between January 2020 and April 2021. Prevalence of self-reported cervical cancer screening by different characteristics was estimated accounting for the survey design using the Taylor series approach. We used univariable and multivariable logistic regression approaches to examine associations between the prevalence of cervical cancer screening and demographic characteristics. Findings A total of 13,067 adult (15 years and older) female individuals were surveyed during the MPHIA 2020 to 2021 survey, corresponding to a weighted total of 5,604,578. The prevalence of self-reported cervical cancer screening was 16.5% (95% CI 15.5–18.0%), with women living with HIV having a higher prevalence of 37.8% (95% CI 34.8–40.9) compared to 14.0% (95% CI 13.0–15.0) in HIV negative women. The highest prevalence of screening was reported in the Southwest zone (SWZ) (24.1%, 95% CI 21.3–26.9) and in major cities of Blantyre (25.9%, 95% CI 22.9–29.0), and Lilongwe (19.6%, 95% CI 18.0–21.3). Higher self-reported screening was observed in women who resided in urban regions ((22.7%; 95% CI 21.4–24.0) versus women who resided in rural areas (15.2%; 95% CI 14.0–16.8). Cervical cancer screening was strongly associated with being HIV positive (aOR 2.83; 95% CI 2.29–3.50), ever having been pregnant (aOR 1.93; 95% CI 1.19–3.14), attaining higher education level than secondary education (aOR 2.74; 95% CI 1.67–4.52) and being in the highest wealth quintile (aOR 2.86; 95% CI 2.01–4.08). Interpretation The coverage of cervical cancer screening in Malawi remains low and unequal by region and wealth/education class. Current screening efforts are largely being focussed on women accessing HIV services. There is need for deliberate interventions to upscale cervical cancer screening in both HIV negative women and women living with HIV.

HPV16 E1 dysregulated cellular genes involved in cell proliferation and host DNA damage: A possible role in cervical carcinogenesis

HPV16 is the most prominent cause of cervical cancer. HPV16 E1, a helicase required for HPV replication exhibits increased expression in association with cervical cancer progression, suggesting that E1 has a similar effect on the host as the HPV16 E6 and E7 oncoproteins. This study aimed to determine whether expression of HPV16 E1 correlated with carcinogenesis by modulating cellular pathways involved in cervical cancer. HEK293T cells were transfected with pEGFP, pEGFPE1 or truncated forms of HPV16 E1. Cell proliferation, cell death, and the impact of HPV16 E1 on host gene expression was then evaluated. HPV16 E1 overexpression resulted in a significant reduction of cell viability and cellular proliferation (p-value&lt;0.0001). Moreover, prolonged expression of HPV16 E1 significantly induced both apoptotic and necrotic cell death, which was partially inhibited by QVD-OPH, a broad-spectrum caspase inhibitor. Microarray, real time RT-PCR and kinetic host gene expression analyses revealed that HPV16 E1 overexpression resulted in the downregulation of genes involved in protein synthesis (RPL36A), metabolism (ALDOC), cellular proliferation (CREB5, HIF1A, JMJDIC, FOXO3, NFKB1, PIK3CA, TSC22D3), DNA damage (ATR, BRCA1 and CHEK1) and immune response (ISG20) pathways. How these genetic changes contribute to HPV16 E1-mediated cervical carcinogenesis warrants further studies.

Barriers and strategies for cervical cancer screening: What do female university students know and want?

Objective This study aimed to identify the distinct barriers and knowledge level of cervical cancer screening among female university students and establish intervention strategies to overcome these barriers. Methods This study used a mixed-methods design with 26 female university students aged 20–29 years. We first conducted a quantitative online survey for the same study participants, divided them into three groups, and conducted focus group interviews (FGIs). Group A: participants who had sexual experience and had undergone cervical cancer screening; Group B: participants who had sexual experience and had not undergone cervical cancer screening; Group C: participants who did not have sexual experience and had not undergone cervical cancer screening. Results The participants’ ages were 21.92 ± 1.26 years. The knowledge levels for cervical cancer and screening were low to moderate. The four main themes that emerged as barriers to cervical cancer screening through the FGIs were: 1) socio-cultural barrier: conservative social perception of unmarried women’s sexual life, 2) knowledge barrier: lack of knowledge and information, 3) psychological barrier: discomfort, and 4) practical barrier: time-consuming. The three themes identified for strategies were: 1) socio-cultural intervention: changing social perceptions and ensuring confidentiality, 2) educational intervention: improvement of knowledge and accessibility, and 3) alternative screening intervention: comfortable screening methods. Conclusions While university students’ sexual experience rapidly increased, the socio-cultural perceptions of sexual health remained closed, and they had a reasonably low level of knowledge about cervical cancer screening. Therefore, various strategies sensitive to female university students’ culture should be implemented to increase the knowledge level, and social efforts should be made to change the socio-cultural perception of unmarried young women’s sexual health.

Antiproliferative activity of Grewia villosa ethyl acetate extract on cervical cancer HeLa cell line: Mechanistic insights through network pharmacology and functional assays approach

Grewia villosa is a plant native to Kenya, with a traditional history among Ambeere people for treating and managing prostate and breast cancers. Previous scientific studies have demonstrated its anti-inflammatory and antioxidant properties. However, a scientific gap exists on the bioactivity of G. villosa against cervical cancer, particularly on in vitro HeLa cell line model. Additionally, the specific molecular targets and mode of antiproliferative action have not been well elucidated. Therefore, this study sought to investigate the antiproliferative activity, putative targets and mode of action of G. villosa using in vitro cell culture, molecular biology and in silico-based approaches. Antiproliferative analyses were evaluated through MTT assay, cell migration inhibition through in vitro scratch assay, and phytochemical profiling through Gas chromatography-mass spectrometry (GC-MS) analysis. Further, putative targets were identified through network pharmacology approach, computationally validated by molecular docking, and functionally through the real-time quantitative polymerase chain reaction (RT-qPCR) method. The G. villosa ethyl acetate (GVEA) extract fraction was the most active extract fraction, with IC50 of 100.7 µg/mL and a selectivity index of 2.38. Dodecan-2-ylbenzene and 2,6,10-trimethyltetradecane compounds were some notable compounds that can partly be associated with reported antiproliferative activity as they demonstrated strong binding affinity to identified putative targets, including EGFR and AKT1. RT-qPCR analysis functionally confirmed the downregulation of EGFR and AKT1, and the upregulation of tumor protein 53 and Caspase 3 molecular targets, suggesting that GVEA extract indeed perturbs the predicted molecular targets. This study therefore reports the selective antiproliferative properties of the G. villosa ethyl acetate extract fraction in a cervical cancer model (HeLa) cell line while at the same time providing putative targets, which is important in shedding light on potential mechanistic basis of its demonstrated antiproliferative activity. This highlights the plant’s potential in discovering products and compounds for further investigation on possible application in cervical cancer management and/or treatment.

Under-screened Aboriginal and Torres Strait Islander women’s perspectives on cervical screening

Aboriginal and Torres Strait Islander women have lower participation in Australia’s National Cervical Screening Program than other Australian women. Under-screened (including never screened) women’s voices are rarely heard in research evidence, despite being a priority group for interventions to increase cervical screening participation. This study aimed to describe under-screened Aboriginal and Torres Strait Islander women’s perspectives on cervical screening. Participants were 29 under-screened (women who had either never screened, had not screened in the previous five years or had recently screened in the past three months after more than five years) Aboriginal and Torres Strait Islander women from five communities across three states/territories. Female Aboriginal and Torres Strait Islander researchers Yarned with women about why they did not participate in screening and how to improve screening. Yarning is an Indigenous qualitative research method in which relationships and trust facilitate culturally safe conversation. Transcripts were analysed thematically. The proportion of eligible women who screened within 30 days after the Yarn was calculated. We identified four themes describing how the harms outweighed the benefits of cervical screening for under-screened women. These were: 1) distress, discomfort, and trauma; 2) lack of privacy and control; 3) complicated relationships with health care providers (HCPs); and 4) pressured, insensitive, and/or culturally unsafe communication from HCPs. Under-screened women who had recently screened had maintained privacy and control through self-collection and had experienced trauma-informed and empathetic care from their HCPs. While we cannot unequivocally attribute women’s subsequent participation in screening to their involvement in this study, it is notable that one third of eligible under-screened women were screened within 30 days after the Yarn. Enhancing privacy, implementing trauma-informed approaches to care and sensitivity to the clinician-client relationship dynamics could enhance women’s sense of comfort in, and control over, the screening procedure. The opportunity to Yarn about cervical screening and self-collection may address these issues and support progress toward cervical cancer elimination in Australia.

Health-related quality of life among cervical cancer survivors at a tertiary hospital in Ghana

Introduction Cervical cancer is the second most common female cancer in Ghana. The disease and its treatment significantly affect survivors’ health-related quality of life (HRQoL). We determined the overall quality of life (QoL) and identified its predictors among cervical cancer survivors after treatment. Materials and methods A hospital-based cross-sectional analytical study was conducted on 153 disease-free cervical cancer survivors who completed curative treatment between January 2004 and December 2018 at Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana. We used the European Organization for Research and Treatment of Cancer core-30 item (EORTC QLQ-C30) and cervical cancer module (EORTC QLQ-CX24) to assess the survivors’ overall QoL. QoL domain scores were dichotomised as affected or unaffected by disease and its treatment. Significant differences between the affected and unaffected groups within each QoL domain were determined using the student T-test. We used Kruskal-Wallis and Dunn’s tests to examine the difference in QoL domains between treatment types, with significance based on Bonferroni corrections. Multivariable logistic regression was performed to identify predictors of overall QoL. A p-value of less than 0.05 was considered statistically significant. Results One hundred and fifty-three (153) women having a mean age of 58.3 (SD 11.4) years were studied. The overall QoL score was 79.6 (SD 16.0), and 74.5% of survivors reported good QoL score within the median follow up time of 41.8 months (interquartile range [IQR], 25.5–71.1 months) after cervical cancer diagnosis. Although the majority (66.0–84.3%) of the QoL functioning scale were unaffected, about a fifth (22.2%) to a third (34.5%) of the subjects had perceptual impairment in cognitive and role functioning. Financial difficulties, peripheral neuropathy and pain were most common symptoms reported as affected. A third of the survivors were worried that sex would be painful, and 36.6% indicated that their sexual activity as affected. The overall QoL scores for survivors who had surgery, chemoradiation and radiation-alone were 86.1 (SD 9.7), 76.9 (SD 17.7), and 80.7 (SD 14.7), respectively (p = 0.025). The predictors of survivor’s overall QoL were loss of appetite [Adjusted Odd Ratio (AOR) = 9.34, 95% Confidence Interval (CI) = 2.13–35.8, p = 0.001], pain (AOR = 3.53, 95% CI = 1.25–9.31, p = 0.017) and body image (AOR = 5.89, 95% CI = 1.80–19.27, p = 0.003). Conclusion About 75% of the survivors had a good overall quality of life. Primary surgical treatment affords the best prospects for quality of life with the least symptom complaints and financial burden. Loss of appetite, pain or diminution in body image perception predicted the overall quality of life of cervical cancer survivors after treatment.

Factors associated with cervical cancer screening among women aged 25–60 years in Lao People’s Democratic Republic

Background Despite cervical cancer being a major public health concern in the Lao People’s Democratic Republic (Lao PDR), screening coverage is very low. The reasons and factors for this are unknown. This study aimed to identify factors associated with uptake of cervical cancer screening among women aged 25–60 years. Methods The case-control study was conducted among women aged 25–60 years in Vientiane Capital and Luang Prabang province from March 15 to May 31, 2018. A total of 360 women were included in the study, a ratio of two controls per case. The cases were women who had undergone cervical cancer screening over the last five years. The controls were women who had never been screened or screened more than five years before, matched to the cases with residency and age (± five years). The cases were selected from central and provincial hospitals and the controls from the same community and districts where the cases resided. Conditional logistic regression was used to determine factors associated with cervical cancer screening. Results The mean age was 42.37±9.4 years (range: 25–60), 66.67% were women from Vientiane Capital, and 86.11% were married. The common reasons for not being screened were the absence of clinical signs and symptoms (45.28%) followed by never having heard about cervical cancer (13.33%). In the multivariable analyses, we found that having sexually transmitted infections (AOR = 3.93; 95% CI = 1.92–8.05), receiving recommendations for screening from health workers (AOR = 3.85; 95% CI = 1.90–7.78), a high score for knowledge (AOR = 7.90; 95% CI = 2.43–25.69) and attitude towards cervical cancer prevention and treatment (AOR = 2.26; 95% CI = 1.18–7.16), and having a car to travel (AOR = 2.97; 95% CI = 1.44–6.11) had a positive impact on undergoing cervical cancer screening. Conclusion Gynecological consultations, increased knowledge and positive attitudes result in women undergoing screening. Therefore, health education and advocacy for cervical cancer prevention should be provided to women.

Navigating cancer: Insights from patient journey mapping

Background Cancer is an increasing public health problem in South Africa, with breast cancer being the most diagnosed cancer and cervical cancer the leading cause of cancer deaths among women. Despite the complexity of breast and cervical cancer patients’ journeys through the healthcare system, patients’ voices are still predominantly missing from the body of literature. Patient journey mapping, as a qualitative research method, offers an opportunity for centring patients in their care journeys and reimagine healthcare provision for the potential improvement of health systems and patient outcomes. Aim The aim of this study was to map journeys of breast and cervical cancer patients across the cancer care continuum. Methods Using patient journey mapping, we conducted six focus group discussions with patients with breast and cervical cancer who had completed treatment in Gauteng, KwaZulu Natal and the Western Cape, South Africa. The process involved three steps: 1.) development of individual maps; 2.) narrative sharing; and 3.) development of a collective map. Results of the study were shared in feedback sessions. Findings A total of 31 people participated in the focus groups: 23 with breast cancer, 7 cervical cancer and one had both cancers during her lifetime. The participants’ ages ranged between 30 and 69 years old. A patient journey map was developed drawing on the individual and collective maps and participant narratives. The findings of the paper constellate around three themes. The first theme, (de)personalised care, offers an examination of how relational, institutional and structural factors shape and are reshaped through participants lived experiences across the cancer care continuum. The second theme, self-advocacy, explores how participants advocate for their healthcare needs throughout the cancer care continuum. The third theme, intersecting vulnerabilities, explores how intersecting social identities, such as socioeconomic factors, gender, comorbidities and mental health, shape their cancer care journeys. Conclusions By centring patient with breast and cervical cancer voices, patient journey mapping not only showed where services and systems fall short but also provided guidance for redesigning a more patient responsive health system.

Effect of different treatment modalities on ovarian cancer patients with liver metastases: A retrospective cohort study based on SEER

BackgroundTo examine the trends in morbidity and mortality among ovarian cancer patients with liver metastases, and investigate the impact of different treatments on both overall survival (OS) and cancer-specific survival (CSS).Methods2,925 ovarian cancer patients with liver metastases from Surveillance, Epidemiology, and End Results 2010–2019 were included. The primary endpoint was considered as OS and CSS. We conducted trend analysis of the incidence, OS and CSS rates of liver metastases in ovarian cancer. Univariate and multivariate COX proportional risk models were used to investigate the association between different treatment methods and OS, and univariate and multivariate competing risk models were employed to evaluate the impact of treatment methods on CSS.ResultsAt the end of follow-up, 689 patients remained alive. The OS and CSS rates were 76.44% and 72.99% for all patients, respectively. There was a significant decreasing trend in the incidence [average annual percent change (AAPC) = -2.3, 95% confidence interval (CI): -3.9, -0.7], all-cause mortality (AAPC = -12.8, 95% CI: -15.6, -9.9) and specific mortality (AAPC = -13.0, 95% CI: -16.1, -9.8) rate of liver metastases in ovarian cancer. After adjusting all confounding factor, only receiving surgery was associated with OS [hazard ratio (HR) = 0.39, 95%CI: 0.31–0.48]/CSS (HR = 0.37, 95%CI: 0.30–0.47). Chemotherapy was found to be protective factor for OS (HR = 0.33, 95%CI: 0.30–0.37)/CSS (HR = 0.44, 95%CI: 0.39–0.50) of ovarian cancer patients, while not receiving surgery remained a risk factor. Additionally, the result of subgroup analyses also showed that only receiving surgery and chemotherapy still were significant protective factor of OS and CSS for patients without other distant metastases, with distant metastases to the bone, lung, brain or other organs, with bone metastasis, and with lung metastasis.ConclusionOur research has elucidated a downward trend in morbidity and mortality rates among patients with liver metastases originating from ovarian cancer. Only receiving surgery and chemotherapy as therapies methods confer survival benefits to patients.

Interventions to increase follow-up of abnormal cervical cancer screening results: A systematic literature review and meta-analysis

Introduction Ensuring timely follow-up of abnormal screening results is essential for eliminating cervical cancer. Objective The purpose of the study was to review single and multicomponent interventions designed to improve follow-up of women with abnormal cervical cancer screening results. We report on effectiveness across studies, and describe what aspects of these interventions might be more impactful. Methods Publications were searched between January 2000 and December 2022. The search included observational, quasi-experimental (pre-post studies) and randomized controlled studies describing at least one intervention to increase follow-up of women with abnormal cervical cancer screening results. Outcomes of studies included completion of any follow-up (i.e., attending a follow-up appointment), timely diagnosis (i.e., colposcopy results within 90 days of screening) and time to diagnostic resolution (i.e., days between screening and final diagnosis). We assessed risk of bias for observational and quasi-experimental studies using the Newcastle-Ottawa Scale (NOS) tool and the Cochrane collaboration tool for randomized studies. We conducted a meta-analysis using studies where data were provided to estimate a summary average effect of the interventions on follow-up of patients and to identify characteristics of studies associated with an increased effectiveness of interventions. We extracted the comparison and intervention proportions of women with follow-up before and after the intervention (control and intervention) and plotted the odds ratios (ORs) of completing follow-up along with the 95% confidence intervals (CIs) using forest plots for the interventions vs. controls when data were available. Findings From 7,457 identified studies, 28 met the inclusion criteria. Eleven (39%) of the included studies had used a randomized design. Most studies (63%) assessed completion of any follow-up visit as the primary outcome, whereas others measured time to definite diagnosis (15%) or diagnostic resolution (22%). Navigation was used as a type of intervention in 63% of the included studies. Most interventions utilized behavioral approaches to improve outcomes. The overall estimate of the OR for completion of follow-up for all interventions was 1.81 (1.36–2.42). The highest impact was for programs using more than one approach (multicomponent interventions) to improve outcomes with OR = 3.01 (2.03–4.46), compared with studies with single intervention approaches with OR = 1.56 (1.14–2.14). No statistical risks were noted from publication bias or small-study effects in the studies reviewed. Conclusion Our findings revealed large heterogeneity in how follow-up of abnormal cervical cancer screening results was defined. Our results suggest that multicomponent interventions were more effective than single component interventions and should be used to improve follow-up after abnormal cervical cancer screening results. Navigation appears to be an important tool for improving follow-up. We also provide recommendations for future studies and implications for policy in terms of better defining outcomes for these interventions.

Equity in awareness and utilization of cervical cancer screening services among women of reproductive age in Uganda: Analysis of vertical equity using evidence from UDHS 2022

Background Cervical cancer poses a severe public health burden in Uganda, which has one of the world’s highest incidence rates. Despite commitments to Universal Health Coverage (UHC), screening utilization remains critically low and inequitable. This study assessed vertical equity in the awareness and utilization of cervical cancer screening services among women in Uganda, evaluating whether distribution aligns with differential need. Methods We conducted a cross-sectional analysis of the 2022 Uganda Demographic and Health Survey (UDHS), including 18,251 women aged 15–49. The primary outcomes were self-reported screening utilization and awareness. Socioeconomic status was measured using the DHS wealth index. Equity was assessed using concentration curves and indices (CIs), with a positive CI indicating pro-rich inequality. P.value of 0.05 (95% confidence interval) was used to test for significance of study findings. Results We found significant pro-rich inequity in both screening utilization (CI = 0.125, p &lt; 0.000) and awareness (CI = 0.178, p &lt; 0.000), demonstrating that wealthier women had a disproportionate advantage. The pro-rich inequality in utilization was more pronounced in the urban (CI = 0.125) than rural (CI = 0.049) areas. Awareness was distributed almost equitably in rural areas (CI = −0.007, p = 0.165) but showed significant pro-rich inequality in urban settings (CI = 0.014, p &lt; 0.016). Conclusion Uganda’s cervical cancer screening services demonstrate significant vertical inequity, disproportionately favoring wealthier and urban women rather than being allocated according to greater need. To achieve elimination goals, deliberate policies must prioritize resource allocation and awareness for the poorer and rural women who bear the highest burden.

Trends and ethnic disparity in endometrial cancer mortality in South Africa (1999–2018): A population-based Age-period-cohort and Join point regression analyses

Background Endometrial cancer is the sixth leading cause of cancer among females and about 97,000 global deaths of endometrial cancer. The changes in the trends of obesity, fertility rates and other risk factors in South Africa (SA) may impact the endometrial cancer trends. The aim of this study was to utilise the age period cohort and join point regression modelling to evaluate the national and ethnic trends in endometrial cancer mortality in South Africa over a 20year period (1999–2018). Methods Data from Statistics South Africa was obtained to calculate the annual number of deaths, and annual crude and age standardised mortality rates (ASMR) of endometrial cancer from 1999–2018. The overall and ethnic trends of endometrial cancer mortality was assessed using the Join point regression model, while Age-period-cohort (APC) regression modelling was conducted to estimate the effect of age, calendar period and birth cohort. Results During the period 1999–2018, 4,877 deaths were due to endometrial cancer which constituted about 3.6% of breast and gynecological cancer deaths (3.62%, 95% CI: 3.52%–3.72%) in South Africa. The ASMR of endometrial cancer doubled from 0.76 deaths per 100,000 women in 1999 to 1.5 deaths per 100,000 women in 2018, with an average annual rise of 3.6% per annum. (Average Annual Percentage change (AAPC): 3.6%, 95%CI:2.7–4.4, P-value &lt; 0.001). In 2018, the overall mean age at death for endometrial cancer was was 67.40 ± 11.04 years and, the ASMR of endometrial cancer among Indian/Asians (1.69 per 100,000 women), Blacks (1.63 per 100,000 women) and Coloreds (1.39 per 100,000 women) was more than doubled the rates among Whites (0.66 deaths per 100,000 women). Indian/Asians had stable rates while other ethnic groups had increased rates. The Cohort mortality risk ratio (RR) of endometrial cancer increased with successive birth cohort from 1924 to 1963 (RR increased from 0.2 to 1.00), and subsequently declined among successive cohorts from 1963 to 1998 (1.00 to 0.09). There was strong age and cohort but not period effect among the South African women. Ethnic disparity showed that there was age effect among all the ethnic groups; Cohort effect among Blacks and Coloureds only, while Period effect occurred only among Blacks. Conclusions The mortality rates of endometrial cancer doubled over a twenty-year period in South Africa from 1999–2018. There was strong ethnic disparity, with age and cohort effect on endometrial cancer trends. Thus, targeted efforts geared towards prevention and prompt treatment of endometrial cancer among the high-risk groups should be pursued by stake holders.

Increased prevalence of obstructive sleep apnea in women diagnosed with endometrial or breast cancer

Background Epidemiological studies demonstrate associations between obstructive sleep apnea (OSA) and cancer incidence and mortality. The aim of this study was to measure OSA in women with breast (BC) or endometrial cancer (EC) and associations with clinico-pathological tumor variables. Methods and findings In a cross sectional study, women with BC (12 months) or EC (3 months) post-diagnosis were recruited from cancer clinics. We collected demographic, anthropometric data, cancer stage, grade, histopathology and history of cancer treatment and all subjects had in-laboratory polysomnography. Sleepiness was assessed with the Epworth Sleepiness Scale (ESS). We compared anthropometric and polysomnographic data between cancer groups (unpaired t-tests), and assessed relationships between cancer characteristics and OSA variables (Fishers exact test). There were no significant differences between average age (BC:59.6±8.7 years(n = 50); EC:60.3±7.7 years(n = 37)), or ESS score (BC:6.4±4.4; EC 6.8±4.7; mean±SD; all p&gt;0.2), however, BMI was higher in EC (BC: 29.7±7.9kgm-2; EC: 34.2±8.0 kgm-2; p&lt;0.05). BC had longer sleep latency (BC:31.8±32minutes; EC:19.3±17.9 minutes), less Stage 3 sleep (BC:20.0±5.2%; EC:23.6±8.2%) and more REM sleep (BC:21.1±6.9%; EC: 16.6±5.7%), all p&lt;0.05. EC had lower average awake and asleep oxygen saturation levels (BC: 95.6±1.3%; EC: 94.6±1.9% [awake]: BC: 94.8±2.1%; EC: 93.3±2.4% [asleep]; both p&lt;0.05). Apnea-Hypopnea Index (AHI) (BC: 21.2(7.3–36.9) events/hr; EC: 15.7 (10–33.5) events/hour (median (interquartile range)) was not different p = 0.7), however, 58% and 57% of women with BC and EC respectively, had an AHI&gt;15 events/hour. In this small sample size group, no significant associations (all p&gt;0.1) were detected between OSA metrics and clinico-pathological tumor variables. Conclusion In postmenopausal women with breast or endometrial cancer there is high prevalence of OSA, with no association with specific tumor characteristics detected. Recognition of the high prevalence of OSA in women with cancer is important to recognise as it may impact on surgical risk and quality of life.

Association between dietary folate intake and HPV infection: NHANES 2005–2016

BackgroundRecent studies have established a correlation between folate levels and the incidence of cervical cancer. Given that Human Papillomavirus (HPV) infection is a primary etiological factor in the development of cervical cancer, the nature of the relationship between dietary folate intake and HPV infection remains an area of ongoing investigation.MethodsTo investigate the association between dietary folate intake and HPV infection, this study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2016. Multivariate logistic regression analysis was employed to examine the potential associations. Furthermore, the use of restricted cubic splines (RCS) facilitated the exploration of any non-linear correlations. Additionally, subgroup analyses were used to explore this correlation in different populations.ResultsThe study encompassed a total of 6747 women aged between 18 and 59 years. For every one mcg increase in folate intake, the incidence of HPV infection is reduced by 1% (OR = 0.99, p&lt;0.05). Besides, folate intake was categorized into quartiles as follows: Q1 (&lt;211 mcg/day), Q2 (211–311 mcg/day), Q3 (311–448 mcg/day), and Q4 (&gt;448 mcg/day). The adjusted odds ratios (OR) for the different folate levels were as follows: Q2: 0.94 (95% CI: 0.76–1.16), Q3: 0.84 (95% CI: 0.67–1.04), and Q4: 0.63 (95% CI: 0.49–0.81). The RCS analysis confirmed a nonlinear relationship between dietary folate intake and HPV infection risk. Notably, a significant inverse association was observed when dietary folate intake exceeded 193.847 mcg/day.ConclusionsIn conclusion, the findings of this study indicate a negative association between dietary folate intake and the risk of HPV infection. This association demonstrates a nonlinear pattern, particularly evident at higher levels of folate consumption.

Herd immunity and prevention in HPV transmission with exogenous reinfection

Cervical cancer is a major global health concern, primarily caused by human papillomavirus (HPV), which spreads through unsafe sexual contact. Natural immunity often fails to provide full protection, permitting exogenous reinfection, which plays a key role in the persistence and transmission of HPV. This paper presents and analyzes a deterministic mathematical model of HPV transmission, incorporating exogenous re-infection. We utilized VIA test result data from 2019 to 2023 in Bangladesh to estimate key parameter values. The findings were validated through numerical simulations using MATLAB, and the analytical results demonstrated strong consistency with the numerical outputs. A critical insight is the presence of reinfection-induced backward bifurcation, indicating that targeting primary infections alone is insufficient for eradication, highlighting the need to address exogenous reinfection for effective control. We propose optimal control strategies tailored to resource-limited settings like Bangladesh, where limited vaccine access presents significant challenges, and community-driven education on safe sexual practices is crucial and continuously evolving. The results emphasize that the most effective approach combines targeted prevention with widespread community education, while precision in intervention implementation is essential to prevent reinfection surges that could prolong disease persistence and undermine control efforts. These insights provide a strong foundation for refining intervention strategies and offer valuable guidance for controlling HPV transmission through non-pharmaceutical interventions, particularly in resource-constrained settings.

Prevalence and genotypic distribution of high-risk human papillomavirus (HPV) among ever-married women in coastal regions of Bangladesh

Background Understanding the distribution of type specific human papillomavirus (HPV) genotypes in screen-detected lesions is crucial to differentiate women who are at a higher risk of developing cervical cancer. This study aimed to find out high-risk HPV genotype distribution among women of the coastal districts of Bangladesh. Methods This cross-sectional study conducted from January 2023 to December 2023 aimed to investigate the prevalence and distribution patterns of high-risk HPV genotypes among ever-married women aged 30–60 years residing in three coastal districts of Bangladesh. Sampling was purposive, with 300 participants per district. Exclusion criteria included prior cervical precancer or cancer treatment, hysterectomy, cervical amputation, and pregnancy. HPV DNA specimens were collected and tested using Cobas 4800. Positive cases underwent further genotype analysis with GenoFlowTM HPV Array Test Kit. Statistical analysis utilized SPSS version 25.0, employing Chi-square and Fisher’s Exact tests. Results Among 900 participants HR-HPV prevalence was 2.56%. HPV 16 was the most prevalent genotype (38.46%), followed by HPV 66 and HPV 68 (11.54% each). Single infections of HPV 16 predominated (39.13%), while for co-infections HPV 66 and HPV 68 were most common (13.04%). HR-HPV positivity increased with age, peaking at 5.5% in the 55–60 years’ age group. Participants education level, occupation, income, and reproductive history showed no significant association with HPV positivity. District-wise prevalence varied insignificantly, with Jhalokathi exhibiting the highest (3.0%), followed by Cox’s Bazar (2.7%), and Bagerhat (2.0%). HPV 16 was the predominant genotype across districts, with Cox’s Bazar and Jhalokathi demonstrating greater genotype diversity than Bagerhat. Conclusion The study concludes that among ever-married women in the coastal districts of Bangladesh, there is a low prevalence of high-risk HPV. The predominant high-risk HPV genotypes identified were HPV 16, followed by HPV 66 and 68. These findings hold significant implications for policy makers, providing guidance for targeted screening strategies and vaccination programs.

Bioinformatics analysis to identify the relationship between human papillomavirus-associated cervical cancer, toll-like receptors and exomes: A genetic epidemiology study

Introduction Genetic variants may influence Toll-like receptor (TLR) signaling in the immune response to human papillomavirus (HPV) infection and lead to cervical cancer. In this study, we investigated the pattern of TLR expression in the transcriptome of HPV-positive and HPV-negative cervical cancer samples and looked for variants potentially related to TLR gene alterations in exomes from different populations. Materials and methods A cervical tissue sample from 28 women, which was obtained from the Gene Expression Omnibus database, was used to examine TLR gene expression. Subsequently, the transcripts related to the TLRs that showed significant gene expression were queried in the Genome Aggregation Database to search for variants in more than 5,728 exomes from different ethnicities. Results Cancer and HPV were found to be associated (p&lt;0.0001). TLR1(p = 0.001), TLR3(p = 0.004), TLR4(221060_s_at)(p = 0.001), TLR7(p = 0.001;p = 0.047), TLR8(p = 0.002) and TLR10(p = 0.008) were negatively regulated, while TLR4(1552798_at)(p&lt;0.0001) and TLR6(p = 0.019) were positively regulated in HPV-positive patients (p&lt;0.05). The clinical significance of the variants was statistically significant for TLR1, TLR3, TLR6 and TLR8 in association with ethnicity. Genetic variants in different TLRs have been found in various ethnic populations. Variants of the TLR gene were of the following types: TLR1(5_prime_UTR), TLR4(start_lost), TLR8(synonymous;missense) and TLR10(3_prime_UTR). The “missense” variant was found to have a risk of its clinical significance being pathogenic in South Asian populations (OR = 56,820[95%CI:40,206,80,299]). Conclusion The results of this study suggest that the variants found in the transcriptomes of different populations may lead to impairment of the functional aspect of TLRs that show significant gene expression in cervical cancer samples caused by HPV.

Randomized experimental population-based study to evaluate the acceptance and completion of and preferences for cervical cancer screening

Cervical cancer has high incidence and mortality rates, especially in less-developed countries. Prevention methods are well established, but there are still barriers preventing some Brazilian women from undergoing a Pap sample. The objective of the study was to evaluate the acceptance, preferences and completion of four screening methods. This has an experimental design (community trial). A total of 164 participants who had never had a Pap sample or had not had one for more than three years were included. The city’s urban area was stratified by census tracts and divided according to income and education levels. Women belonging to the lower-income strata were considered in the study. Random blocks were numbered into five intervention groups (Group 1- Pap sample at the hospital; Group 2- Pap sample in the mobile unit; Group 3- urine self-collection; Group 4- vaginal self-collection; Group 5- woman’s choice). Only 164 women met all of the eligibility criteria (15.3%). Most of them accepted the assigned method (92%), but only 84% of the women completed the collection step. The acceptance rates were as follows: Group 1 (100%), Group 2 (64.5%), Group 3 (100%) and Group 4 (91.4%). In Group 5, the women’s preferences were distributed as follows: examination performed at the hospital, 13 women (33.3%); examination performed at the mobile unit, 11 women (28.2%); urine self-collection, 11 women (28.2%); and vaginal self-collection, 4 women (10.3%). This study suggests that methods that allow cervical sampling collected near the women’s domicile might improve the acceptance and completion of preventive tests. This finding is relevant for the development of new cervical cancer screening strategies.

Provider and female client economic costs of integrated sexual and reproductive health and HIV services in Zimbabwe

A retrospective facility-based costing study was undertaken to estimate the comparative cost per visit of five integrated sexual and reproductive health and HIV (human immuno-deficiency virus) services (provider perspective) within five clinic sites. These five clinics were part of four service delivery models: Non-governmental-organisation (NGO) directly managed model (Chitungwiza and New Africa House sites), NGO partner managed site (Mutare site), private-public-partnership (PPP) model (Chitungwiza Profam Clinic), and NGO directly managed outreach (operating from New Africa House site. In addition client cost exit interviews (client perspective) were conducted among 856 female clients exiting integrated services at three of the sites. Our costing approach involved first a facility bottom-up costing exercise (February to April 2015), conducted to quantify and value each resource input required to provide individual SRH and HIV services. Secondly overhead financial expenditures were allocated top-down from central office to sites and then respective integrated service based on pre-defined allocation factors derived from both the site facility observations and programme data for the prior 12 months. Costs were assessed in 2015 United States dollars (USD). Costs were assessed for HIV testing and counselling, screening and treatment of sexually transmitted infections, tuberculosis screening with smear microscopy, family planning, and cervical cancer screening and treatment employing visual inspection with acetic acid and cervicography and cryotherapy. Variability in costs per visit was evident across the models being highest for cervical cancer screening and cryotherapy (range: US$6.98—US$49.66). HIV testing and counselling showed least variability (range; US$10.96—US$16.28). In general the PPP model offered integrated services at the lowest unit costs whereas the partner managed site was highest. Significant client costs remain despite availability of integrated sexual and reproductive health and HIV services free of charge in our Zimbabwe study setting. Situating services closer to communities, incentives, transport reimbursements, reducing waiting times and co-location of sexual and reproductive health and HIV services may help minimise impact of client costs.

High-risk HPV prevalence and vaccination coverage among Indigenous women in the Colombian Amazon: Implications for cervical cancer prevention. Cross-sectional study

Cervical cancer, primarily caused by Human Papillomavirus (HPV) transmission through sexual contact, necessitates comprehensive strategies to combat its impact on women’s health. Yet, certain underserved populations, such as low socioeconomic and ethnic minority groups, encounter barriers in accessing timely interventions and early diagnosis. This cross-sectional study was conducted with the aim of assessing HPV prevalence, genotype distribution, and co-infections among 280 adult women residing in a Colombian Indigenous Reserve within the Amazon region. The research adhered to a community-centric approach that respected cultural norms, native languages, and Indigenous authorities’ permission. The study revealed an overall HPV infection prevalence of 31.1% (n = 87, 95% CI 25.7–36.8), with 22.5% (n = 63, 95% CI 17.7–27.8) of women infected by at least one high-risk HPV genotype and 15.0% (n = 42, 95% CI 11–19.7) infected by at least one LR genotype. These results align with the findings of other Colombian studies. Notable high-frequency genotypes included 16, 52, 66, 56, and 68, with the most common combinations being [66–52] and [66–58]. The study also assessed the prevalence of HPV vaccination, revealing a rate of 22.9%, lower than the national average. In vaccinated women, the prevalence of genotypes 16 and 18 was significantly reduced, as anticipated. Importantly, it was observed that 57.1% of all high-risk HPV infections could have been prevented with the use of the nonavalent vaccine. These findings underscore the critical need to enhance adherence to early cervical cancer detection and monitor positive cases to evaluate high-risk HPV persistence. Efforts should be directed toward continuing vaccination coverage against high-risk HPV 16 and 18 with the quadrivalent vaccine, while also striving to make the nonavalent vaccine accessible for inclusion in large-scale public health programs. Additionally, the study did not identify a specific pattern of co-infection. The study emphasizes the significance of adopting a locally tailored epidemiological approach to guide and promote cervical cancer prevention efforts in Indigenous communities.

Strategies for data normalization and missing data imputation and consequences for potential diagnostic microRNA biomarkers in epithelial ovarian cancer

MicroRNAs (miRNAs) are small non-coding RNA molecules regulating gene expression with diagnostic potential in different diseases, including epithelial ovarian carcinomas (EOC). As only a few studies have been published on the identification of stable endogenous miRNA in EOC, there is no consensus which miRNAs should be used aiming standardization. Currently, U6-snRNA is widely adopted as a normalization control in RT-qPCR when investigating miRNAs in EOC; despite its variable expression across cancers being reported. Therefore, our goal was to compare different missing data and normalization approaches to investigate their impact on the choice of stable endogenous controls and subsequent survival analysis while performing expression analysis of miRNAs by RT-qPCR in most frequent subtype of EOC: high-grade serous carcinoma (HGSC). 40 miRNAs were included based on their potential as stable endogenous controls or as biomarkers in EOC. Following RNA extraction from formalin-fixed paraffin embedded tissues from 63 HGSC patients, RT-qPCR was performed with a custom panel covering 40 target miRNAs and 8 controls. The raw data was analyzed by applying various strategies regarding choosing stable endogenous controls (geNorm, BestKeeper, NormFinder, the comparative ΔCt method and RefFinder), missing data (single/multiple imputation), and normalization (endogenous miRNA controls, U6-snRNA or global mean). Based on our study, we propose hsa-miR-23a-3p and hsa-miR-193a-5p, but not U6-snRNA as endogenous controls in HGSC patients. Our findings are validated in two external cohorts retrieved from the NCBI Gene Expression Omnibus database. We present that the outcome of stability analysis depends on the histological composition of the cohort, and it might suggest unique pattern of miRNA stability profiles for each subtype of EOC. Moreover, our data demonstrates the challenge of miRNA data analysis by presenting various outcomes from normalization and missing data imputation strategies on survival analysis.

Feasibility of extended cycles of neoadjuvant chemotherapy in patients with advanced ovarian cancer in terms of prognosis and surgical outcomes

Objective We aimed to identify the effect of an extended number of neoadjuvant chemotherapy (NAC) cycles on prognosis and surgical morbidity after interval debulking surgery (IDS) in patients with newly diagnosed advanced ovarian cancer. Methods Medical records of patients with advanced ovarian cancer treated with NAC and having undergone IDS were retrospectively reviewed. Clinicopathological factors were compared between two groups: conventional (≤4 cycles) and extended (≥5 cycles) NAC groups. Kaplan–Meier analysis was performed to evaluate progression-free survival (PFS) and overall survival (OS). Results A total of 156 patients were included, 112 patients in the conventional group and 44 patients in the extended NAC group. The extended NAC group had a significantly higher frequency of cancer antigen (CA)-125 normalization after NAC (59.1% vs. 33.9%, P = 0.004), a lower rate of bowel surgery (18.2% vs. 34.8%, P = 0.042), and a lower rate of transfusion during or after IDS (36.4% vs. 59.8%, P = 0.008) as compared to the conventional group. The complete cytoreduction rate after IDS was similar between the groups. In multivariate Cox regression analysis for PFS, radiologically stable and progressive disease after NAC (Hazard ratio [HR], 1.983; 95% Confidence interval [CI], 1.141–3.446; P = 0.015) and gross residual tumor after IDS (HR, 2.054; 95% CI, 1.414–2.983; P &lt; 0.001) were independent risk factors for poor PFS. However, extended NAC cycles were not significantly associated with poor PFS. The median PFS was 19.5 and 16.9 months (P = 0.830), and the 5-year OS was 71.4 and 63.2% (P = 0.677) in the conventional and extended NAC groups, respectively. Conclusion Our study showed that extended NAC cycles were not inferior to conventional NAC cycles in terms of survival in patients with advanced ovarian cancer and reduced surgical morbidity such as bowel surgery and transfusion during or after IDS.

VISTA+/CD8+ status correlates with favorable prognosis in Epithelial ovarian cancer

Immunotherapy by blocking immune checkpoint regulators has emerged as a new targeted therapy for some cancers. Among them V-domain Ig suppressor of Tcell activation (VISTA) which is identified as a novel checkpoint regulator in ovarian cancer. This study aimed to investigate the VISTA role in Epithelial ovarian cancer (EOC), and its relationship with tumor-infiltrating lymphocytes (TILs) markers and its prognostic value. The expression of VISTA, CD3, CD8, CD4, FOXP3, and CD56 was assessed in 168 EOC tissue microarrays (TMA) by immunohistochemistry (IHC). In addition, associations between VISTA, TILs, clinicopathological variables, and overall survival (OS) were analyzed. VISTA expression in IGRov1 cells, as well as in PBMC of EOC patient, was evaluated by western blot. VISTA expression was detected in 64,28% of tissues, among which 42.3% were positive for tumor cells (TCs), and 47,9% were positive for immune cells (ICs). In univariate analysis, VISTA expression was significantly associated with a high density of TILs:CD3+ (p = 0,001), CD4+ (p = 0,002) and CD8+ (p≤0,001), in ICs but not in TCs. In terms of OS, multivariate analysis showed a significant association between the high density of CD8+ TILs and VISTA positive staining in ICs (p = 0,044), but not in TCs (p = 0,108). Kaplan-Meier curves demonstrated no correlation between VISTA expression and prolonged OS in both ICs (p = 0,841) and TCs (p = 0,090). Classification of EOC tumor microenvironment based on VISTA and CD8+TILs expression, demonstrated four immune subtypes: VISTA+/CD8+, VISTA+/CD8-, VISTA-/CD8+ and VISTA-/CD8-. The dual positive VISTA+/CD8+ subtype was significantly associated with prolonged OS in both TCs and ICs (p = 0,012 and p≤0,01, respectively), whereas patients with VISTA+/CD8- had the worst OS. Our results showed that VISTA is highly expressed in the IGRov1 cell line and LT-CD8 from a patient with EOC. Our results highlighted the association of VISTA expression and CD8+ TILs in EOC, with prolonged OS in patients with VISTA+/CD8+ and proposed VISTA as a potential immunotherapeutic target in EOC.

Diffusion-weighted magnetic resonance sequence and CA125/CEA ratio can be used as add-on tools to ultrasound for the differentiation of ovarian from non-ovarian pelvic masses

Objective To provide a straightforward approach to the sequential use of ultrasound (US), magnetic resonance (MR) and serum biomarkers in order to differentiate the origin of pelvic masses, making the most efficient use of these diagnostic resources. Study design This is a cross-sectional study with 159 patients (133 with ovarian and 26 with non-ovarian tumors) who underwent surgery/biopsy for an adnexal mass. Preoperative CA125 and CEA serum measurements were obtained and a pelvic/abdominal ultrasound was performed. Preoperative pelvic MR studies were performed for all patients. Morphological and advanced MR sequences were obtained. Using a recursive partitioning algorithm to predict tumor origin, we devised a roadmap to determine the probability of non-ovarian origin using only statistically significant US, laboratory and MR parameters. Results Upfront US classification as ovarian versus non-ovarian and CA125/CEA ratio were significantly associated with non-ovarian tumors. Signal diffusion (absent/low versus high) was the only MR parameter significantly associated with non-ovarian tumors. When upfront US designated a tumor as being of ovarian origin, further MR signal diffusion and CA125/CEA ratio were corrected nearly all US errors: patients with MR signal diffusion low/absent and those with signal high but CA125/CEA ratio ≥25 had an extremely low chance (&lt;1%) of being of non-ovarian origin. However, for women whose ovarian tumors were incorrectly rendered as non-ovarian by upfront US, neither MR nor CA125/CEA ratio were able to determine tumor origin precisely. Conclusion MR signal diffusion is an extremely useful MR parameter to help determine adnexal mass origin when US and laboratory findings are inconclusive.

Upregulation of programmed death ligand-1 in tumor-associated macrophages affects chemotherapeutic response in ovarian cancer cells

To better understand the mechanism of chemoresistance in ovarian cancer cells, we aimed to investigate the influence of macrophages on the tumor cell response to carboplatin and identify the genes associated with chemoresistance. We mimicked the tumor microenvironment (TME) using a co-culture technique and compared the proliferation of ovarian cells with and without macrophages. We also examined M1 and M2 marker expression and the expression of key TME genes. Post the co-culture, we treated ovarian cancer cells with carboplatin and elucidated the function of programmed death–ligand 1 (PD-L1) in carboplatin chemoresistance. We investigated CD68 and PD-L1 expression in normal and cancerous ovarian tissues using immunohistochemistry (IHC). Finally, we analyzed the association between CD68 or PD-L1 expression and survival outcomes. Inducible nitric oxide synthase (iNOS) was downregulated, while the gene expression of M2 macrophage markers was increased in ovarian cancer cells. PD-L1, vascular endothelial growth factor (VEGF), Interleukin (IL)-6, IL-10, IL-12, signal transducer and activator of transcription 3 (STAT3), B-cell lymphoma 2 (BCL2), multidrug resistance 1 (MDR1), and colony stimulating factor 1 (CSF-1) were upregulated. Notably, PD-L1 was upregulated in both the ovarian cancer cells and macrophages. Ovarian cancer cells co-cultured with macrophages exhibited statistically significant carboplatin resistance compared to single-cultured ovarian cancer cells. PD-L1 silencing induced chemosensitivity in both types of co-cultured ovarian cancer cells. However, IHC results revealed no correlation between PD-L1 expression and patient survival or cancer stage. CD68 expression was significantly increased in cancer cells compared to normal or benign ovarian tumor cells, but it was not associated with the survival outcomes of ovarian cancer patients. Our study demonstrated that ovarian cancer cells interact with macrophages to induce the M2 phenotype. We also established that PD-L1 upregulation in both ovarian cancer cells and macrophages is a key factor for carboplatin chemoresistance.

Determinants of cervical cancer screening utilization among HIV-positive women, in public general hospitals of Central Zone, Tigray, Ethiopia, 2020: Case-control study

Introduction Cervical cancer is the second leading cause of cancer-related morbidity and mortality in Ethiopia. Evidence showes that, despite the magnitude and severity of cervical cancer, utilization of cervical cancer screening in the study area among HIV-positive women is low. Objective This study aimed to assess the determinants of cervical cancer screening utilizationamong HIV-positive women in general public hospitals in the central zone of Tigray, Ethiopia. Method This study was a facility-based unmatched case-control study conductedamong HIV-infected womenin public general hospitals in the central zone of Tigray. Cases were HIV infected women not screened for cervical cancer, and controls were HIV infected women screened for cervical cancer. A total of 800participants (400 cases and 400 controls) wereselected using systematic random sampling with a 1:1 case-to-control ratio.Data collection was done using a pre-tested interviewer-administered questionnaire and a medical record review.The determinants of cervical cancer screeningutilization were identified through binary logistic regression. Result Significant determinants of cervical cancer screening utilization among HIV-infected women in the central zone of Tigray werebeing in the age group of 18–30 [AOR = 0.46, 95% CI = 0.22, 0.98], living in rural areas [AOR = 0.47, 95% CI = 0.26, 0.87], no formal education [AOR = 0.25, 95% CI = 0.14, 0.45] and primary education [AOR = 0.28, 95% CI = 0.16,0.49], not working outside the home [AOR = 0.21, 95% CI = 0.10, 0.44], poor knowledge about cervical cancer [AOR = 0.29, 95% CI = 0.19, 0.44], and about cervical cancer screening [AOR = 0.44, 95% CI = 0.28, 0.70], and unfavorable attitudes toward cervical cancer screening [AOR = 0.52, 95% CI = 0.34, 0.79]. Conclusion Being in the age group of 18–30, living in rural areas, lacking formal education or havingonly primary level education, not working outside of the home, having poor knowledge of cervical cancer and screening,and having unfavourable attitudestowards cervical cancer screeningare significant determinat factors in cervical cancer screening utilization among HIV-infected women in the central zone of Tigray, Ethiopia. Considering such factors during the design of policies and programs could enhance the utilization of cervical cancer screening in the region.

Cervical cancer screening in Brazilian Amazon Indigenous women: Towards the intensification of public policies for prevention

BackgroundIndigenous women are vulnerable to cervical cancer. Screening is a strategy to reduce the burden of the disease.ObjectiveTo evaluate the prevalence profile of cervical cancer screening cytological results in Brazilian indigenous women by age and frequency of tests compared to non-indigenous women.MethodsA cross-sectional study evaluating the prevalences of screening test results in indigenous women assisted in the Brazilian Amazon from 2007 to 2019 (3,231 tests), compared to non-indigenous women (698,415 tests). The main outcome was the cytological result. Other variables were frequency, age groups, and population. The frequency was categorized as "1sttest", the first test performed by the women in their lifetime, or "screening test," tests from women who had previously participated in screening. Analyzes were based on prevalences by age group and population. We used Prevalence Ratios (PR) and 95% Confidence Intervals for risks and linear regression for trends.ResultsData from the 1sttest showed a higher prevalence of Low-grade Squamous Intraepithelial Lesion (LSIL) in indigenous women. Peaks were observed in indigenous under 25, 35 to 39, 45 to 49, and 60 to 64. The prevalence of High-grade Squamous Intraepithelial Lesion or more severe (HSIL+) was low in both groups in women younger than 25. The indigenous HSIL+ prevalence curve showed a rapid increase, reaching peaks in women from 25 to 34 years, following a slight decrease and a plateau. In screening tests, HSIL+ was more prevalent in indigenous from 25 to 39 (PR 4.0,2.3;6.8) and 40 to 64 (PR 3.8,1.6;9.0). In indigenous, the PR of HSIL+ results in screening tests over 1sttests showed no screening effect in all age groups. In non-indigenous, there was a significant effect toward protection in the age groups over 25.ConclusionThis screening study of indigenous women from diverse ethnicities showed a higher prevalence of cytological LSIL and HSIl+ than in non-indigenous women. The protective screening effect in reducing HSIL+ prevalence was not observed in indigenous.

Global perspectives of determinants influencing HPV vaccine introduction and scale-up in low- and middle-income countries

Achieving WHO cervical cancer elimination goals will necessitate efforts to increase HPV vaccine access and coverage in low-and-middle-income countries (LMICs). Although LMICs account for the majority of cervical cancer cases globally, scale-up of HPV vaccine programs and progress toward coverage targets in LMICs has been largely insufficient. Understanding the barriers and facilitators that stakeholders face in the introduction and scale-up of HPV vaccination programs will be pivotal in ensuring that LMICs are equipped to optimize the implementation of HPV vaccination programs. This qualitative study interviewed 13 global stakeholders categorized as either academic partners or global immunization partners to ascertain perspectives regarding factors affecting the introduction and scale-up of HPV vaccination programs in LMICs. Global stakeholders were selected as their perspectives have not been as readily highlighted within the literature despite their key role in HPV vaccination programming. The results of this investigation identified upstream (e.g., financial considerations, vaccine prioritization, global supply, capacity and delivery, and vaccine accessibility, equity, and ethics) and downstream (e.g., vaccine acceptability and hesitancy, communications, advocacy, and social mobilization) determinants that impact program introduction and scale-up and confirmed that strong political commitment and governance are significant in garnering support for HPV vaccines. As LMICs introduce HPV vaccines into their national immunization programs and develop plans for scaling up vaccination efforts, strategic approaches to communications and advocacy will also be needed to successfully meet coverage targets.

Prognostic model for survival in patients with neuroendocrine carcinomas of the cervix: SEER database analysis and a single-center retrospective study

Objective Neuroendocrine carcinoma of the cervix (NECC) is extremely rare in clinical practice. This study aimed to methodologically analyze the clinicopathological factors associated with NECC patients and to develop a validated survival prediction model. Methods A total of 535 patients diagnosed with NECC between 2004 and 2016 were identified from the Surveillance, Epidemiology and End Results (SEER) database, while 122 patients diagnosed with NECC at Yunnan Cancer Hospital (YCH) from 2006 to 2019 were also recruited. Patients from the SEER database were divided into a training cohort (n = 376) and a validation cohort (n = 159) in a 7:3 ratio for the construction and internal validation of the nomogram. External validation was performed in a cohort at YCH. The Kaplan-Meier method was used for survival analysis, the Log-rank method test was used for univariate analysis of prognostic influences, and the Cox regression model was used for multivariate analysis. Results The 3-year and 5-year overall survival (OS) rates for patients with NECC in SEER were 43.6% and 39.7%, respectively. In the training cohort, multivariate analysis showed independent prognostic factors for NECC patients including race, tumor size, distant metastasis, stage, and chemotherapy (p&lt;0.05). For extended application in other cohorts, a nomogram including four factors without race was subsequently created. The consistency index (C-index) of the nomogram predicting survival was 0.736, which was well-validated in the validation cohorts (0.746 for the internal validation cohort and 0.765 for the external validation cohort). In both the training and validation cohorts, the 3-year survival rates predicted by the nomogram were comparable to the actual ones. We then succeeded in dividing patients with NECC into high- and low-risk groups concerning OS using the nomogram we developed. Besides, univariate analysis showed that chemotherapy ≥4 cycles may improve the OS of patients at YCH with NECC. Conclusion We successfully constructed a nomogram that precisely predicts the OS for patients with NECC based on the SEER database and a large single-center retrospective cohort. The visualized and practical model can distinguish high-risk patients for recurrence and death who may benefit from clinical trials of boost therapy effectively. We also found that patients who received more than 4 cycles of chemotherapy acquired survival benefits than those who received less than 4 cycles.

Motives and attitudes of parents toward HPV vaccination: Results from the initial period of HPV vaccine rollout in Serbia

Human papillomavirus (HPV) infection is one of the most common viral infections in sexually active population worldwide, and is the main cause of cervical cancer, which is the fourth most common cancer among women. Serbia ranks third in incidence and mortality rate of cervical cancer in Europe. We conducted a cross-sectional study considering parents’ motivation for the HPV vaccination of their children. Statistical analysis included descriptive statistics and a logistic regression model. We found that the strongest motive was “Recommendation from paediatrician” (20.2%), followed by the attitude that HPV vaccine protects against cancers in different localization (15.4%), the motive “It is better to vaccinate a child than expose them to potential risk of HPV infection” (13.3%) and “Feeling anxiety due to a possible infection and cancer in the child” (13.1%). For those parents that vaccinated their child for some other strongest motive, reasons like “Vaccine is free of charge”, “Recommendation from friends and family” and motive „My child received all obligatory vaccines, so I want to receive this one as well“, were significantly more frequently selected. In the group where paediatricians’ recommendation was not a motive for accepting the HPV vaccine, the largest percentage of parents (89.6%) selected motive “HPV vaccine protects against cancers in different localization” and the motive “It is better to vaccinate a child than expose them to potential risk of HPV infection” (78.1%). Paediatrician’s recommendation is very important for parents’ decision to vaccinate, however, other motives also influenced and had significance in making the parents’ decision to vaccinate their children against HPV. Encouraging trust in public health authorities in Serbia, highlighting the advantages of the HPV vaccine and further encouraging healthcare workers to give stronger recommendations can increase the HPV vaccine uptake. Finally, we provided the basis to create more targeted messages that will empower parents to vaccinate their children.

Association of missense variant DCLRE1B rs3761936 with breast and cervical cancer risk—A case-control study

Background Overexpression of rs3761936 of DCLRE1B gene has been observed in both breast cancer and cervical cancer patients. To justify the association of this polymorphism with these cancers, we performed this case-control study. Method A total of 245 cancer patients and 108 healthy controls participated in the research. An efficient T-ARMS PCR method was used for genotyping. Results The cancer patients showed higher mutant allele frequency compared to the controls. Mutant allele carrier breast cancer patients showed significantly increased risk in four genetic models, including additive model 1 (TC vs. TT: OR=2.31, 95% CI = 1.33–3.99, p-value = 0.0028), additive model 2 (CC vs. TT: OR=3.93, 95% CI = 1.36–11.38, p-value = 0.0116), dominant model (TC + CC vs. TT: OR=2.52, 95% CI = 1.50–4.25, p-value = 0.0005), and over-dominant model (TC vs. TT + CC: OR=1.93, 95% CI = 1.13–3.28, p-value = 0.0152). The allele frequency analysis showed that mutant allele C carriers among breast cancer patients had a significantly higher risk than the wild type T allele carriers (C vs. T: OR=2.15, 95% CI = 1.41–3.26, p-value = 0.0003). Likewise, the cervical cancer patients showed significant risk in three genetic models, including additive model 1 (TC vs. TT: OR=1.80, 95% CI = 1.01–3.20, p-value = 0.0444), additive model 2 (CC vs. TT: OR=3.17, 95% CI = 1.05–9.55, p-value = 0.0403), and dominant model (TC + CC vs. TT: OR=1.98, 95% CI = 1.15–3.41, p-value = 0.0138). The mutant allele C carriers had a significantly higher risk than the wild-type T allele carriers (C vs. T: OR=1.84, 95% CI = 1.19–2.85, p-value = 0.0065). Conclusion DCLRE1B rs3761936 is strongly associated with breast cancer and cervical cancer risk in Bangladeshi women.

Development and anticancer properties of Up284, a spirocyclic candidate ADRM1/RPN13 inhibitor

Bortezomib has been successful for treatment of multiple myeloma, but not against solid tumors, and toxicities of neuropathy, thrombocytopenia and the emergence of resistance have triggered efforts to find alternative proteasome inhibitors. Bis-benzylidine piperidones such as RA190 covalently bind ADRM1/RPN13, a ubiquitin receptor that supports recognition of polyubiquitinated substrates of the proteasome and their subsequent deububiqutination and degradation. While these candidate RPN13 inhibitors (iRPN13) show promising anticancer activity in mouse models of cancer, they have suboptimal drug-like properties. Here we describe Up284, a novel candidate iRPN13 possessing a central spiro-carbon ring in place of RA190’s problematic piperidone core. Cell lines derived from diverse cancer types (ovarian, triple negative breast, colon, cervical and prostate cancers, multiple myeloma and glioblastoma) were sensitive to Up284, including several lines resistant to bortezomib or cisplatin. Up284 and cisplatin showed synergistic cytotoxicity in vitro. Up284-induced cytotoxicity was associated with mitochondrial dysfunction, elevated levels of reactive oxygen species, accumulation of very high molecular weight polyubiquitinated protein aggregates, an unfolded protein response and the early onset of apoptosis. Up284 and RA190, but not bortezomib, enhanced antigen presentation in vitro. Up284 cleared from plasma in a few hours and accumulated in major organs by 24 h. A single dose of Up284, when administered to mice intra peritoneally or orally, inhibited proteasome function in both muscle and tumor for &gt;48 h. Up284 was well tolerated by mice in repeat dose studies. Up284 demonstrated therapeutic activity in xenograft, syngeneic and genetically-engineered murine models of ovarian cancer.

Determinants of cervical high-risk human papillomavirus positivity among Rwandan women living with human immunodeficiency virus

Introduction There are few data on the prevalence of cervical high-risk human papillomavirus (hrHPV), the necessary cause of cervical cancer, and its determinants among Rwandan women living with human immunodeficiency virus (HIV). We therefore aimed to assess the determinants of hrHPV positivity among Rwandan women living with HIV (WLWH). Methods We conducted a cervical cancer screening study of ~5,000 WLWH aged 30–54 years and living in Kigali, Rwanda, but originally from all provinces in the country, from 2016–2018. Women were tested for hrHPV by the Xpert assay (Cepheid, Sunnyvale, CA, USA). A nurse-administered questionnaire collected data on demographics and HPV/cervical cancer risk factors. Women without evidence of cervical precancer and cancer were included in the analysis. Results Women included in this analysis (N = 4,880) had a mean age of 40 years, &gt; 98% were on antiretroviral therapy, and 61% had a CD4 count of ≥500 cells/µL. High-risk HPV prevalence was 25.5% [95% confidence interval (CI)=24.3%−26.8%] and the prevalence decreased with older ages and higher CD4 counts (ptrend&lt;0.001 for both). High-risk HPV prevalence was higher for those who reported their first sex before 16 years, had their first child before 18 years, had more sexual partners over their lifetime and in the last six months, and those with lower CD4 cell count (ptrend&lt;0.001 for all). A CD4 count of &lt;200 (vs. &gt; 500) per µL was most strongly associated with being hrHPV positive (adjusted odds ratio = 2.7, 95%CI = 2.1–3.6). Conclusions Our findings highlight the role of CD4 counts, as a measure of HIV control and immunity, in controlling hrHPV infection, which could potentially impact cervical cancer control among this high-risk population. Raising awareness on various associated factors coupled with integrating HPV and cervical cancer awareness in HIV care could help control this double burden of disease.

Psychological repercussions of breast or uterine cervical cancer disclosure to women in Gabon

Background Breast and cervical cancers are major health issues globally, with particularly high burdens in sub-Saharan Africa, including Gabon. Limited epidemiological data and insufficient attention to the psychological impacts of these cancers highlight critical research gaps. This study aimed to explore the psychological repercussions experienced by Gabonese women following the disclosure of a breast or cervical cancer diagnosis. Methods A mixed-methods cross-sectional study was conducted from March to May 2023 at the Institut de Cancérologie d’Akanda. Women recently diagnosed with breast or cervical cancer were recruited using a consecutive sampling method. Data were collected through semi-structured individual interviews and one focus group to explore emotional responses, coping strategies, and perceptions of patient–provider interactions. In addition, the Patient Health Questionnaire-9 (PHQ-9) was administered to assess depressive symptoms. Results Thirteen Gabonese women diagnosed with breast (n = 10) or cervical cancer (n = 3) participated in this mixed-methods study. Following the disclosure, all patients reported depressive symptoms ranging from minimal to moderately severe (PHQ-9). Qualitative analysis revealed intense emotional distress, including anxiety, sadness, sleep disturbances, and despair. The diagnosis affected participants’ identity, body image, and social relationships, reinforcing feelings of stigma, isolation, and loss. Beliefs about disease etiology and social representations shaped emotional responses. While some relied on spirituality, social support, or personal resilience to cope, others expressed unmet psychological needs. Participants emphasized the importance of clear, compassionate communication from healthcare professionals, highlighting the need for empathy, trust, and active listening during diagnosis disclosure. Conclusion This pioneering study in Gabon identifies profound psychological effects associated with breast and cervical cancer diagnosis disclosure. The findings underscore the urgent need for improved psychosocial support, effective communication training for healthcare providers, and culturally tailored interventions to address mental health concerns in this population.

Predictors of time to death among cervical cancer patients at Tikur Anbesa specialized hospital from 2014 to 2019: A survival analysis

Background Cervical cancer (CC) is the 4th most prevalent cancer among females globally. In Ethiopia, around 7,095 new CC cases are diagnosed every year and it is the second common cause of cancer deaths in women. There is limited evidence on survival status as well as about predictors of time to death among CC patients in Ethiopia. Thus, this study investigated the five-year survival status and predictors of time to death among CC patients who had been admitted at Tikur Anbesa specialized Hospital (TASH) from 2014–2019. Methods Facility-based, retrospective-cohort study was conducted at Tikur Anbesa specialized Hospital among 348 patients from June 2014 to June 2019. A systematic random sampling method was employed to select the study participants. Data were extracted from the patient card, and through phone calls. The data was collected using the android version CS-Entry tool. Data was analyzed by SPSS version 23. Kaplan and Meier’s method was used to estimate survival functions and Cox-proportional hazard regression analysis was carried out in order to identify the independent predictors of time to death. Results The overall incidence of death was 31 per 100 person-years of follow up. The median (IQR) follow-up time of the entire cohorts was 18.55 (8.96–49.65) months. The independent predictors for time to death included; age older than 50 years [AHR: 1.4; 95% CI: 1.1–1.9], late stage of CC at diagnosis [AHR: 2.2; 95% CI: 1.7–2.9], No CC treatment [AHR: 2.1; 95% CI: 1.5–3.1] and HIV positive [AHR: 2.3; 95% CI: 1.4–3.8]. Conclusion and recommendation The death rate of CC patients was high. The significant predictors associated with shorten time to death of CC patients were older age, advanced cancer stage at diagnosis, HIV infection and not receiving cancer treatment. Therefore, improving early detection and initiation of treatment for all CC patients is necessary in order to improve patient’s survival status. The government needs to strengthen the routine CC screening programs to address high-risk women such as elderly and HIV positive women in Ethiopia.

Impact of PARP inhibitor maintenance therapy in newly diagnosed advanced epithelial ovarian cancer: A meta-analysis

Objectives This meta-analysis was undertaken to systematically evaluate the effects of poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy on the survival of newly diagnosed advanced epithelial ovarian cancer (EOC) patients. Methods/Materials A systematic literature search revealed 3,227 studies. A subsequent selection process identified seven suitable randomized studies that assessed the survival outcomes in newly diagnosed advanced EOC patients administered PARPi (n = 1921; the PARPi group) or placebo (n = 1150; the placebo group). The survival outcomes were compared with respect to the PARPi treatment regardless of bevacizumab maintenance therapy. All adverse events ≥ grade 3 were analyzed. Review Manager Version 5.4.1 software was used for the meta-analysis. Results The two-year progression-free survival (PFS) was significantly better in the PARPi group than the placebo (Hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.41 to 0.68). Furthermore, patients in the PARPi group with the BRCA1/2 mutation (BRCAm), BRCA wild type, homologous-recombination deficiency (HRD), or HRD without BRCAm, but not with homologous-recombination proficiency had a significantly better two-year PFS than the patients in the placebo group. The five-year overall survival (OS) was comparable in the two groups, but patients in the PARPi group with BRCAm had a significantly better five-year OS than those in the placebo group (HR, 0.57; 95% CI, 0.44 to 0.74). In addition, the adverse event rate (≥ grade 3) was significantly higher in the PARPi group than in the placebo group (HR, 2.94; 95% CI, 1.13 to 7.63). Conclusions In patients with newly diagnosed advanced EOC, PARPi maintenance therapy was significantly more effective in terms of survival than no PARPi treatment. However, the risk of serious adverse events was higher for patients who received PARPi maintenance therapy.

Cardamonin suppresses mTORC1/SREBP1 through reducing Raptor and inhibits de novo lipogenesis in ovarian cancer

Metabolic reprogramming is a hallmark of cancer and de novo lipogenesis (DNL) accelerates the progression of ovarian cancer. In this study, we investigated the effects of cardamonin, a natural compound potential to suppress various malignancies, on the lipid anabolism in ovarian cancer. Cell proliferation was assessed using CCK-8 and clone formation assay. Cell apoptosis was detected by flow cytometry with Annexin V-FITC/PI staining and mitochondrial membrane potential (MMP) was measured with JC-10 probe. Free fatty acids (FFA) was measured by fluorescence using acyl-CoA oxidation and carnitine palmitoyl transferase-1 (CPT-1) activity was analyzed by spectrophotometric assay using palmitoyl-CoA and DTNB (5,5’-dithio-bis-(2-nitrobenzoic acid)) reaction. mRNA expression was measured by Quantitative Real-Time PCR. Protein expression was analyzed through western blotting and immunofluorescence. Raptor was knocked down by shRNA and Raptor was overexpressed by lentiviral transfection. The antitumor effect of cardamonin was evaluated using a xenotransplantation tumor bearing mouse model. Cardamonin suppressed the cell proliferation, induced cell apoptosis and triggered mitochondrial damage in ovarian cancer cells. Cardamonin inhibited the protein expression of sterol regulatory element binding protein 1 (SREBP1) and its downstream lipogenic enzymes and decreased FFA content and CPT-1 activity. Additionally, cardamonin inhibited the activation of mechanistic target of rapamycin complex 1 (mTORC1) and expression of regulatory-associated protein of mTOR (Raptor). Raptor knockdown abolished the inhibitory effect of cardamonin on mTORC1 and SREBP1. Furthermore, cardamonin inhibited mTORC1 activation and lipogenic proteins expression induced by Raptor overexpression. Cardamonin reduced the tumor growth and fatty acid synthase of the tumors, as evidenced by decreased expression of Ki-67 and FASN. It suggests that cardamonin suppresses mTORC1/SREBP1 through reducing the protein level of Raptor and inhibits DNL of ovarian cancer.

High-risk human papillomavirus prevalence among South African women diagnosed with other STIs and BV

Introduction Human papillomavirus (HPV) infection is a leading cause of cervical cancer. Although this relies on infection and persistence of HPV in epithelial cells, often occurring in the context of other sexually transmitted infections (STIs) and bacterial vaginosis (BV), data on the relationships between these and their relative effects on epithelial barrier integrity in women remain sparse. This study describes the epidemiology of HPV combined with STI and/or BV prevalence and the relative impact on matrix metalloproteinases (MMPs) among South African women. Methods Roche Linear Array was used for HPV genotyping in menstrual cup pellets of 243 HIV-negative women participating in the CAPRISA 083 cohort study. Vulvovaginal swabs were tested for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis using Xpert® CT/NG assay and lateral flow assay, and Gram staining was performed to diagnose BV using Nugent scoring criteria. Concentrations of 5 MMPs were measured in menstrual cup supernatants by multiplexed ELISA. Fisher’s exact tests, Mann-Whitney U tests, and multivariable regression models determined associations between HPV infection, STI and/or BV, and MMP concentrations. Results HPV was prevalent in 34% of women (83/243; median 23 years, interquartile range (IQR) 21–27 years). Low-risk (lr) (71%, 59/83) and high-risk (hr)-HPV infections (54.2%, 45/83) were common. Hr-HPV was frequently detected in STI and/or BV-positive women compared to women without STIs or BV (p = 0.029). In multivariable analysis, BV was associated with increased odds of hr-HPV detection (OR: 2.64, 95%CI: 1.02–6.87, p = 0.046). Furthermore, Gardasil®9 vaccine-type strains were more frequently detected in women diagnosed with STI and/or BV (55.2%, 32/58 vs 24%, 6/25; p = 0.009). Among STI and/or BV-positive women, HPV detection was significantly associated with increased MMP-10 concentrations (b = 0.55, 95% CI 0.79–1.01; p = 0.022). Conclusion Most women with hr-HPV had another STI and/or BV, emphasizing an urgent need for STI and BV screening and intensive scale-up of cervical cancer screening and HPV vaccination programmes. Furthermore, the study highlights the need for more extensive research to confirm and understand the relationship between HPV infection and barrier integrity.

Digital health interventions for cervical cancer care: A systematic review and future research opportunities

Background Cervical cancer is a malignancy among women worldwide, which is responsible for innumerable deaths every year. The primary objective of this review study is to offer a comprehensive and synthesized overview of the existing literature concerning digital interventions in cervical cancer care. As such, we aim to uncover prevalent research gaps and highlight prospective avenues for future investigations. Methods This study adopted a Systematic Literature Review (SLR) methodology where a total of 26 articles were reviewed from an initial set of 1110 articles following an inclusion-exclusion criterion. Results The review highlights a deficiency in existing studies that address awareness dissemination, screening facilitation, and treatment provision for cervical cancer. The review also reveals future research opportunities like explore innovative approaches using emerging technologies to enhance awareness campaigns and treatment accessibility, consider diverse study contexts, develop sophisticated machine learning models for screening, incorporate additional features in machine learning research, investigate the impact of treatments across different stages of cervical cancer, and create more user-friendly applications for cervical cancer care. Conclusions The findings of this study can contribute to mitigating the adverse effects of cervical cancer and improving patient outcomes. It also highlights the untapped potential of Artificial Intelligence and Machine Learning, which could significantly impact our society.

Factors associated with uptake and acceptability of cervical cancer screening among female sex workers in Northeastern Uganda: A cross-sectional study

Background Cervical cancer screening program in Uganda is opportunistic and focuses mainly on women aged 25–49 years. Female sex workers (FSWs) are at increased risk of developing invasive cervical cancer. There is limited data regarding the uptake and acceptability of cervical cancer screening among FSWs in Uganda. This study aimed at identifying factors associated with uptake and acceptability of cervical cancer screening among FSWs in Eastern Uganda. Methods This was a cross-sectional study conducted among 423 FSWs aged 18–49 years attending care at six health facilities serving Key Populations (FSWs, Men who have sex with men, transgender people, people who inject drugs and people in prisons) in the Teso sub-region. Data was collected using structured investigator administered questionnaire and analyzed using Stata statistical software version 15.0 (Stata Corp, Texas, USA). The primary outcome was uptake of cervical cancer screening measured as the proportion of female sex workers who have ever been screened for cervical cancer. Chi-square test was used to compare the differences in uptake of cervical cancer screening by HIV status. Modified Poisson regression model with a robust variance estimator was used to determine association between the outcome variables and selected independent variables including demographic characteristics. Prevalence ratios (PR) with accompanying 95% confidence intervals have been reported. Statistical significance was considered at two-sided p-values ≤ 0.05. Results The mean age of the participants was 28.1 (±SD = 6.6) years. The self-reported HIV prevalence was 21.5% (n = 91). There were 138 (32.6%) participants who had ever been screened for cervical cancer (uptake), while 397 (93.9%) were willing to be screened (acceptability). There was a significant difference in cervical cancer screening uptake between women living with HIV (WLHIV) and those who were HIV negative, 59.3% vs 26.9% respectively (P &lt; 0.001). The significant factors associated with uptake of cervical cancer screening included living with HIV, adjusted prevalence ratio (aPR) = 1.53 (95%CI: 1.15–2.07), increasing number of biological children, aPR = 1.14 (1.06–1.24) living near a private not for profit (PNFP) facility, aPR = 2.84 (95% CI; 1.68–4.80) and availability of screening services at the nearest health facility, aPR = 1.83 (95% CI, 1.30–2.57). Factors significantly associated with acceptability of cervical cancer screening included being 40 years or older, aPR = 1.22 (95%CI: 1.01–1.47), having a family history of cervical cancer, aPR = 1.05 (1.01–1.10), and living near a PNFP facility, aPR = 1.17 (95% CI, 1.09–1.27) and having ever screened before, aPR = 0.92 (0.86–0.98). Conclusion Female sex workers living with HIV are more likely to screen for cervical cancer than the HIV negative clients. Cervical cancer screening uptake is relatively low among the female sex workers. However, majority of the FSWs are willing to be screened for cervical cancer if the services are provided in the nearby healthcare facilities. There is need to make cervical cancer screening services available to all eligible women especially the female sex workers and integrate the services with sexual reproductive health services in general and not just HIV/ART clinics services.

Joint modeling HIV and HPV using a new hybrid agent-based network and compartmental simulation technique

Persons living with human immunodeficiency virus (HIV) have a disproportionately higher burden of human papillomavirus infection (HPV)-related cancers. Causal factors include both behavioral and biological. While pharmaceutical and care support interventions help address biological risk of coinfection, as social conditions are common drivers of behaviors, structural interventions are key part of behavioral interventions. Our objective is to develop a joint HIV-HPV model to evaluate the contribution of each factor, to subsequently inform intervention analyses. While compartmental modeling is sufficient for faster spreading HPV, network modeling is suitable for slower spreading HIV. However, using network modeling for jointly modeling HIV and HPV can generate computational complexities given their vastly varying disease epidemiology and disease burden across sub-population groups. We applied a recently developed mixed agent-based compartmental (MAC) simulation technique, which simulates persons with at least one slower spreading disease and their immediate contacts as agents in a network, and all other persons including those with faster spreading diseases in a compartmental model, with an evolving contact network algorithm maintaining the dynamics between the two models. We simulated HIV and HPV in the U.S. among heterosexual female, heterosexual male, and men who have sex with men (men only and men and women) (MSM), sub-populations that mix but have varying HIV burden, and cervical cancer among women. We conducted numerical analyses to evaluate the contribution of behavioral and biological factors to risk of cervical cancer among women with HIV. The model outputs for HIV, HPV, and cervical cancer compared well with surveillance estimates. Model estimates for relative prevalence of HPV (1.67 times) and relative incidence of cervical cancer (3.6 times), among women with HIV compared to women without, were also similar to that reported in observational studies in the literature. The fraction attributed to biological factors ranged from 22–38% for increased HPV prevalence and 80% for increased cervical cancer incidence, the remaining attributed to behavioral. The attribution of both behavioral and biological factors to increased HPV prevalence and cervical cancer incidence suggest the need for behavioral, structural, and pharmaceutical interventions. Validity of model results related to both individual and joint disease metrics serves as proof-of-concept of the MAC simulation technique. Understanding the contribution of behavioral and biological factors of risk helps inform interventions. Future work can expand the model to simulate sexual and care behaviors as functions of social conditions to jointly evaluate behavioral, structural, and pharmaceutical interventions for HIV and cervical cancer prevention.

Screening and hospitalization of breast and cervical cancer in Brazil from 2010 to 2022: A time-series study

In Brazil, during the pandemic caused by COVID-19, screening for breast and cervical cancers was postponed or interrupted due to the prevailing health conditions. These neoplasms, however, are responsible for high morbidity and mortality among women in Brazil and have a major impact on the quality of life of this population and public health. Thus, this study aims to evaluate the epidemiological behavior of hospitalization for cervical and breast cancer in Brazilian women, as well as the trend of screening tests of breast and cervical cancer in the years 2010 to 2022 according to the regions of Brazil. This is ecological research of time series, based on secondary data obtained from information systems of the country, about hospital admissions for breast and cervical cancer and screening methods used for these tumors. The data were analyzed in the Joinpoint Regression Program, to obtain the linear regression and temporal analysis of the variables. As a result, between 2010 and 2022, the rates of mammography varied from 36 to 71 exams, while in the pap smear, the variations were 126 and 226 cytopathological exams per 1000 women. Hospitalizations for these cancers peaked in 2019, with 48 hospitalizations for cervical cancer per 100,000 women and 147 hospitalizations for breast cancer for the same population. For both, in the pandemic years, between 2020 and 2022, there is a decrease in Brazil and in all its regions. As for the tracking of these diseases, it was observed that the performance of mammograms and preventive tests showed a similar behavior, in which there is a higher supply of these tests until 2019 and a drop during the pandemic period. This leads to the conclusion that even though Brazil has several policies for the screening of these diseases, there is still instability in the offering of these tests and that there was instability in this area during the pandemic.

Women and health providers’ perspectives on male support for cervical cancer screening in Gwanda district, Zimbabwe

Several studies have shown that male involvement increases the uptake of sexual and reproductive health programmes for improved family health outcomes. The role of men in reducing the burden of cervical cancer has however not been researched in Zimbabwe. It is for this reason that this study explores male support for cervical cancer screening programmes from the perspective of women and health providers in the Gwanda district of Zimbabwe. A qualitative approach that engaged thirty-six women aged 25–50 years in focus group discussions, and twenty-five health providers with different roles in the cervical cancer screening programme in in-depth interviews was used to determine their perspectives on male support for cervical cancer screening. Data were analysed thematically using ATLAS.ti Computer Assisted Qualitative data analysis software. Key findings reflected that men lacked knowledge on cervical cancer and its risk factors and prevention. Subsequently, they engaged in sexual behaviours that increased their partners’ risk of acquiring Human Papillomavirus infection, the virtually necessary cause of cervical cancer. Furthermore, men did not provide the necessary emotional and financial support for their women to access screening and treatment. Participants were optimistic that innovative awareness creation strategies and intense, sustained cervical cancer education efforts targeting men could increase male partner support. Involvement of community leaders was seen as crucial in the facilitation of male involvement for programme acceptance and improved uptake of cervical cancer screening. Male involvement is seen as an integral component of the cervical cancer prevention and control programme that has to be implemented in Gwanda district to minimise male partner-related barriers to cervical cancer screening. Further research focusing on men is required to identify specific knowledge gaps that would enable development of appropriate strategies that best involve men in cervical cancer prevention and control interventions.

Awareness and knowledge of physicians and residents on the non-sexual routes of human papilloma virus (HPV) infection and their perspectives on anti-HPV vaccination in Jordan

Background and objectives Although penetrative sex is the most common route of HPV infection, there is strong evidence of non-sexual modes of transmission. As the first of its kind, this study aimed to investigate the knowledge and awareness of Jordanian physicians on such routes. Methods A questionnaire was conducted among a national Jordanian sample of physicians from Jordanian health sectors. The survey included questions assessing participants’ knowledge on HPV, non-sexual routes of infection and HPV vaccines. Physicians’ attitudes towards HPV screening and vaccination were covered. Statistical analysis was carried out using SAS 9.4, ANOVA, post-hoc Tukey-Honest test and Kruskal-Wallis test. All significant differences were set at α = 0.05. Results A total of 412 participants completed the survey. Physicians showed a huge deficit in knowledge on nonsexual routes of HPV transmission. They agreed that the most and least common routes of non-sexual transmission are skin to mucosa (64%) and contaminated water (15%), respectively. Females showed significantly better knowledge in all aspects of HPV transmission and vaccination (p&lt;0.0001) and more positive attitudes towards HPV screening and vaccination compared to males (p = 0.03). Age group ≤ 25 and academic physicians demonstrated higher knowledge on HPV vaccines compared to their counterparts in non-academic places (p = 0.002). Specialty and experience seemed to have no impact on knowledge or attitudes of participants. Higher knowledge physicians had more positive attitude towards vaccination and screening compared to lower knowledge fellows (p&lt;0.001). Conclusions The noteworthy findings of this study is the extremely low level of knowledge on non-sexual routes of HPV infection among Jordanian physicians. Increasing the level of awareness of physicians and healthcare workers on these routes and their association with cervical and other cancers through university curricula and other reliable sources is strongly recommended.

The HPV-TP53-MALAT1 Axis: Unravelling interactions in cervical cancer development

Introduction Cervical cancer, primarily driven by Human Papillomavirus (HPV) infection, stands as a substantial global health challenge. The TP53 gene’s, Arg72Pro polymorphism has emerged as a noteworthy player in cervical cancer development, particularly among individuals harboring high-risk (HR) HPV types. Additionally, long non-coding RNAs (lncRNAs), exemplified by metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), exert critical roles in cancer biology. This study delves into unravelling the intricate connections linking HPV infection, TP53 Arg72Pro polymorphism, and MALAT1 expression in the context of cervical cancer. Materials and methods Within a cohort of cervical cancer patients, we discerned HPV infection statuses, executed genotyping for the TP53 Arg72Pro polymorphism, and quantified MALAT1 expression through quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Statistical analyses meticulously probed relationships intertwining HPV infection, TP53 polymorphism, and MALAT1 expression. Findings Our investigation revealed a striking prevalence of the TP53 Arg72Pro polymorphism among HPV-positive subjects, accompanied by a robust and statistically significant correlation linking MALAT1 overexpression (p&lt;0.01) and HR-HPV positivity (p&lt;0.03). Importantly, a subset of MALAT1 overexpression cases unveiled a concomitant TP53 Pro72Pro polymorphism. In contrast, HPV-negative invasive cervical carcinoma samples exhibited no discernible shifts in MALAT1 expression. Conclusion The contours of our findings sketch a compelling landscape wherein HR-HPV infection, TP53 polymorphism, and MALAT1 expression intertwine significantly in cervical cancer. The voyage ahead entails delving deeper into molecular underpinnings to decipher MALAT1’s nuanced role and its dance with TP53 within HPV-associated cervical carcinogenesis. This expedition promises insights that may engender targeted therapeutic interventions and bespoke prognostic markers, tailored to the realm of HR-HPV-related cervical cancer.

Prognostic significance of index (LANR) composed of preoperative lymphocytes, albumin, and neutrophils in patients with stage IB-IIA cervical cancer

Background The purpose of this study was to investigate the role of preoperative lymphocytes, albumin, neutrophils, and LANR in the prognosis of patients with stage IB-IIA cervical cancer (CC). Methods We made a retrospective analysis of the clinical information and related materials of 202 patients with stage IB-IIA primary cervical cancer who had undergone a radical hysterectomy in the Department of Gynecology at the Affiliated Hospital of Jiangnan University between January 2017 and December 2018. The definition of LANR was as follows: LANR, lymphocyte × albumin / neutrophil. The receiver operating characteristic curve (ROC) was generated to determine the best cut-off values for these parameters, as well as the sensitivity and specificity of LANR in predicting recurrence and survival. The Kaplan–Meier method was employed to draw survival curves in our survival analysis. Univariate analysis, multifactorial analysis, and subgroup analysis were used to evaluate the prognostic significance of LANR in overall and progression-free survival. Results The median follow-up time of the study was 55 months. In overall survival, the area under the curve for LANR was 0.704 (95% CI: 0.590–0.818, p&lt;0.05). And in progression-free survival, the area under the curve for LANR was 0.745 (95% CI: 0.662–0.828, p&lt;0.05). Univariate and multivariate analyses showed that the value of LANR was associated with both overall survival and progression-free survival (p&lt; 0.05). Kaplan-Meier analysis demonstrated that OS (p&lt; 0.001) and PFS (p&lt; 0.001) in patients with high LANR levels were significantly higher than those with low LANR levels. Conclusions Our findings suggested that LANR might serve as a clinically reliable and effective independent prognostic indicator in patients with stage IB-IIA cervical cancer.

Exploring the prevalence of Human Papillomavirus (HPV) genotypes in PAP smear samples of women in northern region of United Arab Emirates (UAE): HPV Direct Flow CHIP system-based pilot study

Objective The aim of this study was to explore the prevalence of low and high-risk HPV genotypes in PAP smear samples of women in northern region of the UAE using HPV direct flow CHIP method. Methods A cross-sectional retrospective study was conducted between September 2021 to April 2022. A total of 104 liquid-based cervical cytology samples were obtained from women aged 20–59 years attending the Gynaecology out-patient department of Thumbay University Hospital and other hospitals of Northern Emirates of UAE, processed for the routine cytological examination to identify and differentiate morphological changes of the PAP smear samples. HPV genotyping was performed using HPV direct flow CHIP method. Results In total, 112 HPV genotypes were detected in 63 women (60.57%) included 18 abnormal cytological and 45 normal epithelial samples. 63 LR and 49 HR HPV genotypes were identified in all the 63 positive samples. Highest rate of infection with multiple LR and HR HPV genotypes were detected in women aged 40–49 years (25.9%) and 20–29 years (23.5%). Infection by HPV6 (13.46%), HPV11 (9.61%), HPV16 (9.61%), HPV62/81 (7.69%) and HPV45 (7.69%) were the most common genotypes. A moderate increase than expected incidence of HPV45 and 62/81 (7.69%) were detected. Co-infection with multiple low and high-risk genotypes is present in 20.2% cases; in that, HPV6 (15.9%) was the most common followed by HPV62/81 (12.7%) and HPV16 (11.11%). The prevalence of HPV18 was found to be 1.6%. Conclusion The genotypes 6, 45, 16, 11, 67, 62/81 were the most common HPV infections in the women between the age group of 21 and 59-years-old. A moderate increase of HPV45, 62/81 and much less prevalence of HPV18 were detected in the study population. 43.27% of the normal epithelia were positive to different low and high-risk HPV genotypes. This finding highlights the importance of molecular genotyping of HPV to emphasize the cervical screening triage.

Factors affecting cervical cancer screening among Yemeni immigrant women in Klang Valley, Malaysia: A cross sectional study

Introduction Cervical cancer is a significant public health problem for women worldwide. It is the fourth most frequent cancer in women globally. While early detection of cancerous lesions through screening tests leads to a better prognosis and a better chance of being cured, the number of people who go for screening is still low, especially for groups that are marginalized, like immigrant women. Objective The purpose of this study was to identify cervical cancer screening practices and factors influencing screening status among Yemeni immigrant women living in the Klang Valley, Malaysia. Method A cross-sectional study among 355 randomly selected respondents between the ages of 20 and 65 was conducted through an online survey. A questionnaire was sent directly to the participants via WhatsApp. The analysis was conducted using SPSS 25 with a significance level of 0.05. It included descriptive analysis, chi-square and multiple logistic regression. Results The response rate was 59%, with the majority of the respondents being married and between the ages of 35 and 49. Screening was reported at 23.1% in the previous three years. The final model revealed that age group 50–65 years (AOR = 5.39, 95% CI: 1.53–18.93), insurance status (AOR 2.22, 95% CI = 1.15–4.3), knowledge (AOR = 6.67, 95% CI = 3.45–12.9), access to health care facilities (AOR = 4.64, 95% CI = 1.29–16.65), and perceived barriers (AOR = 2.5, 95% CI = 1.3–4.83) were significant predictors of cervical screening uptake among Yemeni immigrant women in Malaysia (p&lt;0.05). Conclusion According to the results, cervical cancer screening was found to be low among Yemeni immigrant women. The predictors were age group 50–65 years, insurance status, knowledge, access to health care facilities and perceived barriers. Efforts to enhance immigrant women’s participation in cervical cancer screening must tackle barriers to access to healthcare services as well as expand cervical cancer screening education programs.

MLK4 as an immune marker and its correlation with immune infiltration in Cervical squamous cell carcinoma and endocervical adenocarcinoma(CESC)

Mixed pedigree kinase 4 (MLK4) is a member of the serine/threonine kinases mixed pedigree kinase (MLKs) family. Few reports on immune-related targets in Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and the role of MLK4 in cervical cancer remains to be studied. The expression of MLK4 in CESC was analyzed by TCGA database containing 306 CESC tissues and 3 peritumoral tissue samples, and the effect of MLK4 on immune invasion was evaluated using the Deseq2 package(Benjamini-Hochberg corrected p-value &lt; 0.05 and log2 fold change ≥|2|). Tissue microarray was used to verify the expression of MLK4 in CESC patients, and it was found that MLK4 was significantly overexpressed in CESC, and significantly correlated with WHO grade. Multiple analysis algorithms revealed that the high expression of MLK4 was negatively correlated with immune cell infiltration in CESC. Analysis showed that MLK4 expression was negatively correlated with the infiltration of various immune cells including CD8+T cells, and MLK4 mRNA expression was positively correlated with immune checkpoints PD-L1,CTLA4, LAG3, and negatively correlated with immune promotion genes CD86 and CD80. Furthermore, vitro assays were performed to investigate the biological characteristics of MLK4 in C33A cells. The EDU and transwell assays demonstrated that the decrease in MLK4 expression in C33A cells resulted in a decrease in cell proliferation and invasion. The silencing of MLK4 resulted in a significant increase in the expression of inflammatory cytokines IL-1β(p&lt;0.05), TNF-α(p&lt;0.01), and IL-6 (p&lt;0.05). The results of cell assays indicate that knocking down MLK4 would inhibit the expression of established biochemical markers CEA, AFP and HCG. Hence, it is plausible that MLK4 could potentially exert a significant influence on the development and progression of Cervical cancer.

The lived experiences and caring needs of women diagnosed with cervical cancer: A qualitative study in Dar es Salaam, Tanzania

BackgroundCervical cancer continues to be a major global public health concern affecting the lives of many women and resulting in financial burdens. In 2020, cervical cancer was the seventh most commonly diagnosed cancer among all cancers worldwide and Tanzania was ranked fourth among the countries with the highest incidence rates (59.1 new cases per 100,000 women) of cervical cancer. The lived experience and caring needs of patients and their families provide insights into the psychosocial aspects of healthcare among the affected population. However, there is inadequate information concerning the lived experiences of cervical cancer patients in Tanzania and Sub-Saharan Africa in general. This study aimed to explore the lived experiences and caring needs of cervical cancer patients at Ocean Road Cancer Institute (ORCI) in Dar es Salaam, Tanzania.MethodsA qualitative descriptive study was carried out among cervical cancer patients at ORCI in Dar es Salaam, Tanzania. Using a purposeful sampling technique, 12 cervical cancer patients were interviewed with the principles of saturation guiding sample size determination. A semi-structured face-to-face interview guide was employed to collect the information. A conventional content analysis approach was used to analyze data after translation with the aid of NVivo 12.0 computer software.ResultsFive themes emerged after data analysis: knowledge and attitude about cervical cancer, sufferings from a disease process, socio-economic disruptions, psychological problems, and sexual and reproductive concerns.ConclusionThe findings of this study provide insights into the life experiences and caring needs of cervical cancer patients and call for response from healthcare stakeholders to develop and implement comprehensive and culturally consonant approaches in providing care to the affected population. More qualitative studies are required to ascertain the lived experiences of advanced cervical cancer patients and those of long-term cervical cancer survivors.

Genotype profiles of high-risk human papillomavirus in women of reproductive age: A community-based study

Purpose This research is a preliminary study to observe the high-risk HPV infection profile among asymptomatic women, as a basis for developing Indonesian-specific reagents and implementing a national vaccination program. Methods The research subjects were female employees/families of BUMN (state-owned enterprises) who underwent annual routine medical check-up. The research sample was a cervical swab which was examined using the Cobas® 6800 platform for HPV identification and INNO Lipa (Fujirebio) kit for identification of the genotype. Results Out of 858 cervical swab samples collected in this study, 31 samples were excluded as they had invalid results from the initial examination, so the remaining 827 samples continued this study protocol. Of those samples, 69 (8%) samples gave positive results, giving an overall HPV prevalence of 8%. Among HPV-positive samples, HPV 52 was the most common genotype (N = 15, 21.7%) found as both single-infection and multiple infections. The median age of subjects was 38 years. There were nine samples (13%) with multiple infections of two or more genotypes and seven samples (10.1%) with no specific genotype identified. Conclusion HPV prevalence was 8%, with HPV 52 being the most common high-risk type, making it a necessity to develop a diagnostic kit and vaccine for national vaccination program that is specific for Indonesian population which includes this genotype.

Trichomonas vaginalis infection and risk of cervical neoplasia: A systematic review and meta-analysis

Objectives The evidence in the literature regarding the relationship between Trichomonas vaginalis (TV) infection and cervical neoplasia is conflicting. The main aim of this study was to evaluate the magnitude of the risk of cervical neoplasia associated with TV infection. Methods A meta-analysis of observational studies, which provided raw data on the association of TV infection with cervical neoplasia, was performed. For this aim, we searched scientific databases (PubMed/Medline, Scopus, the Web of Sciences, and Embase) from inception to March 15, 2023. A random-effects model was applied by Stata 17.0 to calculate the pooled and adjusted odds ratios (ORs) with 95% confidence intervals (CI), including subgroup, sensitivity, and cumulative analyses to explore sources of heterogeneity. Results Of the 2584 records initially identified, 35 eligible studies contributed data for 67,856 women with cervical neoplasia, and 933,697 healthy controls from 14 countries were included. The pooled (2.15; 1.61–2.87; I2 = 87.7%) and adjusted (2.17; 1.82–2.60; I2 = 31.27%) ORs indicated a significant positive association between TV infection and the development of cervical neoplasia. There was no significant change in pooled and adjusted ORs by applying sensitivity and cumulative analyses, indicating the robustness of our findings. The pooled OR was significant in most sub-group analyses. There was no publication bias in the included studies. Conclusion Our findings indicated that women with a TV infection are at significantly greater risk of cervical neoplasia. Future research, particularly longitudinal and experimental studies, should be done to better understand the various aspects of this association.

Advanced gynecological cancer: Quality of life one year after diagnosis

Objective Gynaecological cancer treatment impacts women’s physical and psychological health. Our objective was to examine quality of life (QoL) in women with advanced gynaecological cancer at diagnosis and one year later, and to identify sociodemographic and clinical characteristics associated with QoL. Methods Women with endometrial, ovarian or cervical cancer treated in Uppsala, Sweden 2012–2019 were included. FIGO stage ≥II was considered advanced gynaecological cancer, whereas women in FIGO stage I were used as a control group. QoL was assessed with SF-36. We obtained information on sociodemographic and clinical characteristics from medical records and health questionnaires. Differences in QoL domains were tested with t-tests, a mixed model ANOVA and multiple linear regression analyses. Results The study population (n = 372) included 150 (40.3%) women with advanced gynaecological cancer. At diagnosis, women with advanced cancer reported lower physical (71.6 vs 81.8 (mean) p&lt;0.05) and role functioning/physical scores (62.6 vs 77.2 (mean) p&lt;0.05) than women in FIGO stage I. One year later, women with advanced cancer reported higher scores in the mental health domain (78.3 vs 73.2 (mean) p&lt;0.05) than women in FIGO stage I. However, no difference was found in the QoL scores of women with advanced disease one year after diagnoses when stratified by diagnosis. Women with a history of psychiatric illness and higher BMI reported poorer physical and mental QoL at follow-up, while advanced stage, level of education and smoking were not associated with QoL. Conclusion Women with advanced gynaecological cancer have equally good QoL one year after diagnosis as women with limited disease. Women with previous psychiatric illness and high BMI, are at risk of impaired physical and mental health.

Equivalence of laboratory-developed test and PD-L1 IHC 22C3 pharmDx across all combined positive score indications

We conducted an analysis across multiple PD-L1 combined positive score (CPS) indications to establish concordance of a 22C3 antibody–based laboratory-developed test (LDT) on the Ventana BenchMark XT or BenchMark ULTRA platform and the regulatory-approved PD-L1 IHC 22C3 pharmDx in cervical cancer (CC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC), triple-negative breast cancer (TNBC), and urothelial carcinoma (UC). Tumor specimens from each tumor type were stained with 22C3 antibody and scored using the 22C3 antibody–based LDT, and scores were compared with those using PD-L1 IHC 22C3 pharmDx. PD-L1 status was measured by the pathologist using CPS as a continuous score and using clinically relevant cutoffs (CC, ≥1 and ≥10; HNSCC, ≥1 and ≥20; ESCC, TNBC, and UC, ≥10). The agreement between the BenchMark platforms and PD-L1 IHC 22C3 pharmDx was assessed by intraclass correlation coefficient (ICC) and a contingency table for clinical interpretation. A total of 522 samples were evaluated for the pan-tumor analysis (CC, n = 77; ESCC, n = 80; HNSCC, n = 126; TNBC, n = 118, UC, n = 121). Most clinical interpretations of PD-L1 status were concordant between the BenchMark XT and PD-L1 IHC 22C3 pharmDx for all five tumor types with regard to negative percentage agreement (NPA; 83–97%), positive percentage agreement (PPA; 86–100%), and overall percentage agreement (OPA; 90–97%); the ICC by tumor type was high (≥0.88). Importantly, the pan-tumor ICC was 0.95 (95% CI 0.94–0.96). Thirty additional TNBC samples were evaluated using the BenchMark ULTRA and PD-L1 IHC 22C3 pharmDx; the NPA, PPA, and OPA were 100%. The 22C3 antibody–based LDT on Ventana BenchMark XT and BenchMark ULTRA platforms demonstrated high concordance with the regulatory-approved PD-L1 IHC 22C3 pharmDx across multiple tumor types. These findings suggest the comparability of PD-L1 IHC 22C3 pharmDx with an LDT based on the 22C3 antibody.

Acceptability of self-sampling human papillomavirus test for cervical cancer screening in Japan: A questionnaire survey in the ACCESS trial

PurposeIn terms of medical policy for cervical cancer prevention, Japan lags far behind other industrialized countries. We initiated a randomized controlled trial to evaluate the self-sampling human papillomavirus (HPV) test as a tool to raise screening uptake and detection of pre-cancer. This study was conducted to explore the acceptability and preference of self-sampling using a subset of the data from this trial.MethodsA pre-invitation letter was sent to eligible women, aged 30−59 years who had not undergone cervical cancer screening for three or more years. After excluding those who declined to participate in this trial, the remaining women were assigned to the self-sampling and control groups. A second invitation letter was sent to the former group, and those wanting to undergo the self-sampling test ordered the kit. A self-sampling HPV kit, consent form, and a self-administered questionnaire were sent to participants who ordered the test.ResultsOf the 7,340 participants in the self-sampling group, 1,196 (16.3%) administered the test, and 1,192 (99.7%) answered the questionnaire. Acceptability of the test was favorable; 75.3−81.3% of participants agreed with positive impressions (easy, convenient, and clarity of instruction), and 65.1−77.8% disagreed with negative impressions (painful, uncomfortable, and embarrassing). However, only 21.2% were confident in their sampling procedure. Willingness to undergo screening with a self-collected sample was significantly higher than that with a doctor-collected sample (89.3% vs. 49.1%; p&lt;0.001). Willingness to undergo screening with a doctor-collected sample was inversely associated with age and duration without screening (both p&lt;0.001), but that with a self-collected sample was not associated.ConclusionsAmong women who used the self-sampling HPV test, high acceptability was confirmed, while concerns about self-sampling procedures remained. Screening with a self-collected sample was preferred over a doctor-collected sample and the former might alleviate disparities in screening rates.

Interventions to increase cervical screening uptake among immigrant women: A systematic review and meta-analysis

Numerous intervention studies have attempted to increase cervical screening uptake among immigrant women, nonetheless their screening participation remains low. This systematic review and meta-analysis aimed to summarise the evidence on interventions to improve cervical screening among immigrant women globally and identify their effectiveness. Databases PubMed, EMBASE, Scopus, PsycINFO, ERIC, CINAHL and CENTRAL were systematically searched from inception to October 12, 2021, for intervention studies, including randomised and clinical controlled trials (RCT, CCT) and one and two group pre-post studies. Peer-reviewed studies involving immigrant and refugee women, in community and clinical settings, were eligible. Comparator interventions were usual or minimal care or attention control. Data extraction, quality appraisal and risk of bias were assessed by two authors independently using COVIDENCE software. Narrative synthesis of findings was carried out, with the main outcome measure defined as the cervical screening uptake rate difference pre- and post-intervention followed by random effects meta-analysis of trials and two group pre-post studies, using Comprehensive Meta-Analysis software, to calculate pooled rate ratios and adjustment for publication bias, where found. The protocol followed PRISMA guidelines and was registered prospectively with PROSPERO (CRD42020192341). 1,900 studies were identified, of which 42 (21 RCTS, 4 CCTs, and 16 pre-post studies) with 44,224 participants, were included in the systematic review, and 28 with 35,495 participants in the meta-analysis. Overall, the uptake difference rate for interventions ranged from -6.7 to 96%. Meta-analysis demonstrated a pooled rate ratio of 1.15 (95% CI 1.03–1.29), with high heterogeneity. Culturally sensitive, multicomponent interventions, using different modes of information delivery and self-sampling modality were most promising. Interventions led to at least 15% increase in cervical screening participation among immigrant women. Interventions designed to overcome logistical barriers and use multiple channels to communicate culturally appropriate health promotion messages are most effective at achieving cervical screening uptake among immigrant women.

Knowledge of Thai women in cervical cancer etiology and screening

Knowledge about cervical cancer screening and Human papilloma virus (HPV) influence on their awareness to the cervical cancer screening program. Most previous studies found inadequate knowledge and attitude among healthy women affect the low rate of screening. This study aimed to assess knowledge of cervical cancer screening and HPV in women who had abnormal cervical cancer screening in Bangkok. Thai women, aged ≥ 18 years old, who had abnormal cervical cancer screening and scheduled to colposcopy clinics of 10 participating hospitals were invited to participate in this cross-sectional study. The participants were asked to complete a self-answer questionnaire (Thai language). The questionnaire composed of 3 parts: (I) demographic data, (II) knowledge about cervical cancer screening and (III) knowledge about HPV. Among 499 women who answered the questionnaires, 2 had missing demographic data. The mean age of the participants was 39.28 ± 11.36 years. 70% of them had experience of cervical cancer screening, with 22.7% had previous abnormal cytologic results. Out of 14 questions, the mean score of knowledge about cervical cancer screening was 10.04 ± 2.37. Only 26.9% had good knowledge about cervical cancer screening. Nearly 96% of woman did not know that screening should be done. After excluding 110 women who had never known about HPV, 25.2% had good knowledge about HPV. From multivariable analysis, only younger age (≤ 40 years) was associated with good knowledge of cervical cancer screening and HPV. In the conclusion, only 26.9% of women in this study had good knowledge regarding cervical cancer screening. Likewise, 20.1% of women who had ever heard about HPV has good knowledge about HPV. Providing information about cervical cancer screening and HPV should improve the women’s knowledge and better adherence to the screening procedure.

Cervical cancer screening utilization and associated factors among female health workers in public health facilities of Hossana town, southern Ethiopia: A mixed method approach

Backgrounds Worldwide, a substantial proportion of women have low cervical cancer screening services utilization. There is a paucity of evidence in utilization of cervical cancer screening services among female health workers and inconsistent findings in Ethiopia. This study aimed to assess the utilization of cervical cancer screening services and associated factors among female health workers in public health facilities of Hossana town, Southern Ethiopia. Methods Facility-based cross-sectional study design complemented with the qualitative inquiry was conducted among randomly selected 241 study participants in Hossana town from June 1 to July 1, 2021. Logistic regression models were used to determine the association between dependent and independent variables with the assumption of a variable with a p-value &lt; 0.05 was considered statistically significant. Qualitative data were transcribed verbatim then translated to English and analyzed using open code version 4.03. Results Out of the total study participants, 19.6% was screened for cervical cancer. Having a diploma level of education (AOR = 0.48;95%CI:0.24,0.98), having three or more children (AOR = 3.65;95%CI:1.44,9.21), having multiple sexual partners(AOR = 3.89;95%CI: 1.38,11.01), and knowledge of cervical cancer screening (AOR = 2.66;95% CI:1.19,5.95) were statistically significantly associated with cervical cancer screening utilization. In-depth interviews suggested additional barriers for low screening utilization including lack of health educational materials, limitation of service to a specific area, service interruption, provider incompetency, and miss-trust and lack of attention by a trained provider. Conclusion Utilization of cervical cancer screening service among female health workers is low. Having a diploma level of education, having three or more children, a history of multiple sexual partners, and knowledge about cervical cancer were predictors of cervical cancer screening utilization. Contextualized health talks and promotion through training with a special focus on low level of knowledge, had lower educational level, and the availability of cervical cancer screening services are critical.

Association between cancer stigma and cervical cancer screening uptake among women of Dhulikhel and Banepa, Nepal

Background Cervical cancer ranks as the most common cancer among Nepalese women with a high incidence and mortality. Despite evidence that effective screening programs reduce disease burden, screening services are under-utilized. Cancer stigma can be a major barrier to cervical cancer screening uptake among Nepalese women. Objectives This study assessed the association between cancer stigma and cervical cancer screening uptake among women residing in semi-urban areas of Kavrepalanchok district (Dhulikhel and Banepa), Nepal. Methods We conducted a cross-sectional study among 426 women aged 30–60 years using telephone interview method from 15th June to 15th October 2021. A validated Cancer Stigma Scale (CASS) was used to measure cancer stigma and categorized women as presence of cancer stigma if the mean total score was greater than three. We obtained information on cervical cancer screening uptake through self-reported responses. Univariable and multivariable logistic regression were performed to assess the association between cancer stigma and cervical cancer screening uptake. We adjusted socio-demographic: age, ethnicity, occupation, religion and education, and reproductive health variables: parity, family planning user, age of menarche and age at first sexual intercourse during multivariable logistic regression. Results Twenty-three percent of women had cancer stigma and 27 percent reported that they had ever been screened for cervical cancer. The odds of being screened was 0.23 times lower among women who had stigma compared to those who had no stigma (95% CI: 0.11–0.49) after adjusting for confounders: age, ethnicity, occupation, religion, education, parity, contraceptive use, age of menarche and age at first sexual intercourse. Conclusion Women residing in semi-urban areas of Nepal and had cancer stigma were less likely to have been screened for cervical cancer. De-stigmatizing interventions may alleviate cancer stigma and contribute to higher uptake of cervical cancer screening.

Using machine learning for predicting cervical cancer from Swedish electronic health records by mining hierarchical representations

Electronic health records (EHRs) contain rich documentation regarding disease symptoms and progression, but EHR data is challenging to use for diagnosis prediction due to its high dimensionality, relative scarcity, and substantial level of noise. We investigated how to best represent EHR data for predicting cervical cancer, a serious disease where early detection is beneficial for the outcome of treatment. A case group of 1321 patients with cervical cancer were matched to ten times as many controls, and for both groups several types of events were extracted from their EHRs. These events included clinical codes, lab results, and contents of free text notes retrieved using a LSTM neural network. Clinical events are described with great variation in EHR texts, leading to a very large feature space. Therefore, an event hierarchy inferred from the textual events was created to represent the clinical texts. Overall, the events extracted from free text notes contributed the most to the final prediction, and the hierarchy of textual events further improved performance. Four classifiers were evaluated for predicting a future cancer diagnosis where Random Forest achieved the best results with an AUC of 0.70 from a year before diagnosis up to 0.97 one day before diagnosis. We conclude that our approach is sound and had excellent discrimination at diagnosis, but only modest discrimination capacity before this point. Since our study objective was earlier disease prediction than such, we propose further work should consider extending patient histories through e.g. the integration of primary health records preceding referral to hospital.

The small heat shock protein αB-Crystallin protects versus withaferin A-induced apoptosis and confers a more metastatic phenotype in cisplatin-resistant ovarian cancer cells

Since a majority of ovarian tumors recur in a drug-resistant form leaving patients few treatment options, the goal of this study was to explore phenotypic and molecular characteristics of a cisplatin-resistant ovarian cancer cell line (OVCAR8R) as compared to its cisplatin-sensitive syngeneic counterpart (OVCAR8) and to explore the effectiveness of a novel chemotherapeutic, Withaferin A (WA). In addition to unique morphological characteristics, the small heat shock proteins (Hsps) αB-Crystallin (HspB5) and Hsp27 are constitutively expressed along with increased expression of vimentin in OVCAR8R cells, while OVCAR8 cells do not endogenously express these Hsps, supporting that Hsp overexpression may confer resistance to chemotherapy and promote more aggressive tumor types. WA increases apoptosis in a dose-dependent manner in OVCAR8 cells, while OVCAR8R cells remain more viable at comparable doses of WA coincident with the upregulation of αB-Crystallin. To determine the significance of αB-Crystallin in conferring a more aggressive phenotype, αB-Crystallin was silenced by CRISPR-Cas9 in OVCAR8R cells. The morphology of the OVCAR8R clones in which αB-Crystallin was silenced reverted to the morphology of the original cisplatin-sensitive OVCAR8 cells. Further, cisplatin-resistant OVCAR8R cells constitutively express higher levels of vimentin and migrate more readily than cisplatin-sensitive OVCAR8 and OVCAR8R cells in which αB-Crystallin was silenced. Transient overexpression of wildtype αB-Crystallin, but not a chaperone-defective-mutant, alters the morphology of these cells to closely resemble the cisplatin-resistant OVCAR8R cells and protects versus WA-induced apoptosis. Together, this research supports the potential effectiveness of WA as a therapy for ovarian cancer cells that have not yet acquired resistance to platinum-based therapies, and importantly, underscores that αB-Crystallin contributes to a more aggressive cellular phenotype and as such, may be a promising molecular target for a better clinical outcome.

Immune environment and antigen specificity of the T cell receptor repertoire of malignant ascites in ovarian cancer

We evaluated the association of disease outcome with T cell immune-related characteristics and T cell receptor (TCR) repertoire in malignant ascites from patients with high-grade epithelial ovarian cancer. Ascitic fluid samples were collected from 47 high-grade epithelial ovarian cancer patients and analyzed using flow cytometry and TCR sequencing to characterize the complementarity determining region 3 TCR β-chain. TCR functions were analyzed using the McPAS-TCR and VDJ databases. TCR clustering was implemented using Grouping of Lymphocyte Interactions by Paratope Hotspots software. Patients with poor prognosis had ascites characterized by an increased ratio of CD8+ T cells to regulatory T cells, which correlated with an increased productive frequency of the top 100 clones and decreased productive entropy. TCRs enriched in patients with an excellent or good prognosis were more likely to recognize cancer antigens and contained more TCR reads predicted to recognize epithelial ovarian cancer antigens. In addition, a TCR motif that is predicted to bind theTP53neoantigen was identified, and this motif was enriched in patients with an excellent or good prognosis. Ascitic fluid in high-grade epithelial ovarian cancer patients with an excellent or good prognosis is enriched with TCRs that may recognize ovarian cancer-specific neoantigens, including mutatedTP53andTEAD1. These results suggest that an effective antigen-specific immune response in ascites is vital for a good outcome in high-grade epithelial ovarian cancer.

Carboplatin sensitivity in epithelial ovarian cancer cell lines: The impact of model systems

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy in North America, underscoring the need for the development of new therapeutic strategies for the management of this disease. Although many drugs are pre-clinically tested every year, only a few are selected to be evaluated in clinical trials, and only a small number of these are successfully incorporated into standard care. Inaccuracies with the initial in vitro drug testing may be responsible for some of these failures. Drug testing is often performed using 2D monolayer cultures or 3D spheroid models. Here, we investigate the impact that these different in vitro models have on the carboplatin response of four EOC cell lines, and in particular how different 3D models (polydimethylsiloxane-based microfluidic chips and ultra low attachment plates) influence drug sensitivity within the same cell line. Our results show that carboplatin responses were observed in both the 3D spheroid models tested using apoptosis/cell death markers by flow cytometry. Contrary to previously reported observations, these were not associated with a significant decrease in spheroid size. For the majority of the EOC cell lines (3 out of 4) a similar carboplatin response was observed when comparing both spheroid methods. Interestingly, two cell lines classified as resistant to carboplatin in 2D cultures became sensitive in the 3D models, and one sensitive cell line in 2D culture showed resistance in 3D spheroids. Our results highlight the challenges of choosing the appropriate pre-clinical models for drug testing.

The role of the MAD2-TLR4-MyD88 axis in paclitaxel resistance in ovarian cancer

Despite the use of front-line anticancer drugs such as paclitaxel for ovarian cancer treatment, mortality rates have remained almost unchanged for the past three decades and the majority of patients will develop recurrent chemoresistant disease which remains largely untreatable. Overcoming chemoresistance or preventing its onset in the first instance remains one of the major challenges for ovarian cancer research. In this study, we demonstrate a key link between senescence and inflammation and how this complex network involving the biomarkers MAD2, TLR4 and MyD88 drives paclitaxel resistance in ovarian cancer. This was investigated using siRNA knockdown of MAD2, TLR4 and MyD88 in two ovarian cancer cell lines, A2780 and SKOV-3 cells and overexpression of MyD88 in A2780 cells. Interestingly, siRNA knockdown of MAD2 led to a significant increase in TLR4 gene expression, this was coupled with the development of a highly paclitaxel-resistant cell phenotype. Additionally, siRNA knockdown of MAD2 or TLR4 in the serous ovarian cell model OVCAR-3 resulted in a significant increase in TLR4 or MAD2 expression respectively. Microarray analysis of SKOV-3 cells following knockdown of TLR4 or MAD2 highlighted a number of significantly altered biological processes including EMT, complement, coagulation, proliferation and survival, ECM remodelling, olfactory receptor signalling, ErbB signalling, DNA packaging, Insulin-like growth factor signalling, ion transport and alteration of components of the cytoskeleton. Cross comparison of the microarray data sets identified 7 overlapping genes including MMP13, ACTBL2, AMTN, PLXDC2, LYZL1, CCBE1 and CKS2. These results demonstrate an important link between these biomarkers, which to our knowledge has never before been shown in ovarian cancer. In the future, we hope that triaging patients into alterative treatment groups based on the expression of these three biomarkers or therapeutic targeting of the mechanisms they are involved in will lead to improvements in patient outcome and prevent the development of chemoresistance.

High expression of Tie-2 predicts poor prognosis in primary high grade serous ovarian cancer

Background Antiangiogenic therapy, although part of standard treatment in ovarian cancer, has variable efficacy. Furthermore, little is known about the prognostic biomarkers and factors influencing angiogenesis in cancer tissue. We evaluated the expression of angiopoietin-2 and two endothelial tyrosine kinase receptors, Tie-1 and Tie-2, and assessed their value in the prediction of survival in patients with malignant epithelial ovarian cancer. We also compared the expression of these factors between primary high grade serous tumors and their distant metastasis. Materials and methods We evaluated 86 women with primary epithelial ovarian cancer. Matched distal omental metastasis were investigated in 18.6% cases (N = 16). The expression levels of angiogenic factors were evaluated by immunohistochemistry in 306 specimens and by qRT-PCR in 111 samples. Results A high epithelial expression level of Tie-2 is a significant prognostic factor in primary high grade serous ovarian cancer. It predicted significantly shorter overall survival both in univariate (p&lt;0.001) and multivariate survival analyses (p = 0.022). Low angiopoietin-2 expression levels in primary ovarian tumors were significantly associated with shorter overall survival (p = 0.015) in the univariate survival analysis. A low expression of angiopoietin-2 was also significantly related to high grade tumors, size of residual tumor after primary surgery and the recurrence of cancer (p = 0.008; p = 0.012; p = 0.018) in the whole study population. The expression of angiopoietin-2 and Tie-2 was stronger in distal omental metastasis than in primary high grade serous tumors in matched-pair analysis (p = 0.001; p = 0.002). Conclusions The angiogenic factor, angiopoietin-2, and its receptor Tie-2 seem to be significant prognostic factors in primary epithelial ovarian cancer. Their expression levels are also increased in metastatic lesions in comparison with primary tumors.

A multiplex biomarker assay improves the diagnostic performance of HE4 and CA125 in ovarian tumor patients

Survival in epithelial ovarian cancer (EOC) remains poor. Most patients are diagnosed in late stages. Early diagnosis increases the chance of survival. We used the proximity extension assay from Olink Proteomics to search for new protein biomarkers with the potential to improve the diagnostic performance of CA125 and HE4 in patients with ovarian tumors. Plasma samples were obtained from 180 women with ovarian tumors; 30 cases of benign tumor, 28 cases with borderline tumors, 25 early EOC cases (FIGO stage I) and 97 advanced EOC cases (FIGO stages II-IV). Proteins were measured using the Olink® Oncology II and Inflammation panels. For statistical analyses, patients were categorized into benign tumors versus cancer and benign tumors versus borderline + cancer, respectively. We analyzed 177 biomarkers. Thirty-four proteins had ROC AUC > 0.7 for discrimination between benign tumors and cancer. Fifteen proteins had ROC AUC > 0.7 for discrimination between benign tumors and borderline tumors + cancer. HE4 ranked highest for both comparisons. A reference model with HE4, CA125 and age (AUC 0.838 for benign tumors vs. cancer and AUC 0.770 for benign tumors vs. borderline tumors + cancer) was compared to the reference model with the addition of each of the remaining proteins with AUC > 0.7. ITGAV was the only individual biomarker found to improve diagnostic performance of the reference model, to AUC 0.874 for benign tumors vs. cancer and AUC 0.818 for benign tumors vs. borderline tumors + cancer (p < 0.05). Cross-validation and LASSO regression was combined to select multiple biomarker combinations. The best performing model for discrimination between benign tumors and borderline tumors + cancer was a 6-biomarker combination (HE4, CA125, ITGAV, CXCL1, CEACAM1, IL-10RB) and age (AUC 0.868, sensitivity 0.86 and specificity 0.82, p = 0.016 for comparison with the reference model). HE4 was the best performing individual biomarker for discrimination between benign ovarian tumors and EOC including borderline tumors. The addition of other carcinogenesis-related biomarkers in a multiplex biomarker panel can improve the diagnostic performance of the established biomarkers HE4 and CA125.

Effect of delayed palliative chemotherapy on survival of patients with recurrent ovarian cancer

For patients with recurrent ovarian cancer, the goals of chemotherapy include palliation of disease-related symptoms with minimum treatment-related side effects. However, there is currently a paucity of data regarding the initiation of palliative chemotherapy. This study aimed to compare the differences in survival rates and toxicities between patients with recurrent ovarian cancer who started palliative chemotherapy immediately versus those who received delayed chemotherapy. Through a retrospective chart review, patients who received more than three lines of chemotherapy were included. Based on the timing of third-line chemotherapy initiation, the patients were divided into two groups: delayed (DTG) and immediate (ITG) treatment groups. The chi-square test or Fisher's exact tests, and t-test or Mann-Whitney U test were used for comparing variables, as appropriate. The Kaplan-Meier method was used for survival analysis. P-value of <0.05 was considered significant. Although there was no statistically significant difference, the total number of regimens and cycles was lower in the DTG than in the ITG. No differences in toxicities and survival rates were observed between the two groups. Overall, survival and toxicity did not differ significantly between the two groups. In a palliative care setting, our findings suggest that delaying the treatment had no adverse effect on survival. Despite the lack of evidence of a survival benefit with aggressive treatment, patients chose to continue chemotherapy. Because recurrent ovarian cancer is a complex condition, patients require sufficient explanation and time to fully understand the costs and benefits related to aggressive chemotherapy.

Determinants of cervical cancer screening intention among reproductive age women in Ethiopia: A systematic review and meta-analysis

Introduction Cervical cancer is a leading cause of cancer-related mortality in Ethiopia, despite being preventable. Screening programs remain underutilized despite multiple initiatives. This systematic review and meta-analysis aimed to assess the pooled prevalence of intention to undergo cervical cancer screening and its associated factors among Ethiopian women, addressing a significant gap in national data. Methods and materials This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases such as PubMed, EMBASE, CINAHL, Web of Science, Cochrane Library, HINARI, Google Scholar, and African Journals online were searched using specific keywords and Medical Subject Headings (MeSH). Studies were assessed using a standardized appraisal format adapted from the Newcastle-Ottawa Scale (NOS). Data extraction and analysis were performed using Microsoft Excel-10 and STATA 17 software, respectively. Heterogeneity was evaluated with the I2 statistic and publication bias was examined using Egger’s test. Meta-analysis employed a random-effects model. Result Out of the 750 articles retrieved, nine were included in this systematic review and meta-analysis. The pooled prevalence of intention to screen for cervical cancer in Ethiopia was 33% (95% CI: 9%-56%). Factors significantly associated with intention to undergo cervical cancer screening included favorable attitude (POR = 2.15, 95% CI: 1.29, 4.26), good knowledge about cervical cancer screening (POR: 3.49; 95% CI: 2.04, 6.93), and direct subjective norm (POR: 1.54; 95% CI: 1.32, 3.54). Conclusion Based on the findings of this meta-analysis, it was observed that women’s intention toward cervical cancer screening was low. Determinants identified included favorable attitude, direct subjective norm, and good knowledge of cervical cancer screening. To enhance women’s intention for cervical cancer screening, strategies, and activities should be developed to positively influence perceptions among women and those who influence their decisions. Additionally, efforts to enhance public awareness about cervical cancer and its prevention are crucial.

Kinome capture sequencing of high-grade serous ovarian carcinoma reveals novel mutations in the JAK3 gene

High-grade serous ovarian carcinoma (HGSOC) remains the deadliest form of epithelial ovarian cancer and despite major efforts little improvement in overall survival has been achieved. Identification of recurring "driver" genetic lesions has the potential to enable design of novel therapies for cancer. Here, we report on a study to find such new therapeutic targets for HGSOC using exome-capture sequencing approach targeting all kinase genes in 127 patient samples. Consistent with previous reports, the most frequently mutated gene was TP53 (97% mutation frequency) followed by BRCA1 (10% mutation frequency). The average mutation frequency of the kinase genes mutated from our panel was 1.5%. Intriguingly, after BRCA1, JAK3 was the most frequently mutated gene (4% mutation frequency). We tested the transforming properties of JAK3 mutants using the Ba/F3 cell-based in vitro functional assay and identified a novel gain-of-function mutation in the kinase domain of JAK3 (p.T1022I). Importantly, p.T1022I JAK3 mutants displayed higher sensitivity to the JAK3-selective inhibitor Tofacitinib compared to controls. For independent validation, we re-sequenced the entire JAK3 coding sequence using tagged amplicon sequencing (TAm-Seq) in 463 HGSOCs resulting in an overall somatic mutation frequency of 1%. TAm-Seq screening of CDK12 in the same population revealed a 7% mutation frequency. Our data confirms that the frequency of mutations in kinase genes in HGSOC is low and provides accurate estimates for the frequency of JAK3 and CDK12 mutations in a large well characterized cohort. Although p.T1022I JAK3 mutations are rare, our functional validation shows that if detected they should be considered as potentially actionable for therapy. The observation of CDK12 mutations in 7% of HGSOC cases provides a strong rationale for routine somatic testing, although more functional and clinical characterization is required to understand which nonsynonymous mutations alterations are associated with homologous recombination deficiency.

Clinicopathological and prognostic significance of caveolin-1 and ATG4C expression in the epithelial ovarian cancer

Altered expression of caveolin-1 (CAV1) and autophagy marker ATG4C is observed in various types of human cancers. However, the clinical significance of CAV1 and ATG4C expression in epithelial ovarian cancer (EOC) remains largely unknown. The present study aims to explore the clinicopathological value and prognostic significance of CAV1 and ATG4C expression in EOC. The expression pattern and prognostic value of CAV1 and ATG4C mRNA in EOC were analyzed using data from the Cancer Genome Atlas (TCGA) database (N = 373). In addition, immunohistochemistry analysis was performed to detect and assay the expression of CAV1 and ATG4C proteins in tissue microarray of EOC. Based on TCGA data, Kaplan-Meier analysis indicated that patients with low CAV1 mRNA (p = 0.021) and high ATG4C mRNA (p = 0.018) expression had a significantly shorter overall survival (OS). Cox regression analysis demonstrated that the expression levels of CAV1 (p = 0.023) and ATG4C mRNA (p = 0.040) were independent prognostic factors for OS in EOC. In addition, the Concordance Index of the nomogram for OS prediction was 0.660. Immunohistochemical analysis showed the expression levels of stromal CAV1 and cancerous ATG4C proteins, and high expression of both CAV1 and ATG4C protein in the stroma were found to significantly correlate with the histologic subtypes of EOC, especially with serous subtype. Decreased expression of CAV1 mRNA and increased expression of ATG4C mRNA in EOC can predict poor overall survival. The expression levels of CAV1 protein in stromal cells and ATG4C protein in cancer cells are significantly associated with histologic subtypes of EOC. These findings suggest that CAV1 and ATG4C serve as useful prognostic biomarkers and candidate therapeutic targets in EOC.

Use of Transabdominal Ultrasound for the detection of intra-peritoneal tumor engraftment and growth in mouse xenografts of epithelial ovarian cancer

To evaluate intraperitoneal (IP) tumor engraftment, metastasis and growth in a pre-clinical murine epithelial ovarian cancer (EOC) model using both transabdominal ultrasound (TAUS) and bioluminescence in vivo imaging system (IVIS). Ten female C57Bl/6J mice at six weeks of age were included in this study. Five mice underwent IP injection of 5x106 ID8-luc cells (+ D- luciferin) and the remaining five mice underwent IP injection of ID8-VEGF cells. Monitoring of tumor growth and ascites was performed weekly starting at seven days post-injection until study endpoint. ID8-luc mice were monitored using both TAUS and IVIS, and ID8-VEGF mice underwent TAUS monitoring only. Individual tumor implant dimension and total tumor volume were calculated. Average luminescent intensity was calculated and reported per mouse abdomen. Tumor detection was confirmed by gross evaluation and histopathology. All data are presented as mean +/- standard deviation. Overall, tumors were successfully detected in all ten mice using TAUS and IVIS, and tumor detection correlated with terminal endpoint histology/ H&E staining. For TAUS, the smallest confirmed tumor measurements were at seven days post-injection with mean long axis of 2.23mm and mean tumor volume of 4.17mm3. However, IVIS imaging was able to detect tumor growth at 14 days post-injection. Ascites formation was detected in mice at 21 days post-injection. TAUS is highly discriminatory for monitoring EOC in pre-clinical murine model, allowing for detection of tumor dimension as small as 2 mm and as early as seven days post-injection compared to IVIS. In addition, TAUS provides relevant information for ascites development and detection of multiple small metastatic tumor implants. TAUS provides an accurate and reliable method to detect and monitor IP EOC growth in mouse xenografts.

Evaluating clinician acceptability of the prototype CanRisk tool for predicting risk of breast and ovarian cancer: A multi-methods study

There is a growing focus on the development of multi-factorial cancer risk prediction algorithms alongside tools that operationalise them for clinical use. BOADICEA is a breast and ovarian cancer risk prediction model incorporating genetic and other risk factors. A new user-friendly Web-based tool (CanRisk.org) has been developed to apply BOADICEA. This study aimed to explore the acceptability of the prototype CanRisk tool among two healthcare professional groups to inform further development, evaluation and implementation. A multi-methods approach was used. Clinicians from primary care and specialist genetics clinics in England, France and Germany were invited to use the CanRisk prototype with two test cases (either face-to-face with a simulated patient or via a written vignette). Their views about the tool were examined via a semi-structured interview or equivalent open-ended questionnaire. Qualitative data were subjected to thematic analysis and organised around Sekhon's Theoretical Framework of Acceptability. Seventy-five clinicians participated, 21 from primary care and 54 from specialist genetics clinics. Participants were from England (n = 37), France (n = 23) and Germany (n = 15). The prototype CanRisk tool was generally acceptable to most participants due to its intuitive design. Primary care clinicians were concerned about the amount of time needed to complete, interpret and communicate risk information. Clinicians from both settings were apprehensive about the impact of the CanRisk tool on their consultations and lack of opportunities to interpret risk scores before sharing them with their patients. The findings highlight the challenges associated with developing a complex tool for use in different clinical settings; they also helped refine the tool. This prototype may not have been versatile enough for clinical use in both primary care and specialist genetics clinics where the needs of clinicians are different, emphasising the importance of understanding the clinical context when developing cancer risk assessment tools.

Assessment of acyl-CoA cholesterol acyltransferase (ACAT-1) role in ovarian cancer progression—An in vitro study

Abnormal accumulation of acyl-CoA cholesterol acyltransferase-1 (ACAT-1) mediated cholesterol ester has been shown to contribute to cancer progression in various cancers including leukemia, glioma, breast, pancreatic and prostate cancers. However, the significance of ACAT-1 and cholesterol esters (CE) is relatively understudied in ovarian cancer. In this in vitro study, we assessed the expression and contribution of ACAT-1 in ovarian cancer progression. We observed a significant increase in the expression of ACAT-1 and CE levels in a panel of ovarian cancer cell lines (OC-314, SKOV-3 and IGROV-1) compared to primary ovarian epithelial cells (normal controls). To confirm the tumor promoting capacity of ACAT-1, we inhibited ACAT-1 expression and activity by treating our cell lines with an ACAT inhibitor, avasimibe, or by stable transfection with ACAT-1 specific short hairpin RNA (shRNA). We observed significant suppression of cell proliferation, migration and invasion in ACAT-1 knockdown ovarian cancer cell lines compared to their respective controls (cell lines transfected with scrambled shRNA). ACAT-1 inhibition enhanced apoptosis with a concurrent increase in caspases 3/7 activity and decreased mitochondrial membrane potential. Increased generation of reactive oxygen species (ROS) coupled with increased expression of p53 may be the mechanism(s) underlying pro-apoptotic action of ACAT-1 inhibition. Additionally, ACAT-1 inhibited ovarian cancer cell lines displayed enhanced chemosensitivity to cisplatin treatment. These results suggest ACAT-1 may be a potential new target for the treatment of ovarian cancer.

Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer

Epithelial ovarian cancer (OC) is the most deadly cancer of the female reproductive system. To date, there is no effective screening method for early detection of OC and current diagnostic armamentarium may include sonographic grading of the tumor and analyzing serum levels of tumor markers, Cancer Antigen 125 (CA-125) and Human epididymis protein 4 (HE4). Microorganisms (bacterial, archaeal, and fungal cells) residing in mucosal tissues including the gastrointestinal and urogenital tracts can be altered by different disease states, and these shifts in microbial dynamics may help to diagnose disease states. We hypothesized that the peritoneal microbial environment was altered in patients with OC and that inclusion of selected peritoneal microbial features with current clinical features into prediction analyses will improve detection accuracy of patients with OC. Blood and peritoneal fluid were collected from consented patients that had sonography confirmed adnexal masses and were being seen at SIU School of Medicine Simmons Cancer Institute. Blood was processed and serum HE4 and CA-125 were measured. Peritoneal fluid was collected at the time of surgery and processed for Next Generation Sequencing (NGS) using 16S V4 exon bacterial primers and bioinformatics analyses. We found that patients with OC had a unique peritoneal microbial profile compared to patients with a benign mass. Using ensemble modeling and machine learning pathways, we identified 18 microbial features that were highly specific to OC pathology. Prediction analyses confirmed that inclusion of microbial features with serum tumor marker levels and control features (patient age and BMI) improved diagnostic accuracy compared to currently used models. We conclude that OC pathogenesis alters the peritoneal microbial environment and that these unique microbial features are important for accurate diagnosis of OC. Our study warrants further analyses of the importance of microbial features in regards to oncological diagnostics and possible prognostic and interventional medicine.

Inflammasome expression is higher in ovarian tumors than in normal ovary

Chronic inflammation fundamentally influences cancer risk and development. A mechanism of chronic inflammation is the formation of inflammasome complexes which results in the sustained secretion of the pro-inflammatory cytokines IL1β and IL18. Inflammasome expression and actions vary among cancers. There is no information on inflammasome expression in ovarian cancer (OvCa). To determine if ovarian tumors express inflammasome components, mRNA and protein expression of NLRP3 (nucleotide-binding domain, leucine-rich repeat family, pyrin domain containing 3), caspase-1, IL1β, and IL18 expression in hen and human OvCa was assessed. Chicken (hen) OvCa a valid model of spontaneous human OvCa. Hens were selected into study groups with or without tumors using ultrasonography; tumors were confirmed by histology, increased cellular proliferation, and expression of immune cell marker mRNA. mRNA expression was higher for hallmarks of inflammasome activity (caspase-1, 5.9x increase, p = 0.04; IL1β, 4x increase, p = 0.04; and IL18, 7.8x increase, p = 0.0003) in hen OvCa compared to normal ovary. NLRP3, caspase-8 and caspase-11 mRNA did not differ significantly between tumor and non-tumor containing ovaries. Similar results occurred for human OvCa. Protein expression by immunohistochemistry paralleled mRNA expression and was qualitatively higher in tumors. Increased protein expression of caspase-1, IL1β, and IL18 occurred in surface epithelium, tumor cells, and immune cells. The aryl hydrocarbon receptor (AHR), a potential tumor suppressor and NLRP3 regulator, was higher in hen (2.4x increase, p = 0.002) and human tumors (1.8x increase, p = 0.038), suggesting a role in OvCa. Collectively, the results indicate that inflammasome expression is associated with hen and human OvCa, although the NLR sensor type remains to be determined.

Association between coffee drinking and telomere length in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Mounting evidence indicates that coffee, a commonly consumed beverage worldwide, is inversely associated with various chronic diseases and overall mortality. Few studies have evaluated the effect of coffee drinking on telomere length, a biomarker of chromosomal integrity, and results have been inconsistent. Understanding this association may provide mechanistic insight into associations of coffee with health. The aim of our study was to test the hypothesis that heavier coffee intake is associated with greater likelihood of having above-median telomere length. We evaluated the cross-sectional association between coffee intake and relative telomere length using data from 1,638 controls from four previously conducted case-control studies nested in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Coffee intake was assessed using a food frequency questionnaire, and relative telomere length was measured from buffy-coat, blood, or buccal cells. We used unconditional logistic regression models to generate multivariable-adjusted, study-specific odds ratios for the association between coffee intake and relative telomere length. We then conducted a random-effects meta-analysis to determine summary odds ratios. We found that neither summary continuous (OR = 1.01, 95% CI = 0.99-1.03) nor categorical (OR <3 cups/day vs. none = 1.37, 95% CI = 0.71-2.65; OR ≥3 cups/day vs. none = 1.47, 95% CI = 0.81-2.66) odds ratio estimates of coffee drinking and relative telomere length were statistically significant. However, in the largest of the four contributing studies, moderate (<3 cups/day) and heavy coffee drinkers (≥3 cups/day) were 2.10 times (95% CI = 1.25, 3.54) and 1.93 times as likely (95% CI = 1.17, 3.18) as nondrinkers to have above-median telomere length, respectively. In conclusion, we found no evidence that coffee drinking is associated with telomere length. Thus, it is unlikely that telomere length plays a role in potential coffee-disease associations.

The blood transcriptome prior to ovarian cancer diagnosis: A case-control study in the NOWAC postgenome cohort

Epithelial ovarian cancer (EOC) has a 5-year relative survival of 50%, partly because markers of early-stage disease are not available in current clinical diagnostics. The aim of the present study was to investigate whether EOC is associated with transcriptional profiles in blood collected up to 7 years before diagnosis. For this, we used RNA-stabilized whole blood, which contains circulating immune cells, from a sample of EOC cases from the population-based Norwegian Women and Cancer (NOWAC) postgenome cohort. We explored case-control differences in gene expression in all EOC (66 case-control pairs), as well as associations between gene expression and metastatic EOC (56 pairs), serous EOC (45 pairs, 44 of which were metastatic), and interval from blood sample collection to diagnosis (≤3 or &gt;3 years; 34 and 31 pairs, respectively). Lastly, we assessed differential expression of genes associated with EOC in published functional genomics studies that used blood samples collected from newly diagnosed women. After adjustment for multiple testing, this nested case-control study revealed no significant case-control differences in gene expression in all EOC (false discovery rate q&gt;0.96). With the exception of a few probes, the log2 fold change values obtained in gene-wise linear models were below ±0.2. P-values were lowest in analyses of metastatic EOC (80% of which were serous EOC). No common transcriptional profile was indicated by interval to diagnosis; when comparing the 100 genes with the lowest p-values in gene-wise tests in samples collected ≤3 and &gt;3 years before EOC diagnosis, no overlap in these genes was observed. Among 86 genes linked to ovarian cancer in previous publications, our data contained expression values for 42, and of these, tests of LIME1, GPR162, STAB1, and SKAP1, resulted in unadjusted p&lt;0.05. Although limited by sample size, our findings indicated less variation in blood gene expression between women with similar tumor characteristics.

Photodiagnosis and photodynamic recognition of cervical cancer with SEM and AFM images

So far, the number of patients who die from cancer is quite high. Continuation of early detection research is important to reduce the number of deaths due to cancer. At the time of the literature review, images of the same patients taken from Scanning Electron Microscope (SEM) and Atomic Force Microscope (AFM) for early diagnosis of cervix cancer have not been addressed to date. This article, Photodiagnosis and Photodynamics with SEM and AFM images are valuable in recognizing cervical cancer and starting treatment early. Simultaneous examination of the, Photodiagnosis and Photodynamics with SEM and AFM cervix images of patients will provide us with a far more powerful solution than a one-way solution. Daubechies (db2, db3, db4, and db5), Coiflet (coif5, coif4, coif3, and coif2), Symlet (sym5, sym4, sym3, and sym2), and Biorthogonal (bior1.3, bior2.8, bior1.5, and bior3.3) 16 discrete wavelet transformation families (DWTF) have been applied to AFM and SEM images. One approximate and three detail coefficients have been obtained for each one AFM and SEM cervix images. Homogeneity, contrast, angular second moment, entropy, mean, standard deviation, correlation, cluster prominence, dissimilarity, and cluster shade values have been calculated for each of these one approximate and three detail coefficients. The classification rate found by the averages of the results obtained from the DWTF_JSD, DWTF_HD and DWTF_TD algorithms for AFM and SEM cervix images are 98.29% and 97.10%, respectively. According to these results, it has been determined that SEM images have lower classification rate than AFM images. It has been also observed that the surface roughness of the mAFM images was larger than nAFM and bAFM images. But, it was observed that the volume of particles of the mAFM images has been smaller than nAFM and bAFM images.

Cervical cancer care at a tertiary oncology facility in Uganda: Comparing daily practice with national treatment targets on cervical cancer control

Objective Treatment of cervical cancer patients in Uganda is hampered by late diagnosis due to the unavailability of timely screening and limited availability of advanced cancer care. This study evaluated the clinical presentation and management of cervical cancer patients presenting at the Uganda Cancer Institute (UCI) in Kampala, the tertiary oncology facility in Uganda with access to radiotherapy and reflected on daily clinical practice to identify priority areas for improving cervical cancer care in Uganda. Patients and methods We retrospectively analyzed medical records of all cervical cancer patients presenting to UCI between January 2017 and March 2018 for sociodemographic characteristics and clinical variables with descriptive statistics. The clinical management of patients with early and advanced stage disease who initiated treatment at UCI was evaluated using the national targets formulated in the Uganda strategic plan for cervical cancer prevention and control. Results Medical records of 583 patients were included, representing less than 10% of the annual estimated incidence in Uganda. The majority (86%) of patients presented with advanced stage of disease. More than half of patients never initiated (31%) or interrupted (30%) treatment. The national treatment targets for surgery (10%) and palliative care (25%) were achieved for eligible patients at UCI, however, the target for chemoradiotherapy (65%) was not met. Conclusion Daily clinical practice differed from the ambitions formulated in the national treatment targets on cervical cancer control. While most women presented in advanced stage requiring chemoradiotherapy, the target was not met due to limited availability of radiotherapy. Although targets for surgery and palliative care were achieved at UCI facility level, they mask the unmet need of the majority of cervical cancer patients who never initiated or completed treatment. This demands for further expansion of oncological surgical capacity, chemotherapy and radiotherapy and warrants to focus on accessible prevention programs.

The residual rate of HPV and the recurrence rate of CIN after LEEP with negative margins: A meta-analysis

Background HPV is detected in up to 47% of CIN and up to 70% of cervical cancers. It can cause intraepithelial neoplasia, which can eventually progress to invasive carcinoma. Almost all cervical cancers are caused by HPV. Therefore, it is especially important to treat high-risk HPV. For patients who have undergone LEEP surgery, this procedure can effectively treat CIN. However, it has not been studied in a meta-analysis whether HPV remains after the surgery and whether residual HPV increases the recurrence risk of CIN. To address this gap, our study collected all relevant literature to investigate the residual rate of HPV and its potential influence on the recurrence rate of CIN. We aim to provide valuable recommendations for clinicians and patients. Methods The Cochrane Library, EMBASE, and PubMed databases were searched from the establishment of the database until October 2023. Stata 12.0 software was used for the statistical analysis. Results Twelve studies were included, with a total sample size of 1192 cases. The meta-analysis found that the recurrence rate of CIN was quite low [95% CI = 0.5% (0.001, 0.012); P = 0.006] when the margins were negative after LEEP and there was no residual HPV. When HPV was present, the recurrence rate of CIN was significantly higher [95% CI = 18% (0.089, 0.291), P = 0.000], even if the margins were negative. The recurrence rate of CIN with residual HPV was 3.6 times higher than the recurrence rate of CIN without residual HPV. The residual rate of HPV after LEEP with negative margins was 22.7% [95% CI (0.167, 0.294), P = 0.000], which remained relatively high. Conclusion This meta-analysis found that the recurrence rate of CIN without residual HPV and with negative margins after LEEP was quite low, at 0.5%. However, when HPV was residual, the recurrence rate of CIN significantly increased to 18%, even if the margins were negative. The residual rate of HPV was 22.7%, even when the margins were negative after LEEP.

Cervical cancer screening knowledge and associated factors among Eswatini women: A cross-sectional study

Background Over recent years, cervical cancer incidence and related mortality have steadily increased in Eswatini. Low cervical cancer screening uptake partly explains the situation. Cervical cancer screening-related knowledge is positively associated with screening uptake. Little is known about women’s cervical cancer screening-related knowledge in Eswatini. Objective This study aimed to assess cervical cancer screening knowledge and associated factors among Eswatini women eligible for screening. Methods A cross-sectional study involving three hundred and seventy-seven women aged 25 to 59 selected from four primary healthcare clinics in Eswatini was conducted. A paper and pen survey assessed knowledge about cervical cancer risk factors, benefits of screening, the meaning of screening results, recommended screening intervals, and socio-demographics. Descriptive analyses were performed to assess participants’ sociodemographic characteristics. Linear regression was applied to examine associations between cervical cancer screening-related knowledge and participants’ sociodemographic characteristics. Results Two hundred and twenty-nine (61%) participants answered 80% or more knowledge questions correctly. Compared to HIV-positive participants, HIV-negative participants had 0.61 times lower cervical cancer screening knowledge scores (β = -0.39, 95% CI: -0.56, -0.19, p = 0.03). Participants who travelled more than 30 minutes to the clinic had 0.3 times lower cervical cancer screening knowledge scores (β = -0.70, 95% CI: -1.15, -0.25, p &lt; 0.01) compared to participants who travelled less than 30 minutes to the clinic. Conclusions Relatively high overall cervical cancer screening knowledge levels were observed among the study participants. Findings from the current study may inform future educational programs to create and sustain an accurate understanding of cervical cancer screening in Eswatini communities.

Reported adverse events following COVID-19 vaccination in gynecologic cancer patients in Thailand: A descriptive study

Objective Data on the safety of coronavirus disease 19 (COVID-19) vaccines in gynecologic cancer patients are scarce. The type of vaccine used in Thailand differs from what has been studied in other countries. This study evaluated the prevalence and characteristics of reported adverse events following COVID-19 vaccines in patients with gynecologic cancer patients. Method A retrospective, single-center descriptive study was performed in patients with gynecologic cancer who received at least one dose of the COVID-19 vaccine at King Chulalongkorn Memorial Hospital, Thailand, from January 2020 to August 2021. Adverse events were collected through structured telephone interviews using a standardized questionnaire. Descriptive statistics summarized patient characteristics and adverse events. Associations with any-grade adverse events were assessed using logistic regression and Fisher’s exact test for categorical variables. Results Of the 294 patients interviewed, 72.8% were in remission, under surveillance, or in palliative treatment at the time of vaccination, and 17.7% were undergoing treatment. The most common adverse effects were grade 1–2 injection site reactions. One patient developed grade 3 fever and seizures 10 days after the first dose of the AstraZeneca vaccine. Between the second and fourth doses of the vaccination, the most common adverse events were grade 1–2 injection site reactions. No severe allergic reactions or grade 4 adverse events were reported. The study concluded that patients under 60 years of age had more adverse events than older patients (adjusted odds ratio 1.99, 95% confidence interval 1.08–3.71 p = 0.029). The treatment status did not affect adverse events. Of 283 patients who received two doses, 27.6% were infected with COVID-19. Conclusion COVID-19 vaccination was generally well tolerated among gynecological cancer patients who received active anticancer therapy and those under surveillance. Younger patients frequently reported more adverse effects than older patients.

Trends in the burden of HPV-associated cancers in Mexico: An analysis from 2011 to 2019

Human papillomavirus (HPV) is a major public health concern, responsible for multiple types of cancer. This study aimed to provide an overview of the burden and temporal trends of HPV-associated cancers in Mexico using national hospital discharge and mortality databases from 2011–2019, including cervical, vulvar, vaginal, penile, anal, oropharyngeal, oral cavity, and laryngeal cancers. Hospitalization and mortality rates per 100,000 population were estimated; HPV-attributable fractions applied, and age-standardized temporal trends evaluated using joinpoint regression. Cervical cancer was the leading contributor, accounting for 88.5% of hospitalizations and 90.9% of HPV-attributable deaths. Hospitalization rates for cervical cancer increased between 2011–2014 (APC = 7.5%, 95% CI: 2.3, 18.0), then declined (APC = −3.0%, 95% CI: −7.8, −0.9). Other HPV-associated cancers had lower hospitalization rates, generally below 1 per 100,000, except for penile and head and neck cancers in males. Significant increases in hospitalization rates were observed in males for anal cancer from 2011–2019 (APC = 7.1%, 95% CI: 0.8, 15.1) and oropharyngeal cancer from 2017–2019 (APC = 18.0%, 95% CI: 4.0, 31.6), while in females, for vaginal cancer from 2017–2019 (APC = 30.7%, 95% CI: 10.6, 45.3) and oral cavity cancer from 2011–2019 (APC = 8.4%, 95% CI: 2.4, 29.1). Mortality for most cancers showed decreasing or stable trends over the study period, except for vulvar cancer in females (AAPC = 1.9%, 95% CI: 0.4, 4.1) and oropharyngeal cancer in both sexes (AAPC = 4.0%, 95% CI: 0.7, 8.0). Across most cancers, males were hospitalized at older ages but died younger than females, except for anal cancer. Overall, the burden of HPV-associated cancers is substantial. While cervical cancer remains prevalent and requires continued elimination efforts, the rising burden of anal and oropharyngeal cancers among males, highlights the need to strengthen public health strategies and raise awareness of HPV’s broader impact across both sexes.

Genotype distribution of human papillomavirus among women with cervical cancer stratified by HIV status in Tanzania

Background Cervical cancer (CC) is the leading cancer among women in Tanzania, especially among those between the ages of 15 and 44. The prevalence of high-risk Human papillomavirus (HR-HPV)-16/18 women in the general population at any given time is 3.3%. HR-HPVs 16 or 18 are the primary cause of CC. The distribution of HPV genotypes among women with CC according to HIV status is unknown in Tanzania. This study aimed to determine the HPV genotype distribution according to HIV status among women with CC in Tanzania. Methods This cross-sectional study was done at Ocean Road Cancer Institute (ORCI) in Tanzania among women with histologically confirmed CC. HIV serology testing was performed. Biopsy was taken from cervical lesions, and DNA was extracted. HPV DNA was amplified by using a previously validated multiplex HPV PCR assay targeting 14 high-risk HPV genotypes (16,18,30,31,33, 35, 39, 45, 51, 52, 56, 58, 59, and 66) and two low‐risk HPV genotypes (6 and 11). Continuous variables were compared using either a student t-test or the Mann-Whitney U test. Fisher’s exact test was employed to compare discrete variables. A P-value less than 0.05 was considered statistically significant. Results We included 100 women with CC. The prevalence of HIV infection in this study was 42%. The prevalence of any HPV infection was 94%, ranging from 1–3 genotypes per woman. HPV. The median age for women living with HIV (WLWH) with CC patients was 45 years (IQR, 31–60), while the median age for HIV-uninfected women with CC patients was 57 years (IQR, 30–78). (p = 0.0001). WLWH and HIV-uninfected women had similar HPV prevalence, except for HPV 35, which was more common in WLWH. There was a trend of high prevalence of HPV 52 and HPV 58 in WLHH compared to HIV-uninfected women, but this difference was not statistically significant. The prevalence of HPV 16 and/or 18 infection in the entire sample was 85%. The combined prevalence of HPV 16 and/or 18 was 76% WLWH and 91% amongst HIV-uninfected women (p = 0.036).The majority of women (77.9%) had single-genotype HPV infection. There was no difference in the distribution of multiple or single HPV genotypes infection by HIV status (p = 0.25). Conclusion In this study, HIV positive women with CC presented at a significantly younger age (45 years) compared to the HIV-negative women (57 years). The prevalence of high-risk HPV is high among women with CC in Tanzania. Distribution of most high-risk HPV genotypes among women with CC was not significantly influenced by HIV status except for HPV 35, which appeared to be more in HIV positive women compared to HIV-negative women. While the majority of the high-risk HPV infections were with single HPV genotypes, the prevalence of multiple high-risk HPV infections was at 22%, with no significant difference between the two HIV statuses. A vaccination program that aptly targets HPV 16 and 18 could prevent up to 85% of CC cases in Tanzania, regardless of HIV. Keywords: Human papillomavirus, cervical cancer, HIV, Tanzania.

Detection of vasculogenic mimicry in equine ocular, oronasal, and genital squamous cell carcinoma

Squamous cell carcinoma (SCC) is the most common malignant tumor disease in horses. It predominantly affects the ocular, oronasal, and anogenital region. Equine SCC is difficult to treat, also because important aspects of SCC development and metastasis are still unclear. We previously provided evidence that equine SCC cells can adopt a stem cell-like phenotype as a hallmark of malignant progression. Here, we investigated whether equine SCCs harbor endothelial-like tumor cells that form an alternative network of pseudo-vessels better known as vasculogenic mimicry (VM). Following histopathological diagnosis, 43 equine SCCs or precursor lesions (15 ocular, 14 genital, 14 oronasal tumors) were PCR-screened for equine papillomavirus (EcPV) infection. Subsequently, formalin-fixed paraffin-embedded (FFPE)-sections of all tumors were analyzed by Periodic Acid-Schiff (PAS) reaction and immunohistochemical (IHC) staining for endothelial cell marker CD31. Obtained micrographs were evaluated by a scientific board to unanimously identify sections of intact tumor tissue displaying PAS-positive, CD31-negative lumens harboring erythrocytes. Thirteen lesions exhibiting these features were subjected to triple immunofluorescence (IF) staining for CD31, pan-cytokeratin (KRT) and type 4 collagen (Col4) or alpha smooth muscle actin (αSMA) to confirm the presence of VM, and to determine whether pericytes have a role in this phenomenon. All genital and 50% of oronasal lesions scored positive for EcPV type 2, whilst ocular lesions tested negative. One mandibular SCC harbored EcPV type 5. Six genital, three oronasal, and four ocular tumors unambiguously exhibited VM as revealed by CD31-/PAS+ vessel-like structures containing erythrocytes, the detection of CD31-negative cells lining their lumens, and the presence of Col4 and αSMA in this lining. Detection of these two proteins in the context of VM suggests that VM-forming cancer cells recruit pericytes to enhance channel formation and stability. To our knowledge, this is the first report providing evidence of VM in equine cancer, and more generally, SCC in animals.

Vitamin D binding protein genetic isoforms, serum vitamin D, and cancer risk in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial

Associations between vitamin D biochemical status and cancer may be modified by vitamin D binding protein isoforms which are encoded by GC (group-specific component). We examined interactions between serum 25-hydroxyvitamin D [25(OH)D], the Gc isoforms Gc1-1, Gc1-2, and Gc2-2, and cancer risk within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort based on 3,795 cases and 3,856 controls. Multivariable-adjusted logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of cancer risk according to 25(OH)D quantiles, stratified by Gc isoform. Separately, the GC-cancer risk association was examined using proportional hazards regression among 109,746 individuals with genetic data and 26,713 diagnosed with cancer. Specific vitamin D binding protein isoform subtypes were delineated and analyzed, including Gc1-1 subtypes (Gc1s-Gc1s, Gc1f-Gc1s, and Gc1f-Gc1f) and Gc2 subtypes (Gc1s-Gc2, Gc1f-Gc2, and Gc2-Gc2). For most cancers, the GC genotype did not modify the risk associations for 25(OH)D; e.g., the OR for high vs. low vitamin D quintile was 1.09 (0.89–1.33) for overall cancer risk among individuals with the Gc1-1 isoform and 1.04 (0.83–1.31) among those with either the Gc1-2 or Gc2-2 isoforms. ORs for high compared to low vitamin D tertile for colorectal, lung, breast, and prostate cancer among those with the Gc1-1 vs. any Gc2 isoforms were, respectively, 0.60 vs. 0.73, 1.96 vs. 1.03, 1.30 vs. 1.18, and 1.19 vs. 1.22 (all p-interaction ≥0.36). However, GC qualitatively modified the vitamin D-bladder cancer risk association: OR = 1.70 (95% CI 0.96–2.98) among those with the Gc1-1 isoform and 0.52 (0.28–0.96) among those with any Gc2 isoforms (p-interaction = 0.03). When modeled without regard for 25(OH)D, Gc isoforms were generally not associated with cancer risk, although melanoma risk was significantly lower among individuals with the “f” subtype of the Gc1-1 isoform, specifically HR = 0.83 (95% CI 0.70–0.98) for Gc1f-1s and 0.67 (0.45–1.00) for Gc1f-1f, compared to individuals with the Gc1s-Gc1s isoform. Vitamin D binding protein genetic isoforms may be associated with melanoma risk but do not modify the association between vitamin D status and cancer, with the possible exception of bladder cancer.

Trend of cancer mortality of the female reproductive system in China from 2005 to 2018 and prediction to 2035: A log-linear regression and Bayesian age-period- cohort analysis

Objective In recent years, the number of deaths from female reproductive system cancer in China has been continuously increasing, and there are relatively few studies on their mortality situation. This study aimed to analyze the mortality rate and its trend of the female reproductive system cancer in China from 2005 to 2018, to predict the situation until 2035, and to provide scientific basis for the prevention and control of the female reproductive system cancer in China. Methods The mortality rate latest data of the female reproductive system cancer was obtained from the Chinese Cancer Registry Annual Report from 2008 to 2021. Using the Joinpoint regression model, the annual percent change (APC) and average annual percentage change (AAPC) were calculated to describe the time trend. Age-period- cohort models were constructed to analyze the effects of age, period, and cohort. The study predicted the situation up to 2035 using a Bayesian age-period-cohort model. Result The age-standardized mortality rate (ASMR) of the female reproductive system cancer in China from 2005 to 2018 was 8.75/100,000, with rural areas being higher than urban areas. The mortality rate showed an upward trend from 2005 to 2018, with AAPC = 1.92% (95% CI: 1.68%, 2.16%). The growth trend in urban areas was more pronounced than that in rural areas, and the mortality risk was highest among the population aged 80–84 years. The period effect showed a trend of first increasing and then decreasing from 2005 to 2018, with the highest risk in the population born between 1990 and 1994. The mortality rate of the female reproductive system cancer in China will increase from 9.96/100,000 (95% CI: 9.37/100,000, 10.54/100,000) in 2019 to 11.98/100,000 (95% CI: 3.64/100,000, 20.31/100,000) in 2035. Conclusion The mortality rate of the female reproductive system cancer in China showed an upward trend from 2005 to 2018, and will continue to rise from 2019 to 2035. The female reproductive system cancer in China require continuous attention.

Translation and validation of the Chinese version of EORTC QLQ-SWB32 assessing the spiritual wellbeing of women with gynecological cancer

Background This study aimed to translate the internationally developed and validated European Organization for Research and Treatment of Cancer measure of spiritual wellbeing (EORTC QLQ-SWB32) into Chinese, validate the translation with women with gynecological cancer, and examine associations between demographic variables and the scales of the measure. Methods The study followed EORTC translation guidelines. After pilot testing with sixteen gynecological cancer patients, we validated the final measure with another 200 patients. We analyzed reliability using Cronbach’s alpha coefficients. Exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and exploratory graphic analysis (EGA) were used to analyze the construct validity. A multiple linear regression model analyzed the relationship of the factors to spiritual well-being. Results Cronbach’s alpha coefficients showed good reliability, ranging from 0.885 to 0.907 in each dimension. The EFA (KMO = 0.876, χ2 = 2865.036, df = 231, P &lt; 0.001) and EGA produced a four-dimension structure. CFA fit statistics indicated adequate fit to a four-dimension solution (χ2/df = 2.178, RMESA = 0.077, GFI = 0.973, SRMR = 0.057, CFI = 0.915, TLI = 0.902), which matched the dimensions and constituent items from the original measure. Regression analysis indicated that higher education levels correlated with higher scores on the Relationships with Others (RO) and Existential (EX) scales; unemployment with lower Relationship with Self (RS) scores, and lower incomes with lower EX scores; patients with religious beliefs scored higher on Relationship with God (RG). Conclusions The Chinese EORTC QLQ-SWB32 exhibits good reliability and validity among gynecological cancer patients, with dimensions aligning with those found in the original validation. This approved, validated instrument is now available for Chinese medical staff to use to assess the spiritual wellbeing of Chinese cancer patients and help improve understanding of the relevance of spiritual wellbeing to people from Chinese cultural backgrounds.

Perioperative immunonutrition intervention on postoperative outcomes among gynecological cancer patients under enhanced recovery after surgery setting: A study protocol of explanatory mixed method study

Background &amp; aims Enhanced Recovery After Surgery (ERAS) has shown significant improvements in postoperative outcomes and a reduction in complications, while immunonutrition (IMN) has been shown to modulate the immune system and inflammatory response. However, many studies have overlooked the crucial aspects of nutrition status and patient perception within the intervention approach. This study aims to investigate the efficacy and explore patients’ acceptance of the IMN intervention in postoperative outcomes among gynecological cancer (GC) patients under the ERAS framework. Methods This two-phase explanatory sequential mixed-method study design comprises an open-labeled randomized control trial and a qualitative study. The GC participants will be randomly allocated into intervention and control groups. Malaysian adults scheduled for elective surgery will be recruited, with the intervention group receiving IMN for five days before and seven days after elective surgery, while the control group undergoes routine nutritional care before the operation. Both groups will adhere to the ERAS protocol. An explanatory qualitative study will be conducted among GC patients to elucidate their expectations following the trial. Study outcomes include hospitalization duration, change in nutrition status, biochemical profile, functional status, and quality of life. Additionally, the secondary outcome focuses on evaluating the perception of the intervention approach. Quantitative and qualitative data will be analyzed on an intention-to-treat basis and through inductive thematic analysis, respectively. Conclusion Implementing perioperative IMN intervention within the ERAS framework may contribute to the preservation of better nutrition status and the provision of sufficient dietary intake to support postoperative recovery, and promote better surgical outcomes. Patients’ perceptions play a pivotal role in enhancing understanding of disease management and adherence to the intervention approach. Trial registration NCT06039306.

Tumor microenvironment characterization in cervical cancer identifies prognostic relevant gene signatures

Objective The aim of this study is to systematically analyze the transcriptional sequencing data of cervical cancer (CC) to find an Tumor microenvironment (TME) prognostic marker to predict the survival of CC patients. Methods The expression profiles and clinical follow-up information of CC were downloaded from the TCGA and GEO. The RNA-seq data of TCGA-CESC samples were used for CIBERSORT analysis to evaluate the penetration pattern of TME in 285 patients, and construct TMEscore. Other data sets were used to validate and evaluate TMEscore model. Further, survival analysis of TMEscore related DEGs was done to select prognosis genes. Functional enrichment and PPI networks analysis were performed on prognosis genes. Results The TMEscore model has relatively good results in TCGA-CESC (HR = 2.47,95% CI = 1.49–4.11), TCGA-CESC HPV infection samples (HR = 2.13,95% CI = 1–4.51), GSE52903 (HR = 2.65, 95% CI = 1.06–6.6), GSE44001 (HR = 2.1, 95% CI = 0.99–4.43). Patients with high/low TMEscore have significant difference in prognosis (log-rank test, P = 0.00025), and the main difference between high TMEscore subtypes and low TMEscore subtypes is immune function-related pathways. Moreover, Kaplan-Meier survival curves found out a list of identified prognosis genes (n = 86) which interestingly show significant enrichment in immune-related functions. Finally, PPI network analysis shows that highly related nodes such as CD3D, CD3E, CD8A, CD27 in the module may become new targets of CC immunotherapy. Conclusions TMEscore may become a new prognostic indicator predicting the survival of CC patients. The prognostic genes (n = 86) may help provide new strategies for tumor immunotherapy.

Uptake of cervical cancer screening and its determinants in Africa: Umbrella review

Background Cervical cancer is the fourth most prevalent type of cancer in women globally. Early detection and treatment of precancerous cervical lesions and human papillomavirus (HPV) infection are strongly advised to decrease the incidence of cervical cancer and death. Cervical cancer is a major public health concern in low- and middle-income nations, where screening and treatment options are constrained. Thus, the main objective of this umbrella review was to determine the pooled uptake of cervical cancer screening and its determinants in Africa. Methods This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol for this umbrella review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) with reference number CRD42024518297. We conduct a systematic and comprehensive search by using Google Scholar, PubMed, Scopus, Hinari, and Science Direct, from January 1, 2014, to September 20, 2024. The data were extracted using Microsoft Excel spreadsheet. The methodological quality of the included studies was examined using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The statistical analysis was carried out using STATA version 17, which includes descriptive analysis, forest plots for prevalence, funnel plot, and an Egger test to examine publication bias. A random-effects model was used to determine the pooled effect estimate. Publication bias was checked by using the funnel plot and Egger’s tests. Results This umbrella review included 11 systematic reviews and meta-analysis studies across Africa with a total of 143,327 study participants. The overall prevalence of cervical cancer screening practice in Africa was 20.94% (95% CI: 15.84%–26.04%). Women’s level of knowledge (AOR: 3.22, 95% CI: 1.64–6.33), positive attitude toward CCS (AOR: 2.48, 95% CI: 2.18–2.81), perceived vulnerability to cervical cancer (AOR = 3.57, 95% CI: 2.75, 4.63), and history of STIs (AOR = 4.89, 95% CI: 3.14, 7.62) were significantly associated with cervical cancer screening practice. In conclusion, the combined estimate of cervical cancer screening use in Africa remains much lower (20.94%) than the World Health Organization (WHO) recommendations target (70%). It indicates that there is a large gap that requires being addressed in collaboration to reduce the burden of cervical cancer and its morbidity and mortality across the continent. Therefore, healthcare professionals, policymakers, and other stakeholders shall implement effective strategies such as empowering women, improving the knowledge and attitude towards cervical cancer screening, advocacy, and expanding screening programs to all eligible women to increase utilization of cervical cancer screening.

A comparison of the burden of cancers between 1990 and 2019 in Iran: A national and subnational study

Background Cancer is a rapidly increasing global problem, and one of the leading causes of burden and mortality. This study aims to compare the burden of cancer in Iran between the year 1990 and 2019. Methods We used Global Burden of Disease data on cancer from 1990 to 2019 by province, year, age group, and sex. We then estimated the trend of age standardized mortality and Disability-Adjusted Life Years (DALYs) of the cancers by sex. Age pattern and geographical variation in the ranking of cancers were assessed at national and sub-national levels from 1990 to 2019. Results The mortality rate decreased from 102 (95% UI: 91, 111) to 96 (95% UI: 88, 103) per 100000 population. Additionally, the DALYs rates decreased from 2619 (95% UI: 2357, 2852) to 2321 (95% UI: 2116, 2497) per 100000 between 1990 and 2019. Both of the mortality and DALYs rate from cancers increased with age. These indicators were significantly higher in men than in women across all age groups. Consequently, the mortality rate and DALYs per 100,000 of cancers were higher in the northwest and northeast of Iran. Notably, stomach cancer was identified as the leading cause of cancer mortality in 23 provinces of Iran in 2019. The highest percentage change of DALYs per 100,000 rate between 1990 and 2019 was observed for malignant skin melanoma, stomach cancer, and cervical cancers with rate of −41.1, −40.1, and −38.4, respectively. Conclusion Overall, the mortality and DALYs per 100,000 rates of all cancers for both sexes in Iran have decreased between 1990 and 2019. However, there is an increasing trend in types of cancers, such as pancreatic, ovarian, and breast cancers.

Histopathologic patterns and factors associated with cervical lesions at Jimma Medical Center, Jimma, Southwest Ethiopia: A two-year cross-sectional study

Background The cervix is the lower portion of the uterus, which connects this organ to the vagina through the endocervical canal. Objective This study aimed to determine the histopathologic patterns and factors associated with cervical lesions at Jimma Medical Center from September 12, 2017, to September 12, 2019. Methods A 2-year facility-based cross-sectional study was conducted from May 1 to June 30, 2020. Result In this study, cervical cancer was the most common (71%) cause of cervical lesions. Squamous cell carcinoma was the most frequent cervical cancer diagnosed during the study, accounting for 96.4% of 331 cancerous cases, followed by adenocarcinoma (3.3%). High-grade squamous intraepithelial lesions were the most frequently diagnosed precancerous lesions, accounting for 68.4% of cases. Endocervical polyps were the most commonly diagnosed benign lesions, accounting for 59.3% of cases. Conclusion The maximum age distribution of cervical lesions was in the 41–50-year age range. Squamous cell carcinoma was the most frequent type of cervical cancer. High-grade squamous intraepithelial lesions were the most frequently diagnosed precancerous cervical lesions. The most common benign cervical lesions were endocervical polyps. Recommendation We recommend educating the community to improve health-seeking behavior and on possible preventive strategies for cervical cancer.

Health impact and cost-effectiveness analysis of gender-neutral versus female-only 9-valent human papillomavirus vaccination in Taiwan

The prevalence of human papillomavirus (HPV)-related diseases in women has declined in countries introducing HPV vaccinations for girls but remains high among men. The objective of this study was to compare the health impact and cost-effectiveness of two HPV vaccination strategies in the pre-adolescent Taiwanese population: nonavalent (9vHPV) gender-neutral vaccination (GNV), and 9vHPV female-only vaccination (FOV). A previously validated dynamic transmission model was adapted to the Taiwanese setting. The model had a 100-year time horizon and assumed an 85% vaccination coverage rate for girls and a 50% rate for boys, lifelong duration of vaccine protection, herd immunity, and a discount rate of 3% for costs and quality-adjusted life-years (QALYs). Costs of vaccination and HPV-related disease (in 2015−2016 new Taiwan dollars [NTD]), QALYs, and incremental cost-effectiveness ratios (ICERs) were estimated. Compared to 9vHPV FOV, GNV prevented 572 additional cases of cervical cancer (a 1.0% decrease) and 57,691 cases of genital warts (−12.6%) in women. In men, 26 additional cases of penile cancer were avoided (−6.6%), as well as 179,207 cases of genital warts (−26.7%), 4,955 cases of head and neck cancer (−9.0%), and 3,880 cases of recurrent respiratory papillomatosis (−15.8%), by use of the 9vHPV GNV strategy versus FOV. Use of 9vHPV GNV instead of FOV would prevent 229 deaths from cervical cancer in women (a 0.6% decrease) and 3,398 deaths from head and neck cancer in men (−8.3%) over 100 years. The 9vHPV GNV strategy resulted in a savings of NTD 1,574,288,155 (1.9%) in disease management costs compared to the 9vHPV FOV strategy and was predicted to be cost-effective, with an ICER of NTD 606,210/QALY. Compared to a 9vHPV FOV strategy, a 9vHPV GNV strategy for 13-year-old girls and boys would result in incremental public health and economic benefits and would be cost-effective in Taiwan.

CHD4 regulates platinum sensitivity through MDR1 expression in ovarian cancer: A potential role of CHD4 inhibition as a combination therapy with platinum agents

Platinum sensitivity is an important prognostic factor in patients with ovarian cancer. Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a core member of the nucleosome remodeling and deacetylase complex, which functions as a chromatin remodeler. Emerging evidence indicates that CHD4 could be a potential therapeutic target for cancer therapy. The purpose of this study was to clarify the role of CHD4 in ovarian cancer and investigate its therapeutic potential focusing on platinum sensitivity. In an analysis of the Cancer Genome Atlas ovarian cancer dataset, CHD4 gene amplification was associated with worse overall survival.CHD4mRNA expression was significantly higher in platinum-resistant samples in a subsequent clinical sample analysis, suggesting that CHD4 overexpression conferred platinum resistance to ovarian cancer cells, resulting in poor patient survival. In concordance with these findings, CHD4 knockdown enhanced the induction of apoptosis mediated by cisplatin in ovarian cancer cells TOV21G and increased cisplatin sensitivity in multiple ovarian cancer cells derived from different subtypes. However, CHD4 knockdown did not affect the expression of RAD51 or p21, the known targets of CHD4 in other cancer types that can modulate platinum sensitivity. Knockdown and overexpression assays revealed that CHD4 positively regulated the expression of multi-drug transporter MDR1 and its coding protein p-glycoprotein. In addition, a first-in-class CHD4/SMARCA5 inhibitor ED2-AD101 showed synergistic interactions with cisplatin. Our findings suggest that CHD4 mediates platinum sensitivity by modulating MDR1 expression in ovarian cancer. Further, CHD4 suppression has a potential to be a novel therapeutic strategy in combination with platinum agents.

Human papillomavirus, sexually transmitted infections, and antimicrobial resistance in West Africa: Estimating population burden and understanding exposures to accelerate vaccine impact and drive new interventions: The PHASE survey protocol

Human papillomavirus (HPV) infection is a primary cause of preventable deaths from cervical cancer, a condition of profound inequality with approximately 90% of deaths occurring in low- and middle-income countries, particularly in sub-Saharan Africa. In May 2018, the WHO Director-General declared a Joint Global Commitment to Cervical Cancer Elimination, highlighting the critical role of HPV vaccines in achieving this goal. However, there is a lack of systemically collected data on HPV prevalence in The Gambia, and impact data from high-income countries may not be reliably extrapolated to West African settings due to geographical variation in HPV types and distinct behavioural, biological, and sociodemographic exposures. The Gambia introduced a two-dose HPV vaccination schedule in 2019, but coverage has been very low, interrupted mainly by the COVID-19 pandemic. This presents a key opportunity to generate vital baseline data on HPV prevalence in the population before potential scale-up of vaccination efforts. The PHASE survey, a multi-stage cluster survey, aims to establish the baseline, population prevalence estimates of high-risk and low-risk, vaccine-type and non-vaccine-type HPV infection in 15- to 49-year-old females in The Gambia by measuring urinary HPV-DNA. The survey will also quantify the effects of various exposures on HPV prevalence, including sexual behaviour, the presence of other sexually-transmitted infections (STIs) - Neisseria gonorrhoea (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), syphilis, as well as blood borne viruses, human immunodeficiency virus (HIV), hepatitis B and hepatitis C; obstetric history, socio-demographic characteristics, and cervical cancer screening and/or treatment. Additionally, the study will provide important antimicrobial resistance (AMR) data for NG and MG in sub-Saharan Africa, a region poorly represented in global surveillance programs. This data is needed to guide regional treatment guidelines and advocate for new solutions, including gonococcal vaccines. The AMR data are expected to immediately influence recommendations regarding the appropriate choice of antibiotics for syndromic STI management in West Africa and hence to address an important driver of AMR in the sub-region. Leveraging on the Medical Research Council Unit The Gambia funded Health Demographic Surveillance system (HDSS) as its sampling frame, the survey will utilize validated diagnostic assays and culturally sensitive data collection methods, to ensure both scientific rigor and local relevance. Tools such as Audio Computer-Assisted Self-Interviewing (ACASI) technology, developed in consultation with local community advisory boards, are included to reduce social desirability bias in reporting sexual behaviour. This approach aims to maximize both the reliability and cultural appropriateness of the findings. This study directly addresses the critical need for baseline epidemiological data on HPV in a West African setting to accelerate vaccine impact and drive new interventions towards cervical cancer elimination. By understanding other factors that influence HPV (like other STIs, sexual behaviour, etc.), the study aims to ensure that, when the vaccine’s impact is measured later, changes in other confounding factors that may impact on HPV prevalence can be accounted for. The study will also establish the population prevalence of the measured STIs and their relationship to common symptoms and other adverse health outcomes related to STIs.

Significance of androgen receptor and its potential for anti-androgen/androgen receptor-antagonist therapy in ovarian cancers

Introduction Androgen promotes tumorigenesis in some cancers; however, androgen receptor (AR) is not commonly examined in ovarian cancers (OCs). In this study, we evaluated AR expression among different types of OCs and compared the results to estrogen and progesterone receptors (ER &amp; PR). Materials and methods AR, ER, and PR expressions were assessed in 62 cases which were categorized into: low-grade serous carcinoma (LGSCA), high-grade serous carcinoma (HGSCA), clear cell carcinoma (CCCA), ovarian endometrioid carcinoma (OECA), and granulosa cell tumor (GCT). The hormone receptors were compared and evaluated in relation to p53 and body mass index (BMI) using Fisher’s Exact test. Results In a majority of cases, expression of AR was concordant with ER and/or PR. Positivity for all three receptors was observed in 100% of OECAs. AR expression was seen in 92% of HGSCAs as opposed to 88% and 44% for ER and PR. LGSCAs had expressed AR and ER (100%), and PR (70%). In GCTs, positivity rates were 92%, 62%, and 92% for AR, ER, and PR. In rare cases of HGSCA and CCCA, AR was positive despite negative ER and PR. Conclusion AR is expressed in a high percentage of OCs, even more frequently than ER and PR in certain high-grade histological types. Overall, our findings are similar to the results of recent studies of AR expression in endometrial cancers. These findings support an important possible role for AR in OCs as a potential marker to serve as a therapeutic target in these malignancies.

Risk factors of progression to endometrial cancer in women with endometrial hyperplasia: A retrospective cohort study

Objective This study aimed to investigate risk factors of progression to endometrial cancer (EC) in women with non-atypical and atypical endometrial hyperplasia (EH). Methods The data of 62,333 women with EH diagnostic codes from 2007 to 2018 were sourced from the Korean Health Insurance Review and Assessment Service databases. The data from 11,525 women with non-atypical EH and 2,219 women with atypical EH who met the selection criteria were extracted for analysis. Results Risk of EC in women with EH decreased in 40–49 year olds compared to other ages (non-atypical EH: [≤39 vs. 40–49 years] HR, 0.557; 95% CI, 0.439–0.708; P&lt;0.001; [≤39 vs. ≥50 years] P = 0.739; atypical EH: [≤39 vs. 40–49 years] HR, 0.391; 95% CI, 0.229–0.670; P = 0.001; [≤39 vs. ≥50 years] P = 0.712). Risk of EC increased with increase in number of follow-up biopsies in women with non-atypical EH (1 biopsy: HR, 1.835; 95% CI, 1.282–2.629; P = 0.001; ≥2 biopsies: HR, 3.644; 95% CI, 2.585–5.317; P&lt;0.001) and in women receiving ≥2 follow-up biopsies with atypical EH (HR, 3.827; 95% CI, 1.924–7.612; P = 0.001). Time of progression to EC decreased in women ≥50 years old with non-atypical EH compared to other ages (P = 0.004) and showed no differences among ages in women with atypical EH (P = 0.576). Progestational agents were a protective factor for EC in women with non-atypical EH (HR, 0.703; 95% CI, 0.565–0.876; P = 0.002). Conclusions In this claim data analysis, women ≤39 and ≥50 years old with EH were at a high risk for progression to EC, and repeat follow-up biopsy after a diagnosis of EH increased detection of EC. Progestational agents were an effective modality to prevent EC in women with non-atypical EH.

Association of a CHEK2 somatic variant with tumor microenvironment calprotectin expression predicts platinum resistance in a small cohort of ovarian carcinoma

High-grade serous ovarian cancer (HGSOC) low overall survival rate is often attributed to platinum resistance. Recent studies suggest that the tumor associated-microenvironment (TME) is a determining factor in malignant tumor progression and DNA damage plays a crucial role in this process. Here, we sought to identify platinum resistance biomarkers associating the TME immune profile and the mutational landscape of the homologous repair pathway genes with the HGSOC patients prognosis and response to chemotherapy. Using a decision tree classifier approach, we found that platinum resistant (PR) patients were characterized by the presence of a novel deep intronic variant, the CHEK2 c.319+ 3943A &gt; T, and higher L1 expression (p =  0.016), (100% accuracy). Chek2 protein is an important component of DNA repair and L1, also known as calprotectin, is one component of the neutrophil extracellular traps (NETs) during inflammation, previously suggested as a key contributor to the metastatic process in HGSOC. Also, PD-L2 levels were significantly higher in PR patients positive for this CHEK2 variant (p =  0.048), underscoring the need to explore its potential therapeutic role for this cancer. Our results suggest an interplay between TME and DNA repair variants that results in a multifactorial nature of HGSOC resistance to platinum chemotherapy.

Perceived effectiveness of messages to address cervical cancer screening barriers: An online experiment

Introduction Cervical cancer is almost entirely preventable through vaccination and screening, but screening rates still lag targets. Communication campaigns can encourage screening; however, the types of message content that are most effective are unknown. Methods We conducted an online randomized experiment testing messages within four themes aligned with previously identified screening barriers: cancer fatalism, inconvenience, lack of knowledge about risk factors, and unawareness of screening guidelines. A national convenience sample of US participants aged 21–65 years and assigned female at birth ( n  = 1,536) viewed one of three messages from each theme assigned at random and one control message in random order. We measured perceived effectiveness to encourage cervical cancer screening, anticipated social interactions, and self-reported learning. Mixed-effects linear models examined the impact of message theme on each outcome on a scale from 1 (low) to 5 (high). Results All four barrier-focused themes encouraged cervical cancer screening more than the control (perceived message effectiveness mean and standard deviation: cancer fatalism = 3.44 (1.21); convenience = 3.43 (1.23); risk factors = 3.25 (1.23); screening guidelines = 3.44 (1.19); control message = 2.45 (1.35), p  &lt; .001). Barrier-focused messages similarly outperformed the control on anticipated social interactions and self-reported learning (all p  &lt; .001). Messages were less effective for participants who had never been screened or were out-of-date. However, regardless of screening status, barrier-focused messages outperformed the control. Conclusions Messages targeting known barriers to cervical cancer screening were perceived as more effective than a control message. These messages could increase cervical cancer screening rates if used in interventions at scale.

Electrothermal bipolar vessel sealing devices are associated with lower rates of postoperative complications compared to ultrasonic devices in vulvar cancer surgery

Introduction Electrothermal bipolar vessel sealing devices (EBVS) and ultrasonic devices (US) – collectively known as advanced hemostasis devices (AHDs) – are considered equally feasible in laparoscopic procedures. However, US devices have been demonstrated to be more susceptible to abnormal heat accumulation when activation cycles are rapidly repeated, causing results from laparoscopic procedures to be poorly translated to vulvar cancer surgery. In this study, we aimed to determine whether EBVS and US are comparable in terms of peri- and postoperative morbidity in vulvar cancer surgery. Methods This retrospective single-center study comprised patients who underwent a primary vulvectomy, partial vulvectomy, or radical local resection with an AHD in Tampere University Hospital, Finland, in 2011–2023. Our primary outcome measure was the Clavien-Dindo grade, which measures the incidence and severity of postoperative complications in the early (30-day) postoperative period. Secondary outcome measures were blood loss, postoperative blood transfusions, operative time, the total volume of groin drain output, and length of hospital stay. Results Eighty-six patients were included (EBVS n = 45, US n = 41). Postoperative complications (Clavien-Dindo grades II – V) were significantly less common in the EBVS group compared to the US group (60% vs 85% in the EBVS and US groups, respectively; p = 0.015). The difference was driven by a discrepancy in grade II complications (49% vs 71%), which consisted primarily of infections in both groups. In a multivariable regression analysis adjusting for the extent of surgery, the use of an EBVS device was independently associated with a lower likelihood of postoperative complications compared to US (aOR 0.3, 95%CI 0.1–0.9 for EBVS vs US; p = 0.030). Both the amount of operative blood loss (median (IQR) 50 (45–200) ml vs 150 (88–400) ml; p = 0.005) and length of hospital stay (median (interquartile range) 6 (4–8) vs. 8 (6–10) days; p = 0.002) were lower in the EBVS group, but surgical device did not independently predict the highest quartile of either variable. The amount of postoperative blood transfusions, operative time, or groin drain output did not significantly differ between the groups. Conclusions The data from this study suggests electrothermal bipolar vessel sealing devices could reduce early postoperative complications, especially those related to the surgical site, in vulvar cancer surgery compared to ultrasonic devices. Prospective studies are needed to ensure the generalizability of the results.

Human papilloma virus vaccination uptake and associated factors among adolescent girls in Merab Abaya district, Gamo zone, Southern Ethiopia: Mixed methods

Background Human papillomavirus (HPV) vaccination is a well-established global strategy for the prevention of cervical cancer. However, the uptake of the vaccine varies across regions and countries due to several factors. Although girls are at risk for cervical cancer, there are limited studies measuring vaccination uptake among female adolescents in the study area. Objective To assess human papilloma virus vaccination uptake and associated factors among adolescent girls, in Merab Abaya district, Gamo Zone, southern Ethiopia, 2024. Method A community-based cross-sectional mixed-method study was conducted among 626 adolescent girls selected using a two-stage sampling technique in Merab Abaya District, Gamo Zone, from February 1 to March 30, 2024. For the qualitative component, participants were selected using a purposive sampling technique. Data were entered using EpiData version 4.62 and analyzed using SPSS version 26. Logistic regression was performed to examine the association between the dependent variable and associated factors. Variables with a p-value &lt; 0.05 in the multivariate analysis were considered statistically significant. For qualitative data analysis, OpenCode 4.02 software was used to conduct thematic content analysis. Result A total of 601 adolescent girls participated in this study, yielding a response rate of 96%. Of these, 324 (53.9%; 95% CI: 49.9–57.9%) had received the human papillomavirus vaccine. Vaccine uptake was significantly associated with: Good knowledge about the HPV vaccine (AOR = 3.4; 95% CI: 2.14–5.38), A positive attitude toward the HPV vaccine (AOR = 1.7; 95% CI: 1.02–2.78), Recommendation from health workers to get vaccinated (AOR = 3.8; 95% CI: 2.25–6.50), Family support for vaccination (AOR = 7.1; 95% CI: 3.97–12.60). Qualitative findings identified mistrust of the HPV vaccine, irregular vaccine provision, and lack of information provision as major barriers to uptake. Conclusion In this study, nearly fifty-four percent of adolescent girls had received the HPV vaccine. The overall uptake of the HPV vaccine among adolescent girls remains low. Good knowledge about the HPV vaccine, a positive attitude toward it, recommendations from health workers, and family support were significantly associated with vaccine uptake. Therefore, health facilities and schools should strengthen community-based health education aimed at promoting behavioral change regarding the HPV vaccine and focus on creating various training opportunities for health workers and teachers.

Patient acceptability of CITOBOT for cervical cancer screening: A mixed-method study

This study assessed the acceptability of CITOBOT, a device for early cervical cancer screening in a real-world pilot setting as part of a translational research project aimed at designing and clinically validating a portable, cost-effective device supported by artificial intelligence. The authors adopted the Theoretical Framework of Acceptability for its utility in evaluating patient acceptability within complex interventions’ development, piloting, and feasibility phases. We employed a mixed-method study, with 20 consecutive participants recruited from a specialized cancer healthcare center in Cali, Colombia. Data collection included a sociodemographic, gynecological-obstetric, behavioral survey, a validated patient acceptability scale, alongside open-ended interview questions. No adverse effects were reported seven days post-testing. The findings were promising, with all participants expressing high overall acceptability. Retrospective acceptability, focusing on the evaluation after device pilot testing, revealed that participants felt comfortable with the device, found it coherent with the purpose of early cervical cancer detection, and did not perceive the test as an additional burden compared to conventional cytology screening. Regarding prospective acceptability, which assesses anticipated acceptability before full implementation, three results stand out: i) All participants stated that they would intend to attend their health service if called for testing with CITOBOT; ii) they perceived opportunity costs, such as timely delivery of results, expedited diagnosis and treatment, and improved accessibility for women with limited resources or geographical barriers to healthcare access; and iii) participants viewed CITOBOT as highly effective in preventing cervical cancer deaths, indicating a strong belief in its potential to impact public health outcomes positively. Addressing concerns related to discomfort, inconvenience, and timely delivery of results, CITOBOT shows promise in enhancing cervical cancer screening participation and adherence, especially among underserved populations.

Associations between genetic HPV 16 diversity and cervical cancer prognosis

Introduction Cervical cancer (CC) arises as a result of chronic and persistent female infection by different oncogenic human papillomaviruses (HPV). The incidence of this disease is still high in developing countries, such as Brazil, where diagnosis is often made in advanced stages. HPV 16 is the most common Papillomavirus genotype in CC worldwide. Studies regarding the association of different HPV 16 lineages with overall and disease-free CC survival rates can contribute to further understanding the behavior of different HPV 16 lineages concerning the prognosis of CC cases. Objective To assess the CC prognosis of patients treated in a Brazilian institution concerning HPV16 lineages. Methods Data were obtained from a prospective cohort of 334 patients with CC recruited between July 2011 and March 2014 and treated at the Brazilian National Cancer Institute (INCA), in Rio de Janeiro, Brazil. HPV 16 lineages were identified in tumor tissue samples. Genetic HPV 16 diversity comprised 218 cases of lineage A, 10 of lineage B, 10 of lineage C, and 96 of lineage D. In addition to HPV 16 lineages, age, histopathological type, staging, and treatment completion were evaluated as predictors of CC prognosis. Results The median patient age was 48 years. The most common histopathological type was squamous cell carcinoma (82.3%), followed by adenocarcinoma. Locally advanced disease staging was the most frequently detected, represented by similar stage II and III percentages (36.2% and 37.7%), followed by initial stage I (19.2%) and stage IV (6.9%). Two hundred two patients completed CC treatment. Age, histological type, staging, and treatment completion were associated with a higher risk of death, which was not observed for the HPV 16 lineage variable. With regard to age, an increase in each year of life led to approximately a 1% increase in the risk of death. Other histopathological types (poorly differentiated carcinoma, adenosquamous, neuroendocrine, and sarcoma) were associated with a higher risk of death compared with adenocarcinoma. Patients diagnosed in advanced stages exhibited a higher risk of death, and those who did not complete treatment exhibited an over 2-fold increased risk of death. Conclusion This study found no associations between HPV 16 lineages A, B, C, and D and CC prognosis.

Computational investigation and experimental validation of the molecular mechanism of Solanecio mannii aqueous roots extract against cervical cancer

Cervical cancer remains one of the leading causes of cancer-related mortality among women worldwide, particularly in low- and middle-income countries, highlighting the need for improved strategies in treatment and management. This study aimed to investigate the anti-cervical cancer potential and molecular mechanisms of Solanecio mannii (S. mannii) aqueous extract using a “multi-compound, multi-target, multi-pathway” approach, integrating both computational and experimental methods. The metabolomics profile of the extract was analysed, and its selective cytotoxicity was assessed against human cervical cancer cell lines (HeLa cells) using the CCK8 assay. A network pharmacology approach identified potential molecular targets and pathways, which was complemented by molecular docking and dynamic simulation. The expression levels of key targets were validated experimentally using quantitative real-time polymerase chain reaction. Additionally, the extract’s effects on apoptosis, autophagy, and cell cycle progression were studied experimentally. The aqueous roots extract exhibited selective cytotoxicity against HeLa cells with an IC50 of 12.53 ± 4.983 μg/ml. The network pharmacology analysis identified 25 drug-like compounds targeting 493 unique cervical cancer-associated proteins, forming a protein-protein interaction network of 465 nodes and 2230 edges, and implicated in 178 enriched KEGG pathways. Key targets, including NFΚB1, PIK3CA, HIF1A, STAT3, HSP90AA1, HSP90AB1, PPARG, and ESR1 were experimentally downregulated. Furthermore, S. mannii aqueous roots extract triggered apoptosis through endoplasmic reticulum stress, DNA damage, and activation of the non-transcriptional, P53-mediated mitochondrial apoptotic pathway. Additionally, the extract inhibited hypoxia and autophagy, and induced cell cycle arrest at the G2/M phase, even in the presence of oncogenic HPV proteins (E6 and E7). In conclusion, Solanecio mannii aqueous roots extract demonstrates a “multi-compound, multi-target, multi-pathway” molecular mechanism against cervical cancer.

Proof of concept study of the posterior quadratus lumborum block for laparoscopic myomectomy: A randomized controlled trial

In the United States, 65,000 myomectomies are performed annually to treat uterine fibroids. The quadratus lumborum block (QLB) is an effective block for laparoscopic pelvic surgery, urologic surgery, hip surgery and cesarean sections, with limited data for laparoscopic myomectomies. We evaluated the posterior QLB in reducing MME consumption and numeric rating scale (NRS) pain scores in patients undergoing laparoscopic myomectomies. Twenty-two subjects were enrolled in this single-center, randomized, controlled study between March 28, 2019 and June 16, 2020 and were randomized to either the QLB or control group. Seven subjects were excluded from the final analysis, 5 after being lost to follow-op and 2 for not meeting the inclusion criteria. Recipients in the QLB group received bilateral posterior QLBs, with 30 mL of 0.25% ropivacaine per injection. The primary outcome of MME use at 24 hours was not significant between the QLB group and the control group (23.3 ± 8.5 mg vs. 25.7 ± 14.4 mg, p = 0.859). The secondary outcome of NRS pain scores was also not significant between groups (p &gt; 0.05). While this study did not provide evidence that QLB may be useful in reducing opioid consumption or pain scores in patients undergoing laparoscopic myomectomies, further studies with a larger sample size will be valuable to determine the effectiveness of this block for laparoscopic myomectomy.

Scutellaria Barbata inhibits epithelial-mesenchymal transformation through PI3K/AKT and MDM2 thus inhibiting the proliferation, migration and promoting apoptosis of Cervical Cancer cells

Background Cervical cancer is the fourth most common malignant tumor among women with high morbidity and mortality. We found the active ingredients, action targets and pathways of Scutellaria Barbata against cervical cancer cells, and verified its effects and mechanisms on the proliferation, migration and apoptosis of cervical cancer cells through cellular experiments. Materials and methods The potential effective components of Scutellaria Barbata were obtained by data mining. CCK 8 experiments were used to verify the optimal action time and concentration of the key active components, Baicalin and Wogonin on Hela cells. Transwell Experiments to verify the migration rate of Hela cells at different time points of action. Hela cell apoptosis was determined by a Tunel assay. RT-qPCR and Western Blot detection of related genes and protein expression after the effects of different concentrations of Baicalein and Wogonin on Hela cells. Results Obtained 27 core intersecting targets. Four genes associated with survival of cervical cancer patients were selected by survival by univariate analysis: EGFR, TNF-α, VEGFA and MDM2 (P&lt;0.1). GO and KEGG pathway enrichment analysis showed the four genes played positive regulatory roles, mainly enriched in cellular extracellular zone and cytoplasm. Pathways include cancer pathways, proteoglycans and PI3K/AKT signal. CCK 8 experiments showed that the proliferation rate of Hela cells was significantly lower than that of the control group, and the optimal drug concentration was 10 mg/mL (P &lt;0.001). The migration assay showed that the incubation of the medium with a mixture of 10 mg/mL each or 72h of 5 ml/mL each significantly inhibited the migration of Hela cells (P &lt;0.001). Tunel results showed that single-agent Baicalein or Wogonin with 10 mg/mL had the highest rate of apoptosis on Hela cells after culturing the cells for 72 h. Baicalein or Wogonin (10 mg/mL + 10 mg/mL) had the highest apoptosis ratio in Hela cells after 72h and a higher combination ratio than in the single agent group (P &lt;0.001). The difference between the single drug group and the corresponding low dose group was significant (P&lt;0.001). After Hela cells were cultured for 72 h, the mRNA and protein expressions corresponding to EGFR, TNF-α, VEGFA, PI3K, AKT and MDM2 were decreased in the experimental group compared with the control group as confirmed by RT-PCR and Western blot, and the extent of the decrease was more obvious with the increase of the drug concentration, and under the condition of the same drug dosage, the effect of the Baicalein group was more pronounced than that of the Wogonin group, and the effect was more obvious in the two-drug group compared with the single-drug group (P&lt;0.05). Conclusion After combining with EGFR, TNF-α and VEGFA, the active ingredient of Sculellaria Barbata can regulate the PI3K/AKT signaling pathway and down-regulate the expression of MDM2 gene to inhibit the epithelial-mesenchymal transition, which can inhibit cervical cancer cell proliferation, migration, and promote their apoptosis. Sculellaria Barbata is a potential therapeutic candidate for cervical cancer.

Introduction of AGPAT3 gene as a regulator of cisplatin resistance in A2780 ovarian endometrioid carcinoma cell line

Ovarian cancer therapy remains a challenge for human health, partly due to chemotherapy resistance. Understanding the molecular mechanisms underlying this resistance is crucial. Therefore, to identify genes involved in cisplatin resistance in ovarian cancer, RNA-seq analysis of A2780cp (cisplatin-resistant) and A2780 (cisplatin-sensitive) cell lines was performed, revealing 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3) as a differentially expressed candidate gene. First, MTT analysis confirmed the drug resistance of A2780cp and the sensitivity of A2780 cell lines. Subsequent reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting analyses revealed elevated AGPAT3 and mTOR expression in A2780cp cells compared with A2780 cells. Additionally, western blotting showed increased p-mTOR (phospho-mTOR)/mTOR and p-S6K (phospho-S6K)/S6K ratios in A2780cp cells. The overexpression of AGPAT3 in A2780 cells led to increased p-mTOR/mTOR and p-S6K/S6K ratios and increased IC50 values, as shown by RT-qPCR, western blotting, and MTT analysis. Conversely, shRNA-mediated downregulation of AGPAT3 resulted in reduced p-mTOR/mTOR and p-S6K/S6K ratios. At the cellular level, AGPAT3 overexpression in A2780 cells increased survival rates, decreased apoptosis, and caused G2/M cell cycle arrest under cisplatin treatment, as detected by apoptosis assay, and cell cycle flow cytometry analysis. Overall, we conclude that AGPAT3 is involved in cisplatin resistance in A2780cp cells and propose that targeting this gene or its enzymatic product could help overcome drug resistance.

Surgical myomectomy followed by oral Myfembree vs standard of care (SOUL trial): Study protocol for a randomized control trial

Background Uterine leiomyomas (often referred to as fibroids or myomas) are common benign, hormone-dependent tumors that grow in the uterus and occur in approximately 25% of reproductive age women, depending on selected population. Treatment recommendation is typically based on fibroid size, location, the patient’s age, reproductive plans, and obstetrical history. Despite the range of treatment options available for uterine fibroids and their symptoms, including hysterectomy, myomectomy, endometrial ablation, endometrial uterine artery embolization, and magnetic resonance-guided focused-ultrasound surgery, myomectomy remains the gold standard treatment for patients who desire fertility-preserving surgery for their uterine fibroids. Myomectomy, while a prevalent surgical option for the removal of fibroids, carries known risks such as fibroid recurrence, symptom recurrence, and the subsequent need for reintervention. Despite ongoing research and advances in medical treatments for fibroids, there currently are no universally recommended therapeutic interventions proven to effectively delay the recurrence of fibroids or the return of symptoms following this procedure. This situation underscores a significant area of unmet medical need and highlights the importance of continued investigation into preventive strategies and long-term management options for patients undergoing fibroid removal with uterine preservation. We designed a study to assess the efficacy of the new FDA-approved GnRH antagonist, Myfembree in delaying the return of fibroids and their associated symptoms. Methods A randomized, prospective, open-label clinical trial. The participants (n = 136) will be randomly distributed into two groups. The Control Group (Standard of care) will receive treatment with standard of care (SoC) after surgical myomectomy and the treatment group will receive Relugolix combination therapy (Myfembree®) after surgical myomectomy. The study protocol was approved by the University of Chicago’s Institutional Review Board (IRB#22–0282), ensuring that all participants would provide written informed consent before their inclusion. Discussion In this project, we propose the use of daily dosed Relugolix combination therapy (Relugolix with estradiol and norethindrone acetate), which is approved for uterine fibroids treatment, has the potential to delay the recurrence of fibroid symptoms, prolong the improved quality of life and delay need for re-intervention after uterine sparing surgery. Trial registration The study protocol was approved by the Institutional Review Board of the University of Chicago on 9/16/2022 and was registered at ClinicalTrials.gov with number NCT05538689 on Sep 7, 2022. All subjects will provide informed consent to participate.

Endothelial cell specific molecule 1 promotes epithelial-mesenchymal transition of cervical cancer via the E-box binding homeobox 1

Objective To investigate the mechanism of endothelial cell specific molecule 1 (ESM1) promoting cervical cancer cell proliferation and EMT characteristics through zinc finger E-box binding homeobox 1 (ZEB1)/EMT pathway. Methods The correlation between ESM1 expression and prognosis of cervical cancer patients was analyzed by bioinformatics. SiHa, HeLa cell lines and corresponding control cell lines with stable ESM1 expression were obtained. Cell proliferation ability was detected by CCK-8 assay. The invasion and migration ability of Hela and SiHa cells were detected by Transwell assay and scratch closure assay. Expressions of EMT-related markers E-cadherin and Vimentin were detected by real-time PCR. The ability of silenced ESM1 to tumor formation in vivo was detected by tumor formation in nude mice. The effects of aloe-emodin on inhibit ESM1 expression and its inhibitory effect on cervical cancer cells in vitro and in vivo were analyzed by the same method. Results ESM1 was highly expressed in cervical cancer, and the high expression of ESM1 was associated with poor prognosis of cervical cancer patients. CCK-8 results showed that the proliferation, invasion and migration of Hela and SiHa cells were significantly reduced after siRNA interfered with ESM1 expression. Overexpression of ESM1 promoted the proliferation and migration of cervical cancer cells. Mechanism studies have shown that the oncogenic effect of ESM1 is realized through the ZEB1/PI3K/AKT pathway. High throughput drug screening found that aloe-emodin can target ESM1. Inhibitory effect of aloe emodin on ESM1/ZEB1/EMT signaling pathway and cervical cancer cells. Conclusion The silencing of ESM1 expression may inhibit the proliferation, invasion, metastasis and epithelial-mesenchymal transformation of cervical cancer cells by inhibiting ZEB1/PI3K/AKT. Aloe-emodin is a potential treatment for cervical cancer, which can play an anti-tumor role by inhibiting ESM1/ZEB1.

Identification of exosomal circSLC26A4 as a liquid biopsy marker for cervical cancer

Objective Circular RNA SLC26A4 (circSLC26A4) functions as an oncogene in the initiation and progression of cervical cancer (CC). However, the clinical role of plasma exosomal circSLC26A4 in CC is poorly known. This study aims to develop an accurate diagnostic method based on circulating exosomal circSLC26A4. Methods In this study, exosomal circSLC26A4 derived from CC cell lines (CaSki, SiHa, and HeLa) and human cervical epithelial cells (HcerEpic) was measured and compared using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Additionally, 56 volunteers, including 18 CC patients, 18 cervical high-grade squamous intraepithelial lesion (HSIL) patients, and 20 healthy volunteers, were enrolled. qRT-PCR was also performed to measure the plasma exosomal circSLC26A4 levels in all participants. Results The exosomal circSLC26A4 expression level derived from CC cells was significantly elevated compared to it derived from HcerEpic cells. Plasma exosomal circSLC26A4 levels in CC patients were significantly higher than in healthy women and HSIL patients (P &lt; 0.05). In addition, high plasma exosomal circSLC26A4 expression was positively associated with lymph node metastasis and FIGO stage (all P &lt; 0.05). However, no significant correlation was found between plasma exosomal circSLC26A4 expression and age, intravascular cancerous embolus, and perineural invasion (P &gt; 0.05). Conclusions The high exosomal circSLC26A4 expression is closely related to the occurrence of CC. Plasma exosomal circSLC26A4 can be used as a diagnostic marker for CC.

Xenoestrogen concentration in women with endometriosis or leiomyomas: A case-control study

Background Xenoestrogens are synthetic or naturally occurring chemicals capable of altering the endocrine system of humans and animals owing to their molecular similarity to endogenous hormones. There is limited data regarding their effects on women´s health. Chronic exposure to xenoestrogens can promote the development of estrogen-related diseases. Objectives To examine xenoestrogen concentration (TEXB-α) differences between women with leiomyomas or endometriosis and control women, and to study the relationship between the clinical and sociodemographic characteristics of these patients and their xenoestrogen levels. Methods Prospective case-control study. We selected 221 women who underwent surgery at Quironsalud Madrid University Hospital between 2017 and 2021. The cases included 117 patients: 74 women who underwent surgery for uterine leiomyomas, 21 with endometriosis, and 22 with both pathologies. The control group comprised 104 healthy women who underwent surgical procedures for other reasons. TEXB-α was determined in the omental fat of all patients. Using a questionnaire and reviewing the patients’ medical records, we collected sociodemographic data and other relevant variables. Results A significant majority of study participants (68.8%) had detectable levels of xenoestrogens. We found no association between TEXB-α levels in omental fat and the presence of myomas or endometriosis. In the case group, women living or working in Madrid Community exhibited, on average, 3.12 Eeq pM/g higher levels of TEXB-α compared to those working in other areas (p = 0.030). Women who referred to the use of estrogen-containing hormonal contraceptives had, on average, 3.02 Eeq pM/g higher levels of TEXB-α than those who had never used them (p = 0.022). Conclusions This study found no association between omental xenoestrogen levels and leiomyomas or endometriosis. However, their presence in most participants and their association with highly polluted areas emphasizes the importance of limiting environmental exposure to these substances. We also identified an association between hormonal contraceptive use and xenoestrogen concentration.

Understanding primary care providers’ attitudes towards preventive screenings to patients with inflammatory bowel disease

Background Preventive care is important for managing inflammatory bowel disease (IBD), yet primary care providers (PCPs) often face challenges in delivering such care due to discomfort and unfamiliarity with IBD-specific guidelines. This study aims to assess PCPs’ attitudes towards, and practices in, providing preventive screenings for IBD patients, highlighting areas for improvement in guideline dissemination and education. Methods Using a web-based opt-in panel of PCPs (DocStyles survey, spring 2022), we assessed PCPs’ comfort level with providing/recommending screenings and the reasons PCPs felt uncomfortable (n = 1,503). Being likely to provide/recommend screenings for depression/anxiety, skin cancer, osteoporosis, and cervical cancer were compared by PCPs’ comfort level and frequency of seeing patients with IBD. We estimated adjusted odd ratios (AORs) of being likely to recommend screenings and selecting responses aligned with IBD-specific guidelines by use of clinical practice methods. Results About 72% of PCPs reported being comfortable recommending screenings to patients with IBD. The top reason identified for not feeling comfortable was unfamiliarity with IBD-specific screening guidelines (55%). Being comfortable was significantly associated with being likely to provide/recommend depression/anxiety (AOR = 3.99) and skin cancer screenings (AOR = 3.19) compared to being uncomfortable or unsure. Percentages of responses aligned with IBD-specific guidelines were lower than those aligned with general population guidelines for osteoporosis (21.7% vs. 27.8%) and cervical cancer screenings (34.9% vs. 43.9%), and responses aligned with IBD-specific guidelines did not differ by comfort level for both screenings. Timely review of guidelines specific to immunosuppressed patients was associated with being likely to provide/recommend screenings and selecting responses aligned with IBD-specific guidelines. Conclusions Despite a general comfort among PCPs in recommending preventive screenings for IBD patients, gaps in knowledge regarding IBD-specific screening guidelines persist. Enhancing awareness and understanding of these guidelines through targeted education and resource provision may bridge this gap.

Psychometric properties of a modified health belief model for cervical cancer and visual inspection with acetic acid among healthcare professionals in Ethiopia

Purpose Evidence supports that the Health Belief Model (HBM) can explain and predicts certain health behaviors, including participation in cervical cancer (CC) screening. The purpose of this study was to evaluate the psychometric properties of a modified HBM for CC and visual inspection with acetic acid (VIA) in female healthcare professionals in Addis Ababa, Ethiopia, 2020. Methods Psychometric properties related to CC and VIA were tested using 42-item modified HBM self-administered questionnaire and a cross-sectional study design with simple random sampling. Kaiser-Meyer-Olkin and Bartlett’s sphericity test indicated that data sampling adequacy for exploratory factor analysis was 0.792 (χ2 = 3189.95, df = 351, p &lt; .001). Items with cross-loading and factor loadings ≥ 0.5 were retained. Confirmatory factor analysis (CFA) was conducted to determine model fit. Results The final analysis included 194 women, (mean age 30±4.34). Twelve items with ≤ 0.5 were removed and 30 retained items loaded into 6 factors; (benefits of VIA, perceived seriousness of CC, barrier (fear of negative outcome), self-efficacy, susceptibility to CC, and barriers (health system delivery)) explained 65% of the total variance. Cronbach’s alpha for the total instrument was 0.8 and reliability for the 6 subscales was 0.76–0.92. Composite reliability and average variance extracted indicated good internal consistency and convergent validity. CFA identified 6 additional items to be removed with high residual covariance. The final 24 items of the modified HBM had an acceptable model fit (goodness-of-fit index (GFI) = 0.861, adjusted GFI = 0.823, comparative fit index = 0.937, root mean square error of approximation = 0.059). Conclusion The modified HBM for CC and VIA with 24 items had adequate psychometric properties and may be used by Ethiopian healthcare professionals for research or clinical purposes. To support external validity the updated 24 items tool is suggested for application in further study in different populations in Ethiopia.

Short video platforms as sources of health information about cervical cancer: A content and quality analysis

BackgroundThe development of short popular science video platforms helps people obtain health information, but no research has evaluated the information characteristics and quality of short videos related to cervical cancer. The purpose of this study was to evaluate the quality and reliability of short cervical cancer-related videos on TikTok and Kwai.MethodsThe Chinese keyword "cervical cancer" was used to search for related videos on TikTok and Kwai, and a total of 163 videos were ultimately included. The overall quality of these videos was evaluated by the Global Quality Score (GQS) and the modified DISCERN tool.ResultsA total of 163 videos were included in this study, TikTok and Kwai contributed 82 and 81 videos, respectively. Overall, these videos received much attention; the median number of likes received was 1360 (403–6867), the median number of comments was 147 (40–601), and the median number of collections was 282 (71–1296). In terms of video content, the etiology of cervical cancer was the most frequently discussed topic. Short videos posted on TikTok received more attention than did those posted on Kwai, and the GQS and DISCERN score of videos posted on TikTok were significantly better than those of videos posted on Kwai. In addition, the videos posted by specialists were of the highest quality, with a GQS and DISCERN score of 3 (2–3) and 2 (2–3), respectively. Correlation analysis showed that GQS was significantly correlated with the modified DISCERN scores (p&lt;0.001).ConclusionIn conclusion, the quality and reliability of cervical cancer-related health information provided by short videos were unsatisfactory, and the quality of the videos posted on TikTok was better than that of videos posted on Kwai. Compared with those posted by individual users, short videos posted by specialists provided higher-quality health information.

Examining cancer screening disparities by race/ethnicity and insurance groups: A comparison of 2008 and 2018 National Health Interview Survey (NHIS) data in the United States

Background Pervasive differences in cancer screening among race/ethnicity and insurance groups presents a challenge to achieving equitable healthcare access and health outcomes. However, the change in the magnitude of cancer screening disparities over time has not been thoroughly examined using recent public health survey data. Methods A retrospective cross-sectional analysis of the 2008 and 2018 National Health Interview Survey (NHIS) database focused on breast, cervical, and colorectal cancer screening rates among race/ethnicity and insurance groups. Multivariable logistic regression models were used to assess the relationship between cancer screening rates, race/ethnicity, and insurance coverage, and to quantify the changes in disparities in 2008 and 2018, adjusting for potential confounders. Results Colorectal cancer screening rates increased for all groups, but cervical and mammogram rates remained stagnant for specific groups. Non-Hispanic Asians continued to report consistently lower odds of receiving cervical tests (OR: 0.42, 95% CI: 0.32–0.55, p&lt;0.001) and colorectal cancer screening (OR: 0.55, 95% CI: 0.42–0.72, p&lt;0.001) compared to non-Hispanic Whites in 2018, despite significant improvements since 2008. Non-Hispanic Blacks continued to report higher odds of recent cervical cancer screening (OR: 1.98, 95% CI: 1.47–2.68, p&lt;0.001) and mammograms (OR: 1.32, 95% CI: 1.02–1.71, p&lt;0.05) than non-Hispanic Whites in 2018, consistent with higher odds observed in 2008. Hispanic individuals reported improved colorectal cancer screening over time, with no significant difference compared to non-Hispanics Whites in 2018, despite reporting lower odds in 2008. The uninsured status was associated with significantly lower odds of cancer screening than private insurance for all three cancers in 2008 and 2018. Conclusion Despite an overall increase in breast and colorectal cancer screening rates between 2008 and 2018, persistent racial/ethnic and insurance disparities exist among race/ethnicity and insurance groups. These findings highlight the importance of addressing underlying factors contributing to disparities among underserved populations and developing corresponding interventions.

Real-world effectiveness of cytology and HPV-based screening strategy in cervical cancer screening: A cross-sectional population-based study in Chengdu, China

Cervical cancer poses a significant health challenge in developing countries, emphasizing the need for appropriate screening strategies to accelerate the elimination of this disease. This study summarized the results of a large-scale community-based cervical cancer screening program conducted in Chengdu, China, to understand the prevalence of HPV infection and cervical lesions in the population, and to compare the real-world effectiveness of two different screening methods implemented in the program. From January 2021 to December 2022, a total of 363,376 women aged 35–64 years in Chengdu received free screenings. Among these participants, 70.1% received cytology screening and 29.9% received HPV testing combined with 16/18 genotyping and cytology triage. Ultimately, 824 cases of high-grade lesions and cervical cancer were detected, with a total detection rate of cervical cancer and precancerous lesions of 226.8 per 100,000. The follow-up rate of patients with high-grade lesions and above was 98.9%, and the treatment rate was 86.6%. The overall high-risk HPV infection rate was 11.7%, with the HPV 16/18 infection rate of 1.4%. The rate of abnormal cytology results was 2.8%. The attendance rates for colposcopy and histopathology were 71.6% and 86.1%, respectively. By calculating the age-standardized rates to eliminate the different age composition between the two group, the HPV-based screening strategy had a higher rate of primary screening abnormalities (3.4% vs. 2.8%, P&lt;0.001), higher attendance rates of colposcopy (76.5% vs. 68.9%, P&lt;0.001) and histopathological diagnosis (94.1% vs. 78.0%, P&lt;0.001), higher percentage of abnormal colposcopy results (76.0% vs. 44.0%, P&lt;0.001), and higher detection rate of cervical precancerous lesions and cancer (393.1 per 100,000 vs. 156.4 per 100,000, P&lt;0.001) compared to cytology screening. Our study indicates that the combination of HPV testing with 16/18 genotyping and cytology triage has demonstrated superior performance in cervical cancer screening compared to cytology alone in large-scale population.

Biobanking of gynecologic cancer biospecimens: Development, quality control, and translational applications

Introduction This study presents a nationwide infrastructure for the collection and utilization of gynecologic cancer biospecimens, established through the Korea Biobank Project. We comprehensively describe the biobanking strategy, quality control protocols, and development of secondary resources to support future translational and discovery-based research. Methods We established a gynecologic cancer biobank within the Korea Biobank Project (KBP) through a multi-institutional consortium. Biospecimens, including blood, tumor tissue, urine, and ascites, were collected from 294 patients with endometrial, cervical, or ovarian cancers. Pre-analytical variables were documented using the Standard PREanalytical Code (SPREC), and all samples were tracked with 2D barcodes. Secondary resources were developed, including whole-genome sequencing (WGS) datasets, immortalized human ovarian surface epithelial (IHOSE) cell lines, patient-derived xenografts (PDX), tumor organoids, and tissue microarrays (TMAs). Results A total of 6,168 biospecimens were archived. WGS was performed on 386 cancer samples, including 172 paired tumor–normal sets. Four IHOSE cell lines were authenticated and validated for stability, 14 PDX models retained histological fidelity across passages, and patient-derived ovarian cancer organoids demonstrated drug sensitivity consistent with clinical response patterns. TMAs were constructed from 519 tumors, supporting large-scale molecular profiling. Industry collaborations further highlighted the translational utility of these resources. Conclusions This study describes the development and application of a gynecologic cancer biobank that integrates standardized biospecimen collection, rigorous QC, and the generation of diverse secondary resources. By linking these resources with clinical and epidemiological data, the biobank provides a scalable and accessible platform for precision oncology and academic–industry collaboration.

Study protocol for a hybrid implementation-effectiveness trial of Game Changers for Cervical Cancer Prevention in Uganda

Introduction Cervical cancer (CC) is the leading cause of cancer-related deaths among Uganda women, yet rates of CC screening are very low. Training women who have recently screened to engage in advocacy for screening among women in their social network is a network-based strategy for promoting information dissemination and CC screening uptake. Methods Drawing on the Exploration, Preparation, Implementation and Sustainment (EPIS) framework for implementation science, this hybrid type 1 randomized controlled trial (RCT) of a peer-led, group advocacy training intervention, Game Changers for Cervical Cancer Prevention (GC-CCP), will examine efficacy for increasing CC screening uptake as well as how it can be implemented and sustained in diverse clinic settings. In the Preparation phase we will prepare the four study clinics for implementation of GC-CCP and the expected increase in demand for CC screening, by using qualitative methods (stakeholder interviews and client focus groups) to identify and address structural barriers to easy access to CC screening. In the Implementation phase, GC-CCP will be implemented over 36 months at each clinic, with screened women (index participants) enrolled as research participants receiving the intervention in the first 6 months as part of a parallel group RCT overseen by the research study team to evaluate efficacy for CC screening uptake among their enrolled social network members. All research participants will be assessed at baseline and months 6 and 12. Intervention implementation and supervision will then be transitioned to clinic staff and offered as part of usual care in the subsequent 30 months as part of the Sustainability phase. Using the RE-AIM framework, we will evaluate engagement in GC-CCP and CC advocacy (reach), alter CC screening (effectiveness), adoption into clinic operations, implementation outcomes (acceptability, feasibility, fidelity, cost-effectiveness) and maintenance. Discussion This is one of the first studies to use a network-driven approach and empowerment of CC screened peers as change agents to increase CC screening. If shown to be an effective and sustainable implementation strategy for promoting CC screening, this peer advocacy model could be applied to other preventative health behaviors and disease contexts. Trial registration NIH Clinical Trial Registry NCT06010160 (clinicaltrials.gov; date: 8/17/2023).

Real world data on cervical cancer treatment patterns, healthcare access and resource utilization in the Brazilian public healthcare system

The aim of the study is to evaluate the treatment patterns, time to start treatment, and healthcare resources utilization (HCRU) of cervical cancer (CC) patients within the Brazilian public health system (SUS). This is an observational retrospective study using SUS administrative database (DATASUS). Data from January-2014 to December-2020 was gathered from patients with the ICD-10 C53 codes. From 2014 to 2020, 206,861 women were included, among whom 90,073 (43.5%) had stage information. Of staged patients, 60.7% (54,719) had advanced disease (stages III and IV) and the most performed treatments were chemoradiotherapy (CRT) (41.6%), surgery + CRT (19.1%), radiotherapy (RT) only (16.8%) and chemotherapy (CT) only (13.3%). The proportion of patients submitted to CT in advanced stages was higher than in non-advanced stages (I and II), in contrast to RT, which was more frequent in stage I than stage IV. Median time to initiate treatment surpassed two months in approximately 30% of the cases, regardless of stage. Conization was the most performed surgical procedure. The hospitalization rate per patient per month for stage IV was twice as high as stage I (0.05 [95%CI 0.05–0.05] and 0.11 [0.11–0.11], respectively). The same trend was observed for outpatient visits (0.54 [95%CI 0.53–0.55] and 0.96 [0.93–0.98], respectively). This study demonstrated a high proportion of advanced CC at diagnosis in Brazil. The treatment pattern showed that chemoradiotherapy was the most frequent regimen overall and the use of chemotherapy and HCRU increased with staging. These results could provide information to improve public policies towards access to prevention, diagnosis, and treatment of CC in Brazil.

Prevalence and correlates of Human Papillomavirus infection in females from Southern Province, Zambia: A cross-sectional study

Background Human papillomavirus (HPV) infection is strongly associated with cervical cancer with almost all cases being associated with the infection. Cervical cancer is the leading cause of cancer death among women in Zambia and the fourth leading cause of cancer death in women worldwide. However, there is limited data on the burden and associated factors of HPV in sub-Saharan Africa. This study therefore aimed to determine the prevalence and correlates of HPV infection in the Southern province of Zambia. Methods This was a cross-sectional study conducted at Livingstone University Teaching Hospital (LUTH) among 4,612 women from different districts of the southern province being screened for HPV infection between September 2021 and August 2022. Demographic and clinical data were collected from an existing laboratory programmatic database. Multivariable logistic regression was used to estimate the factors associated with HPV infection. Results The study participants had a median age of 39 years [interquartile range (IQR) 30, 47]. The prevalence of HPV infection was 35.56% (95%CI). At multivariable analysis, the factors associated with a positive HPV result were younger age (adjusted odds ratio (AOR) 0.98; 95% confidence interval (CI) 0.98–0.99; p. value 0.001), having provider collected sample (AOR 2.15; 95%CI 1.66–2.79; p. value &lt;0.001) and living with HIV (AOR 1.77; 95%CI 1.22–2.55; p. value &lt;0.002). Conclusion The prevalence of HPV in women in the southern province of Zambia is high, and likely influenced by age and HIV status. Additionally, the outcome of the HPV test is affected by the sample collection method. Therefore, there is a necessity to enhance HPV and cervical cancer screening, especially among people with HIV.

Unique features of KGN granulosa-like tumour cells in the regulation of steroidogenic and antioxidant genes

The ovarian KGN granulosa-like tumour cell line is commonly used as a model for human granulosa cells, especially since it produces steroid hormones. To explore this further, we identified genes that were differentially expressed by KGN cells compared to primary human granulosa cells using three public RNA sequence datasets. Of significance, we identified that the expression of the antioxidant gene TXNRD1 (thioredoxin reductase 1) was extremely high in KGN cells. This is ominous since cytochrome P450 enzymes leak electrons and produce reactive oxygen species during the biosynthesis of steroid hormones. Gene Ontology (GO) analysis identified steroid biosynthetic and cholesterol metabolic processes were more active in primary granulosa cells, whilst in KGN cells, DNA processing, chromosome segregation and kinetochore pathways were more prominent. Expression of cytochrome P450 cholesterol side-chain cleavage (CYP11A1) and cytochrome P450 aromatase (CYP19A1), which are important for the biosynthesis of the steroid hormones progesterone and oestrogen, plus their electron transport chain members (FDXR, FDX1, POR) were measured in cultured KGN cells. KGN cells were treated with 1 mM dibutyryl cAMP (dbcAMP) or 10 μM forskolin, with or without siRNA knockdown of TXNRD1. We also examined expression of antioxidant genes, H2O2 production by Amplex Red assay and DNA damage by γH2Ax staining. Significant increases in CYP11A1 and CYP19A1 were observed by either dbcAMP or forskolin treatments. However, no significant changes in H2O2 levels or DNA damage were found. Knockdown of expression of TXNRD1 by siRNA blocked the stimulation of expression of CYP11A1 and CYP19A1 by dbcAMP. Thus, with TXNRD1 playing such a pivotal role in steroidogenesis in the KGN cells and it being so highly overexpressed, we conclude that KGN cells might not be the most appropriate model of primary granulosa cells for studying the interplay between ovarian steroidogenesis, reactive oxygen species and antioxidants.

Understanding cervical cancer awareness in hard-to-reach areas of Bangladesh: A cross-sectional study involving women and household decisionmakers

Introduction In Bangladesh, the uptake of cervical cancer screening is low. Lack of knowledge and understanding of symptoms and risk factors contributes to low screening uptake. The purpose of this study was to explore the knowledge of cervical cancer risk factors and symptoms and to measure the association with socio-demographic characteristics among women and household decisionmakers living in hard-to-reach areas of Bangladesh. Methods A cross-sectional survey was conducted in five districts in Bangladesh among women aged between 30 and 60 years, their husbands, and their mothers-in-law from April to September 2022. Data were collected using a modified version of the validated AWACAN questionnaire tool. The significance level was considered at p-value &lt;0.05 and odds ratios with 95% confidence. Results Nearly 50% of participating women in hard-to-reach areas of Bangladesh and their family decisionmakers had low levels of knowledge of the risk factors and symptoms of cervical cancer. Only 20% of respondents in our survey knew about HPV, the most important risk factor for developing cervical cancer. Most respondents were familiar with the terminology of cervical cancer as a disease; however, approximately 40% of respondents did not know that not adhering to cervical cancer screening could be seen as a risk factor. Women do not make decisions about participation in cervical cancer screening on their own. Knowledge of cervical cancer risk factors and symptoms among decisionmakers was significantly associated with higher education and higher household monthly expenditure. Conclusion Women, their husbands, and mothers-in-law in hard-to-reach areas of Bangladesh had limited knowledge about cervical cancer risk factors and symptoms. Engaging these key decision-makers in targeted health education is vital to improve screening uptake. Conduction of future research to identify and address screening barriers is also essential for effective prevention efforts.

Preclinical studies of RA475, a guanidine-substituted spirocyclic candidate RPN13/ADRM1 inhibitor for treatment of ovarian cancer

There is an urgent unmet need for more targeted and effective treatments for advanced epithelial ovarian cancer (EOC). The emergence of drug resistance is a particular challenge, but small molecule covalent inhibitors have promise for difficult targets and appear less prone to resistance. Michael acceptors are covalent inhibitors that form bonds with cysteines or other nucleophilic residues in the target protein. However, many are categorized as pan-assay interference compounds (PAINS) and considered unsuitable as drugs due to their tendency to react non-specifically. Targeting RPN13/ADRM1-mediated substrate recognition and deubiquitination by the proteasome 19S Regulatory Particle (RP) is a promising treatment strategy. Early candidate RPN13 inhibitors (iRPN13) produced a toxic accumulation of very high molecular weight polyubiquitinated substrates, resulting in therapeutic activity in mice bearing liquid or solid tumor models, including ovarian cancer; however, they were not drug-like (PAINS) because of their central piperidone core. Up284 instead has a central spiro-carbon ring. We hypothesized that adding a guanidine moiety to the central ring nitrogen of Up284 would produce a compound, RA475, with improved drug-like properties and therapeutic activity in murine models of ovarian cancer. RA475 produced a rapid accumulation of high molecular polyubiquitinated proteins in cancer cell lines associated with apoptosis, similar to Up284 although it was 3-fold less cytotoxic. RA475 competed binding of biotinylated Up284 to RPN13. RA475 shows improved solubility and distinct pharmacodynamic properties compared to Up284. Specifically, tetraubiquitin firefly luciferase expressed in leg muscle was stabilized in mice more effectively upon IP treatment with RA475 than with Up284. However, pharmacologic analysis showed that RA475 was more rapidly cleared from the circulation, and less orally available than Up284. RA475 shows reduced ability to cross the blood-brain barrier and in vitro inhibition of HERG. Treatment of mice with RA475 profoundly inhibited the intraperitoneal growth of the ID8-luciferase ovarian tumor model. Likewise, RA475 treatment of immunocompetent mice inhibited the growth of spontaneous genetically-engineered peritoneal tumor, as did weekly cisplatin dosing. The combination of RA475 and cisplatin significantly extended survival compared to individual treatments, consistent with synergistic cytotoxicity in vitro. In sum, RA475 is a promising candidate covalent RPN13i with potential utility for treatment of patients with advanced EOC in combination with cisplatin.

Overexpression of miR-200s inhibits proliferation and invasion while increasing apoptosis in murine ovarian cancer cells

Women diagnosed with ovarian cancer frequently have a poor prognosis as their cancer is often diagnosed at more advanced stages when the cancer has metastasized. At this point surgery cannot remove all the tumor cells and while ovarian cancer cells often initially respond to chemotherapeutic agents like carboplatin and paclitaxel, resistance to these agents frequently occurs. Thus, novel therapies are required for the treatment of advanced stage ovarian cancer. One therapeutic option being explored is the regulation of non-coding RNAs such as microRNAs. An advantage of microRNAs is that they can regulate tens, hundreds and sometimes thousands of mRNAs in cells and thus may be more effective than chemotherapeutic agents or targeted therapies. To investigate the therapeutic potential of miR-200s in ovarian cancer, lentiviral vectors were used to overexpress both miR-200 clusters in two murine ovarian cancer cell lines, ID8 and 28–2. Overexpression of miR-200s reduced the expression of several mesenchymal genes and proteins, significantly inhibited proliferation as assessed by BrdU flow cytometry and significantly reduced invasion through Matrigel coated transwell inserts in both cell lines. Overexpression of miR-200s also increased basal apoptosis approximately 3-fold in both cell lines as determined by annexin V flow cytometry. Pathway analysis of RNA sequencing of control and miR-200 overexpressing ovarian cancer cells revealed that genes regulated by miR-200s were involved in processes like epithelial mesenchymal transition (EMT) and cell migration. Therefore, miR-200s can inhibit proliferation and increase apoptosis while suppressing tumor cell invasion and thus simultaneously target three key cancer pathways.

Predictive modeling of gene mutations for the survival outcomes of epithelial ovarian cancer patients

Epithelial ovarian cancer (EOC) has a low overall survival rate, largely due to frequent recurrence and acquiring resistance to platinum-based chemotherapy. EOC with homologous recombination (HR) deficiency has increased sensitivity to platinum-based chemotherapy because platinum-induced DNA damage cannot be repaired. Mutations in genes involved in the HR pathway are thought to be strongly correlated with favorable response to treatment. Patients with these mutations have better prognosis and an improved survival rate. On the other hand, mutations in non-HR genes in EOC are associated with increased chemoresistance and poorer prognosis. For this reason, accurate predictions in response to treatment and overall survival remain challenging. Thus, analyses of 360 EOC cases on NCI’s The Cancer Genome Atlas (TCGA) program were conducted to identify novel gene mutation signatures that were strongly correlated with overall survival. We found that a considerable portion of EOC cases exhibited multiple and overlapping mutations in a panel of 31 genes. Using logistical regression modeling on mutational profiles and patient survival data from TCGA, we determined whether specific sets of deleterious gene mutations in EOC patients had impacts on patient survival. Our results showed that six genes that were strongly correlated with an increased survival time are BRCA1, NBN, BRIP1, RAD50, PTEN, and PMS2. In addition, our analysis shows that six genes that were strongly correlated with a decreased survival time are FANCE, FOXM1, KRAS, FANCD2, TTN, and CSMD3. Furthermore, Kaplan-Meier survival analysis of 360 patients stratified by these positive and negative gene mutation signatures corroborated that our regression model outperformed the conventional HR genes-based classification and prediction of survival outcomes. Collectively, our findings suggest that EOC exhibits unique mutation signatures beyond HR gene mutations. Our approach can identify a novel panel of gene mutations that helps improve the prediction of treatment outcomes and overall survival for EOC patients.

Extracellular ATP/P2X7 receptor, a regulatory axis of migration in ovarian carcinoma-derived cells

ATP is actively maintained at high concentrations in cancerous tissues, where it promotes a malignant phenotype through P2 receptors. In this study, we first evaluated the effect of extracellular ATP depletion with apyrase in SKOV-3, a cell line derived from metastatic ovarian carcinoma. We observed a decrease in cell migration and an increase in transepithelial electrical resistance and cell markers, suggesting a role in maintaining a mesenchymal phenotype. To identify the P2 receptor that mediated the effects of ATP, we compared the transcript levels of some P2 receptors and found that P2RX7 is three-fold higher in SKOV-3 cells than in a healthy cell line, namely HOSE6-3 (from human ovarian surface epithelium). Through bioinformatic analysis, we identified a higher expression of the P2RX7 transcript in metastatic tissues than in primary tumors; thus, P2X7 seems to be a promising effector for the malignant phenotype. Subsequently, we demonstrated the presence and functionality of the P2X7 receptor in SKOV-3 cells and showed through pharmacological approaches that its activity promotes cell migration and contributes to maintaining a mesenchymal phenotype. P2X7 activation using BzATP increased cell migration and abolished E-cadherin expression. On the other hand, a series of P2X7 receptor antagonists (A438079, BBG and OxATP) decreased cell migration. We used a CRISPR-based knock-out system directed to P2RX7. According to the results of our wound-healing assay, SKOV3-P2X7KO cells lacked receptor-mediated calcium mobilization and decreased migration. Altogether, these data let us propose that P2X7 receptor is a regulator for cancer cell migration and thus a potential drug target.

The association between smoking and cervical human papillomavirus infection among women from indigenous communities in western Botswana

Introduction Cervical cancer, a malignancy caused by infection with oncogenic human papillomavirus, disproportionally affects women from low resource settings. Persistence of human papillomavirus infection may mediate an association between tobacco use and cervical cancer. In limited resource settings, women from indigenous communities are often marginalized and do not benefit from evidence-based interventions to prevent tobacco use or cervical cancer due to the limited reach of mainstream healthcare services to these communities. This study determined the association between smoking and high-risk human papillomavirus infection among women from indigenous communities in western Botswana. Methods A cross-sectional study of women in indigenous communities was conducted between June and October 2022. Demographic, clinical and self-reported smoking data were collected. Cervical cytology and HPV DNA testing for high-risk human papillomavirus genotypes were performed. Multilevel multivariable logistic regression models were fit to evaluate the association between smoking and high-risk human papillomavirus infection while adjusting for potential confounders. Results A total of 171 participants with a median (interquartile range) age of 40 (31–50) years from three settlements and two villages were recruited for the study. Of these, 17% were current smokers, 32.8% were living with HIV and high-risk human papillomavirus DNA was detected in 32.8% of the cervical specimens. Women who were current smokers, were nearly twice as likely to have cervical high-risk human papillomavirus infection compared to non-smokers (Adjusted Odds Ratio (95% CI); 1.74(1.09, 2.79)) after controlling for confounders. Conclusion These data underscore the need for effective tobacco control to help mitigate cervical cancer risk in this setting. These findings can help inform decisions about targeted cervical cancer prevention and tobacco cessation interventions for women from indigenous communities.

The every woman study™ low- and middle-income countries edition protocol: A multi-country observational study to assess opportunities and challenges to improving survival and quality of life for women with ovarian cancer

Background Ovarian cancer is a challenging disease to diagnose and treat effectively with five-year survival rates below 50%. Previous patient experience research in high-income countries highlighted common challenges and opportunities to improve survival and quality of life for women affected by ovarian cancer. However, no comparable data exist for low-and middle-income countries, where 70% of women with the disease live. This study aims to address this evidence gap. Methods This is an observational multi-country study set in low- and middle-income countries. We aim to recruit over 2000 women diagnosed with ovarian cancer across multiple hospitals in 24 countries in Asia, Africa and South America. Country sample sizes have been calculated (n = 70–96 participants /country), taking account of varying national five-year disease prevalence rates. Women within five years of their diagnosis, who are in contact with participating hospitals, are invited to take part in the study. A questionnaire has been adapted from a tool previously used in high-income countries. It comprises 57 multiple choice and two open-ended questions designed to collect information on demographics, women’s knowledge of ovarian cancer, route to diagnosis, access to treatments, surgery and genetic testing, support needs, the impact of the disease on women and their families, and their priorities for action. The questionnaire has been designed in English, translated into local languages and tested according to local ethics requirements. Questionnaires will be administered by a trained member of the clinical team. Conclusion This study will inform further research, advocacy, and action in low- and middle-income countries based on tailored approaches to the national, regional and global challenges and opportunities. In addition, participating countries can choose to repeat the study to track progress and the protocol can be adapted for other countries and other diseases.

Effects of speculum lubrication on cervical smears for cervical cancer screening: A double blind randomized clinical trial

Background Speculum lubrication may help to reduce the pain experienced during Pap-smear collection and hence increase uptake of cervical cancer screening and repeat testing, but there are fears of its interference with cytological results. Aim To determine and compare the adequacy of cervical cytology smears and the mean pain scores of women undergoing cervical cancer screening with or without speculum lubrication. Methods This was a randomised controlled study of 132 women having cervical cancer screening at a tertiary hospital in Nigeria. Sixty-six participants were randomly assigned to the ‘Gel’ and ‘No Gel’ groups, respectively. Pap smears were collected from each participant with a lubricated speculum (‘Gel group’) or a non-lubricated speculum (‘No Gel group’). The primary outcome measures were the proportion of women with unsatisfactory cervical cytology smears and the mean numeric rating scale pain scores, while the secondary outcome measures were the proportion of women who were willing to come for repeat testing and the cytological diagnosis of Pap-smear results. Results The baseline socio-demographic variables were similar in both groups. There was no significant difference in the proportion of unsatisfactory cervical smear results between the two groups (13.6% vs. 21.2%, p = 0.359). However, the mean pain scores were significantly lower in the gel group than in the no gel group (45.04 vs. 87.96; p&lt;0.001). An equal proportion of the participants in each group (90.9% vs. 90.9%; p &gt; 0.999) were willing to come for repeat cervical smears in the future. Conclusion Speculum lubrication did not affect the adequacy of cervical smears but significantly reduced the pain experienced during pap smear collection. Also, it did not significantly affect the willingness to come for repeat cervical smears in the future. Trial registration The trial was registered with the Pan-African Clinical Trial Registry with a unique identification and registration number: PACTR2020077533364675 .

Combined oral contraceptive utilization and uterine fibroid incidence: A prospective study in a cohort of African-American women

Published associations between combined oral contraceptive use and uterine fibroid development have lacked prospective imaging with ultrasound to distinguish between incident and prevalent fibroids. The Study of Environment, Lifestyle, and Fibroids prospectively followed fibroid-free, African-American women (the group with the highest disease burden in the U.S.) to identify incident cases. We examined associations between combined oral contraceptive use and the 40-month cumulative risk of fibroids. History of hormonal contraceptive use was collected via telephone interview at enrollment. Fibroid identification was performed using transvaginal ultrasonography at enrollment, and at 20 and 40-months of follow-up. Inverse probability weights for exposures and censoring were used to construct weighted risk ratios (wRR) and weighted risk different (wRD) estimators which control for differences in fibroid risk factors between exposure groups. In addition, unweighted fully adjusted log-binomial regression models (aRR) were run for comparison. Of the 1,308 participants in the analysis sample, 70% had used combined oral contraceptives and 17% developed fibroids by 40 months. We observed an inverse association between ever use of combined oral contraceptives and cumulative fibroid incidence (wRR: 0.78; 95% Confidence Interval (CI): 0.60, 1.00; wRD: -0.05, 95% CI: -0.11, 0; aRR: 0.76, 95% CI: 0.60, 0.98). Fibroid incidence was greater in participants who started using combined oral contraceptives after age 17 years than among younger initiators, though the restriction to ever-users made this estimate less precise (wRR: 1.25; 95% CI: 0.89, 1.76; wRD: 0.04, 95% CI: -0.02, 0.10). No consistent patterns of fibroid incidence were seen among ever-users for duration of, or years since, last combined oral contraceptives use.

Factors associated with interobserver variation amongst pathologists in the diagnosis of endometrial hyperplasia: A systematic review

Objective Reproducible diagnoses of endometrial hyperplasia (EH) remains challenging and has potential implications for patient management. This systematic review aimed to identify pathologist-specific factors associated with interobserver variation in the diagnosis and reporting of EH. Methods Three electronic databases, namely MEDLINE, Embase and Web of Science, were searched from 1st January 2000 to 25th March 2023, using relevant key words and subject headings. Eligible studies reported on pathologist-specific factors or working practices influencing interobserver variation in the diagnosis of EH, using either the World Health Organisation (WHO) 2014 or 2020 classification or the endometrioid intraepithelial neoplasia (EIN) classification system. Quality assessment was undertaken using the QUADAS-2 tool, and findings were narratively synthesised. Results Eight studies were identified. Interobserver variation was shown to be significant even amongst specialist gynaecological pathologists in most studies. Few studies investigated pathologist-specific characteristics, but pathologists were shown to have different diagnostic styles, with some more likely to under-diagnose and others likely to over-diagnose EH. Some novel working practices were identified, such as grading the “degree” of nuclear atypia and the incorporation of objective methods of diagnosis such as semi-automated quantitative image analysis/deep learning models. Conclusions This review highlighted the impact of pathologist-specific factors and working practices in the accurate diagnosis of EH, although few studies have been conducted. Further research is warranted in the development of more objective criteria that could improve reproducibility in EH diagnostic reporting, as well as determining the applicability of novel methods such as grading the degree of nuclear atypia in clinical settings.

Cervical microbiota dysbiosis associated with high-risk Human Papillomavirus infection

High-risk Human Papillomavirus (HR-HPV) genotypes, specifically HPV16 and HPV18, pose a significant risk for the development of cervical intraepithelial neoplasia and cervical cancer. In the multifaceted cervical microenvironment, consisting of immune cells and diverse microbiota, Lactobacillus emerges as a pivotal factor, wielding significant influence in both stabilizing and disrupting the microbiome of the reproductive tract. To analyze the distinction between the cervical microbiota and Lactobacillus-dominant/non-dominant status of HR-HPV and non-infected healthy women, sixty-nine cervical swab samples were analyzed, included 44 with HR-HPV infection and healthy controls. All samples were recruited from Human Papillomavirus-based cervical cancer screening program and subjected to 16s rRNA sequencing analysis. Alpha and beta diversity analyses reveal no significant differences in the cervical microbiota of HR-HPV-infected women, including 16 and 18 HPV genotypes, and those with squamous intraepithelial lesion (SIL), compared to a control group. In this study we identified significantly lower abundance of Lactobacillus mucosae in women with HR-HPV infection compared to the control group. Furthermore, changes in bacterial diversity were noted in Lactobacillus non-dominant (LND) samples compared to Lactobacillus-dominant (LD) in both HR-HPV-infected and control groups. LND samples in HR-HPV-infected women exhibited a cervical dysbiotic state, characterized by Lactobacillus deficiency. In turn, the LD HR-HPV group showed an overrepresentation of Lactobacillus helveticus. In summary, our study highlighted the distinctive roles of L. mucosae and L. helveticus in HR-HPV infections, signaling a need for further research to demonstrate potential clinical implications of cervical microbiota dysbiosis.

Inhibition of cytosine 5-hydroxymethylation during progression of cancer precursor lesions in the uterine cervix

Methylation and hydroxymethylation of cytosine moieties in CpG islands of specific genes are epigenetic processes shown to be involved in the development of cervical (pre)neoplastic lesions. We studied global (hydroxy)methylation during the subsequent steps in the carcinogenic process of the uterine cervix by using immunohistochemical protocols for the detection of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in paraffin-embedded tissues of the normal epithelia and (pre)malignant lesions. This approach allowed obtaining spatially resolved information of (epi)genetic alterations for individual cell populations in morphologically heterogeneous tissue samples. The normal ectocervical squamous epithelium showed a high degree of heterogeneity for both modifications, with a major positivity for 5-mC in the basal and parabasal layers in the ectocervical region, while 5-hmC immunostaining was even more restricted to the cells in the basal layer. Immature squamous metaplasia, characterized by expression of SOX17, surprisingly showed a decrease of 5-hmC in the basal compartments and an increase in the more superficial layers of the epithelium. The normal endocervical glandular epithelium showed a strong immunostaining reactivity for both modifications. At the squamocolumnar junctions, a specific 5-hmC pattern was observed in the squamous epithelium, resembling that of metaplasia, with the typical weak to negative reaction for 5-hmC in the basal cell compartment. The reserve cells underlying the glandular epithelium were also largely negative for 5-hmC but showed immunostaining for 5-mC. While the overall methylation status remained relatively constant, about 20% of the high-grade squamous lesions showed a very low immunostaining reactivity for 5-hmC. The (pre)malignant glandular lesions, including adenocarcinoma in situ (AIS) and adenocarcinoma showed a progressive decrease of hydroxymethylation with advancement of the lesion, resulting in cases with regions that were negative for 5-hmC immunostaining. These data indicate that inhibition of demethylation, which normally follows cytosine hydroxymethylation, is an important epigenetic switch in the development of cervical cancer.

Androgen receptor and its correlation with estrogen and progesterone receptors, aimed for identification of cases for future anti-androgen therapy in endometrial cancers

Introduction The expression of androgen receptor (AR) is not commonly tested or studied in uterine cancers, unlike estrogen receptor (ER) and progesterone receptor (PR) which are positive in most endometrial carcinomas. In this series, we evaluated the expression of AR and its comparison to ER and PR in different types of endometrial cancers and have reviewed the literature. Materials and methods The status of AR, ER, and PR expression were evaluated in 71 cases which were categorized into endometrial endometrioid cancer (EEC), non-endometrioid endometrial cancers (NEEC), and metastatic carcinomas of endometrium. Expression of the receptors were compared to each other as well as to mismatch repair proteins (MMR), p53, and body mass index (BMI) using Fisher’s Exact test in the StatPlus software. Results In EECs, the positivity was 97% for all the three receptors. In NEEC, positivity rates were 68%, 48%, and 35% for AR, ER, and PR respectively. In Metastatic carcinomas, AR and ER positivity was seen in 100% while PR was positive in 75% of the cases. In all cancers, the rates were 17% (11/66) for MMR loss, 57% (30/53) for p53 aberrant expression, and 76% (54/71) for the patients with BMI of ≥ 25 (kg/m2). Conclusion AR is expressed in a high percentage of endometrial cancers. Its significance is more evident in high-grade NEEC where ER and PR may not be expressed. These findings warrant further evaluation of AR expression and candidacy of this pathway as a potential therapeutic target in endometrial cancers.

Detection of driver mutations and genomic signatures in endometrial cancers using artificial intelligence algorithms

Analyzed endometrial cancer (EC) genomes have allowed for the identification of molecular signatures, which enable the classification, and sometimes prognostication, of these cancers. Artificial intelligence algorithms have facilitated the partitioning of mutations into driver and passenger based on a variety of parameters, including gene function and frequency of mutation. Here, we undertook an evaluation of EC cancer genomes deposited on the Catalogue of Somatic Mutations in Cancers (COSMIC), with the goal to classify all mutations as either driver or passenger. Our analysis showed that approximately 2.5% of all mutations are driver and cause cellular transformation and immortalization. We also characterized nucleotide level mutation signatures, gross chromosomal re-arrangements, and gene expression profiles. We observed that endometrial cancers show distinct nucleotide substitution and chromosomal re-arrangement signatures compared to other cancers. We also identified high expression levels of the CLDN18 claudin gene, which is involved in growth, survival, metastasis and proliferation. We then usedin silicoprotein structure analysis to examine the effect of certain previously uncharacterized driver mutations on protein structure. We found that certain mutations in CTNNB1 and TP53 increase protein stability, which may contribute to cellular transformation. While our analysis retrieved previously classified mutations and genomic alterations, which is to be expected, this study also identified new signatures. Additionally, we show that artificial intelligence algorithms can be effectively leveraged to accurately predict key drivers of cancer. This analysis will expand our understanding of ECs and improve the molecular toolbox for classification, diagnosis, or potential treatment of these cancers.

Cervical cancer prevention: Feasibility of self-sampling and HPV testing in rural and urban areas of Bolivia: An observational study

Background Cervical cancer is a major health problem in Latin America. In 2019, the Italian Agency for Development Cooperation (La Paz regional site) conducted a pilot study to estimate the prevalence of high-risk human papillomavirus (HPV) and the feasibility of HPV screening in Bolivia through self-sampling and portable and transportable laboratory instruments for HPV testing in urban and rural areas. Methods Women aged 20–65 years from La Paz (urban area), Toro Toro (rural area), and Acasio (rural area) were enrolled in local public health centers between Dec 1, 2019, and June 30, 2021. Self-sampling was carried out with the Viba-Brush system (Rovers, Oss, Netherlands) and samples were preserved in ThinPrep containers (Hologic Corporation, San Diego, CA, USA). The GeneXpert system (Cepheid, Sunnyvale, CA, USA) for high-risk HPV testing detects HPV E6 and E7 DNA via real-time PCR in a mobile system of easy execution requiring minimal manual intervention. The system provides results in about 1 h. The hr- HPV prevalence data, overall and partial genotyping, were analyzed considering the following age groups: 20–34, 35–44, and 45–65 years old. Findings 2168 women were enrolled: 614 (28.3%) in La Paz, 743 (34.3%) in Toro Toro, and 811 (37.4%) in Acasio. Only one sample was collected from each participant. 2043 (94.2%) of 2168 samples were adequate for HPV testing. 255 (12.5%) samples were positive for high-risk HPV. Comparing the urban area (La Paz) versus rural combined areas (Acasio+Toro Toro), using a logistic model, the HPV total rate was statistically significantly higher in the city of La Paz (15.0% vs 11.4%; OR:1.37;95% CI: 1.04–1.80). Furthermore, the HPV prevalence was declining by age, and the urban/rural odds ratio was 1.50; (95% IC 1.13–19). The overall HPV 16 positivity was 2.7% (55/2043) and for HPV 18/45 was 1.8% (37/2043) without any statistically significant differences between the three BHU enrolling centers. Only the prevalence of HPV group ‘39/56/66/68’ was significantly higher in La Paz (p&lt;0,001) in comparison to Acasio and Toro Toro. Interpretation The total and age-adjusted prevalence of high-risk HPV infection in rural and urban areas in Bolivia, as measured with a validated test for screening, is similar to that observed in Europe and the USA. Our study shows that a screening protocol for HPV testing with self-sampling would be feasible in urban and rural areas in Bolivia, and that the reported high occurrence of cervical cancer in Bolivia is not related to a higher rate of high-risk HPV infections. Carrying out HPV tests locally avoids the issues associated with transportation and storage of the collected material and allows the participant to wait in the clinic for the test result, overcoming the very long response time for screening test in Bolivia.

Prevalence of viral DNA in high-grade serous epithelial ovarian cancer and correlation with clinical outcomes

Introduction Currently 11 infectious agents are classified as carcinogenic but the role of infectious agents on outcomes of epithelial ovarian cancer is largely unknown. Objective To explore the association between infectious agents and ovarian cancer, we investigated the prevalence of viral DNA in primary ovarian cancer tumors and its association with clinical outcomes. Methods Archived tumors from 98 patients diagnosed with high-grade serous epithelial ovarian cancer were collected between 1/1/1994 and 12/31/2010. After DNA extraction, Luminex technology was utilized to identify polymerase chain reaction-amplified viral DNA for 113 specific viruses. Demographic data and disease characteristics were summarized using descriptive statistics. We used logistic regression and Cox proportional hazards model to assess associations between tumor viral status and disease outcome and between tumor viral presence and overall survival (OS), respectively. Results Forty-six cases (45.9%) contained at least one virus. Six highly prevalent viruses were associated with clinical outcomes and considered viruses of interest (VOI; Epstein-Barr virus 1, Merkel cell polyomavirus, human herpes virus 6b, and human papillomaviruses 4, 16, and 23). Factors independently associated with OS were presence of VOI (HR 4.11, P = 0.0001) and platinum sensitivity (HR 0.21, P&lt;0.0001). Median OS was significantly decreased when tumors showed VOI versus not having these viruses (22 vs 44 months, P&lt;0.0001). Women &lt;70 year old with VOI in tumors had significantly lower median OS versus age-matched women without VOI (20 vs 57 months, P = 0.0006); however, among women ≥70 years old, there was no difference in OS by tumor virus status. Conclusions The presence of a VOI was significantly associated with a lower OS. These findings may have implications for clinical management of ovarian cancer but require additional studies.

Novel ensemble learning approach with SVM-imputed ADASYN features for enhanced cervical cancer prediction

Cervical cancer remains a leading cause of female mortality, particularly in developing regions, underscoring the critical need for early detection and intervention guided by skilled medical professionals. While Pap smear images serve as valuable diagnostic tools, many available datasets for automated cervical cancer detection contain missing data, posing challenges for machine learning models’ efficacy. To address these hurdles, this study presents an automated system adept at managing missing information using ADASYN characteristics, resulting in exceptional accuracy. The proposed methodology integrates a voting classifier model harnessing the predictive capacity of three distinct machine learning models. It further incorporates SVM Imputer and ADASYN up-sampled features to mitigate missing value concerns, while leveraging CNN-generated features to augment the model’s capabilities. Notably, this model achieves remarkable performance metrics, boasting a 99.99% accuracy, precision, recall, and F1 score. A comprehensive comparative analysis evaluates the proposed model against various machine learning algorithms across four scenarios: original dataset usage, SVM imputation, ADASYN feature utilization, and CNN-generated features. Results indicate the superior efficacy of the proposed model over existing state-of-the-art techniques. This research not only introduces a novel approach but also offers actionable suggestions for refining automated cervical cancer detection systems. Its impact extends to benefiting medical practitioners by enabling earlier detection and improved patient care. Furthermore, the study’s findings have substantial societal implications, potentially reducing the burden of cervical cancer through enhanced diagnostic accuracy and timely intervention.

Prevalence of Cervical Cancer and Clinical Management of Women Screened positive using visual inspection with acetic acid and Cervicography in selected public sector health facilities of Manicaland and Midlands provinces of Zimbabwe, 2021

Background Zimbabwe has high cervical cancer (CC) burden of 19% and mortality rate of 64%. Zimbabwe uses Visual Inspection with Acetic Acid and Cervicography (VIAC) for CC screening. Manicaland and Midlands provinces recorded low VIAC positivity of 3% (target 5–25%) and treatment coverage of 78% (target = 90%) between October 2020 and September 2021. Objectives We explored VIAC positivity rate and clinical management of clients screening positive in Manicaland and Midlands provinces. Methods We conducted a retrospective cross-sectional study using routine VIAC and CC management data for period October 2020 to September 2021. Two samples were used, 1) a sample drawn from 48,000 women VIAC screened to measure positivity rate, and 2) a sample of 1,763 VIAC positive women to assess clinical management. Kobo-based tool was used to abstract data from facility registers, and data were analyzed using STATA 15. Results We analyzed data for 2,454 out of 48,000 women screened through VIAC. About 82% (2,007/2,454) were HIV positive, median ages were 40 and 38 years for HIV positives and negatives respectively. Most (64% and 77%) of HIV positive and negative clients respectively were married. VIAC positivity was 5.9% and 3.4% among HIV positive and negative women screened for the first time, and 3.2% and 5.6% for repeat visits respectively. Overall, 89.1% (1,571/1,763) of VIAC positive women received treatment. Most (41%) of those treated received thermocoagulation. Overall, 43.1% of clients received treatment on VIAC day, and 77.4% within 30 days. Six-month post-treatment coverage was 3.8%. Conclusion VIAC positivity among HIV positive women screening for the first time was 5.9%, within the expected 5–25%. Treatment coverage was high, and turnaround time from diagnosis to treatment met national standards. Post-treatment coverage was suboptimal. We recommend continued implementation of quality improvement initiatives, capacity building of clinicians, and optimization of post-treatment review of clients.

Identification of a disulfidptosis-related genes signature for diagnostic and immune infiltration characteristics in cervical cancer

Background Cervical cancer (CC) ranks as the fourth most common malignancy affecting women globally, with research highlighting a rising incidence among younger age groups. Disulfidptosis, a newly identified form of regulated cell death, has been implicated in the pathogenesis of numerous diseases. This study employs bioinformatics analyses to explore the expression profiles and functional roles of disulfidptosis-related genes (DRGs) in the context of cervical cancer. Methods Differential analysis of the gene expression matrix in CC was performed to identify differentially expressed genes. The overlap between these genes and disulfidptosis-related genes was then determined. Key hub genes were identified using multiple machine learning approaches, including LASSO regression, support vector machines (SVM), and random forest (RF). These hub genes were subsequently used to construct a predictive model, which was validated using external datasets to ensure robustness and reliability. Results In this study, 11 overlapping genes were identified, among which four hub genes—BRK1, NDUFA11, RAC1, and NDUFS1—were extracted using machine learning techniques. The diagnostic performance of these hub genes was validated with external datasets, and a predictive model was constructed based on their expression. The model demonstrated an exceptionally high area under the curve (AUC) of 0.997. Moreover, AUC values exceeding 0.85 for two independent validation datasets further confirmed the model’s accuracy and stability. Notably, NDUFA11 and BRK1 showed significant associations with patient survival, highlighting their prognostic importance in cervical squamous cell carcinoma. Using CMAP and DGIdb databases, Metformin and Coenzyme-I were identified as potential targeted therapies for NDUFS1 and NDUFA11, respectively, offering new therapeutic avenues for patients. Conclusion This study uncovered a strong association between disulfidptosis and CC and developed a predictive model to assess the risk in CC patients. These findings offer novel insights into identifying biomarkers and potential therapeutic targets for CC, paving the way for improved diagnostic and treatment strategies.

Adenomyosis in women undergoing hysterectomy for abnormal uterine bleeding associated with uterine leiomyomas

Background Uterine leiomyomas and adenomyosis are both common and often associated with abnormal uterine bleeding (AUB), including the symptom of heavy menstrual bleeding (HMB). Understanding the prevalence of adenomyosis in women with uterine leiomyomas could inform clinicians and patients in a way that may improve therapeutic approaches. Objective To explore the prevalence of adenomyosis in a group of women who underwent hysterectomy for AUB-L, to determine the prevalence of submucous leiomyomas, and to examine the utility of preoperative ultrasound to detect the presence of adenomyosis. Methods The Kaiser Permanente Hysterectomy Database (KPHD) was searched for women aged 18–52 undergoing hysterectomy for leiomyoma-associated chronic AUB (AUB-L) in 2018 and 2019. A target sample of 400 comprised those with at least 3 years in the Health System. Radiologists evaluated preoperative pelvic ultrasound images to determine leiomyoma size and level 2 FIGO type (submucous or other), and the linked electronic medical record abstracted for clinical features, including histopathological evidence of adenomyosis. Results Of the 370 subjects that met the study criteria, adenomyosis was identified via histopathology in 170 (45.9%). There was no difference in the adenomyosis prevalence with (47.1%) and without (43.0%) at least one submucous leiomyoma. Subgroup analysis of ultrasound images by an expert radiologist for the presence of adenomyosis demonstrated a positive predictive value of 54.0% and a negative predictive value of 43.4%. Conclusions Adenomyosis was present in almost half of this AUB-L cohort undergoing hysterectomy and was equally prevalent in those with and without submucous leiomyomas as determined by sonographic evaluation. The imaging findings are in accord with prior investigators and demonstrate that 2-D ultrasound is insensitive to the presence of adenomyosis when the uterus is affected by leiomyomas. Further research is necessary to determine the impact of various adenomyosis phenotypes on the presence and severity of the symptom of HMB.

Prevalence characteristics of cervical human papillomavirus infection in Chengdu and Aba District, Sichuan Province, China

Purpose The genotype distribution of human papillomavirus (HPV) infection varies greatly in different regions. This study aims to determine the prevalence and type-specific distribution of HPV among females from Chengdu and Aba in Sichuan Province, which differ in geographical location, economic status, and living habits. These can serve as evidence of epidemic patterns for future design and implementation of vaccination and screening programs. Methods A retrospective cross-sectional study was conducted on 144 113 women who underwent cervical screening at Chengdu Women’s and Children’s Central Hospital from January 2015 to September 2020. Meanwhile, 1799 samples from February 2018 to December 2021 were collected from Aba Maternal and Child Health Hospital. HPV DNA genotype testing was performed using real‐time PCR. The overall prevalence, annual trend, age-specific prevalence, and type distribution were analyzed. Results The overall HPV prevalence was 22.51% in Chengdu. During 2015–2020, the highest prevalence rate was observed in 2018. Age-specific HPV distribution displayed a bimodal distribution among women aged ≤25 or ≥46 years old. The top three prevalent genotypes were HPV52, -16, and -58. Although the total prevalence of HPV in Aba was 14.23%, there was an upward trend from 2018 to 2021. However, no significant differences were identified in HPV infection rate across all age groups. HPV52, -53, and -16 were the major genotypes. Furthermore, single-type HPV infections and high-risk HPV infections were identified as the most common infection types in both regions. Conclusion Our findings demonstrate the overall prevalence of HPV was still high in Chengdu and Aba. The age-specific prevalence distribution demonstrated different patterns. Non-vaccine-covered HR-HPV53, -51and LR-HPV81, -CP8304 were frequently detected, which was worth significant clinical attention. In summary, regional HPV screening provides valuable clinical guidance for cervical cancer prevention and vaccine selection in Western China.

Strengthening the role of community pharmacy in HPV vaccination roll-out in Serbia at national and local levels: A pharmacy-based education approach

Cervical cancer is a significant public health concern in Serbia, with high morbidity and mortality rates (27 and 14.2 per 100,000 women, respectively in 2020). The primary cause of cervical cancer is human papillomavirus (HPV) infection, and HPV vaccination has proven to be an effective prevention strategy. This publication discusses the implementation of the first pharmacy-based education (PBE) program realized through the project of Pharmaceutical Chamber of Serbia – “Ask me about HPV” which aimed at raising awareness of the general population about the importance of HPV vaccination. The program aimed to strengthen the role of community pharmacists in the HPV vaccination roll-out. A total of 250 pharmacists were selected and trained to provide information on HPV infection and promote vaccination uptake. The program aimed to counsel and to educate young adults and parents/guardians. A total of 24,327 subjects were educated during the program’s implementation from February to May 2023, young adults (N=11,313) and parents/guardians (N=13,014). Data showed that only 4.9% of young adults and 6.4% of children (of the parents/guardians surveyed) in Serbia are vaccinated against HPV. The questionaries of 1,387 subjects already vaccinated were excluded from the further analysis and final analysis was performed based on the counseling of 22,941 participants. A significantly higher percentage of parents/guardians stated that they would have their children vaccinated against HPV after counseling at the pharmacy than young adults (42.3% and 34.1% respectively). On the other hand, of those respondents who stated they would get vaccinated after consulting at the pharmacy, a significantly higher number of young adults (51%), compared to parents/guardians (48%), would receive the vaccine specifically at the pharmacy. The results of the project indicate that education of the general population on the benefits of HPV vaccination is highly needed. The expected outcomes of this educational program are increased awareness of the burden of illness, improved consumer education, the potential for higher vaccination rates, and consequently a reduction in cervical cancer incidence and mortality in Serbia.

Optimal use of radiotherapy in the definitive treatment of non-bulky IB–IIA cervical cancer: A population-based long-term survival analysis

Purpose Although current clinical guidelines recommend surgery or radiotherapy for non-bulky IB-IIA cervical cancer, clinical data supporting the curative role of radiotherapy in the early-stage disease are insufficient. We evaluated the prognostic implications of definitive radiotherapy and determined its optimal use in clinical practice. Methods Patients with non-bulky (&lt;4 cm) IB-IIA cervical cancer who underwent hysterectomy or primary radiotherapy between 1988 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Based on the use of brachytherapy and/or chemotherapy, the primary radiotherapy group was classified into three cohorts: hysterectomy vs. radiotherapy overall, with/without brachytherapy and/or chemotherapy (cohort A); radiotherapy and brachytherapy with/without chemotherapy (patients with external beam radiation alone were excluded, cohort B); radiotherapy with brachytherapy and chemotherapy (patients who did not receive chemotherapy were additionally excluded, cohort C). Disease-specific survival (DSS) after hysterectomy was compared to that after primary radiotherapy in each cohort. Results Among the 9,391 initially identified patients, 1,762, 1,244, and 750 patients were classified into cohorts A, B, and C, respectively, after propensity score matching. In cohort A, DSS after primary radiotherapy was inferior to that after hysterectomy (P = 0.001). In cohort B, a trend toward differential survival in favor of hysterectomy was observed with marginal significance (P = 0.061). However, in cohort C, DSS after primary radiotherapy was not significantly different to that after hysterectomy (P = 0.127). According to hazard rate function plots, patients receiving external beam radiation alone had an increased short-term risk of disease-specific mortality, whereas patients without evidence of chemotherapy had a distinct late risk surge at approximately 15 years of follow-up. Conclusion Optimizing radiotherapy methods with brachytherapy and the use of chemotherapy should be considered for the long-term curative efficacy of primary radiotherapy for non-bulky IB-IIA cervical cancer. Further studies are warranted to corroborate our results.

Analysis of survival-related factors in patients with endometrial cancer using a Bayesian network model

Background In recent years, remarkable progress has been made in the use of machine learning, especially in analyzing prognosis survival data. Traditional prediction models cannot identify interrelationships between factors, and the predictive accuracy is lower. This study aimed to construct Bayesian network models using the tree augmented naïve algorithm in comparison with the Cox proportional hazards model. Methods A Bayesian network model and a Cox proportional hazards model were constructed to analyze the prognostic factors of endometrial cancer. In total, 618 original cases obtained from the Surveillance, Epidemiology, and End Results database were used to construct the Bayesian network model, which was compared with the traditional Cox proportional hazards model by analyzing prognostic factors. External validation was performed using a dataset from The First Affiliated Hospital of Shandong First Medical University. Results The predictive accuracy, area under the receiver operating characteristic curve, and concordance index for the Bayesian network model were 74.68%, 0.787, and 0.72, respectively, compared to 68.83%, 0.723, and 0.71, respectively, for the Cox proportional hazards model. Tumor size was the most important factor for predicting survival, followed by lymph node metastasis, distant metastasis, chemotherapy, lymph node resection, tumor stage, depth of invasion, tumor grade, histological type, age, primary tumor site, radiotherapy and surgical sequence, and radiotherapy. Conclusion The findings indicate that the Bayesian network model is preferable to the Cox proportional hazards model for predicting survival in patients with endometrial cancer.

Is there an association between intimate partner violence and the prevalence of cervical cancer screening in Jordan?

Background Major health inequalities exist surrounding the utilisation of cervical cancer screening services globally. Jordan, a low- and middle-income country, has poor screening rates (15.8%), with barriers to accessing services, including lack of education. Emerging studies demonstrate that intimate partner violence (IPV) impacts reproductive health decisions. As a large proportion of Jordanian women have reported experiencing IPV, this study examines the association between IPV and cervical cancer screening in Jordan, the first of its kind using national-level data. Methods Using Jordan’s Demographic Health Survey 2017–18, cervical cancer screening awareness and self-reported screening were estimated in participants who answered questions on IPV (n = 6679). After applying sample weights, Heckman’s two-stage probit model determined the association of awareness and utilisation of cervical cancer screening with experience of IPV, adjusting for the socio-economic factors. Results Of the women with privacy to answer the IPV module, 180 (3.4%) were found to be victims of sexual violence, 691 of physical violence (12.6%) and 935 (16.2%) of emotional violence. Women subjected to sexual violence were less likely to admit to having awareness of a Pap smear test; however, this did not impact screening rates. Victims of emotional violence were more likely to be screened than non-victims. No association between physical violence and cervical cancer screening was found. Conclusions A significant association between cervical screening awareness and IPV demonstrates that cancer screening policies must consider IPV among women to improve screening awareness. The paper further sheds light on the paradoxical association between emotional violence and screening. It is acknowledged this situation may be far worse than reported, as women without autonomy were unlikely to answer IPV questions that may endanger them—targeted surveys on cervical cancer screening warrant further investigation.

Connections between prolactin and ovarian cancer

Ovarian cancer (OC) is characterized by a high morbidity and mortality, highlighting a great need for a better understanding of biological mechanisms that affect OC progression and improving its early detection methods. This study investigates effects of prolactin (PRL) on ovarian cancer cells, analyzes PRL receptors (PRLR) in tissue micro arrays and relates PRLR expression to survival of ovarian cancer. A database, composed of transcript profiles from OC, was searched for PRLR expression and results were put in relation to survival. Expression of PRLR in OC tissue sections and OC cell lines SKOV3, OV2008 and OVSAHO was assessed using immunohistochemistry, western blots and quantitative real-time PCR. The biological function of PRLR was evaluated by proliferation, colony formation and wound healing assays. Levels of PRLR mRNA are related to survival; in epithelial OC a high PRLR mRNA expression is related to a shorter survival. Analysis of a tissue micro array consisting of 84 OC showed that 72% were positive for PRLR immuno-staining. PRLR staining tended to be higher in OC of high grade tumors compared to lower grades. PRLR mRNA and protein can further be detected in OC cell lines. Moreover, in vitro treatment with PRL significantly activated the JAK/STAT pathway. PRLR expression is associated with OC survivals. PRL and its receptor may play an onco-modulatory role and promote tumor aggressiveness in OC. Alternatively, increased PRLR levels may form a base for the development of PRLR antagonist or PRLR antagonist-drug conjugate to increase selective uptake of anti-cancer drugs.

Activated heme synthesis regulates glycolysis and oxidative metabolism in breast and ovarian cancer cells

Heme is an essential cofactor for enzymes of the electron transport chain (ETC) and ATP synthesis in mitochondrial oxidative phosphorylation (OXPHOS). Heme also binds to and destabilizes Bach1, a transcription regulator that controls expression of several groups of genes important for glycolysis, ETC, and metastasis of cancer cells. Heme synthesis can thus affect pathways through which cells generate energy and precursors for anabolism. In addition, increased heme synthesis may trigger oxidative stress. Since many cancers are characterized by a high glycolytic rate regardless of oxygen availability, targeting glycolysis, ETC, and OXPHOS have emerged as a potential therapeutic strategy. Here, we report that enhancing heme synthesis through exogenous supplementation of heme precursor 5-aminolevulinic acid (ALA) suppresses oxidative metabolism as well as glycolysis and significantly reduces proliferation of both ovarian and breast cancer cells. ALA supplementation also destabilizes Bach1 and inhibits migration of both cell types. Our data indicate that the underlying mechanisms differ in ovarian and breast cancer cells, but involve destabilization of Bach1, AMPK activation, and induction of oxidative stress. In addition, there appears to be an inverse correlation between the activity of oxidative metabolism and ALA sensitivity. Promoting heme synthesis by ALA supplementation may thus represent a promising new anti-cancer strategy, particularly in cancers that are sensitive to altered redox signaling, or in combination with strategies that target the antioxidant systems or metabolic weaknesses of cancer cells.

Using a new diagnostic tool to predict lymph node metastasis in advanced epithelial ovarian cancer leads to simple lymphadenectomy decision rules: A multicentre study from the FRANCOGYN group

Objective The aim of this study was to develop a new diagnostic tool to predict lymph node metastasis (LNM) in patients with advanced epithelial ovarian cancer undergoing primary cytoreductive surgery. Materials and method The FRANCOGYN group’s multicenter retrospective ovarian cancer cohort furnished the patient population on which we developed a logistic regression model. The prediction model equation enabled us to create LNM risk groups with simple lymphadenectomy decision rules associated with a user-friendly free interactive web application called shinyLNM. Results 277 patients from the FRANCOGYN cohort were included; 115 with no LNM and 162 with LNM. Three variables were independently and significantly (p&lt;0.05) associated with LNM in multivariate analysis: pelvic and/or para-aortic LNM on CT and/or PET/CT (p&lt;0.00), initial PCI ≥ 10 and/or diaphragmatic carcinosis (p = 0.02), and initial CA125 ≥ 500 (p = 0.02). The ROC-AUC of this prediction model after leave-one-out cross-validation was 0.72. There was no difference between the predicted and the observed probabilities of LNM (p = 0.09). Specificity for the group at high risk of LNM was 83.5%, the LR+ was 2.73, and the observed probability of LNM was 79.3%; sensitivity for the group at low-risk of LNM was 92.0%, the LR- was 0.24, and the observed probability of LNM was 25.0%. Conclusion This new tool may prove useful for improving surgical planning and provide useful information for patients.

Accurate deep learning model using semi-supervised learning and Noisy Student for cervical cancer screening in low magnification images

Deep learning technology has been used in the medical field to produce devices for clinical practice. Deep learning methods in cytology offer the potential to enhance cancer screening while also providing quantitative, objective, and highly reproducible testing. However, constructing high-accuracy deep learning models necessitates a significant amount of manually labeled data, which takes time. To address this issue, we used the Noisy Student Training technique to create a binary classification deep learning model for cervical cytology screening, which reduces the quantity of labeled data necessary. We used 140 whole-slide images from liquid-based cytology specimens, 50 of which were low-grade squamous intraepithelial lesions, 50 were high-grade squamous intraepithelial lesions, and 40 were negative samples. We extracted 56,996 images from the slides and then used them to train and test the model. We trained the EfficientNet using 2,600 manually labeled images to generate additional pseudo labels for the unlabeled data and then self-trained it within a student-teacher framework. Based on the presence or absence of abnormal cells, the created model was used to classify the images as normal or abnormal. The Grad-CAM approach was used to visualize the image components that contributed to the classification. The model achieved an area under the curve of 0.908, accuracy of 0.873, and F1-score of 0.833 with our test data. We also explored the optimal confidence threshold score and optimal augmentation approaches for low-magnification images. Our model efficiently classified normal and abnormal images at low magnification with high reliability, making it a promising screening tool for cervical cytology.

Incidence of extraovarian clear cell cancers in women with surgically diagnosed endometriosis: A cohort study

Background Endometriosis is associated with increased risk of clear cell ovarian cancer and has even suggested being an etiological factor for this cancer. Association between endometriosis and extraovarian clear cell cancers is unclear. This study aimed to assess the association between surgically diagnosed endometriosis and risk of extraovarian clear cell cancers according to the type of endometriosis (i.e., ovarian, peritoneal, and other endometriosis) and the site of clear cell cancer. Methods In this register-based historic cohort study we identified all women with surgically diagnosed endometriosis from the Finnish Hospital Discharge Registry 1987–2012. Data on extraovarian clear cell cancers of these women were obtained from the Finnish Cancer Registry. The follow-up started January 1st, 2007 or at endometriosis diagnosis (if later), and ended at emigration, death or on the December 31st, 2014. Standardized incidence ratios were calculated for each site of clear cell carcinoma (intestine, kidney, urinary tract, gynecological organs other than ovary), using the Finnish female population as reference. Results The endometriosis cohort consisted of 48,996 women, including 22,745 women with ovarian and 19,809 women with peritoneal endometriosis. Altogether 23 extraovarian clear cell cancers were observed during 367,386 person-years of follow-up. The risk of extraovarian clear cell cancer was not increased among all women with surgically diagnosed endometriosis (standardized incidence ratio 0.89, 95% confidence interval 0.56–1.33) nor in different types of endometriosis. The incidence of clear cell cancer in any specific site was not increased either. Conclusions The risk of extraovarian clear cell cancers in women with surgically diagnosed endometriosis is similar to that in the general population in Finland.

Identification and analysis of genes associated with epithelial ovarian cancer by integrated bioinformatics methods

Background Though considerable efforts have been made to improve the treatment of epithelial ovarian cancer (EOC), the prognosis of patients has remained poor. Identifying differentially expressed genes (DEGs) involved in EOC progression and exploiting them as novel biomarkers or therapeutic targets is of great value. Methods Overlapping DEGs were screened out from three independent gene expression omnibus (GEO) datasets and were subjected to Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. The protein-protein interactions (PPI) network of DEGs was constructed based on the STRING database. The expression of hub genes was validated in GEPIA and GEO. The relationship of hub genes expression with tumor stage and overall survival and progression-free survival of EOC patients was investigated using the cancer genome atlas data. Results A total of 306 DEGs were identified, including 265 up-regulated and 41 down-regulated. Through PPI network analysis, the top 20 genes were screened out, among which 4 hub genes, which were not researched in depth so far, were selected after literature retrieval, including CDC45, CDCA5, KIF4A, ESPL1. The four genes were up-regulated in EOC tissues compared with normal tissues, but their expression decreased gradually with the continuous progression of EOC. Survival curves illustrated that patients with a lower level of CDCA5 and ESPL1 had better overall survival and progression-free survival statistically. Conclusion Two hub genes, CDCA5 and ESPL1, identified as probably playing tumor-promotive roles, have great potential to be utilized as novel therapeutic targets for EOC treatment.

BCL6 (B-cell lymphoma 6) expression in adenomyosis, leiomyomas and normal myometrium

Adenomyosis and leiomyomas are common benign uterine disorders characterized by abnormal cellular proliferation. The BCL6 protein, a transcriptional repressor implicated in cell proliferation and oncogenesis, has been linked to the pathogenesis of endometriosis. This study investigates BCL6 expression in adenomyosis, leiomyomas, and normal myometrium using immunohistochemistry and deep learning neural networks. We analyzed paraffin blocks from total hysterectomies performed between 2009 and 2017, confirming diagnoses through pathological review. Immunohistochemistry was conducted using an automated system, and BCL6 expression was quantified using Fiji-ImageJ software. A supervised deep learning neural network was employed to classify samples based on DAB staining. Our results show that BCL6 expression is significantly higher in leiomyomas compared to adenomyosis and normal myometrium. No significant difference in BCL6 expression was observed between adenomyosis and controls. The deep learning neural network accurately classified samples with a high degree of precision, supporting the immunohistochemical findings. These findings suggest that BCL6 plays a role in the pathogenesis of leiomyomas, potentially contributing to abnormal smooth muscle cell proliferation. The study highlights the utility of automated immunohistochemistry and deep learning techniques in quantifying protein expression and classifying uterine pathologies. Future studies should investigate the expression of BCL6 in adenomyosis and endometriosis to further elucidate its role in uterine disorders.

In Silico screening of circulating tumor DNA, circulating microRNAs, and long non-coding RNAs as diagnostic molecular biomarkers in ovarian cancer: A comprehensive meta-analysis

Background Ovarian cancer (OC) is a leading cause of death in gynecological malignancies worldwide. Multitudinous studies have suggested the potential of circulating tumor DNA (ctDNA), circulating microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) as novel diagnostic molecular biomarkers for OC. Here, we include three updated meta-analysis methods using different molecular biomarkers to evaluate their discriminative value in OC diagnosis. Methods We conducted three meta-analyses after searching different databases, and 23 eligible articles, including 8 concerning ctDNA, 11 concerning miRNAs, and 4 concerning lncRNAs, were found. Further, we pooled data concerning the sensitivity, specificity, and other indicators of accuracy for ctDNA/miRNAs/lncRNAs in the diagnosis of OC. The heterogeneity was further explored by meta-regressions and subgroup analyses, and Deeks’ funnel plots were used to measure the publication bias of these three meta-analyses. Results In all, this meta-analysis included 1732 OC patients and 3958 controls. The sensitivity of ctDNA for OC diagnosis was superior to that of lncRNA and miRNA (84% vs. 81% vs. 78%). Moreover, the specificity and area under the receiver-operating characteristic (ROC) curve (AUC) of ctDNA were 91% and 94%, which were significantly higher than those of miRNA and lncRNAs (78% and 85%; 78% and 86%, respectively). No significant difference was observed among the two meta-analyses of ctDNA and lncRNA (P &gt; 0.05) with regard to publication bias, while the meta-analysis of miRNA observed a significantly small publication bias (P &lt; 0.05). Conclusion ctDNA/miRNAs/lncRNAs may be promising molecular biomarkers for OC diagnosis. Further large-scale studies are needed to verify the potential applicability of ctDNA/miRNAs/lncRNAs molecular signatures alone or in combination as diagnostic molecular biomarkers for OC.

Incidence and risk of venous thromboembolism according to primary treatment in women with ovarian cancer: A retrospective cohort study

Objective This study aimed to investigate incidence and risk for venous thromboembolism (VTE) according to primary treatment in women with ovarian cancer. Methods We selected 26,863 women newly diagnosed with ovarian cancer between 2009 and 2018 from the Korean Health Insurance Review and Assessment Service databases. During the total follow-up period and the first six months after initiation of primary treatments, incidence and risk of VTE were evaluated according to primary treatment as no treatment, surgery, radiotherapy, or chemotherapy. Results The mean follow-up period was 1285.5±6 days. The VTE incidence was highest in women who underwent chemotherapy (306 per 10,000 women). Among women who underwent surgery, VTE was highest in surgery with neoadjuvant chemotherapy (536 per 10,000 women), followed by surgery with adjuvant chemotherapy (360 per 10,000 women) and surgery alone (132 per 10,000 women). During the first 12 months, monthly incidence of VTE decreased. Compared with women with no treatment, risk of VTE significantly increased in women undergoing chemotherapy (HR 1.297; 95% CI, 1.08–1.557; P = 0.005) during the total follow-up period and decreased in women undergoing surgery (HR 0.557; 95% CI, 0.401–0.775; P&lt;0.001) and radiotherapy (HR 0.289; 95% CI, 0.119–0.701; P = 0.006) during the first six months. Among women who underwent surgery, VTE risk significantly increased in surgery with neoadjuvant chemotherapy (HR 4.848; 95% CI, 1.86–12.632; P = 0.001) followed by surgery with adjuvant chemotherapy (HR 2.807; 95% CI, 1.757–4.485; P&lt;0.001) compared with surgery alone during the total follow-up period and in surgery with neoadjuvant chemotherapy (HR 4.223; 95% CI, 1.37–13.022; P = 0.012) during the first six months. Conclusions In this large Korean cohort study, incidence and risk of VTE were highest in women with ovarian cancer who underwent chemotherapy and surgery with neoadjuvant chemotherapy as a primary cancer treatment. Incidence of VTE decreased over time.

A novel small molecule LLL12B inhibits STAT3 signaling and sensitizes ovarian cancer cell to paclitaxel and cisplatin

Ovarian cancer is the fifth most common cause of cancer deaths among American women. Platinum and taxane combination chemotherapy represents the first-line approach for ovarian cancer, but treatment success is often limited by chemoresistance. Therefore, it is necessary to find new drugs to sensitize ovarian cancer cells to chemotherapy. Persistent activation of Signal Transducer and Activator of Transcription 3 (STAT3) signaling plays an important role in oncogenesis. Using a novel approach called advanced multiple ligand simultaneous docking (AMLSD), we developed a novel nonpeptide small molecule, LLL12B, which targets the STAT3 pathway. In this study, LLL12B inhibited STAT3 phosphorylation (tyrosine 705) and the expression of its downstream targets, which are associated with cancer cell proliferation and survival. We showed that LLL12B also inhibits cell viability, migration, and proliferation in human ovarian cancer cells. LLL12B combined with either paclitaxel or with cisplatin demonstrated synergistic inhibitory effects relative to monotherapy in inhibiting cell viability and LLL12B-paclitaxel or LLL12B-cisplatin combination exhibited greater inhibitory effects than cisplatin-paclitaxel combination in ovarian cancer cells. Furthermore, LLL12B-paclitaxel or LLL12B-cisplatin combination showed more significant in inhibiting cell migration and growth than monotherapy in ovarian cancer cells. In summary, our results support the novel small molecule LLL12B as a potent STAT3 inhibitor in human ovarian cancer cells and suggest that LLL12B in combination with the current front-line chemotherapeutic drugs cisplatin and paclitaxel may represent a promising approach for ovarian cancer therapy.

High expression of ENPP1 in high-grade serous ovarian carcinoma predicts poor prognosis and as a molecular therapy target

Recent studies have shown that the expression of ENPP1 is related to differentiation, death, dissemination and chemosensitivity of tumor cells. So far, there is no research in ovarian carcinoma. This study aimed at exploring the role of ENPP1 gene in ovarian carcinoma, the relationship with prognostic indicators and chemotherapy resistance, and investigates the possibility of molecular targeted therapy. The expression of ENPP1 in 41 normal ovarian epithelial tissues, 97 ovarian serous cystadenoma and 103 HGSOC tissues was detected by IHC. In ovarian cancer tissues and ovarian cancer cell lines, mRNA and protein expression of ENPP1 was determined by qRT-PCR and Western blot. The ENPP1 expression was knockdowned by siRNA. Cell proliferation was measured with the BrdU Cell Proliferation ELISA. Cell migration and invasion were detected by Wound-Healing, Transwell migration and Matrigel invasion assay. Caspase 3 activity was determined by the CaspACE. The expression of EMT markers such as E-cadherin, N-cadherin, and Vimentin was measured, and the expression of PCNA and MMP9 was also be detected. The results showed that the expression of ENPP1 was significantly increased in high-grade ovarian serous carcinoma, the number of strong expression was 85.4% (22.3%+63.1%) and only 1.03% (1.03%+0.0%) in serous cystadenoma, but no in normal ovarian epithelium (P&lt; 0.05). And the stronger the expression of ENPP1, the later the FIGO stage and the poorer differentiation of cells (P = 0.001 or &lt;0.001, respectively). However, no correlation was found between the expression of ENPP1 and chemosensitivity. ENPP1 was also highly expressed in ovarian cancer tissues and in epithelial ovarian cancer cell lines (A2780, CaoV3, OVCAR3, SKOV3 and 3ao). After down-regulation of ENPP1 expression by RNA interference, the cell proliferation, migration and invasion of ovarian cancer cell decreased significantly, the expression of apoptosis related gene caspase 3 increased significantly, while the expression of PCNA and MMP9 was significantly down regulated. In addition, EMT biological characteristics of A2780 and SKOV3 cells were also inhibited. In summary, the increased expression of ENPP1 may be related to the occurrence of HGSOC, and indicate that the disease progresses rapidly and the prognosis is poor. ENPP1 may be considered as a potential molecular therapeutic target.

Radon-220 diffusion from 224Ra-labeled calcium carbonate microparticles: Some implications for radiotherapeutic use

Alpha-particle emitting radionuclides continue to be the subject of medical research because of their high energy and short range of action that facilitate effective cancer therapies. Radium-224 (224Ra) is one such candidate that has been considered for use in combating micrometastatic disease. In our prior studies, a suspension of224Ra-labeled calcium carbonate (CaCO3) microparticles was designed as a local therapy for disseminated cancers in the peritoneal cavity. The progenies of224Ra, of which radon-220 (220Rn) is the first, together contribute three of the four alpha particles in the decay chain. The proximity of the progenies to the delivery site at the time of decay of the224Ra-CaCO3microparticles can impact its therapeutic efficacy. In this study, we show that the diffusion of220Rn was reduced in labeled CaCO3suspensions as compared with cationic224Ra solutions, both in air and liquid volumes. Furthermore, free-floating lead-212 (212Pb), which is generated from released220Rn, had the potential to be re-adsorbed onto CaCO3microparticles. Under conditions mimicking anin vivoenvironment, more than 70% of the212Pb was adsorbed onto the CaCO3at microparticle concentrations above 1 mg/mL. Further, the diffusion of220Rn seemed to occur whether the microparticles were labeled by the surface adsorption of224Ra or if the224Ra was incorporated into the bulk of the microparticles. The therapeutic benefit of differently labeled224Ra-CaCO3microparticles after intraperitoneal administration was similar when examined in mice bearing intraperitoneal ovarian cancer xenografts. In conclusion, both the release of220Rn and re-adsorption of212Pb are features that have implications for the radiotherapeutic use of224Ra-labeled CaCO3microparticles. The release of220Rn through diffusion may extend the effective range of alpha-particle dose deposition, and the re-adsorption of the longer lived212Pb onto the CaCO3microparticles may enhance the retention of this nuclide in the peritoneal cavity.

Community cervical cancer screening: Barriers to successful home-based HPV self-sampling in Dabat district, North Gondar, Ethiopia. A qualitative study

Objective To explore the barriers to successful home-based human papillomavirus (HPV) self-sampling in North Gondar, Ethiopia. Methods The study participants were women who had previously participated in a community-wide home-based HPV self-sampling pilot study, community health workers, women’s development army leaders, and the sample collectors of the home-based HPV self-sampling pilot study. A community based qualitative descriptive study was conducted. We applied purposive and convenience sampling. In total, 47 women participated in the study (in-depth interviews n = 22, four focus group discussions n = 25, 6–7 participants each). The study employed thematic analysis for clustering the emerged themes. Results Husband disapproval was identified as the main barrier to the acceptance of home-based HPV self-sampling. Social influence, lack of knowledge about cervical cancer and screening, lack of health education on cervical cancer and HPV-based screening, feeling healthy, and religious influence were identified as additional barriers. Fear of using Evalyn brush® for self-sampling was found to be the main barrier to the provision of a quality sample. The inability of the sample collectors to check the proper utilization of Evalyn brush® and the difficulty in understanding the instructions did also contribute to the low-quality. Providing health education concerning cervical cancer and HPV self-sapling to women, male involvement in the screening program, and linking the screening service to existing local health facilities were suggested to guarantee the success of home-based HPV self-sampling. Conclusions Educating women regarding cervical cancer and HPV testing, providing clear instructions on how to collect self-sample, and male involvement in the screening program are prerequisites for a successful implementation of home-based HPV testing. Women empowerment should also be focused to overcome the identified sociocultural barriers. Furthermore, the screening program should guarantee the timely provision of the test results and offering women follow-up examinations and treatment for abnormal findings.

Cost-effectiveness of PARP inhibitors in malignancies: A systematic review

Objectives Poly (ADP-ribose) polymerase inhibitor (PARPi) have become a mainstay for the treatment of BRCA-mutant malignancies. PARPis are likely to be more effective but also bring an increase in costs. Thus, we aimed at evaluating the cost effectiveness of PARPis in the treatment of malignancies. Methods Studies of cost effectiveness of PARPis were searched from PubMed, Web of Science, and Cochrane Library. Key information was extracted from the identified studies and reviewed. Quality of the included studies was evaluated using Quality of Health Economic Studies (QHES) instrument. Modeling techniques, measurement of parameters and uncertainty analysis were analyzed across studies. Interventions and cost-effectiveness results were reported stratified by patient population. Results Among the 25 studies identified, we included 17 on ovarian cancer, 2 on breast cancer, 3 on pancreatic cancer, and 3 on prostate cancer that involved olaparib, niraparib, rucaparib, and talazoparib. All studies had a QHES score of above 75. In the maintenance therapy of ovarian cancer, additional administration of olaparib was cost-effective for newly diagnosed patients after first-line platinum-based chemotherapy but was not cost-effective for platinum-sensitive recurrent patients in majority studies. However, the economic value of other PARPis in ovarian cancer as well as all PARPis in other tumors remained controversial. Cost-effectiveness of PARPi was primarily impacted by the costs of PARPi, survival time, health utility and discount rate. Moreover, genetic testing improved the cost-effectiveness of PARPi treatment. Conclusions PARPi is potentially cost-effective for patients with ovarian, pancreatic, or prostate cancer. Genetic testing can improve the cost-effectiveness of PARPi.

Obesity in children and adolescents and the risk of ovarian cancer: A systematic review and dose‒response meta-analysis

Objective The relationship between obesity in children and adolescents and the risk of ovarian cancer remains controversial. The aim of this meta-analysis was to explore the exact shape of this relationship. Methods We conducted dose‒response meta-analyses of cohort and case‒control studies, including published studies derived from searches in the PubMed, Embase, Web of Science and Cochrane Library databases until October 2022. Pooled effect size estimates are expressed as relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) and were evaluated by fixed-effect models. A nonlinear dose‒response meta-analysis was performed by using a restricted cubic spline model. Results After screening 4215 publications, 10 studies were included in the present meta-analysis. Overall analyses revealed statistically significant associations of obesity in children and adolescents with ovarian cancer (adjusted RR = 1.19, 95% CI: 1.11 to 1.28, P &lt; 0.001). Moreover, the association was consistently significant in most subgroup analyses, for example, using geographic stratification, the results remained stable both in the Americas(RR = 1.11; 95% CI: 1.01 to 1.21; P = 0.022) and Europe (RR = 1.46; 95% CI: 1.21 to 1.77; P&lt;0.001). For the dose‒response analyses, the risk of ovarian cancer increased with the degree of obesity, and the trend increased rapidly when body mass index (BMI) was over 25.95 kg/m2. Conclusion Our findings indicate that obesity in children and adolescents is a risk factor for ovarian cancer, and the risk increases with increasing BMI.

Impact of knowledge and attitude on the utilization rate of cervical cancer screening tests among Ethiopian women: A systematic review and meta-analysis

IntroductionCervical cancer is a major public health problem, particularly in resource-limited settings. The use of vaccination and screening tests has reduced the burden of cervical cancer in developed countries. However, the situation is quite the reverse in developing countries, including Ethiopia. Hence, this study aimed to estimate the pooled impact of knowledge and attitude on the prevalence of cervical cancer screening service utilization rates among Ethiopian women.MethodsStudies that examined cervical cancer screening service utilization among women in Ethiopia were searched from five international databases. Cochran’s Q chi-square and the I-squared test statistics were used to check the presence of heterogeneity among the included studies. The funnel plot and Egger’s regression tests were also used to assess the presence of publication bias. A weighted DerSimonian and Laird random-effects model was employed. Subgroup analysis was performed by the study population concerning the prevalence of cervical cancer screening service utilization rates. Sensitivity analysis was also conducted to assess the effect of a single study on the pooled estimates. Data analysis was performed using STATA™ Version 14 software.ResultsA total of 44 studies with 28,186 study participants were included. The estimated pooled prevalence of cervical cancer screening service utilization was 8.11% (95% CI: 7.26, 8.97). After adjustment for publication bias with the trim and fill analysis, the estimated prevalence rate appeared to be 5.47% (95% CI: 4.66, 6.28). The prevalence of cervical cancer screening service utilization was higher among HIV-positive women, 16.85%, and in studies conducted among health care workers, 10.24%, than the general population. The pooled effect of knowledge on the utilization of cervical cancer screening tests among Ethiopian women was statistically significant (AOR=3.20, 95% CI: 1.63, 6.31). Similarly, the pooled estimated odds of utilizing cervical cancer screening tests were 6.1 times higher (AOR=6.09, 95% CI: 1.09, 34.36) among women who had a favorable attitude towards the screening tests.ConclusionKnowledge and attitude had a significant impact on the prevalence of cervical cancer screening test utilization rates among women in Ethiopia. However, the prevalence of cervical cancer screening service utilization among Ethiopian women is very low. Hence, large-scale awareness programs and situation-based strategies need to be designed to increase the uptake of cervical cancer screening services in the country.

Predictors of cervical cancer screening uptake in two districts of Central Uganda

Uganda’s cervical cancer age standardized incidence rate is four times the global estimate. Although Uganda’s ministry of health recommends screening for women aged 25–49 years, the screening remains low even in the most developed region (Central Uganda) of the country. This study examined the demographic, social, and economic predictors of cervical cancer screening in Central Uganda with the aim of informing targeted interventions to improve screening. The cross-sectional survey was conducted in Wakiso and Nakasongola districts in Central Uganda. A total of 845 women age 25–49 years participated in the study. Data were analyzed at bivariate and multivariate levels to examine the predictors of CC (cervical cancer) screening. Only 1 in 5 women (20.6%) had ever screened for cervical cancer. Our multivariate logistic regression model indicated that wealth index, source of information, and knowledge about CC and CC screening were significantly associated with cervical cancer screening. The odds of cervical cancer screening were higher among rich women compared with poor women [AOR = 1.93 (95%CI: 1.06–3.42), p = 0.031)], receiving information from health providers compared with radios [AOR = 4.14 (95%CI: 2.65–6.48), p&lt;0.001, and being more knowledgeable compared with being less knowledgeable about CC and CC screening [AOR = 2.46 (95%CI: 1.49–3.37), p&lt;0.001)]. Overall cervical cancer screening uptake in central Uganda was found to be low. The findings of the study indicate that women from a wealthy background, who had been sensitized by health workers and with high knowledge about CC and CC screening had higher odds of having ever screened compared with their counterparts. Efforts to increase uptake of screening must address disparities in access to resources and knowledge.

Bibliometric analysis of hotspots and frontiers in cancer-related fatigue among ovarian cancer survivors

Objectives To explore and analyze research hotspots and frontiers in CRF in ovarian cancer patients to provide an evidence-based basis for scholars and policymakers. Background Ovarian cancer is one of the most common and lethal gynecological malignancies. Cancer-related fatigue (CRF) is an annoying and pervasive side-effect that seriously affects the activities of daily living and decreases the quality of life (QoL) of cancer survivors. Methods The literature was retrieved from the Web of Science Core Collection (WOSCC) from inception to 2021-12-31. CiteSpace was used to discuss research countries, institutions, authors, and keywords. Results This study ultimately included 755 valid publications, and the number of publications showed a gradual upward trend. The countries, institutions, authors, and journals that have published the most articles and cited the most frequently were the United States, the University of Texas MD Anderson Cancer Center, Michael Friedlander and Amit M Oza, Gynecologic Oncology, and Journal of Clinical Oncology. The top three high-frequency keywords were Ovarian cancer, chemotherapy, and clinical trial. The top three keywords with the strongest citation bursts were cyclophosphamide, double-blind, and open-label. Conclusions Conducting multi-center, large-sample, randomized controlled clinical trials to determine whether chemotherapeutic agents have severe adverse effects and to discuss the relationship between CRF and QoL and overall survival in cancer survivors are hotspots in this field. The new trends may be applying double-blind, randomized controlled trials to clarify the causes of CRF and open-label, randomized trials to determine the efficacy, safety, and tolerability of chemotherapeutic agents.

Progression-free survival and overall survival after BRCA1/2-associated epithelial ovarian cancer: A matched cohort study

Introduction Germline BRCA1/2-associated epithelial ovarian cancer has been associated with better progression-free survival and overall survival than sporadic epithelial ovarian cancer, but conclusive data are lacking. Methods We matched 389 BRCA1-associated and 123 BRCA2-associated epithelial ovarian cancer patients 1:1 to sporadic epithelial ovarian cancer patients on year of birth, year of diagnosis, and FIGO stage (&lt; = IIA/&gt; = IIB). Germline DNA test was performed before or after epithelial ovarian cancer diagnosis. All patients received chemotherapy. We used Cox proportional hazards models to estimate the associations between mutation status (BRCA1 or BRCA2 versus sporadic) and progression-free survival and overall survival. To investigate whether DNA testing after epithelial ovarian cancer diagnosis resulted in survival bias, we performed additional analyses limited to BRCA1/2-associated epithelial ovarian cancer patients with a DNA test result before cancer diagnosis (n = 73 BRCA1; n = 9 BRCA2) and their matched sporadic controls. Results The median follow-up was 4.4 years (range 0.1–30.1). During the first three years after epithelial ovarian cancer diagnosis, progression-free survival was better for BRCA1 (HR 0.88, 95% CI 0.74–1.04) and BRCA2 (HR 0.58, 95% CI 0.41–0.81) patients than for sporadic patients. Overall survival was better during the first six years after epithelial ovarian cancer for BRCA1 (HR 0.7, 95% CI 0.58–0.84) and BRCA2 (HR 0.41, 95% CI 0.29–0.59) patients. After surviving these years, survival benefits disappeared or were in favor of the sporadic patients. Conclusion For epithelial ovarian cancer patients who received chemotherapy, we confirmed survival benefit for BRCA1 and BRCA2 germline pathogenic variant carriers. This may indicate higher sensitivity to chemotherapy, both in first line treatment and in the recurrent setting. The observed benefit appears to be limited to a relatively short period after epithelial ovarian cancer diagnosis.

Effects of mobile Health (mHealth) application on cervical cancer prevention knowledge and screening among women social support groups with low-socioeconomic status in Mysuru city, Southern India

Background Cervical cancer is an important area of action because of the mortality and morbidity of the disease, and the potential for effective prevention by screening. Involving the social support groups by health education improves cervical cancer screening and early detection of the disease in the community. In the ongoing efforts to strengthen cervical cancer prevention, control, and management, digital health and technology will have a significant role to play. Objective To assess the effectiveness of the mHealth-based intervention on cervical cancer preparedness among women social support groups. Materials &amp; methods A pre-post interventional study was conducted among women social support groups from lower socio-economic status, identified from the field practice area. Purposive sampling technique was employed. A Cervical Cancer Awareness Measure (CAM) instrument was used to assess the cancer preparedness among the social support group women After taking inputs from the stakeholders’ mobile health application was developed. The mHealth educational intervention was given to 102 women. Both pre-and post-test questionnaires were administered through mHealth application to assess the change in knowledge after a gap of 1 month to 2 months. The data obtained was coded and entered into Microsoft Excel worksheet 2016 and was later imported and analyzed using SPSS version 22 (licensed to the Institute). The difference in median scores of knowledge and practice were interpreted as statistically significant at p value of &lt; 0.05. Results &amp; conclusion Before the intervention only 13 (12.7%) of them had heard about cervical cancer. There was a significant increase in the knowledge about warning signs &amp; symptoms, risk factors of cervical cancer, and HPV vaccination. Around 5% increase in Pap smear test uptake.

PROM1, CXCL8, RUNX1, NAV1 and TP73 genes as independent markers predictive of prognosis or response to treatment in two cohorts of high-grade serous ovarian cancer patients

Considering the vast biological diversity and high mortality rate in high-grade ovarian cancers, identification of novel biomarkers, enabling precise diagnosis and effective, less aggravating treatment, is of paramount importance. Based on scientific literature data, we selected 80 cancer-related genes and evaluated their mRNA expression in 70 high-grade serous ovarian cancer (HGSOC) samples by Real-Time qPCR. The results were validated in an independent Northern American cohort of 85 HGSOC patients with publicly available NGS RNA-seq data. Detailed statistical analyses of our cohort with multivariate Cox and logistic regression models considering clinico-pathological data and different TP53 mutation statuses, revealed an altered expression of 49 genes to affect the prognosis and/or treatment response. Next, these genes were investigated in the validation cohort, to confirm the clinical significance of their expression alterations, and to identify genetic variants with an expected high or moderate impact on their products. The expression changes of five genes, PROM1, CXCL8, RUNX1, NAV1, TP73, were found to predict prognosis or response to treatment in both cohorts, depending on the TP53 mutation status. In addition, we revealed novel and confirmed known SNPs in these genes, and showed that SNPs in the PROM1 gene correlated with its elevated expression.

Human papillomavirus genotype distribution and factors associated among female sex workers in West Africa

ObjectivesThis study aimed to: (1) Estimate HPV prevalence and genotype distribution among female sex workers (FSWs) in Mali and Benin as well as the prevalence of multiple HPV type infections in this group, and (2) Identify potential risk factors associated with high-risk (HR) HPV infections.MethodsWe analyzed baseline data of 665 FSWs aged ≥ 18 years recruited during a prospective cohort of cervical cancer screening in Cotonou (Benin) and Bamako (Mali) from 2017 to 2018. The Linear Array HPV genotyping test was used to identify HPV genotypes. Descriptive statistics and multivariate log-binomial regression were used. Adjusted prevalence ratios (APR) with 95% confidence intervals (95%CI) were estimated to identify risk factors associated with HR-HPV infections.ResultsHPV data were available for 659 FSWs (Benin: 309; Mali: 350). The mean age was 35.0 years (± 10.7) in Benin and 26.8 years (± 7.6) in Mali. The overall HPV prevalence rates were 95.5% in Benin and 81.4% in Mali. About 87.7% and 63.4% of FSWs harbored ≥ 2 HPV types in Benin and Mali, respectively. The top three prevalent HR-HPV among FSWs in Benin were: HPV58 (37.5%), HPV16 (36.6%) and HPV52 (28.8%). Corresponding patterns in Mali were HPV16 (15.7%), HPV51 (14.3%) and HPV52 (12.9%). In Benin, the main factors associated with HR-HPV were vaginal douching (APR = 1.17; 95%CI:1.02–1.34) and gonococcal infection (APR = 1.16; 95%CI:1.04–1.28), while in Mali they were sex work duration ≤ 1 year (APR = 1.35; 95%CI:1.10–1.65) and HIV infection (APR = 1.26; 95%CI: 1.06–1.51).ConclusionOur study found a very high prevalence of HPV infection as well as high frequency of multiple HPV type infections in FSWs in two countries in West Africa. These findings suggest the necessity to emphasize cervical cancer prevention in this high-risk group.

Histone deacetylase inhibitor, panobinostat, exerts anti-proliferative effect with partial normalization from aberrant epigenetic states on granulosa cell tumor cell lines

The prognosis of the patients with inoperable or advanced granulosa cell tumors (GCTs) is still poor, and therefore it is important to establish a novel treatment strategy. Here we investigated the in vitro effects of a histone deacetylase inhibitor, panobinostat (PS) on two GCT cell lines (KGN and COV434). GCT cell lines were found to be susceptible to PS treatment and it inhibited cell growth mainly by apoptosis. In cell cycle analysis, PS reduced only the ratio of S phase in GCT cell lines. Combined treatment of PS with a deubiquitinase inhibitor, VLX1570 enhanced the expression of p21, cleaved PARP, cleaved caspase-9, heme oxygenase-1, and the acetylation of histone H4 and α-tubulin, leading to an additive anti-proliferative effect on KGN and COV434. The gene set enrichment analysis revealed that PS treatment suppressed DNA replication- or cell cycle-related gene expression which led to chemotherapeutic cell death and in addition, this treatment induced activation of the gene set of adherens junction towards a normalized direction as well as activation of neuron-related gene sets that might imply unexpected differentiation potential due to epigenetic modification by a HDAC inhibitor in KGN cells. Exposure of KGN and COV434 cells to PS increased the expression of E-cadherin, one of the principal regulators associated with adherens junction in quantitative RT-PCR and immunoblotting analysis. In the present study, we indicate a basis of a novel therapeutic availability of a HDAC inhibitor for the treatment of GCTs and further investigations will be warranted.

VEGF-C serum level is associated with response to bevacizumab maintenance therapy in primary ovarian cancer patients

Objective At present, maintenance therapy with the antiangiogenic agent bevacizumab or with PARP-inhibitors represent two options for BRCA-wildtype ovarian cancer patients, after platinum-based first line chemotherapy. The identification of molecular markers to predict patient response to different maintenance therapies remains a major challenge. In the present study we analyzed the predictive potential of vascular endothelial growth factor C (VEGF-C) to identify ovarian cancer patients that might benefit from an antiangiogenic therapy. Methods 101 patients with primary epithelial ovarian cancer were analyzed for serum levels of VEGF-A,–C and CA-125 by ELISA. Serum levels were compared between patients with low pT-stage (pT1a-pT2c n = 11), healthy individuals (n = 27) and patients with higher pT-stage (&gt; = pT3 n = 90). Adjusted ROC curves and an adjusted logistic regression model were carried out to evaluate the potential impact of VEGF-A and -C, as well as CA-125 serum level concentration on bevacizumab-therapy response, under consideration of covariates such as FIGO, pM, pN and residual tumor after surgery. Results A patient which has in comparison twice the VEGF-C concentration in serum, has a significant increased chance of response to bevacizumab by a factor of 2.79. Further, only VEGF-C serum levels were significantly higher in the group of patients with lower pT-stage compared to healthy individuals, whereas VEGF-A or CA-125 serum levels could not discriminate between healthy individuals and patients with ovarian cancer at low pT-stages. Conclusion VEGF-C serum level might serve as as a biomarker to evaluate treatment response under bevacizumab.

The p16/ki-67 assay is a safe, effective and rapid approach to triage women with mild cervical lesions

Objective The aim of this study was to evaluate the diagnostic accuracy and efficiency of p16/ki-67 dual stain in the identification of CIN2+ lesions, in Greek women with ASCUS or LSIL cytology. Methods A total of 200 women, 20 to 60 years old, were enrolled in the study. All samples were cytologically evaluated and performed for p16/ki-67 and high-risk HPV (HR-HPV) test. All patients were referred to colposcopy for biopsy and histological evaluation. Three cervical cancer (CC) screening strategies were designed and the total direct medical costs of the procedures during our clinical trial were evaluated, from a healthcare perspective. Results HPV 16 as expected was the most common HR-HPV type followed by HPV 31 and HPV 51. The risk for CIN2+ was significantly higher in HPV 16/18 positive cases. p16/ki-67 demonstrated a high sensitivity for CIN2+ identification in both ASCUS and LSIL groups (90.4% and 95%, respectively). HR-HPV test with sensitivity 52.3% and 65.5%, as well as colposcopy with sensitivity 14.3% and 36% respectively in ASCUS and LSIL group, showed inferior results compared to p16/ki-67. The specificity of p16/ki-67 for ASCUS and LSIL was 97.2% and 95.2% respectively, inferior only to colposcopy: 100% and 100%, lacking however statistical significance. HR-HPV test instead, presented the lowest specificity: 76.4% and 71.4% respectively in comparison to the other two methods. From a healthcare perspective, the costs and benefits of the tests implementation for the annual screening and triaging, in three CC screening strategies, were also calculated and discussed. Conclusions The results of the study indicate that p16/ki-67 is a safe and rapid assay that could be used to detect CIN2+ among women with mild cervical lesions, presenting both high sensitivity and specificity and could minimize the psychological and economic burden of HPV screening.

Single-cell analysis of a high-grade serous ovarian cancer cell line reveals transcriptomic changes and cell subpopulations sensitive to epigenetic combination treatment

Ovarian cancer (OC) is a lethal gynecological malignancy with a five-year survival rate of only 46%. Development of resistance to platinum-based chemotherapy is a common cause of high mortality rates among OC patients. Tumor and transcriptomic heterogeneity are drivers of platinum resistance in OC. Platinum-based chemotherapy enriches for ovarian cancer stem cells (OCSCs) that are chemoresistant and contribute to disease recurrence and relapse. Studies examining the effect of different treatments on subpopulations of HGSOC cell lines are limited. Having previously demonstrated that combined treatment with an enhancer of zeste homolog 2 inhibitor (EZH2i) and a RAC1 GTPase inhibitor (RAC1i) inhibited survival of OCSCs, we investigated EZH2i and RAC1i combination effects on HGSOC heterogeneity using single cell RNA sequencing. We demonstrated that RAC1i reduced expression of stemness and early secretory marker genes, increased expression of an intermediate secretory marker gene and induced inflammatory gene expression. Importantly, RAC1i alone and in combination with EZH2i significantly reduced oxidative phosphorylation and upregulated Sirtuin signaling pathways. Altogether, we demonstrated that combining a RAC1i with an EZH2i promoted differentiation of subpopulations of HGSOC cells, supporting the future development of epigenetic drug combinations as therapeutic approaches in OC.

A randomized controlled trial comparing self-referred message to family-referred message promoting men’s adherence to evidence-based guidelines on BRCA1/2 germline genetic testing: A registered study protocol

Background This is a registered study protocol on a randomized controlled trial (RCT) testing an intervention aimed to improve men’s adherence to evidence-based guidelines on BRCA1/2 germline genetic testing. BRCA1- and BRCA2-associated Hereditary Breast and Ovarian Cancer Syndrome (HBOC) increases the relative and absolute risk of developing breast and ovarian cancer and, to a lesser extent, prostate and pancreatic cancer. Men face BRCA-related cancer risks as women do, although with a different magnitude, and they may also transmit the mutations to their children. Notwithstanding, men are under-tested compared to women and the communication is not tailored on their needs. The present RCT applies principles of the Health Action Process Approach (HAPA) in testing the psychological determinants of the men’s adherence to evidence based guidelines on BRCA1/2 germline genetic and testing the efficacy of two messages. Methods A total of 264 participants will be involved, among the men’s relatives of women with verified germline mutations. The study entails a pre- post- evaluation with randomization of the participants in two conditions corresponding to the two messages. Discussion The expected results provide answers related to the impact of action self-efficacy, outcome expectancy (personal or familiar), risk perception, health risk aversion, intolerance of uncertainty, perceived barriers, and coping self-efficacy on informed decision-making. Data gathered from this study may inform health care providers, policy makers, and public health managers about the communication strategy for men and about the psychological variables influencing decision-making. Trail registration Name of the Registry: Clinical Trials. Trial registration number: NCT04683068. Date of registration: 16/12/2020. URL of trial registry record: https://www.clinicaltrials.gov/.

Applying citizen science to engage families affected by ovarian cancer in developing genetic service outreach strategies

Citizen science (CS) approaches involving non-professional researchers (citizens) as research collaborators has been used infrequently in health promotion generally and specifically, in cancer prevention. Standardized CS approaches may be especially useful for developing communication interventions to encourage families to consider cancer genetic services. We engaged survivors of ovarian cancer and their close relatives as CS collaborators to collect and help interpret data to inform content for a website, printed invitation materials, and short-message reminders. We applied an implementation quality framework, and posed four research questions regarding the feasibility of CS: recruitment, data collection, data quality and evaluation of the experience. CS members were recruited through three networks: clinical sites, local and national cancer support organizations, and online ovarian cancer patient support groups. The professional research team operationalized theory-aligned CS tasks, five data collection options, question banks/scripts for creating surveys, structured interviews, online training and ongoing support from research coaches. 14 CS members agreed to the 12-week and 20-hour commitment for an honorarium. CS members opted to do both qualitative and quantitative assessments. CS members collected 261 surveys and 39 structured interviews. The largest number of surveys were collected for Task 1 (n = 102) to assess survivors’ reactions to different possible options for motivating survivors to visit a study website; 77% of this data were complete (i.e., no missing values). Data collected for tasks 2, 3, 4, and 5 (e.g., assessment of survivors’ and relatives’ respective communication preferences) ranged from 10 to 58 surveys (80% to 84% completeness). All data were collected within the specified time frame. CSs reported 17 hours of work on average and regarded the experience positively. Our experience suggests that CS engagement is feasible, can yield comprehensive quantitative and qualitative data, and is achievable in a relatively a short timeline.

Implementation of Australia’s renewed cervical screening program: Preparedness of general practitioners and nurses

The National Cervical Screening Program (NCSP) in Australia underwent major changes on December 1st, 2017. The program changed from 2-yearly Pap testing for women aged 18-69 years to 5-yearly HPV testing for women aged 25-74 years including differential management pathways for oncogenic HPV 16/18 positive versus HPV non16/18 positive test results and the option of self-collection for under-screened women. We conducted a survey among cervical screening providers in primary care to assess their level of preparedness in undertaking cervical screening before (pre-renewal) and after (post-renewal) the new program was implemented. Surveys were conducted between 14th August and 30th November 2017 (pre-renewal) and 9th February and 26th October 2018 (post-renewal) among cervical screening providers who attended education sessions related to the new guidelines. Preparedness was assessed in three areas: 1) level of comfort implementing the new guidelines (7 questions), 2) level of confidence in their ability to convey information about the new guidelines (9 questions) and 3) level of agreement regarding access to resources to support implementation (11 questions). Proportions were calculated for each question response and pre- and post-renewal periods compared using generalised linear models. Open-ended questions related to anticipated barriers and ways to overcome barriers were also included in the questionnaires. Compared to the pre-renewal period, a higher proportion of practitioners in the post-renewal period were more comfortable offering routine screening to women ≥25 years (p = 0.005) and more confident explaining the rationale for not screening before 25 years (p = 0.015); confident explaining a positive HPV 16/18 (p = 0.04) and HPV non 16/18(p = 0.013) test result and were comfortable with not referring women with a positive HPV non 16/18 test result and low grade/negative cytology for colposcopy (p = 0.01). A higher proportion of Victorian practitioners in the post-renewal period sample were also comfortable (p = 0.04) and confident (p = 0.015) recommending self-collection to under-screened women and agreed that self-collection is a reliable test (p = 0.003). The most commonly reported suggestion was to provide information, education and communication materials to both patients and practitioners. Compared to the pre-renewal period, practitioners in the post-renewal period were better prepared to implement the renewed screening program. Healthcare providers require further support to implement the self-collection pathway.

A deep hybrid learning pipeline for accurate diagnosis of ovarian cancer based on nuclear morphology

Nuclear morphological features are potent determining factors for clinical diagnostic approaches adopted by pathologists to analyze the malignant potential of cancer cells. Considering the structural alteration of the nucleus in cancer cells, various groups have developed machine learning techniques based on variation in nuclear morphometric information like nuclear shape, size, nucleus-cytoplasm ratio and various non-parametric methods like deep learning have also been tested for analyzing immunohistochemistry images of tissue samples for diagnosing various cancers. We aim to correlate the morphometric features of the nucleus along with the distribution of nuclear lamin proteins with classical machine learning to differentiate between normal and ovarian cancer tissues. It has already been elucidated that in ovarian cancer, the extent of alteration in nuclear shape and morphology can modulate genetic changes and thus can be utilized to predict the outcome of low to a high form of serous carcinoma. In this work, we have performed exhaustive imaging of ovarian cancer versus normal tissue and developed a dual pipeline architecture that combines the matrices of morphometric parameters with deep learning techniques of auto feature extraction from pre-processed images. This novel Deep Hybrid Learning model, though derived from classical machine learning algorithms and standard CNN, showed a training and validation AUC score of 0.99 whereas the test AUC score turned out to be 1.00. The improved feature engineering enabled us to differentiate between cancerous and non-cancerous samples successfully from this pilot study.

Acceptability of self- collection for human papillomavirus detection in the Eastern Cape, South Africa

Human papillomavirus (HPV) testing on vaginal self-collected and cervical clinician-collected specimens shows comparable performance. Self-sampling on FTA cards is suitable for women residing in rural settings or not attending regular screening and increases participation rate in the cervical cancer screening programme. We aimed to investigate and compare high-risk (HR)-HPV prevalence in clinician-collected and self-collected genital specimens as well as two different HPV tests on the clinician collected samples. A total of 737 women were recruited from two sites, a community health clinic (n = 413) and a referral clinic (n = 324) in the Eastern Cape Province. Cervical clinician-collected (FTA cards and Digene transport medium) and vaginal self-collected specimens were tested for HR-HPV using the hpVIR assay (FTA cards) and Hybrid Capture-2 (Digene transport medium). There was no significant difference in HR-HPV positivity between clinician-collected and self-collected specimens among women from the community-based clinic (26.4% vs 27.9%, p = 0.601) or the referral clinic (83.6% vs 79.9%, p = 0.222). HPV16, HPV35, and HPV33/52/58 group were the most frequently detected genotypes at both study sites. Self-sampling for HPV testing received a high positive response of acceptance (77.2% in the community-based clinic and 83.0% in referral clinic). The overall agreement between hpVIR assay and HC-2 was 87.7% (k = 0.754). The study found good agreement between clinician-collected and self-collected genital specimens. Self-collection can have a positive impact on a cervical screening program in South Africa by increasing coverage of women in rural areas, in particular those unable to visit the clinics and women attending clinics where cytology-based programs are not functioning effectively.

Determining behavioral intention and its predictors towards cervical cancer screening among women in Gomma district, Jimma, Ethiopia: Application of the theory of planned behavior

BackgroundCervical Cancer is the leading cause of cancer-related deaths among Ethiopian women. Despite many interventions were conducted, there is low uptake of cervical cancer screening services. Also, limited evidence was available on the women’s intention and its predictors towards cervical cancer screening. Therefore, this study was aimed at determining the intention and predicators of behavioral intention toward cervical cancer screening.MethodsA cross-sectional study was conducted in the Gomma district, Jimma, Ethiopia from August 1–30, 2019. The total sample sizes were 422 and a systematic random sampling technique was employed to select the samples. Data were collected through interviews using a structured questionnaire guide. Data were entered in epidata, and exported and analyzed using SPSS version 20.0 software. Descriptive, correlation, and multicollinearity analysis were done. Also, simple and multiple linear regression analysis were performed to identify the predictors for behavioral intention. The p-value&lt;0.05 was used to declare a significant association.ResultThe response rate was 382 (90.5%). The mean age of the participants was of 26.45 (SD = 4.76). Direct attitude, subjective norm, and perceived behavioral control had a mean score of 16.78 (SD = 2.87), 15.61(SD = 1.92), and 12.86 (SD = 4.85), respectively. The intention has a mean score of 14.52 (SD = 4.01). From regression analysis, direct attitude (B = 0.346, p&lt;0.001), direct subjective norm (B = 0.288, p = 0.008), direct perceived behavioral control (B = 0.132, p = 0.002) indirect attitude (B = 0.015, p = 0.019) and the indirect perceived behavioral control (B = 0.132, p = 0.002) were statistically significant with intention.ConclusionFrom this study, it was understood that women’s intention towards cervical cancer screening was low. The predictors were the direct and indirect attitude, direct and indirect subjective norm, direct and indirect perceived behavioral control. This calls a need to develop strategies and take action to improve the attitude of women and their influential peoples and increase sense of control to improve their intention to screen for cervical cancer. Moreover, health care providers should have to conduct social and behavioral change communication to improve women’s health seeking behavior towards cervical cancer screening applying the concept of theory of planned behavior.

Trends in clinical stage distribution and screening detection of cancer in Osaka, Japan: Stomach, colorectum, lung, breast and cervix

We examined clinical stage distribution and proportion of screen-detected cases of stomach, colorectal, lung, female breast and cervical cancer by sex and age group using Osaka Cancer Registry data from 2000–2014. The proportion of local or in situ stage cancer had increased for all age groups in all sites, except stomach cancer in the 0–49 years group and female breast cancer in the 80 years and older group. The proportion of screen-detected cases had increased during the study period for all age groups in all cancer sites. While the proportion increased noticeably in the younger groups, there was only a slight increase in the older groups. Regarding stomach, colorectal and lung cancers, the proportion of local and in situ stage had similarly increased in the 65–79 years and 80 years and older age groups compared with younger groups, despite lower exposure to cancer screening. Regarding breast and cervical cancers, the increases in local and in situ cancer paralleled the increase in screen-detected cases. These findings suggest that the increases in early stage stomach, colorectal and lung cancers might be due not only to the expansion of screening programs but also the development of clinical diagnostic imaging or other reasons. The increases in local and in situ stage breast and cervical cancers seemed to be due to the expansion of screening. Continued monitoring of trends in cancer incidence by clinical stage may be helpful for estimating the effectiveness of screening.

Downregulation of 5-hydroxymethylcytosine is associated with the progression of cervical intraepithelial neoplasia

Around the world, cervical cancer is one of the most common neoplastic diseases among women, and the prognosis of patients in an advanced stage remains poor. To reduce the mortality rate of cervical cancer, early diagnosis and treatment are essential. DNA methylation is an important aspect of gene regulation, and aberrant DNA methylation contributes to carcinogenesis and cancer progression in various cancers. Although 5-methylcytosine (5mC) has been analyzed intensively, the function of 5-hydroxymethylcytosine (5hmC) has not been clarified. The purpose of our study was to identify the molecular biomarkers for early diagnosis of cervical tumors due to epigenetic alterations. To assess the clinical relevance of DNA methylation, we used immunohistochemistry (IHC) to characterize the level of 5hmC in 102 archived human cervical intraepithelial neoplasia (CIN) samples and cervical cancer specimens. The level of 5hmC was significantly decreased between CIN2 and CIN3. The progression of cervical tumors is caused by a reduction of TP53 and RB1 because of HPV infection. We observed that Tp53 and Rb1 were knocked down in mouse embryonic fibroblasts (MEF), a model of normal cells. The level of 5hmC was reduced in Tp53-knockdown cells, and the expression levels of DNA methyltransferase 1 (DNMT1) and ten-eleven translocation methylcytosine dioxygenase 1 (TET1) were induced. In contrast, there was no significant change in Rb1-knockdown cells. Mechanistically, we focused on apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) 3B (A3B) as a cause of 5hmC reduction after TP53 knockdown. In the human cell line HHUA with a wild-type TP53 gene, A3B was induced in TP53-knockdown cells, and A3B knockdown recovered 5hmC levels in TP53-knockdown cells. These data indicate that TP53 suppression leads to 5hmC reduction in part through A3B induction. Moreover, IHC showed that expression levels of A3B in CIN3 were significantly higher than those in both normal epithelium and in CIN2. In conclusion, 5hmC levels are decreased between CIN2 and CIN3 through the TP53-A3B pathway. Since A3B could impair genome stability, 5hmC loss might increase the chances of accumulating mutations and of progressing from CIN3 to cervical cancer. Thus, these epigenetic changes could predict whether CINs are progressing to cancer or disappearing.

Experiences of cervical cancer survivors in Chitwan, Nepal: A qualitative study

Introduction Cervical cancer is a global leading cause of morbidity and mortality. The majority of cervical cancer deaths occur in developing countries including Nepal. Though knowledge of cervical cancer is an important determinant of women’s participation in prevention and screening for cervical cancer, little is known about this topic in Nepal. This study explores the experiences of cervical cancer survivors and assesses the attitude of family and community towards it and stigma related to this disease in Bharatpur, Nepal. Methods The study design was qualitative methods involving two focus-group discussions. A total of 17 cervical cancer survivors, who have completed two years of cancer treatment were selected purposively from Chitwan. All qualitative data were transcribed and translated into English and were thematically analyzed. Results The majority of the participants had scant knowledge about cervical cancer, its causative agent, showed less cervical cancer screening, delayed healthcare-seeking behavior despite having persistent symptoms before the diagnosis. The main reasons identified for not uptaking the cervical screening methods were an embarrassment and having no symptoms at all. Most of them endured social stigma related to cervical cancer in the form of physical isolation and verbal abuse. Conclusions There is an urgent need for interventions to make women and the public aware of cervical cancer and launch effective health education campaigns, policies for cervical cancer prevention programs. This implementation can save the lives of hundreds of women and help them avoid going through all the negative experiences related to cervical cancer. More studies are required to gain the perspectives, knowledge, experiences, and attitudes of cervical cancer survivors to add to the research.

Mapping awareness of breast and cervical cancer risk factors, symptoms and lay beliefs in Uganda and South Africa

Breast and cervical cancer are leading causes of cancer burden in Sub-Saharan Africa (SSA). We measured breast and cervical cancer symptom and risk factor awareness and lay beliefs in Uganda and South Africa (SA). Between August and December 2018 we conducted a cross-sectional survey of women ≥18 years in one urban and one rural site per country. Households were selected using systematic random sampling, then one woman per household randomly selected to participate. Data were collected by interviewers using electronic tablets customised with the locally validated African Women Awareness of Cancer (AWACAN) tool. This has unprompted questions (testing recall) followed by prompted questions (testing recognition) on risk factor, symptom awareness and lay beliefs for breast and cervical cancer. Mann Whitney and Kruskal Wallis tests were used to compare the association between socio-demographic variables and outcomes. Poisson regression with robust variance was conducted to identify independent socio-demographic predictors. Of the 1758 women interviewed, 90.8% had heard of breast and 89.4% of cervical cancer. 8.7% recalled at least one breast risk factor and 38.1% recalled at least one cervical cancer risk factor. 78.0% and 57.7% recalled at least one breast/cervical cancer symptom respectively. Recognition of risk factors and symptoms was higher than recall. Many women were unaware that HPV, HIV, and not being screened were cervical cancer risk factors (23.7%, 46.8%, 26.5% respectively). In SA, urban compared to rural women had significantly higher symptom and risk factor awareness for both cancers. In Uganda married women/living with a partner had higher awareness of breast cancer risk factors and cervical cancer symptoms compared to women not living with a partner. Women mentioned several lay beliefs (e.g. putting money in their bra as a breast cancer risk factor). We identified gaps in breast and cervical cancer symptom and risk factor awareness. Our results provide direction for locally targeted cancer awareness intervention programs and serve as a baseline measure against which to evaluate interventions in SSA.

Study protocol for the development of a real-time interface showing the availability of breast and cervical cancer services in Ghana

Background The 5-year survival rates for breast and cervical cancers in Ghana are low in comparison to rates in developed countries. This striking disparity is attributed to numerous factors, including limited access and navigability to appropriate services. A one-time cross-sectional, hospital-based survey was performed by the University of Utah in collaboration with Ghana Health Services (GHS) and Health Facilities Regulatory Agency (HeFRA) from November, 2020 to October, 2021 so as to determine existing hospital-based breast and cervical cancer care services capacity and their geographic availability nationwide. This related information remains dynamic in nature and time. The current project employs a public-academic implementation science and research configuration to explore and develop a real-time interface (RTIF) showing the availability of breast and cervical cancer care services at hospital facilities in-country so as to anchor up-to-date data products for the government, private-sector, and patient-centric consumption. Methods and analysis Multiple methods will be employed to achieve the study objectives between December 2023 to November 2024. The first three objectives shall focus on contextual, needs, and feasibility assessments guided by the domains and constructs within the updated Consolidated Framework for Implementation Research (CFIR) during coding and thematic qualitative analysis. Using purposive sampling, breast and cervical cancer care service stakeholders shall be identified for individual in-depth interviews. The fourth objective will involve creating the RTIF prototype and piloting it in the Eastern Region of Ghana. The final and fifth objective shall employ the systems usability scale (SUS) amongst ten randomly selected individual stakeholders to assess the technical functionality of the interface. A nationwide scale-up shall follow this.

The role of health education on cervical cancer screening uptake at selected health centers in Addis Ababa

Cervical cancer is one of the most common causes of morbidity and mortality among women in developing countries including Ethiopia. Unlike other types of cancers, the grave outcomes of cervical cancer could be prevented if detected at its early stage. However, in Ethiopia, awareness about the disease and the availability of screening and treatment services is limited. This study aims to determine the role of health education on cervical cancer screening uptake in selected health facilities in Addis Ababa. Two-pronged clustered randomized controlled trial was conducted in 2018 at eight public health centers that provide cervical cancer screening services using visual inspection with acetic acid (VIA) in Addis Ababa, Ethiopia. Each of the eight health centers were randomly assigned to serve as either an intervention or a control center. A two-pronged clustered randomized controlled trial was conducted in eight public health care centers. All the selected facilities provided cervical cancer screening services using visual inspection with acetic acid (VIA). Four health centers were randomly assigned to the intervention and control arms. The study participants were women aged 30-49 years who sought care at maternal and child health clinics but who had never been screened for cervical cancer. In the intervention health centers, all eligible women received one-to-one health education and educational brochures about cervical cancer and cervical cancer screening. In the control health centers, participants received standard care. Baseline data were collected at recruitment and follow-up data were collected two months after the baseline. For the follow-up data collection, participants (both in the intervention and control arms) were interviewed over the phone to check whether they were screened for cervical cancer. From the 2,140 women who participated in the study, 215 (10%) screened for cervical cancer, where 152(71%) were from the intervention health centers. Seventy-four percent of these participants reported that they learned about the benefits of screening from the one-to-one health education or the brochure. Women from the intervention health centers had higher odds of getting screened (AOR = 2.43,95%CI;1.58-2.90) than the controls. Women with the educational status of the first degree and those who have a history of sexually transmitted infections (STIs) had higher odds of getting screened (AOR = 2.03,95%CI;(1.15-2.58) and (AOR = 1.55,95%CI;1.01-2.36), respectively. Providing focused health education supported by printed educational materials increased the uptake of cervical cancer screening services. Integrating one-to-one health education and providing a take-home educational material into the existing maternal and child health services can help increase cervical cancer screening uptake.

Knowledge and practice of cervical cancer screening and associated factors among reproductive age group women in districts of Gurage zone, Southern Ethiopia. A cross-sectional study

Cervical cancer is a malignant tumor of the lower-most part of the uterus and major cause of morbidity and mortality among women's in the world. Its high mortality rate in the globe can be reduced through comprehensive approaches' that include; primary prevention, early diagnosis, effective screening, and treatment packages. This study was aimed to assess the knowledge and practice of cervical cancer screening and its associated factors among reproductive age group women in districts of Gurage zone, Southern Ethiopia, 2019. A community-based cross-sectional study design was conducted from March 1-30, 2019. A total of 268 respondents were selected using a systematic sampling technique. Data was collected using pretested, semi-structured, and interviewer-administered questionnaires. Data were entered into Epi data version 3.1software and exported to SPSS 24 for analysis. Bivariate and multivariate analyses with a 95% confidence level was done and variables (P <0.05) were deemed statistically significant. A total of 260 respondents participated in the study with a response rate of 97%. About 3.8% of the respondents had experiences cervical cancer screening and 26.2% of respondents had good knowledge. Early age at first sex [AOR = 6.05 (95%CI; 1.167-31.36)], having information about cervical cancer [(AOR = 10.2 (95% CI 1.9-96.4)], and multiple sexual partners [AOR = 3.96 (95% CI; 1.48-10.58)] were factors affecting the practice of cervical cancer screening. Being uneducated [AOR = 15.5 (95%CI; 3.82-62.967)], family history of cervical cancer [AOR = 14.158 (95%CI;3.88-51.7)], having plans to screen for cervical cancer [AOR = 0.352 (95%CI;.175-.710)], menarcheal age [AOR = 2.63 (95%CI;1.28-5.37)] and age at first sex [AOR = 3.17 (95%CI;1.283-7.837)] were factors affecting knowledge of cervical screening. The study findings indicate that respondents' practice and knowledge of cervical cancer is mainly affected by early age at first sex, having information about cervical cancer, multiple sexual partners, Educational status, family history of cervical cancer, having plans to screen for cervical cancer, age at first sex and age of menarche. Therefore, all concerned bodies need to focus on women in the reproductive age group to increase the level of knowledge and practice of cervical cancer screening through appropriate interventions.

Exploring the p53 connection of cervical cancer pathogenesis involving north-east Indian patients

As per WHO, Cervical cancer (CaCx) is a global issue, being the fourth common cancer in women with incidence rate of 13.1 per 1 lakh women globally and accounting for 311000 deaths in the year 2018 itself globally. The molecular pathogenesis in Human papillomavirus (HPV) infected cases is inconclusive. The detection of molecular factors leading to progression of CaCx can be important in the diagnosis and management of the disease. p53 a known tumor suppressor gene having a regulative role in cell cycle has been highlighted as key factor in the prevention of cancer but its significance in CaCx cases has been variably documented. The present study therefore targeted to evaluate the significance of p53 profile in CaCx cases in ethnically distinct northeast Indian population. Blood and Tissue samples (N = 85) of cervical cancer patients were collected and screening for HPV was performed using PCR. Thereafter the differential mRNA expression(qPCR), Immunohistochemistry, Mutation (PCR direct sequencing method) of p53 was studied. Further p53 epigenetic profiling was done by Methylation specific PCR (MS-PCR) and western blotting by using p53 acetylation specific antibodies. Our findings revealed that the downregulation of p53 was associated with the progression of disease and the variation in downregulation based on p53 polymorphism was observed. Further hypermethylation and deacetylation of p53 was also found to be associated with the pathogenesis of CaCx. The downregulated expression and hypermethylation of p53 in lower grade of CaCx, together established its association with the progression of CaCx from lower to severe grade. Therefore, in CaCx patients of northeast Indian population, malfunctioning of p53 is found to have significant role in cervical cancer progression.

The effectiveness of HPV viral load, reflected by Cobas 4800 HPV-Ct values for the triage of HPV-positive women in primary cervical cancer screening: Direct endocervical samples

To explore the relationship between the viral load reflected by the Ct value of Cobas 4800 HPV test and cervical lesions, and the effectiveness of the viral load for secondary triage of HPV-positive women. The Chinese Multi-Center Screening Trial (CHIMUST) evaluated both self-collected samples and physician-collected samples from women, aged 30 to 59, who were screened for cervical cancer in 6 regions across China. Using physician collected samples, the relationship between the HPV-Ct values of different subtypes and the cervical lesions was analyzed. Then the combined use of the HPV-Ct values with the HPV subtypes was evaluated as a secondary screening algorithm for the women who were HPV positive. The Ct values of HPV16 and 12 other HPV subtypes(12-type pool), tested with Cobas decreased with the progression of cervical lesion (HPV16: r = -0.429, P0.05). Compared with HPV16/18 and cytology (HPV16/18 positive and 12-type pool plus cytology ≥ ASC-US), the sequential secondary screening using HPV16/18 and the viral load of 12-type pool (cut-point HPV-Ct≤31) had equal sensitivities for CIN2+ and CIN3+ (83.1%vs.80.3%,100%vs.92.6%,P>0.05), with slightly lower specificities (96.2%vs.94.4%,96.5%vs.93.9%,P<0.001) and higher colposcopy referral rate (4.90%vs.6.59%, P<0.05), but required no cytology. Type-specific HPV viral load is closely related to cervical lesions severity. It is feasible and efficient to use HPV16/18 and the viral load of 12 other HPV subtypes (with cut-point HPV-Ct≤31) as the secondary screening for HPV positive women. This algorithm may be useful in low resource regions.

Cost effectiveness of strategies for cervical cancer prevention in India

The establishment of link between high-risk human papillomavirus (HPV) infection and occurrence of cervical cancer has resulted in development of various HPV related control strategies for the prevention of cervical cancer. The objective of the present study was to assess the cost effectiveness of various screening strategies for cervical cancer and human papilloma virus (HPV) vaccination in India. A Markov model based on societal perspective was designed to estimate the lifetime costs and consequences of screening (with either visual inspect with acetic acid (VIA), Papanicolaou test or HPV DNA test at various time intervals) in a hypothetical cohort of 30-65 years age women or vaccination among adolescent girls. Diagnostic accuracy of the screening strategies, efficacy of HPV vaccination and data on transition probabilities was based on the results of the existing meta-analyses. Primary data was collected for assessing per person cost of screening, cost of treating cervical cancer and quality of life. We found that introduction of different screening strategies leads to reduction in lifetime occurrence of cervical cancer cases caused by HPV 16/18 from 20% to 61%, and cervical cancer deaths from 28% to 70%, as compared to no screening. Among various screening strategies, screening with both VIA 5 yearly and VIA 10 yearly came out to be cost effective at 1-time per capita GDP, with VIA every 5 years providing greater health benefits as compared to VIA 10 years. Hence, screening with VIA 5 years at an incremental cost of US$ 829 (INR 54,881) per QALY gained is the recommended strategy for India. Further, with regards to HPV vaccination, it leads to 60% reduction in cancer cases and mortality caused by HPV 16/18 as compared to no vaccination. Moreover, when this vaccinated cohort of adolescent girls is also screened later in their life (with VIA every 10 years and VIA 5 years), it leads to 69%-76% reduction in cancer cases and 71%-81% reduction in cancer deaths. As compared to no vaccination and no screening, both HPV vaccination alone and vaccination plus screening (with VIA every 5 yearly and VIA 10 yearly) appears to be cost effective with ICERs in the range of US$ 86 (INR 5,693) to US$ 476 (INR 31,511) per QALY gained. In the long run, when the cohort of adolescent girls, who were immunized for HPV, reach the age of 30 years, the screening frequency using VIA should be determined based on the coverage of HPV vaccination in that cohort.

Innovative prototypes for cervical cancer prevention in low-income primary care settings: A human-centered design approach

This article presents the design process of innovative prototypes for cervical cancer prevention in primary care centers located in low-income settings in Cali, Colombia, using the Human-Centered Design (HCD). The project was developed in collaboration with a public healthcare network comprised of 38 urban and rural centers with women between the ages of 25 and 65 years, healthcare providers of the cancer program, healthcare administrators and the general manager of said network. Our HCD process involved five stages: research, need synthesis, ideation and co-design process, prototyping and in-context usability testing. In practice, some of the stages are overlapped and iterated throughout the design process. We conducted observations, open-ended interviews and conversations, multi-stakeholder workshops, focus groups, systematic text condensation analyses and tests in real contexts. As a result, we designed four prototypes: (1) 'Encanto': An educational manicure service, (2) 'No le des la espalda a la citología': A media-based strategy, (3) An educational wireless queuing device in the waiting room, and (4) Citobot: A cervical cancer early detection device, system, and method. The tests carried out with each prototype showed their value, limitations and possibilities in terms of subsequent development and validation through public health research or clinical research. We recognize that a longer-term evaluation is required in order to determine whether the prototypes will be used regularly, integrated into cervical cancer screening services and effectively improve access to cytology as a screening test. We conclude that HCD is a useful for design-based prevention in the field of cervical cancer. The integration of this approach with public health research would allow the generation of evidence during to the formulation of policies and programs as well as optimize existing interventions and, ultimately, facilitate the scalability and financing of what actually works.

Perceptions of cervical cancer prevention among a group of ethnic minority women in Denmark—A qualitative study

Background Cervical cancer screening (CCS) and human papillomavirus vaccination (HPVV) are effective measures against cervical cancer (CC). Attendance in HPVV and CCS provides the greatest protection, while combined non-attendance in HPVV and CCS provides little to no protection. It is hence concerning that some large ethnic minority groups show considerably lower HPVV and CCS attendance than other women–especially women from Middle-Eastern and North African (MENA) countries and Pakistan. Little is, however, known about the reasons for this low combined attendance pattern n. Aim To explore perceptions of and barriers to HPVV and CCS, among MENA and Pakistani women in Denmark. Method Focus group interviews were conducted. Data was transcribed verbatim, and analysed using systematic text condensation. Findings Seventeen long-term resident women originating from six major MENA countries and Pakistan were included. Mean age was 36 years. We found that these women, across different age groups and descent, had sparse knowledge and understanding about CC, and their perceived relevance of disease prevention was low. Compared to HPVV, their barriers to CCS were more fixed and often linked to socio-cultural factors such as taboos related to female genitals and sexuality. Moreover, they presented unmet expectations and signs of mistrust in the healthcare system. However, at the end of the interviews, participants became more attentive toward CC prevention, particularly toward HPVV. Conclusion Elements of insufficient knowledge and understanding of CC and its prevention were found among a group of MENA and Pakistani women. Their socio-cultural background further represents a barrier particularly towards CCS. Additionally, negative experiences and unmet expectations lessen their trust in the healthcare system. All of which underlines the need for new tailored CC preventive strategies for this group. Based on our findings we suggest that future studies develop and evaluate interventions aiming to improve HPVV and CCS, including user-involvement.

Clinical characteristics and risk of second primary lung cancer after cervical cancer: A population-based study

Lung cancer is increasingly common as a second primary malignancy. However, the clinical characteristics of second primary non-small cell lung cancer after cervical cancer (CC-NSCLC) compared with first primary non-small cell lung cancer (NSCLC1) is unknown. The Surveillance, Epidemiology, and End Results (SEER) cancer registry between 1998 and 2010 was used to conduct a large population-based cohort analysis. The demographic and clinical characteristics, as well as prognostic data, were systematically analyzed. The overall survival (OS) in the two cohorts was further compared. The risk factors of second primary lung cancer in patients with cervical cancer were also analyzed. A total of 557 patients (3.52%) developed second primary lung cancer after cervical cancer, and 451 were eligible for inclusion in the final analyses. Compared with NSCLC1, patients with CC-NSCLC had a higher rate of squamous cell carcinoma (SCC) (36.59% vs 19.07%, P < 0.01). The median OS was longer for CC-NSCLC than for NSCLC1 before propensity score matching (PSM) (16 months vs. 13 months) but with no significant difference after PSM (16 months vs. 17 months). The high-risk factors for the development of cervical cancer to CC-NSCLC include age 50-79 years, black race [odds ratio (OR) 1.417; 95% confidence interval (CI) 1.095-1.834; P < 0.05], and history of radiotherapy (OR 1.392; 95% CI 1.053-1.841; P < 0.05). Age 50-79 years, black race, and history of radiotherapy were independent risk factors for second primary lung cancer in patients with cervical cancer. Patients with CC-NSCLC had distinctive clinical characteristics and better prognosis compared with patients with NSCLC1.

Plan optimization with L0-norm and group sparsity constraints for a new rotational, intensity-modulated brachytherapy for cervical cancer

The aim of this work is to build a framework that comprehends inverse planning procedure and plan optimization algorithm tailored to a novel directional beam intensity-modulated brachytherapy (IMBT) of cervical cancer using a rotatable, single-channel radiation shield. Inverse planning is required for finding optimal beam emitting direction, source dwell position and dwell time, which begin with creating a kernel matrix for each structure based on Monte-Carlo simulated dose distribution in the rotatable shield. For efficient beam delivery and less transit dose, the number of source dwell positions and angles needs to be minimized. It can be solved by L0-norm regularization for fewest possible dwell points, and by group sparsity constraint in L2,p-norm (0≤p<1) besides L0-norm for fewest active applicator rotating angles. The dose distributions from our proposed algorithms were compared to those of conventional tandem-based intracavitary brachytherapy (ICR) plans for six cervical cancer patients. The algorithmic performance was evaluated in delivery efficiency and plan quality relative to the unconstrained algorithm. The proposed framework yielded substantially enhanced plan quality over the conventional ICR plans. The L0-norm and (group sparsity+L0-norm) constrained algorithms reduced the number of source dwell points by 60 and 70% and saved 5 and 8 rotational angles on average (7 and 11 angles for highly modulated cases), relative to the unconstrained algorithm, respectively. Though both algorithms reduced the optimal source dwell positions and angles, the group sparsity constrained optimization with L0-norm was more effective than the L0-norm constraint only, mainly because of considering physical constraints of the new IMBT applicator. With much fewer dwell points compared to the unconstrained, the proposed algorithms led to statistically similar plan quality in dose volume histograms and iso-dose lines. It also demonstrated that the plan optimized by rotating the applicator resulted in much better plan quality than that of conventional applicator-based plans.

Comparison of the detection rate of cervical lesion with TruScreen, LBC test and HPV test: A Real-world study based on population screening of cervical cancer in rural areas of China

China carries a heavy burden of cervical cancer and has an alarmingly low cervical cancer screening rate. In order to achieve the goal of cervical cancer elimination, there is an urgent need for suitable methods and strategies in China. A total 9972 woman who received cervical cancer screening services of National Cervical Cancer Screening Program in Rural Areas (NCCSPRA) in 8 project counties participated in this study. TruScreen, HPV test and LBC test were performed in all participants. A total of 1945women had one or more than one positive or abnormal screening results of the above three screening tests subsequently received colposcopy. The detection rate of CIN2+ between the three tests were compared. No matter what kind of screening method is used, the CIN2+ detection rate in the eastern regions was much higher than that in the central and western regions. The total detection rate of CIN2+ in HPV group was highest (0.73%), following in LBC group (0.44%) and TS group (0.31%). There was statistically significant difference in the total detection rate of CIN2+ between TS and HPV groups, LBC and HPV groups, respectively. There was no statistical difference in the total detection rate of CIN2+ between TS and LBC screening groups. Moreover, except for the eastern regions, there was no statistical difference in the detection rate of CIN2+ between TS group and the other two groups in central and western regions. If it can meet the requirements of the laboratory and personnel, HPV test seems to be the preferred method for cervical cancer screening in rural areas of China. The characteristics of minimal training requirements, simple operation, real-time results obtained without the collection of cervical cell samples and the help of laboratory equipment and cytologists of TS make it ideal for cervical cancer screening in low-resource regions.

Participation in interventions and recommended follow-up for non-attendees in cervical cancer screening -taking the women’s own preferred test method into account—A Swedish randomised controlled trial

Cervical cancer is a highly preventable disease. To not attend an organized cervical cancer screening program increases the risk for cervical dysplasia and cervical cancer. The aim was to investigate the participation rate in three different intervention groups for non- attendees in the Swedish national program for cervical screening. The participation in the recommended follow up, and the histology found were also examined. Population-based randomized control trial. It included10,614 women that had not participated in the cervical cancer screening programme during the last six years (ages 30-49) and the last eight years (ages 50-64) were randomised 1:1:1(telephone call from a midwife (offering the choice between a visit for a pap smear or an HPV self-sampling test); an HPV self-sampling test only; or the routine procedure with a yearly invitation). In the intention to treat analysis the participation rates were 25.5% (N = 803/3146) vs 34.1% (N = 1047/3068) and 7.0% (N = 250/3538) (p<0.001) for telephone, HPV self-test and control groups respectively. In the by protocol analysis including women that answered the phone call the participation rates were 31.7% (N = 565/1784) vs 26.1% (N = 788/3002) and 7.0% (N = 250/3538) (p<0.001) for telephone, HPV self-test and control groups. The corresponding results in the by protocol analysis including women that did not answer the phone call was 19.7% (N = 565/2870) vs 26.1% (N = 788/3002) and 7.0% (N = 250/3538) (p< 0.001). The majority of the women 63,4% (1131/1784) who answered the telephone wanted to participate either by booking a visit for pap smear (38,5%) or to be sent a HPV self- sampling test (24,9%) (p<0.001). Women who chose an HPV self-test were older and gave anxiety/ fear as a reason to decline participation, and they were also less likely to participate in the follow-up if found to be HPV-positive compared to the women who chose a Pap smear. The attendance to the recommended follow-up after abnormality was in total 87%. The non-attendees had a three or eight times higher risk of having a cytology result of HSIL or suspected SCC respectively, in the index sample compared to women screened as recommended (OR 3.3 CI 95% 1.9-5.2, OR 8.6 CI 1.6-30). A total of ten SCC and one adenocarcinoma were found in the histopathology results from the non-attendee group with a study intervention, while there was only one SCC in the non-attendee group without any study intervention (p = 0.02, OR 8.1 CI 95% 1.2-350). Our study suggests, according to intention to treat analysis, that the best intervention to get as many non-attendees as possible to participate is to send an HPV self-sampling test together with an invitation letter. Almost 90% of women in the study with an abnormal index sample attended follow-up. This is high enough to indicate that interventions to increase the participation among non-attendees are meaningful. International Standard Randomised Controlled Trial Number (ISRCTN) Registration number ISRCTN78719765.

Indigenous Australian women's experiences of participation in cervical screening

Aboriginal and Torres Strait Islander (collectively, Indigenous Australian) women experience a higher burden of cervical cancer than other women. The National Cervical Screening Program (NCSP) is failing to meet the needs of Indigenous Australian women, resulting in many women not regularly participating in cervical screening. However, one third of Indigenous Australian women do participate in cervical screening. The reasons that some women in this population commence and continue to screen remain unheard but could provide insights to support women who currently do not participate. We aimed to describe Indigenous Australian women's experiences and views of participation in cervical screening by yarning (a culturally-appropriate interview technique) with 50 Indigenous Australian women aged 25-70 years who had completed cervical screening in the past five years, recruited via Primary Health Care Centres (PHCCs) from three jurisdictions. Aboriginal or Torres Strait Islander women researchers conducted the interviews. Thematic analysis identified six themes: screening as a means of staying strong and in control; overcoming fears, shame, and negative experiences of screening; needing to talk openly about screening; the value of trusting relationships with screening providers; logistical barriers; and overcoming privacy concerns for women employed at PHCCs. Despite describing screening as shameful, invasive, and uncomfortable, women perceived it as a way of staying healthy and exerting control over their health. This ultimately supported their participation and a sense of empowerment. Women valued open discussion about screening and strong relationships with health providers. We identified logistical barriers and specific barriers faced by women employed at PHCCs. This study is strengthened by a research approach that centred Indigenous Australian women's voices. Understanding the experiences of Indigenous Australian women who participate in screening will help screening providers support women to start and continue to screen regularly. Recommendations for practice are provided.

Comparative genomics of high grade neuroendocrine carcinoma of the cervix

In order to improve treatment selection for high grade neuroendocrine carcinomas of the cervix (NECC), we performed a comparative genomic analysis between this rare tumor type and other cervical cancer types, as well as extra-cervical neuroendocrine small cell carcinomas of the lung and bladder. We performed whole exome sequencing on fresh-frozen tissue from 15 NECCs and matched normal tissue. We then identified mutations and copy number variants using standard analysis pipelines. Published mutation tables from cervical cancers and extra-cervical small cell carcinomas were used for comparative analysis. Descriptive statistical methods were used and a two-sided threshold of P < .05 was used for significance. In the NECC cohort, we detected a median of 1.7 somatic mutations per megabase (range 1.0-20.9). PIK3CA p.E545K mutations were the most frequency observed oncogenic mutation (4/15 tumors, 27%). Activating MAPK pathway mutations in KRAS (p.G12D) and GNAS (p.R201C) co-occurred in two tumors (13%). In total we identified PI3-kinase or MAPK pathway activating mutations in 67% of NECC. When compared to NECC, lung and bladder small cell carcinomas exhibited a statistically significant higher rate of coding mutations (P < .001 for lung; P = .001 for bladder). Mutation of TP53 was uncommon in NECC (13%) and was more frequent in both lung (103 of 110 tumors [94%], P < .001) and bladder (18 of 19 tumors [95%], P < .001) small cell carcinoma. These comparative genomics data suggest that NECC may be genetically more similar to common cervical cancer subtypes than to extra-cervical small cell neuroendocrine carcinomas of the lung and bladder. These results may have implications for the selection of cytotoxic and targeted therapy regimens for this rare disease.

Chemoradiation for cervical cancer treatment portends high risk of pelvic floor dysfunction

To assess the impact of chemoradiation on pelvic floor (PF) muscle function after the treatment of cervical cancer (CC). We performed a prospective cohort study of women between the ages of 20 and 70 years old who had a diagnosis of CC. Patients were treated with chemoradiation at the Barretos Cancer Hospital (BCH), between August 2016 and July 2017. We performed three evaluations at different time points after chemoradiation treatment to compare changes in muscle function. Pelvic floor muscle function was assessed through perineometry (PNM) and surface electromyography (EMG) at the following time points: Pretreatment Moment 1 (M1): evaluated before chemoradiation; Moment 2 (M2): at the first follow-up medical visit (usually 3 to 4 months after treatment); and Moment 3 (M3): at the second follow-up medical visit (usually after 6 to 9 months after treatment). Mean vaginal squeeze pressure levels were determined by PNM and muscle electromyographic activity by EMG and the results were evaluated by Generalized Linear Model comparisons. Forty-nine patients were evaluated at M1; 35 at M2; and 32 at M3, so that 32 patients had all three muscle evaluations performed. There was a statistically significant increase in the frequency of women with urgency urinary incontinence at the M2 evaluation time (41.9%), compared to pretreatment M1 (18.6%), p<0.001. The means of the vaginal squeeze pressures reduced through M1 to M3 in the phasic (M1: 17.7 mmHg; M3: 11.27mmHg) and tonic contractions (M1: 10.56 mmHg; M3: 7.52mmHg), p = 0.01 and p = 0.03 respectively. There was no difference in pelvic floor function in the three evaluations M1-M3, measured by EMG. The pelvic floor strength assessed by PMN and their interactions with anthropometric, parity and hormonal status variables, showed that a high body mass index (BMI) significantly influenced decreases in pelvic floor muscle function before and after treatment. These results show that chemoradiation causes reduction of muscle function of the pelvic floor, especially in the late phase after the end of treatment. Both the high BMI and urgent urinary incontinence symptoms were related to decreased muscle strength.

Two ways of epigenetic silencing of TFPI2 in cervical cancer

Comparison of human mRNA microarray results from tumor-associated and normal cervical fibroblasts revealed significant TFPI2 downregulation in tumor-associated fibroblasts isolated from cervical cancer, indicating that TFPI2 downregulation may play an important role in the pathogenesis of the disease. In the present work, we investigated the mechanism of TFPI2 downregulation in tumor-associated fibroblasts and tumor cells. In vitro models of monocultures and co-cultures were established with tumor cells and fibroblasts to explore the changes of TFPI-2 expression and epigenetic modifications of the TFPI2 gene. The TFPI2 gene was hypermethylated only in tumor cells. Reduction of TFPI-2 protein levels in tumor-associated fibroblasts, although the gene was not methylated, suggested alternative regulatory mechanisms of gene expression, such as inhibition by microRNAs. The expression pattern of miR-23a, a gene thought to inhibit TFPI2 translation, showed changes strongly correlated to detected TFPI-2 protein alterations. Transfections with miR-23a mimics resulted in a decrease of TFPI-2 protein expression whereas miR-23a inhibitors increased the TFPI-2 amount. Due to downregulation of miR-23a expression by HPV in cancer cells, TFPI2 was silenced by promoter methylation. In contrary, miR-23a was active in HPV-free fibroblasts and inactivated TFPI2. These results indicate dual epigenetic inhibition of TFPI2 on the transcription level by promoter methylation in cancer cells and on the translation level by miR-23a in tumor-associated fibroblasts. As a consequence, inactivation of the TFPI2 gene plays a strategic role in the progression of cervical cancer.

Trends in cervical cancer and its precursor forms to evaluate screening policies in a mid-sized Northeastern Brazilian city

Cervical cancer is a health issue that disproportionately affects developing countries, where the Papanicolaou test (Pap smear) remains an important screening tool. Brazilian government recommendations have focused screening on the female population aged from 25 to 64 years old. In this study, we examined the incidence and mortality rates of invasive cervical cancer lesions and the incidence rates of in situ precancerous cervical lesions, aiming to calculate their respective statistics over time in a mid-sized Brazilian city, Aracaju. The 1996-2015 database from the Aracaju Cancer Registry and Mortality Information System was used to calculate age standardized rates for all invasive cervical tumors (International code of diseases, ICD-10: C53) and preinvasive cervical lesions (ICD-10: D06) in the following patient age ranges; ≤ 24, 25-34, 35-44, 45-54, 55-64 and ≥ 65 years old. We identified 1,030 cancer cases, 1,871 in situ lesions and 334 deaths. Using the Joinpoint Regression Program, we calculated the annual percentage incidence changes and our analyses show that cervical cancer incidence decreased up to 2008, increased up to 2012 and decreased again thereafter, a significant trend in all age groups from 25 years. The incidence of precursor lesions increased from 1996 to 2005 and has since decreased, a result significant in all age groups until 64 years. Cervical cancer mortality has decreased by 3.8% annually and trend analysis indicates that Pap smears have been effective in decreasing cancer incidence and mortality. However, recent trends shown here show a decreasing incidence of in situ lesions and may indicate either a real decrease or incomplete catchment. Thus, we suggest health policies should be re-considered and include sufficient screening and HPV vaccination strategies to avoid cervical cancer resurgence in the population.

Serum and cervicovaginal IgG immune responses against α7 and α9 HPV in non-vaccinated women at risk for cervical cancer: Implication for catch-up prophylactic HPV vaccination

Cervical cancer associated with high risk-human papillomavirus (HR-HPV) infection is becoming the one of the most common female cancer in many sub-Saharan African countries. First-generation immigrant African women living in Europe are at-risk for cervical cancer, in a context of social vulnerability, with frequent lack of cervical cancer screening and HPV vaccination. Our objective was to address immunologically the issue of catch-up prophylactic HPV vaccination in first-generation African immigrant women living in France. IgG immune responses and cross-reactivities to α7 (HPV-18, -45 and -68) and α9 (HPV-16, -31, -33, -35, -52 and -58) HPV types, including 7 HR-HPV targeted by the Gardasil-9® prophylactic vaccine, were evaluated in paired serum and cervicovaginal secretions (CVS) by HPV L1-virus-like particles-based ELISA. Genital HPV were detected by multiplex real time PCR (Seegene, Seoul, South Korea). Fifty-one immigrant women (mean age, 41.7 years; 72.5% HIV-infected) were prospectively included. More than two-third (68.6%) of them carried genital HPV (group I) while 31.4% were negative (group II). The majority (90.2%) exhibited serum IgG to at least one α7/α9 HR-HPV. Serum HPV-specific IgG were more frequently detected in group I than group II (100% versus 68.7%; P = 0.002). The distribution of serum and genital HPV-specific IgG was similar, but mean number of IgG reactivities to α7/α9 HR-HPV was higher in serum than CVS (5.6 IgG per woman in serum versus 3.2 in CVS; P<0.001). Rates of IgG cross-reactivities against HPV different from detected cervicovaginal HPV were higher in serum and CVS in group I than group II. Finally, the majority of groups I and II women (68.6% and 68.7%, respectively) exhibited serum or cervicovaginal IgG to Gardasil-9® HR-HPV, with higher mean rates in group I than group II (6.1 Gardasil-9® HR-HPV per woman versus 1.4; P<0.01). One-third (31.2%) of group II women did not show any serum and genital HPV-specific IgG. Around two-third of first-generation African immigrant women living in France showed frequent ongoing genital HPV infection and high rates of circulating and genital IgG to α7/α9 HPV, generally cross-reacting, avoiding the possibility of catch-up vaccination. Nevertheless, about one-third of women had no evidence of previous HPV infection, or showed only low levels of genital and circulating HR-HPV-specific IgG and could therefore be eligible for catch-up vaccination.

The association between cervical cancer screening participation and the deprivation index of the location of the family doctor’s office

Cervical cancer screening rates are known to be strongly associated with socioeconomic status. Our objective was to assess whether the rate is also associated with an aggregated deprivation marker, defined by the location of family doctors' offices. To access this association, we 1) collected data from the claim database of the French Health Insurance Fund about the registered family doctors and their enlisted female patients eligible for cervical screening; 2) carried out a telephone survey with all registered doctors to establish if they were carrying out Pap-smears in their practices; 3) geotracked all the doctors' offices in the smallest existing blocks of socioeconomic homogenous populations (IRIS census units) that were assigned a census derived marker of deprivation, the European Deprivation Index (EDI), and a binary variable of urbanization; and 4) we used a multivariable linear mixed model with IRIS as a random effect. Of 348 eligible doctors, 343 responded to the telephone survey (98.6%) and were included in the analysis, encompassing 88,152 female enlisted patients aged 25-65 years old. In the multivariable analysis (adjusted by the gender of the family doctor, the practice of Pap-smears by the doctor and the urbanization of the office location), the EDI of the doctor's office was strongly associated with the cervical cancer screening participation rate of eligible patients (p<0.001). The EDI linked to the location of the family doctor's office seems to be a robust marker to predict female patients' participation in cervical cancer screening.

The past, present and future impact of HIV prevention and control on HPV and cervical disease in Tanzania: A modelling study

Women with HIV have an elevated risk of HPV infection, and eventually, cervical cancer. Tanzania has a high burden of both HIV and cervical cancer, with an HIV prevalence of 5.5% in women in 2018, and a cervical cancer incidence rate among the highest globally, at 59.1 per 100,000 per year, and an estimated 9,772 cervical cancers diagnosed in 2018. We aimed to quantify the impact that interventions intended to control HIV have had and will have on cervical cancer in Tanzania over a period from 1995 to 2070. A deterministic transmission-dynamic compartment model of HIV and HPV infection and natural history was used to simulate the impact of voluntary medical male circumcision (VMMC), anti-retroviral therapy (ART), and targeted pre-exposure prophylaxis (PrEP) on cervical cancer incidence and mortality from 1995-2070. We estimate that VMMC has prevented 2,843 cervical cancer cases and 1,039 cervical cancer deaths from 1995-2020; by 2070 we predict that VMMC will have lowered cervical cancer incidence and mortality rates by 28% (55.11 cases per 100,000 women in 2070 without VMMC, compared to 39.93 with VMMC only) and 26% (37.31 deaths per 100,000 women in 2070 without VMMC compared to 27.72 with VMMC), respectively. We predict that ART will temporarily increase cervical cancer diagnoses and deaths, due to the removal of HIV death as a competing risk, but will ultimately further lower cervical cancer incidence and mortality rates by 7% (to 37.31 cases per 100,000 women in 2070) and 5% (to 26.44 deaths per 100,000 women in 2070), respectively, relative to a scenario with VMMC but no ART. A combination of ART and targeted PrEP use is anticipated to lower cervical cancer incidence and mortality rates to 35.82 and 25.35 cases and deaths, respectively, per 100,000 women in 2070. HIV treatment and control measures in Tanzania will result in long-term reductions in cervical cancer incidence and mortality. Although, in the near term, the life-extending capability of ART will result in a temporary increase in cervical cancer rates, continued efforts towards HIV prevention will reduce cervical cancer incidence and mortality over the longer term. These findings are critical background to understanding the longer-term impact of achieving cervical cancer elimination targets in Tanzania.

Role of gender in perspectives of discrimination, stigma, and attitudes relative to cervical cancer in rural Sénégal

Cervical cancer is the leading cause of female cancer deaths in Sénégal which is ranked 17th in incidence globally, however, the screening rate there is very low. Nuanced gendered perceptions and health behaviors of both women and men play a significant role in women's health. Our study analyzed gender differences on perceptions of gender roles, discrimination, cancer attitudes, cancer stigma, and influences in healthcare decision making within our study population to inform ongoing cervical cancer prevention work in the rural region of Kédougou, Sénégal. We conducted a cross-sectional survey of 158 participants, 101 women and 57 men (ages 30-59) across nine non-probability-sampled communities from October 2018 through February 2019. Bivariate analysis was conducted to assess gender differences across all variables. We also conducted analyses to determine whether there were significant differences in beliefs and attitudes, by screening behavior and by education. We found significant gender differences regarding the perception of a woman's role (P < 0.001) and a man's role (P = 0.007) as well as in the everyday discrimination questions of "decreased respect by spouse" (P < 0.001). Regarding cancer stigma, among women, 18.00% disagreed and 10.00% strongly disagreed while among men, 3.6% disagreed and 1.8% strongly disagreed that "If I had cancer, I would want my family to know that I have it." When making decisions about one's healthcare, women are more likely than men to trust social contacts such as their spouse (46.5% vs 5.3%, p < 0.001) while men are more likely than women to trust health service personnel such as a nurse (50.9% vs 18.8%, p < 0.001). Furthermore, men and women were both more likely to state that men have the final decision regarding the healthcare decisions of women (p < 0.001). Our data reveal structural disadvantages for women within our study population as well as gender differences in the adapted everyday discrimination scale and cancer stigma scale. Higher rates of both personal and perceived cancer stigma among women has profound implications for how population and community level communication strategies for cancer prevention and control should be designed. Efforts to advance the goal of the elimination of cervical cancer should, in the short-term, seek to gain a more profound understanding of the ways that gender, language, and other social determinants impact negative social influences and other barriers addressable through interventions. Social and behavior change communication may be one approach that can focus both on education while seeking to leverage the social influences that exist in achieving immediate and long-term goals.

High prevalence of human papillomavirus and European variants of HPV 16 infecting concomitantly to cervix and oral cavity in HIV positive women

Identify the prevalence of HPV infections in the uterine cervix and oral cavity and HPV16 variants in HIV+ women. A total of 174 HIV+ women attended an HIV+ specialized clinic in Mexico City. Cells were obtained from the oral cavity and cervix to extract DNA. Polymerase chain reaction (PCR) was used to amplify the HPV sequence with generic primers. We detected specific HPV types using the INNO-LiPA HPV Genotyping Extra II Kit (INNOGENETICS). The identification of variants was studied by sequencing the E6 gene with a Big Dye Terminator Kit and an Applied Biosystems 3500/3500xL genetic analyzer. HPV infection was very high in the uterine cervix (168/174, 96.6%) and oral cavity (161/174, 92.5%). The prevalence of HPV concurrent infections in the cervix and oral cavity was 155/174 (89.1%). We found hrHPVs to be more prevalent than low-risk HPVs (lrHPVs) in the oral cavity (90.2% versus 45.4%) and that infections simultaneously affected the cervix (94.3% versus 36.2%) and oral cavity (85.1% versus 20.1%). Surprisingly, only European variants of HPV type 16 were found in the uterine cervix of women and the oral cavity of all tested samples (52 oral cavity samples and 52 uterine cervix samples). The high prevalence of HPV, multiple infections and presence of the EP350G intravariant in both anatomical regions are strongly related to the persistence of the virus, which is fundamental for the development of cancer. Therefore, it is very important to control and monitor this high-risk population as well as implement programs for the early detection of HPV and vaccination.

Knowledge gaps and acquisition about HPV and its vaccine among Brazilian medical students

To analyze factors associated with knowledge gaps and acquisition about HPV and its vaccine among medical students. Cross-sectional and analytical study conducted at the University of São Paulo Medicine School, in 2016. A convenience sample of students completed a data collection instrument containing questions on knowledge about HPV and its vaccine, and vaccine acceptability. The level of knowledge and acceptability established as a "good level" was 80% of correct answers on the questionnaire. Internal validity was calculated with Cronbach's alpha value (α) = 0.74. Bivariate and multiple analyzes were performed using the Stata® program (Stata Corp, College Station, USA) 14.0. To evaluate the internal consistency of the instrument applied, the Cronbach's alpha equation was used, obtaining the alpha value (α) = 0.74 for this population. This value attests that the consistency of the answers obtained with this questionnaire is considered substantial and acceptable. Among the 518 medical students who completed the survey, the majority were men 312 (60.4%) with a mean age of 23 (± 2.8) years old; 199 (38.3%) of the students were in the final years of graduation (5th and 6th years). Students in the first, second and third year of study had a 51% higher risk of a knowledge gap when compared to students in the final years of graduation [PR 1.51 (1.3:1.8); p <0.001]. Men were at 22% higher risk of unsatisfactory knowledge than women are [PR 1.22 (1.07: 1.39). There was no knowledge acquisition during medical school in the following questions (p <0.05), indication of vaccine for individuals with HIV and contraindication in pregnant patients. Male medical students, in the first year of medical school, and those who were not vaccinated had significant knowledge gaps about HPV. The novelty of the study includes the finding of non- acquisition of knowledge during the medical school graduation on safety and vaccination schedule and vaccine administration in specific populations.

Cervical cancer prevention in Indonesia: An updated clinical impact, cost-effectiveness and budget impact analysis

The clinical and economic impact of cervical cancer consistently become a serious burden for all countries, including Indonesia. The implementation of HPV vaccination policy for a big country such as Indonesia requires a strong commitment from several decision-makers. The aim of this study was to provide a comprehensive description on cost-effectiveness and the budget-impact of HPV vaccination policy in Indonesia. A cohort Markov model was used to evaluate the cost and the clinical impact of HPV vaccination for 10 years old girls in Indonesia. The researchers consider two doses of all three available HPV vaccines adjusted with the HPV infection profilewith 95% vaccination coverage to estimate the national cervical cancer incidence and mortality. The Budget impact analysis explores three different scenarios covering (1) Two districts per year expansion, (2) oneprovince per year expansion and (3) achieving the National Immunization Program in 2024. Upon fully vaccinating almost 2.3 million 10-year-old girls, 34,723; 43,414; and 51,522 cervical cancer cases were prevented by Quadrivalent, Bivalent and Nonavalent vaccines, consecutively. Furthermore, the highest (591 cases) and lowest (399 cases) mortality were prevented by Nonavalent and Quadrivalent vaccines, respectively. Most of the vaccines were considerably cost-effective and only the Bivalent vaccine with the GAVI/UNICEF price which will be considered a cost-saving strategy.To provide national coverage of HPV vaccination in Indonesia, the government has to provide an annual budget of about US$49 million and US$22 million using the government contract price and GAVI/UNICEF price, respectively. HPV vaccination shows a cost-effective strategy and the budget required to provide this policy is considerably affordable for Indonesia.

Development and validation of a multiplex immunoassay for the simultaneous quantification of type-specific IgG antibodies to E6/E7 oncoproteins of HPV16 and HPV18

More than 170 types of human papilloma viruses (HPV) exist with many causing proliferative diseases linked to malignancy in indications such as cervical cancer and head and neck squamous cell carcinoma. Characterization of antibody levels toward HPV serology is challenging due to complex biology of oncoproteins, pre-existing titers to multiple HPV types, cross-reactivity, and low affinity, polyclonal responses. Using multiplex technology from MSD, we have developed an assay that simultaneously characterizes antibodies against E6 and E7 oncoproteins of HPV16 and 18, the primary drivers of HPV-associated oncogenesis. We fusion tagged our E6 and E7 proteins with MBP via two-step purification, spot-printed an optimized concentration of protein into wells of MSD 96-well plates, and assayed various cynomolgus monkey, human and HPV+ cervical cancer patient serum to validate the assay. The dynamic range of the assay covered 4-orders of magnitude and antibodies were detected in serum at a dilution up to 100,000-fold. The assay was very precise (n = 5 assay runs) with median CV of human serum samples ~ 5.3% and inter-run variability of 11.4%. The multiplex serology method has strong cross-reactivity between E6 oncoproteins from human serum samples as HPV18 E6 antigens neutralized 5 of 6 serum samples as strongly as HPV16 E6. Moderate concordance (Spearman's Rank = 0.775) was found between antibody responses against HPV16 E7 in the multiplex assay compared to standard ELISA serology methods. These results demonstrate the development of a high-throughput, multi-plex assay that requires lower sample quantity input with greater dynamic range to detect type-specific anti-HPV concentrations to E6 and E7 oncoproteins of HPV16 and 18.

Cervical cancer screening rates before and after the Great East Japan Earthquake in the Miyagi Prefecture, Japan

After disasters, issues pertaining to women's health such as irregular periods and bleeding are well surveyed. However, the management of women's health, especially changes in the rate of health checkups, has not been investigated. In the present study, we focused on the change in the cervical cancer screening rates (CCS-Rs) before and after the Great East Japan Earthquake in Miyagi Prefecture, Japan. The earthquake had a magnitude of 9.0, a profound disaster. We examined the CCS-R from 2009 to 2016 in 45 areas of the Miyagi Prefecture. Screening was completed using mobile vans. In the 4 areas impacted by the tsunami after the earthquake, a marked decrease in the CCS-R was observed in 2011 when the earthquake took place (more than a 3% decrease compared with that in the previous year). The CCS-Rs in these 4 regions remained lower in 2016 than in the previous year. In 2009-2016 except for 2014, CCS-Rs in coastal areas (9 areas) were significantly lower than those in the non-coastal areas (36 areas). A delay in seeking healthcare, also known as "patient's delay," is considered as one of the problems of cancer treatment in affected areas. It is possible that a decrease in the CCS-R may lead to low detection of advanced stages of cancer. Therefore, the establishment of a comprehensive medical system including medical screening after a disaster is important for the management of women's health.

Factors associated with hindering the acceptance of HPV vaccination among caregivers - A cross-sectional study in Argentina

The northeastern region of Argentina has the highest age-adjusted cervical cancer mortality rates. Given the strong link between HPV infections and cervical cancer, one of the main interventions is the population-based use of HPV vaccines. However, the acceptability is not very clear in low- and middle-income countries. The purpose of this study was to estimate the level of HPV vaccine acceptance and associated determinants among caregivers of girls in a northeastern city of Argentina. A school-based survey was conducted in 2015 using a multistage sampling method. The primary sample unit were schools stratified by socioeconomic status selected at random, and caregivers of school girls were interviewed. The acceptability was determined using the adapted Theory of Planned Behavior. We performed logistic regression models to assess associated determinants. The study included 347 caregivers. The intention to vaccinate was 59.88%. A positive attitude of caregivers (aOR 4.67; 3.11-7.03) and positive influence of social norms (aOR 1.95; 1.03-3.70) were the main predictors independently associated to the intention to vaccinate against HPV. In contrast, practicing a Christian non-Catholic religion decreased the intention to vaccinate against HPV (OR 0.59; 0.36-0.95). All other factors evaluated were not significantly associated with intention to vaccinate against HPV. This study shows that evaluating attitudes, normative social beliefs, and perceived self-efficacy regarding HPV vaccination can be of utmost importance for mapping and planning of health-related strategies in developing countries.

Analysis of the effects of the age-period-birth cohort on cervical cancer mortality in the Brazilian Northeast

Cervical cancer (CC) is a public health problem with a high disease burden and mortality in developing countries. In Brazil, areas with low human development index have the highest incidence rates of Brazil and upward temporal trend for this disease. The Northeast region has the second highest incidence of cervical cancer (20.47 new cases / 100,000 women). In this region, the mortality rates are similar to rates in countries that do not have a health system with a universal access screening program, as in Brazil. Thus, this study aimed to analyze the effects of age, period and birth cohorts on mortality from cervical cancer in the Northeast region of Brazil. Estimable functions predicted the effects of age, period and birth cohort. The average mortality rate was 10.35 deaths per 100,000 women during the period analyzed (1980-2014). The highest mortality rate per 100,000 women was observed in Maranhão (24.39 deaths), and the lowest mortality rate was observed in Bahia (11.24 deaths). According to the period effects, only the state of Rio Grande do Norte showed a reduction in mortality risk in the five years of the 2000s. There was a reduction in mortality risk for birth cohorts of women after the 1950s, except in Maranhão State, which showed an increasing trend in mortality risk for younger generations. We found that the high rates of cervical cancer mortality in the states of northeastern Brazil remain constant over time. Even after an increase in access to health services in the 2000s, associated with increased access to the cancer care network, which includes early detection (Pap Test), cervical cancer treatment and palliative care. However, it is important to note that the decreased risk of death and the mortality rates from CC among women born after the 1960s may be correlated with increased screening coverage, as well as increased access to health services for cancer treatment observed in younger women.

Circulating HPV cDNA in the blood as a reliable biomarker for cervical cancer: A meta-analysis

The applications of liquid biopsy have attracted much attention in biomedical research in recent years. Circulating cell-free DNA (cfDNA) in the serum may serve as a unique tumor marker in various types of cancer. Circulating tumor DNA (ctDNA) is a type of serum cfDNA found in patients with cancer and contains abundant information regarding tumor characteristics, highlighting its potential diagnostic value in the clinical setting. However, the diagnostic value of cfDNA as a biomarker, especially circulating HPV DNA (HPV cDNA) in cervical cancer remains unclear. Here, we performed a meta-analysis to evaluate the applications of HPV cDNA as a biomarker in cervical cancer. A systematic literature search was performed using PubMed, Embase, and WANFANG MED ONLINE databases up to March 18, 2019. All literature was analyzed using Meta Disc 1.4 and STATA 14.0 software. Diagnostic measures of accuracy of HPV cDNA in cervical cancer were pooled and investigated. Fifteen studies comprising 684 patients with cervical cancer met our inclusion criteria and were subjected to analysis. The pooled sensitivity and specificity were 0.27 (95% confidence interval [CI], 0.24-0.30) and 0.94(95% CI, 0.92-0.96), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 6.85 (95% CI, 3.09-15.21) and 0.60 (95% CI, 0.46-0.78), respectively. The diagnostic odds ratio was 15.25 (95% CI, 5.42-42.94), and the area under the summary receiver operating characteristic curve was 0.94 (95% CI, 0.89-0.99). There was no significant publication bias observed. In the included studies, HPV cDNA showed clear diagnostic value for diagnosing and monitoring cervical cancer. Our meta-analysis suggested that detection of HPV cDNA in patients with cervical cancer could be used as a noninvasive early dynamic biomarker of tumors, with high specificity and moderate sensitivity. Further large-scale prospective studies are required to validate the factors that may influence the accuracy of cervical cancer diagnosis and monitoring.

The economic burden of cervical cancer in Eswatini: Societal perspective

Background Cervical cancer imposes considerable economic burden on societies and individuals. There is lack of evidence regarding this from the developing world and particularly from sub-Saharan Africa. Therefore, the study aimed to estimate the societal costs of cervical cancer in Eswatini. Materials and methods The cost of illness study (CoI) was applied using national specific clinical and registry data from hospitals, registries and reports to determine the prevalence of cervical intraepithelial neoplasia (CIN) and cervical cancer in Eswatini in 2018. Cost data included direct medical costs (health care utilization in inpatient and outpatient care), direct non-medical costs (patient costs for traveling) and indirect costs based on productivity loss due to morbidity (patient time during diagnosis and treatment) and premature mortality. Results The estimated total annual cost for cervical cancer was $19 million (ranging between $14 million and $24 million estimated with lower and upper bounds). Direct cost represented the majority of the costs at 72% ($13.7 million) out of which total pre-cancerous treatment costs accounted for 0.7% ($94,161). The management of invasive cervical cancer was the main cost driver with costs attributable to treatment for FIGO III and FIGO IV representing $1.7 million and $8.7 million respectively. Indirect costs contributed 27% ($5.3 million) out of which productivity loss due to premature mortality represented the majority at 67% ($3.5 million). Conclusion The economic burden of cervical cancer in Eswatini is substantial. National public health prevention strategies with prophylactic HPV vaccine and screening for cervical lesions should therefore be prioritized to limit the extensive costs associated with cervical cancer.

Study protocol for a two-site clinical trial to validate a smartphone-based artificial intelligence classifier identifying cervical precancer and cancer in HPV-positive women in Cameroon

Introduction Cervical cancer remains a major public health challenge in low- and middle-income countries (LMICs) due to financial and logistical issues. WHO recommendation for cervical cancer screening in LMICs includes HPV testing as primary screening followed by visual inspection with acetic acid (VIA) and treatment. However, VIA is a subjective procedure dependent on the healthcare provider’s experience. Its accuracy can be improved by computer-aided detection techniques. Our aim is to assess the performance of a smartphone-based Automated VIA Classifier (AVC) relying on Artificial Intelligence to discriminate precancerous and cancerous lesions from normal cervical tissue. Methods The AVC study will be nested in an ongoing cervical cancer screening program called “3T-study” (for Test, Triage and Treat), including HPV self-sampling followed by VIA triage and treatment if needed. After application of acetic acid on the cervix, precancerous and cancerous cells whiten more rapidly than non-cancerous ones and their whiteness persists stronger overtime. The AVC relies on this key feature to determine whether the cervix is suspect for precancer or cancer. In order to train and validate the AVC, 6000 women aged 30 to 49 years meeting the inclusion criteria will be recruited on a voluntary basis, with an estimated 100 CIN2+, calculated using a confidence level of 95% and an estimated sensitivity of 90% +/-7% precision on either side. Diagnostic test performance of AVC test and two current standard tests (VIA and cytology) used routinely for triage will be evaluated and compared. Histopathological examination will serve as reference standard. Participants’ and providers’ acceptability of the technology will also be assessed. The study protocol was registered under ClinicalTrials.gov (number NCT04859530). Expected results The study will determine whether AVC test can be an effective method for cervical cancer screening in LMICs.

Knowledge and awareness of human papillomavirus infection and human papillomavirus vaccine among Kazakhstani women attending gynecological clinics

Cervical cancer remains one of the top causes of cancer-related morbidity and mortality all over the world. Currently, however, there are no published studies to assess the knowledge of HPV and cervical cancer in Kazakhstan. This study aimed to assess the awareness of HPV, the knowledge of HPV as a cause of cervical cancer, and the awareness of HPV vaccination among Kazakhstani women visiting gynecological clinics across the country. In addition, the study aimed to identify the factors associated with the awareness of HPV and the HPV vaccine and knowledge of HPV as a major cause of cervical cancer. This was a cross-sectional survey-based study with 2,272 women aged between 18–70 years attending gynecological clinics, who were administered paper-based questionnaires. Data analysis included descriptive statistics consisting of mean values, standard deviations, and frequencies, where applicable. Differences in categorical variables between groups were analyzed using the Chi-square test with a significance value of &lt;0.005. Crude odds ratio (OR) and adjusted odds ratio (AOR) with 95% corresponding confidence intervals were calculated in regression analysis using univariate and multivariable logistic regression models. The mean age of participants was 36.33±10.09 years. More than half (53%) of the participants had been screened for cervical cancer. Among those who were aware of HPV, 46% knew that HPV causes cervical cancer and 52% were aware of the HPV vaccine. The key factors related to outcome variables were age, ethnicity, education, family, number of deliveries, and menarche. From a subgroup analysis, results from the HPV test and Pap smear test were factors related to dependent variables such as awareness of HPV and awareness of HPV vaccination.

ThinPrep cytology combined with HPV detection in the diagnosis of cervical lesions in 1622 patients

The timely detection of precancerous lesions and early intervention can greatly reduce cervical cancer occurrence. The current study aimed to assess the diagnostic value and accuracy of different methods of cervical lesion screening. A total of 1622 females who visited the Outpatient Department of Xinjiang Uyghur Autonomous Region People’s Hospital between January and December 2018 were consecutively enrolled. All participants underwent separate high-risk human papilloma virus (HR-HPV) DNA detection, ThinPrep cytology testing (TCT) and colposcopic biopsy. Their medical records were retrospectively analyzed. While considering biopsy outcomes as the gold standard, the diagnostic values of TCT, HR-HPV testing, and TCT+HR-HPV testing for cervical cancer screening were compared. The sensitivity, specificity and Youden index of each method were calculated. Among the different methods, TCT+HR-HPV testing had the highest sensitivity (89.8%), followed by TCT (79.9%) and HR-HPV testing (49.2%). The combined method also had the highest Youden value, and its screening outcomes exhibited the highest consistency with those of biopsy. In addition, the combined method had the largest area under the receiver operating characteristic (ROC) curve, which was 0.673 (0.647, 0.699), compared with any other screening method. Compared with TCT or HR-HPV testing alone, TCT+HR-HPV testing serves as a better screening method for cervical cancer and precancerous lesions.

Genome-wide host methylation profiling of anal and cervical carcinoma

HPV infection results in changes in host gene methylation which, in turn, are thought to contribute to the neoplastic progression of HPV-associated cancers. The objective of this study was to identify joint and disease-specific genome-wide methylation changes in anal and cervical cancer as well as changes in high-grade pre-neoplastic lesions. Formalin-fixed paraffin-embedded (FFPE) anal tissues (n = 143; 99% HPV+) and fresh frozen cervical tissues (n = 28; 100% HPV+) underwent microdissection, DNA extraction, HPV genotyping, bisulfite modification, DNA restoration (FFPE) and analysis by the Illumina HumanMethylation450 Array. Differentially methylated regions (DMR; t test q&lt;0.01, 3 consecutive significant CpG probes and mean Δβ methylation value&gt;0.3) were compared between normal and cancer specimens in partial least squares (PLS) models and then used to classify anal or cervical intraepithelial neoplasia-3 (AIN3/CIN3). In AC, an 84-gene PLS signature (355 significant probes) differentiated normal anal mucosa (NM; n = 9) from AC (n = 121) while a 36-gene PLS signature (173 significant probes) differentiated normal cervical epithelium (n = 10) from CC (n = 9). The CC progression signature was validated using three independent publicly available datasets (n = 424 cases). The AC and CC progression PLS signatures were interchangeable in segregating normal, AIN3/CIN3 and AC and CC and were found to include 17 common overlapping hypermethylated genes. Moreover, these signatures segregated AIN3/CIN3 lesions similarly into cancer-like and normal-like categories. Distinct methylation changes occur across the genome during the progression of AC and CC with overall similar profiles and add to the evidence suggesting that HPV-driven oncogenesis may result in similar non-random methylomic events. Our findings may lead to identification of potential epigenetic drivers of HPV-associated cancers and also, of potential markers to identify higher risk pre-cancerous lesions.

Knowledge, attitude and practice of cervical cancer screening among women infected with HIV in Africa: Systematic review and meta-analysis

Background To establish successful strategies and increasing the utilization of preventive services, there is a need to explore the extent to which the general female population is aware and use the service for cervical cancer-screening among women infected with HIV in Africa. Available evidences in this regard are controversial and non-conclusive on this potential issue and therefore, we estimated the pooled effect of the proportion of knowledge, attitude and practice of HIV infected African women towards cervical cancer screening to generate evidence for improved prevention strategies. Methods We applied a systematic review and meta-analysis of studies conducted in Africa and reported the proportion of knowledge, attitude and practice towards cervical cancer screening. We searched electronic databases: PubMed/Medline, SCOPUS, ScienceDirect, Web of science, Cumulative Index of Nursing and allied Health Sciences (CINAHL) and Google scholar databases to retrieve papers published in English language till August 2020. We used random-effects model to estimate the pooled effect, and funnel plot to assess publication bias. The registration number of this review study protocol is CRD42020210879. Results In this review, we included eight published papers comprising 2,186 participants. The estimated pooled proportion of knowledge of the participants was 43.0% (95%CI:23.0–64.0) while the pooled estimates of attitudes and practices were 38.0% (95%CI: 1.0–77.0) and 41.0% (95%CI: 4.0–77.0), respectively. The proportion of the outcome variables were extremely heterogeneous across the studies with I2&gt; 98%). Conclusion The pooled estimates of knowledge, attitude and practice were lower than other middle income countries calls for further activities to enhance the uptake of the services and establish successful strategies.

Impact of HPV mRNA types 16, 18, 45 detection on the risk of CIN3+ in young women with normal cervical cytology

BackgroundDespite a well-established cervical cancer (CC) screening program in Norway, the incidence of CC in young women is increasing, peaking at 35 years of age. 25 percent of all women diagnosed with CC had normal cytology within 3 years prior to cancer diagnosis, addressing the need to improve the screening programme to further reduce cancer incidences missed by cytology.ObjectiveWe wanted to investigate the detection rate of CIN3+ in women 25–39 years with normal cytology by using a 3-type HPV mRNA test as a targeted quality assurance measure. The control group is women with normal cytology.MethodsDuring 2014–2017, samples from 13,021 women 25–39 years of age attending cervical cancer screening were analysed at Nordlandssykehuset, Bodø, Norway, including 1,896 women with normal cytology and HPV mRNA test (intervention group), and 11,125 women with cytology only (control group). The HPV mRNA testing was performed using a 3-type HPV E6/E7 mRNA test (PreTect SEE; direct genotyping 16, 18 and 45). The women were followed-up according to national guidelines throughout December 2021.ResultsOf the 13,021 women, 429 women (3.3%) had CIN3+ confirmed by biopsy in the follow-up, including 13 cases of invasive cervical cancer. Of the 1,896 women with normal cytology and HPV mRNA test (intervention group), 49 women (2.6%) had a positive test. The risks of CIN3+ among women with either a positive or negative HPV mRNA test were 28.6% (14/49) and 0.8% (14/1847). None of the women in the intervention group developed cervical cancer during follow-up. Of the 11,125 women with cytology only (control group), 712 women (6.4%) had abnormal cytology (ASC-US+). The risks of CIN3+ among women with abnormal and normal cytology were 17.7% (126/712) and 2.6% (275/10,413).ConclusionBy testing women 25–39 years of age with a normal cytology result using a specific 3-type HPV mRNA test, an increase in screening programme sensitivity can be achieved without an excessive additional workload. Women with normal cytology and a negative HPV mRNA test have a very low risk of cervical cancer.

Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania

Introduction Biomarkers yield important information for early diagnosis of cervical cancer. However, they are rarely applied for prognosis of cervical cancer in Tanzania, where visual inspection assay with acetic acid or Lugol’s iodine and Pap test are being used as the standard screening/ diagnostic methods. Methods This was a retrospective hospital-based cross-sectional study that was conducted to assess cyclin-dependent kinase inhibitor (p16) and topoisomerase II-alpha (TOP2A) proteins expression among women seeking cervical cancer care at Kilimanjaro Christian Medical Centre, Tanzania between May 1, 2017 and May 10, 2018. Immunohistochemistry technique was used to detect the expressions of p16 and TOP2A proteins from the retrieved formalin-fixed and paraffin-embedded (FFPE) cervical biopsies. Results A total of 145 patients, with a mean age of 52.1 ± 12.9 years, were included in this study. Upon immunohistochemistry staining, 103 (71.0%) and 90 (62.1%) were p16 and TOP2A positive respectively. There was a strong association between histopathological class and p16/TOP2A expression levels (Fisher’s exact test, p&lt;0.001). Moreover, there was a strong positive correlation between p16/TOP2A and cancerous cervical lesions (Spearman’s rank correlation coefficients = 0.833 and 0.687, p = 0.006 and 0.005, respectively). The age-adjusted odds ratio for predicting cervical cancer lesions were independently significant for p16/TOP2A biomarkers in FFPE cervical tissues [p16: OR = 1.142 (95% CI: 1.059–1.232, p&lt;0.001) and TOP2A: OR = 1.046 (95% CI: 1.008–1.085, p = 0.015)]. Importantly, the diagnostic performance of p16 was higher than that of TOP2A in the diagnosis of cancerous lesions from non-cancerous cervical lesions (sensitivity: 97.2% versus 77.6%, accuracy: 92.8% versus 87.8%, respectively). Conclusion Our study has highlighted that over-expression of TOP2A is related to the grade of cervical intraepithelial neoplasia but does not predict prognosis in cervical cancer. Similarly, expression of p16 is related to degree of histological dysplasia and malignancy, suggesting its prognostic and predictive value in the management of cervical cancers. Further bigger studies are needed to validate their applications in the early diagnosis of cervical cancer.

Moving towards a strategy to accelerate cervical cancer elimination in a high-burden city—Lessons learned from the Amazon city of Manaus, Brazil

The World Health Organization Call to Eliminate Cervical Cancer resonates in cities like Manaus, Brazil, where the burden is among the world’s highest. Manaus has offered free cytology-based screening since 1990 and HPV immunization since 2013, but the public system is constrained by many challenges and performance is not well-defined. We obtained cervical cancer prevention activities within Manaus public health records for 2019 to evaluate immunization and screening coverage, screening by region and neighborhood, and the annual Pink October screening campaign. We estimated that among girls and boys age 14–18, 85.9% and 64.9% had 1+ doses of HPV vaccine, higher than rates for age 9–13 (73.4% and 43.3%, respectively). Of the 90,209 cytology tests performed, 24.9% were outside the target age and the remaining 72,230 corresponded to 40.1% of the target population (one-third of women age 25–64). The East zone had highest screening coverage (49.1%), highest high-grade cytology rate (2.5%) and lowest estimated cancers (38.1/100,000) compared with the South zone (32.9%, 1.8% and 48.5/100,000, respectively). Largest neighborhoods had fewer per capita screening locations, resulting in lower coverage. During October, some clinics successfully achieved higher screening volumes and high-grade cytology rates (up to 15.4%). Although we found evidence of some follow-up within 10 months post-screening for 51/70 women (72.9%) with high-grade or worse cytology, only 18 had complete work-up confirmed. Manaus has successfully initiated HPV vaccination, forecasting substantial cervical cancer reductions by 2050. With concerted efforts during campaigns, some clinics improved screening coverage and reached high-risk women. Screening campaigns in community locations in high-risk neighborhoods using self-collected HPV testing can achieve widespread coverage. Simplifying triage and treatment with fewer visits closer to communities would greatly improve follow-up and program effectiveness. Achieving WHO Cervical Cancer Elimination goals in high-burden cities will require major reforms for screening and simpler follow-up and treatment.

Synergistic effects of exosomal crocin or curcumin compounds and HPV L1-E7 polypeptide vaccine construct on tumor eradication in C57BL/6 mouse model

Cervical cancer is the most common malignant tumor in females worldwide. Human papillomavirus (HPV) infection is associated with the occurrence of cervical cancer. Thus, developing an effective and low-cost vaccine against HPV infection, especially in developing countries is an important issue. In this study, a novel HPV L1-E7 fusion multiepitope construct designed by immunoinformatics tools was expressed in bacterial system. HEK-293T cells-derived exosomes were generated and characterized to use as a carrier for crocin and curcumin compounds. The exosomes loaded with crocin and curcumin compounds as a chemotherapeutic agent (ExoCrocin and ExoCurcumin) were used along with the L1-E7 polypeptide for evaluation of immunological and anti-tumor effects in C57BL/6 mouse model.In vitrostudies showed that ExoCrocin and ExoCurcumin were not cytotoxic at a certain dose, and they could enter tumor cells.In vivostudies indicated that combination of the L1-E7 polypeptide with ExoCrocin or ExoCurcumin could produce a significant level of immunity directed toward Th1 response and CTL activity. These regimens showed the protective and therapeutic effects against tumor cells (the percentage of tumor-free mice: ~100%). In addition, both ExoCrocin and ExoCurcumin represented similar immunological and anti-tumor effects. Generally, the use of exosomal crocin or curcumin forms along with the L1-E7 polypeptide could significantly induce T-cell immune responses and eradicate tumor cells.

Genotype distribution of cervical HPV among Caribbean women in a population-based study in Martinique: The DEPIPAPUFR study

The Caribbean ranks seventh among the world regions most affected by cervical cancer. HPV-prevalence and genotype distributions also differ from regions. Knowledge of HPV genotype profiles is important for patients care and HPV vaccination implementation. The objective of this study was to describe HPV genotype distribution and risk factors in a population-based cohort of women in Martinique. In this study, 1312 women were included and underwent cervical cancer screening with successful sample collection between 2009 and 2014. Sociodemographic and clinical variables were recorded. Cytological examination of cervical vaginal smear was performed and classified(Bethesda). Detection of HPV DNA was performed with the PapilloCheck© Kit from Greiner Bio-one. Genotypes were analyzed for18 high-risk HPV (hrHPV) and 6low-risk HPV(lrHPV) types. A total of 1075 women were included with a mean age of 49.1±10.5 years. HPV prevalence was 27.6% (297/1075) with 19.4% (209/1075) women with only hrHPV, 5.3% (57/1075) with only lrHPV. Multiple infections (hrHPV/lrHPV) were detected in 31/240 cases of hrHPV (12.9%). A total of 353 hrHPV genotypes were analyzed; the most common HPV types were HPV51 (11.0%), HPV68 (10.8%), HPV53 (9.1%) and HPV 52 (7.1%). HPV16 and HPV18 represented respectively 4.8% and 4.0% of hrHPV genotypes. Abnormal cytology was observed in 34 cases (3.2%), with 14 ASCUS (1.3%), 10 LSIL (0.9%), 5 HSIL (0.5%), 3 ASC-H (0.3%) and 2 AGC (0.2%). Fifteen (44.1%) were hrHPV and 4 (14.7%) lrHPV; 7 cases of hrPHV were in the age-group 25–34 years. Among 1041cases of normal cytology, 225 had positive hrHPV detection (21.6%). This is the first population-based study of HPV profiles in our country, and we found a high prevalence of hrHPV. The most common genotypes were HPV51, 68, 53. These results could serve for cancer vaccination strategies and HPV surveillance in Martinique.

Risk factors of precancerous cervical lesions: The role of women’s socio-demographic, sexual behavior and body mass index in Amhara region referral hospitals; case-control study

Background Cervical cancer remains one of the major public health challenges in low and middle-income countries including Ethiopia. There was a scarce of evidence regarding the effect of woman’s socio-demographic characteristics and body mass index on the development of precancerous cervical lesions in Ethiopia. Therefore, the current study aimed at identifying the risk factors of precancerous cervical lesions among women visiting referral hospitals for cervical cancer screening in Amhara national regional state. Methods A hospital-based case-control study was conducted from 22 December 2019 to 8 April 2020 among 200 women including 67 visual inspections with acetic acid (VIA) positive women (i.e., cases) and 133 visual inspections with acetic acid (VIA) negative women (i.e., controls). The study was conducted at randomly selected referral hospitals in Amhara national regional state. Data were collected mainly through face to face interview and chart review using structured questionnaire and checklist respectively. Data were then entered to EpiData version 4.6 and exported to SPSS version 25 for analysis. Binary logistic regression model was fitted and variables with p-value of &lt; 0.2 at bivariable logistic regression analysis were candidates for the multivariable analysis. Level of significance was claimed based on adjusted odds ratio (AOR) with 95% confidence interval (CI) at p-value of ≤ 0.05. Results This study illustrates that the odds of being positive for precancerous cervical lesion (PCL) were higher among women who had body mass index (BMI) of &lt;18.5 kg/m2 (AOR = 3.83; 95% CI: 1.26, 8.76), early coitarche (AOR = 3.15; 95% CI: 1.50, 11.49, history of using oral contraceptive pills (AOR = 2.74; 95% CI: 1.6, 7.4), lifetime sexual transmitted infections (AOR = 3.73; 95% CI: 2.5, 12.28) and multiple sexual partners (AOR = 3.23; 95% CI: 1.82, 9.29). On the other hand, participants’ BMI of ≥25 kg/m2 (AOR = 0.46; 95% CI: 0.36, 0.75) and level of education of college and above (AOR = 0.29; 95% CI: 0.23, 0.77) were identified to be protective factors of PCL. Conclusion Most of the determinants of precancerous cervical lesions were modifiable and mainly related to women’s socio-demographic characteristics, sexual behaviors and body mass index. Therefore, strengthening awareness on safe sexual practices and healthy life styles through information, education and communication (IEC), and behavioral change communication (BCC) would decrease the incidence of precancerous cervical lesions.

Do vulnerable groups access prevention services? Cervical cancer screening and HIV testing among homeless migrant women in the Paris metropolitan area

IntroductionHomeless migrant women, facing adverse living conditions and barriers to legal status, are at risk of cervical cancer, HIV infection and may encounter barriers to screening services. We investigate factors associated with each screening in a population of migrant women in France and aim to determine the mean time since last HIV testing according to duration of residence in France.MethodsWe use data from the DSAFHIR study (Rights and Health of Migrant Women in Emergency Housing) investigating health and migration experience of homeless migrant women housed in emergency housing hotels in the Paris Metropolitan area in 2017. We computed multivariate logistic regression models to investigate no lifetime cervical cancer screening (CCS) and no lifetime HIV test. We used linear regression models to analyze time since last HIV test.ResultsWe included 469 women. 46% of respondents had no lifetime CCS, 31% had no lifetime HIV test. Both screenings were associated with educational attainment and French proficiency. Compared with duration of residence &lt; 1 year, duration ≥ 7 years was associated with a lower likelihood of no lifetime CCS (adjusted Odd Ratio = 0.17; 95% CI = 0.07–0.39). Compared to women born in North Africa, women born in West (aOR = 0.15; 95% CI = 0.07–0.33) and East Africa (aOR = 0.06; 95% CI = 0.02–0.20) were less likely to have no lifetime HIV test. Time since last HIV test increased for each additional year spent in France (coef = 0.21; 95% CI = 0.09, 0.33).ConclusionWhile access to CCS remains poor for recent migrants, HIV testing is more likely to occur shortly after migration.

Factors associated with and socioeconomic inequalities in breast and cervical cancer screening among women aged 15–64 years in Botswana

Background The most commonly diagnosed cancers among women are breast and cervical cancers, with cervical cancer being a relatively bigger problem in low and middle income countries (LMICs) than breast cancer. Methods The main aim of this study was to asses factors associated with and socioeconomic inequalities in breast and cervical cancer screening among women aged 15–64 years in Botswana. This study is part of the broad study on Chronic Non-Communicable Diseases in Botswana conducted (NCD survey) in 2016. The NCD survey was conducted across 3 cities and towns, 15 urban villages and 15 rural areas of Botswana. The survey collected information on several NCDs and risk factors including cervical and breast cancer screening. The survey adopted a multistage sampling design and a sample of 1178 participants (males and females) aged 15 years and above was selected in both urban and rural areas of Botswana. For this study, a sub-sample of 813 women aged 15–64 years was selected and included in the analysis. The inequality analysis was conducted using decomposition analysis using ADePT software version 6. Logistic regression models were used to show the association between socioeconomic variables and cervical and breast cancer screening using SPSS version 25. All comparisons were considered statistically significant at 5%. Results Overall, 6% and 62% of women reported that they were screened for breast and cervical cancer, respectively. Women in the poorest (AOR = 0.16, 95% CI = 0.06–0.45) and poorer (AOR = 0.37, 95% CI = 0.14–0.96) wealth quintiles were less likely to report cervical cancer screening compared to women in the richest wealth quintile. Similarly, for breast cancer, the odds of screening were found to be low among women in the poorest (AOR = 0.39, 95% CI = 0.06–0.68) and the poorer (AOR = 0.45, 95% CI = 0.13–0.81)) wealth quintiles. Concentration indices (CI) showed that cervical (CI = 0.2443) and breast cancer (CI = 0.3975) screening were more concentrated among women with high SES than women with low SES. Wealth status was observed to be the leading contributor to socioeconomic inequality observed for both cervical and breast cancer screening. Conclusions Findings in this study indicate the need for concerted efforts to address the health care needs of the poor in order to reduce cervical and breast cancer screening inequalities.

Effect of comorbid mood and anxiety disorders on breast and cervical cancer screening in immune-mediated inflammatory disease

We aimed to examine rates of breast and cervical cancer screening in women with immune-mediated inflammatory diseases (IMID), including inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA) versus a matched cohort with IMID; and examine the association of psychiatric comorbidity with screening in these populations. We conducted a retrospective cohort study in Manitoba, Canada using administrative data. We identified women with IBD, MS and RA, and controls without these IMID matched on age and region. Annually, we identified individuals with any active mood/anxiety disorder. Using physician claims, we determined the proportion of each cohort who had cervical cancer screening within three-year intervals, and mammography screening within two-year intervals. We modeled the difference in the proportion of the IMID and matched cohorts who underwent mammography; and pap tests using log-binomial regression with generalized estimating equations, adjusting for sociodemographics, comorbidity and immune therapy use. We tested for additive interactions between cohort and mood/anxiety disorder status. During 2006–2016, we identified 17,230 women with IMID (4,623 with IBD, 3,399 with MS, and 9,458 with RA) and 85,349 matched controls. Having an IMID was associated with lower (-1%) use of mammography; however, this reflected a mixture of more mammography in the IBD cohort (+2.9%) and less mammography in the MS (-4.8 to -5.2%) and RA (-1.5%) cohorts. Within the IBD, MS and RA cohorts, having an active mood/anxiety disorder was associated with more mammography use than having an inactive mood/anxiety disorder. The MS and RA cohorts were less likely to undergo Pap testing than their matched cohorts. In the absence of an active mood/anxiety disorder, the IBD cohort was more likely to undergo Pap testing than its matched cohort; the opposite was true when an active mood/anxiety disorder was present. Among women with an IMID, mood/anxiety disorder influence participation in cancer screening.

Performance of an affordable urine self-sampling method for human papillomavirus detection in Mexican women

Introduction Urine self-sampling for human papillomavirus (HPV)-based cervical cancer screening is a non-invasive method that offers several logistical advantages and high acceptability, reducing barriers related to low screening coverage. This study developed and evaluated the performance of a low-cost urine self-sampling method for HPV-testing and explored the acceptability and feasibility of potential implementation of this alternative in routine screening. Methods A series of sequential laboratory assays examined the impact of several pre-analytical conditions for obtaining DNA from urine and subsequent HPV detection. Initially, we assessed the effect of ethylaminediaminetetraacetic acid (EDTA) as a DNA preservative examining several variables including EDTA concentration, specimen storage temperature, time between urine collection and DNA extraction, and first-morning micturition versus convenience sample collection. We further evaluated the agreement of HPV-testing between urine and clinician-collected cervical samples among 95 women. Finally, we explored the costs of self-sampling supplies as well as the acceptability and feasibility of urine self-sampling among women and healthcare workers. Results Our results revealed higher DNA concentrations were obtained when using a 40mM EDTA solution, storing specimens at 25°C and extracting DNA within 72 hrs. of urine collection, regardless of using first-morning micturition or a convenience sampling. We observed good agreement (Kappa = 0.72) between urine and clinician-collected cervical samples for HPV detection. Furthermore, urine self-sampling was an affordable method (USD 1.10), well accepted among cervical cancer screening users, healthcare workers, and decision-makers. Conclusion These results suggest urine self-sampling is feasible and appropriate alternative for HPV-testing in HPV-based screening programs in lower-resource contexts.

Risk factors for precancerous cervical lesion among women screened for cervical cancer in south Ethiopia: Unmatched case-control study

Background Nearly 90% of deaths from cervical cancer occur in a low resource setting. In Ethiopia, the magnitude of precancerous cervical lesions ranges from 7% to 28%. Precancerous cervical lesions may progress to cervical cancer. Early screening and treatment of precancerous cervical lesions is a cost-effective way to avert the growth of cervical cancer. However, there has been limited research on risk factors for precancerous cervical lesions in Ethiopia. Therefore, this study aimed to identify risk factors for precancerous cervical lesions among women screened for cervical cancer in south Ethiopia. Method A facility-based unmatched case-control study was carried out in five health facilities in south Ethiopia between 8 May to 28 September 2018. Interviewer administered questionnaires were used to collect data from 98 cases and 197 controls. Multivariate logistic regression was employed to identify determinants of precancerous cervical lesions. Results Women aged 30–39 years (AOR = 2.51, 95% CI: 1.03–6.08), monthly income ≤66 (AOR = 3.51, 95% CI: 1.77–6.97), initiation of first sexual intercourse at age less than or equal to 20 (AOR = 2.39, 95% CI: 1.14–5.47), having more than one lifetime sexual partner (AOR = 4.70, 95% CI: 2.02–10.95), having a partner/ husband with more than one lifetime sexual partner (AOR = 2.98, 95% CI: 1.35–6.65) had higher odds of precancerous cervical lesions. Conclusion and recommendation Strategies to prevent precancerous cervical lesions should focus on modification of lifestyle and sexual behaviour. The findings of this study highlight several implications for policymakers: targeting older women for cervical cancer screening, addressing inequalities and education relating to risky sexual behaviour may reduce precancerous cervical lesions. Furthermore, future longitudinal studies are needed to assess the awareness of women about cervical cancer screening.

Impact of opportunistic screening on squamous cell and adenocarcinoma of the cervix in Germany: A population-based case-control study

Background We investigated the uptake of opportunistic cervical cancer screening (CCS) and other risk factors and their association with cervical cancer in Germany in a case-control study. Methods and findings We recruited incident cases of cervical cancer (ICD-10 C53) diagnosed between 2012 and 2016 and matched with three population-based controls, based on age and region of residence. Cases and controls reported their CCS participation during the past ten years (frequent: every three years; no or infrequent: less than every three years) and other relevant variables. We fitted conditional logistic regression models, reporting odds ratios (OR) and 95% confidence intervals (95% CI). We report overall and stratified analyses by histologic group (squamous cell–SCC, and adenocarcinoma–AC), T category (T1 and T2+), and age (&lt;50 and ≥50 years). We analysed 217 cases and 652 matched controls. 53.0% of cases and 85.7% of controls attended CCS frequently. In the overall adjusted model, no or infrequent participation in CCS (OR 5.63; 95% CI 3.51 to 9.04), having had more than one sexual partner (OR 2.86; 95%CI 1.50 to 5.45) and obesity (OR 1.69; 95% CI 1.01 to 2.83) were associated with cervical cancer. Twelve years of schooling (OR 0.37; 95% CI 0.23 to 0.60) and a net monthly income of €3000 or more (OR 0.50; 95% CI 0.30 to 0.82) were protective factors. In the stratified analyses, no or infrequent participation was associated with T1 (OR 4.37; 95% CI 2.48 to 7.71), T2+ (OR 10.67; 95% CI 3.83 to 29.74), SCC (OR 6.88; 95% CI 4.08 to 11.59) and AC (OR 3.95; 95% CI 1.47 to 10.63). Conclusion Although women who frequently attended CCS were less likely to develop cervical cancer, especially larger tumours, the high proportion of cases who had been frequently screened prior to diagnosis underscores the need to investigate the quality of cytology and treatment of precancerous lesions in Germany.

Population-based utility scores for HPV infection and cervical squamous cell carcinoma among Australian Indigenous women

Objective Working in partnership with Indigenous communities in South Australia, we aimed to develop, pilot test and estimate utility scores for health states relating to cervical cancer screening, precancer, and invasive cervical cancer and precancer/cancer treatment among Indigenous women. Methods Development and pilot testing of hypothetical cervical cancer health states, specifically through the lens of being an Indigenous Australian woman, was done with an Indigenous Reference Group in conjunction with five female Indigenous community members. Six health states were developed. These included: (1) Screened: cytology normal; (2) human papillomaviruses (HPV) positive with cytology normal; (3) low grade cytology (LSIL);(4) high grade cytology (HSIL); (5) early stage cervical cancer and; (6) later stage cervical cancer. Utility scores were calculated using a two-stage standard gamble approach among a large cohort of Indigenous Australian women taking part in a broader study involving oral HPV infection. The mean and standard deviation (SD) of the rank, percentage of respondents with a utility = 1 (perfect health) and utility score of each health state was summarised. Mean (SD) and medians and inter-quartile range (IQR) over 12 months and lifetime duration were calculated. Potential differences by age and residential location were assessed using the Wilcox Sum Rank test. Results Data was obtained from 513 Indigenous women aged 19+ years. Mean utility scores were higher for the four non-cancer health states than for invasive cervical cancer states (p-values &lt;0.05). Lower mean utility scores were observed for late stage cervical cancer, with 0.69 at 12 months and 0.70 for lifetime duration (Intra-class correlation coefficients = 0.425). Higher utility scores were observed for the four non-cancer health states among non-metropolitan participants (ranged from 0.93 to 0.98) compared with metropolitan participants (ranged from 0.86 to 0.93) (p-values&lt;0.05). Conclusion Among a large cohort of Indigenous Australian women, the reduction in quality of life (which utilities reflect) was perceived to be greater with increasing severity of cervical cancer health states. There were differences observed by geographic location, with positive cervical screening and precursor cancer-related quality of life being much higher among non-metropolitan-dwelling participants. These utility values, from one of the largest such studies ever performed in any population will be uniquely able to inform modelled evaluations of the benefits and costs of cervical cancer prevention interventions in Indigenous women.

A transfer learning approach to facilitate ComBat-based harmonization of multicentre radiomic features in new datasets

Purpose To facilitate the demonstration of the prognostic value of radiomics, multicenter radiomics studies are needed. Pooling radiomic features of such data in a statistical analysis is however challenging, as they are sensitive to the variability in scanner models, acquisition protocols and reconstruction settings, which is often unavoidable in a multicentre retrospective analysis. A statistical harmonization strategy called ComBat was utilized in radiomics studies to deal with the “center-effect”. The goal of the present work was to integrate a transfer learning (TL) technique within ComBat—and recently developed alternate versions of ComBat with improved flexibility (M-ComBat) and robustness (B-ComBat)–to allow the use of a previously determined harmonization transform to the radiomic feature values of new patients from an already known center. Material and methods The proposed TL approach were incorporated in the four versions of ComBat (standard, B, M, and B-M ComBat). The proposed approach was evaluated using a dataset of 189 locally advanced cervical cancer patients from 3 centers, with magnetic resonance imaging (MRI) and positron emission tomography (PET) images, with the clinical endpoint of predicting local failure. The impact performance of the TL approach was evaluated by comparing the harmonization achieved using only parts of the data to the reference (harmonization achieved using all the available data). It was performed through three different machine learning pipelines. Results The proposed TL technique was successful in harmonizing features of new patients from a known center in all versions of ComBat, leading to predictive models reaching similar performance as the ones developed using the features harmonized with all the data available. Conclusion The proposed TL approach enables applying a previously determined ComBat transform to new, previously unseen data.

Comparison of the complications between minimally invasive surgery and open surgical treatments for early-stage cervical cancer: A systematic review and meta-analysis

Background This meta-analysis comprehensively compared intraoperative and postoperative complications between minimally invasive surgery (MIS) and laparotomy in the management of cervical cancer. Even though the advantages of laparotomy over MIS in disease-free survival and overall survival for management of gynecological diseases have been cited in the literature, there is a lack of substantial evidence of the advantage of one surgical modality over another, and it is uncertain whether MIS is justifiable in terms of safety and efficacy. Methods In this meta-analysis, the studies were abstracted that the outcomes of complications to compare MIS (laparoscopic or robot-assisted) and open radical hysterectomy in patients with early-stage (International Federation of Gynecology and Obstetrics classification stage IA1-IIB) cervical cancer. The primary outcomes were intraoperative overall complications, as well as postoperative aggregate complications. Secondary outcomes included the individual complications. Two investigators independently performed the screening and data extraction. All articles that met the eligibility criteria were included in this meta-analysis. Results The meta-analysis finally included 39 non-randomized studies and 1 randomized controlled trial (8 studies were conducted on robotic radical hysterectomy (RRH) vs open radical hysterectomy (ORH), 27 studies were conducted on laparoscopic radical hysterectomy (LRH) vs ORH, and 5 studies were conducted on all three approaches). Pooled analyses showed that MIS was associated with higher risk of intraoperative overall complications (OR = 1.41, 95% CI = 1.07–1.86, P&lt;0.05) in comparison with ORH. However, compared to ORH, MIS was associated with significantly lower risk of postoperative aggregate complications (OR = 0.40, 95% CI = 0.34–0.48, P = 0.0143). In terms of individual complications, MIS appeared to have a positive effect in decreasing the complications of transfusion, wound infection, pelvic infection and abscess, lymphedema, intestinal obstruction, pulmonary embolism, deep vein thrombosis, and urinary tract infection. Furthermore, MIS had a negative effect in increasing the complications of cystotomy, bowel injury, subcutaneous emphysema, and fistula. Conclusions Our meta-analysis demonstrates that MIS is superior to laparotomy, with fewer postoperative overall complications (wound infection, pelvic infection and abscess, lymphedema, intestinal obstruction, pulmonary embolism, and urinary tract infection). However, MIS is associated with a higher risk of intraoperative aggregate complications (cystotomy, bowel injury, and subcutaneous emphysema) and postoperative fistula complications.

The epidemiologic and economic impact of a quadrivalent human papillomavirus vaccine in Thailand

Background The human papillomavirus (HPV) vaccine was introduced into Thailand’s national immunization program in 2017 for 11–12 year old school girls. The objectives of this study were to examine the epidemiological consequences and cost-effectiveness of a routine quadrivalent HPV (4vHPV) vaccination and the routine 4vHPV vaccination plus 5-year catch-up vaccination by comparing with cervical cancer screening only (no vaccination) in Thailand. Method A transmission dynamic model was used to assess the cost-effectiveness of the routine 4vHPV vaccination and the routine 4vHPV vaccination plus catch-up vaccination, compared with no vaccination (screening only) in Thai population. The vaccination coverage rate assumptions were 95% in 11-12-year-old girls for the routine vaccination and 70% in 13–24 year-old females for the 5-year catch-up vaccination. Vaccination costs, direct medical costs of HPV-related diseases, and the number of quality of life years (QALYs) gained were calculated for over a 100-year time horizon with discount rate of 3%. Result The model indicated that the routine 4vHPV vaccination and the routine plus catch-up 4vHPV vaccination strategies could prevent approximately 434,130 and 472,502 cumulative cases of cervical cancer, 182,234 and 199,068 cumulative deaths from cervical cancer and 12,708,349 and 13,641,398 cumulative cases of HPV 6/11 related genital warts, respectively, when compared with no vaccination over 100 years. The estimated cost per QALY gained (ICER) when compared to no vaccination in Thailand was 8,370 THB/QALY for the routine vaccination and 9,650 THB/QALY for the routine with catch-up vaccination strategy. Conclusion Considering the recommended threshold of 160,000 THB/QALY for Thailand, the implementation of the routine 4vHPV vaccination either alone or plus the catch-up vaccination was cost-effective as compared to the cervical cancer screening only.

Validation of the cobas 6800 human papillomavirus test in primary cervical screening

Evaluation of Human Papillomavirus (HPV) testing systems suitable for large-scale organized cervical screening programs is required. We evaluated the cobas 6800 HPV test system for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) when nested in an organized primary HPV screening program, using the cobas 4800 test as comparator. The Karolinska University Hospital Cervical Cytology Biobank, containing frozen cervical samples from &gt;700,000 women participating in organized cervical screening, was linked to the Swedish national cervical screening registry to identify 470 stored cervical samples taken &lt;180 days before histopathological diagnosis of CIN3+. Two controls per case, with no abnormal results for 2 screening rounds, matched for age and sampling time were also retrieved. Aliquots from 1406 women were retrieved and re-tested on the cobas 4800 system and tested on the cobas 6800 system. There was high reproducibility between the original cobas 4800 HPV test results, and the cobas 4800 HPV re-testing performed on the samples retrieved from biobank storage. 462/464 biobanked samples from women with CIN3+ tested HPV-positive on the cobas 6800 system, corresponding to a relative sensitivity of 99.6%. 925/932 biobanked samples from control women tested HPV-negative on the cobas 6800 platform, corresponding to a relative specificity of 99.2%. By conventional criteria, the cobas 6800 was non-inferior both regarding relative sensitivity of &gt;90% (non-inferiority p-value &lt;0.0001) and relative specificity of &gt;98% (non-inferiority p-value 0.006). We conclude that the cobas 6800 HPV test system had similar, high performance as the cobas 4800 such, when evaluated using cervical samples taken before CIN3+ in a real-life primary HPV screening program.

Beliefs and perceptions regarding cervical cancer and screening associated with Pap smear uptake in Johannesburg: A cross-sectional study

BackgroundCervical cancer is a major global public health concern, with 85% of cases occurring in low- and middle-income countries. In South Africa, it is the second most common cancer amongst women. Screening and treatment of cervical cancer precursor lesions is associated with a lower incidence and mortality. This research determines the associations between women’s beliefs about cervical cancer and screening and the uptake of Papanicolaou (Pap) smears in Johannesburg, where cervical screening uptake is suboptimal.MethodsThis research was approved by the University of Witwatersrand Human Research Ethics Committee (Medical), clearance certificate number: M170243 and the Johannesburg District Heath Research Committee prior to conducting the study. All participants signed a consent form prior to participating in this study. This cross-sectional analytical study used an interviewer-administered validated measurement scale based on the Health Belief Model (HBM) to describe health beliefs regarding cervical cancer and screening among 280 women aged 30 years and older, attending Johannesburg primary care facilities in 2017. Logistic regression models, with robust estimation of variance to account for clustering of women within clinics, were fitted to identify health beliefs (perceived susceptibility, severity, barriers and benefit, cues to action, and self-efficacy) associated with ever having had a Pap smear (screening uptake), while controlling for knowledge of screening and potential confounders.ResultsOf the 280 women, 177 (63.2%) had ever been screened, 180 (64.3%) were never married, 199 (71.1%) attained secondary education and 133 (47.5%) were employed full time. Women of older age (AOR = 1.6 for a 5-year increase in age; CI: 1.3–1.9; P&lt;0.001), with higher knowledge scores (AOR = 2.5 for a 5-point increase in knowledge score; 95% CI:1.0–6.3;P = 0.051), with lower perceived barriers scores (AOR = 0.4 for a 5-point increase in barriers score; 95% CI:0.3–0.5; P&lt;0.001) and higher perceived severity scores (AOR = 1.3 for a 5-point increase in severity score; 95% CI:1.0–1.6; P = 0.017) were more likely to have had a Pap smear.ConclusionsThis study shows that women who take up screening are older, more knowledgeable regarding cervical cancer and screening, less likely to perceive screening barriers, and more likely to perceive cervical cancer as a severe disease. This highlights that for public health interventions to increase screening uptake, the focus should include tailored behaviour change communication strategies that address women’s beliefs regarding screening barriers and emphasize the severity of cervical cancer.

Histological outcomes in HPV-screened elderly women in Denmark

Introduction Danish women exit cervical cancer screening at age 65 years, but 23% of cervical cancer cases occur beyond this age. In addition, due to gradual implementation of cervical cancer screening, older women are underscreened by today´s standards. A one-time screening with HPV test was therefore offered to Danish women born before 1948. Methods Register based study reporting histology diagnoses and conizations in women found HPV positive in the one-time screening. Number and proportion of women with severe or non-severe histology results were calculated for screened and HPV-positive women by age group or region of residence. Number of women with biopsy and/or conization per case of cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) or CIN3+ were also calculated by age groups and region. Results 4,479 (4.1% of screened women) had positive HPV test. 94% of these had one or more additional tests. 2,785 (62%) of HPV-positive women had histology results, and conization was performed in 1,076 (24% of HPV-positive and 1% of all screened women). HPV positivity and CIN3+ detection varied little between regions, but the proportions of HPV positive women undergoing histology varied between regions from 40% to 86% and the proportion with conization from 13% to 36%. Correspondingly, the number of histologies and conizations per CIN3+ detected varied from 5.9 to 11.2 and 1.8 to 4.7, respectively. In total, 514 CIN2+ (0.47% of screened women, 11% of HPV-positive) and 337 CIN3+ (0.31% of screened women, 7.5% of HPV-positive) were diagnosed, including 37 cervical cancer cases. Discussion HPV screening of insufficiently screened birth cohorts can potentially prevent morbidity and mortality from cervical cancer but longer follow-up is needed to see if cancer incidence declines in the screened women in the coming years. Management strategies differed among regions which influenced the proportions undergoing biopsy/conization.

A randomized clinical trial of a new anti–cervical stenosis device after conization by loop electrosurgical excision

Background The complications inherent to conization include vaginal bleeding, cervical stenosis, amenorrhea, dysmenorrhea, and deep dyspareunia. Cervical stenosis is the most important complication due to the clinical repercussions. Studies show rates of cervical stenosis ranging from 1.3 to 19% after the Loop Electrosurgical Excision Procedure (LEEP). Objective Our primary outcome was to compare the role of a new endocervical device to prevent cervical stenosis after LEEP in patients with high-grade squamous intraepithelial lesions (HSILs). Methods A randomized clinical trial was performed including phases II and III for evaluation of a new device for cervical stenosis prevention. In Phase II, we included 25 patients who underwent LEEP and placement of the device to assess its toxicity and efficacy. In phase III, we compared two groups (with and without the use of an anti-stenosis device) to evaluate its efficacy and safety. Results From August 2015 to June 2018, 265 participants were randomized (Phase II: 25, Phase III: 120 with DUDA and 120 without DUDA). The toxicity during phase II was observed in only one patient (4%) with pain grade &gt; 7. There were 7 cases of toxicity during Phase III, 2 in the DUDA group (1.8%), and 5 in the No DUDA group (4.5%). The complications rate was numerically higher in the No DUDA group (2.5x higher) than the DUDA group, but this difference did not reach statistical significance (p = 0.52). The rate of cervical stenosis in DUDA group was (4–7,3%), and in No DUDA group was (4.3–5.8%) (p = 0.5). We did not find a significant difference when comparing the evolution at 3, 6, and 12 months in terms of cervical patency and visualization of the squamocolumnar junction (SCJ) during colposcopy. The DUDA group exhibited 15% to 19% nonvisualization of the SCJ, whereas that rate ranged from 10 to 12% in the No DUDA group. Conclusions The rate of cervical stenosis was not different comparing the use of a new device, specifically produced to prevent cervical stenosis, compared to no use after LEEP procedure. This clinical trial opens up space for a discussion of the utility of using cervical stenosis devices after LEEP. Perhaps in another type of conization it can be evaluated to avoid cervical stenosis.

Cervical cancer screening practices and its associated factors among females of reproductive age in Durame town, Southern Ethiopia

Background An estimated 22 million Ethiopian women between the ages of 15 and 49 are affected by cervical cancer each year, with 7095 cases and 4732 fatalities. Cervical cancer screening is one of the prevention methods, although Ethiopia has a low coverage rate. Furthermore, data on the use of cervical cancer screening services in the country is scarce. Therefore, we aimed to assess cervical cancer screening practices and its associated factors among females of reproductive age in Durame, Southern Ethiopia. Methods A community-based cross-sectional study was conducted using a multi-stage sampling technique among 460 females of reproductive age from March to April 2020. Data were collected using interviewer-administered questionnaires and analyzed using the Statistical Package for Social Science (SPSS) Version 20. Bivariable and multivariable logistic regressions were carried out to determine the association between independent and dependent variables. The adjusted odds ratio (AOR) with a 95% confidence interval (CI) and a P-value &lt; 0.05 were used to declare the statistical association. Results We found that cervical cancer screening practice in this study was 13.8% [95% CI:(10.4–17.2)]. Having a positive attitude [AOR = 5.2, 95% CI:(1.4, 20.0)], having a good knowledge [AOR = 5.4, 95% CI:(1.5,19.5)], being informed about cervical cancer by health professionals [AOR = 3.5, 95% CI:(1.3,9.8)], average monthly income greater than 3000 Ethiopian Birr (ETB) [AOR = 4.9, 95% CI:(1.1, 22)], and having a history of sexually transmitted infections [AOR = 4.2, 95% CI:(1.4,12.85)] were the factors associated with cervical cancer screening practice. Conclusions The practice of cervical cancer screening was found to be very low, being influenced by women’s attitudes, knowledge, having health professionals as sources of information, monthly income, and history of sexually transmitted infections. Thus, it is necessary to increase awareness and knowledge about cervical cancer and improve attitudes toward cervical screening services to improve the uptake of the screening. Health professionals also have to play a pivotal role in properly addressing information about cervical cancer.

Stemness and EMT profiles shift in xenografts derived from cisplatin-sensitive and cisplatin-tolerant ovarian cancer cells

The transcriptional alterations underlying epithelial-to-mesenchymal transition (EMT) in chemoresistant ovarian cancer remain a matter of debate, with emerging evidence pointing to tumour cell plasticity and subclone reprogramming. In this study, we developed a cisplatin-tolerant ovarian cancer model by treating the cisplatin-sensitive OVCAR-3 cell line with a single dose of cisplatin, generating the OVCAR-3 CP variant. These cisplatin-tolerant cells exhibited distinct EMT-related changes at both transcriptomic and protein levels, potentially regulated by epigenetic mechanisms. EMT profiling revealed that OVCAR-3 CP cells did not display a pronounced mesenchymal phenotype but rather retained epithelial characteristics and showed elevated expression of ALDH3A1 . In contrast, the parental chemosensitive OVCAR-3 cells expressed canonical mesenchymal markers ( CDH2, VIM, ZEB1/2, SNAIL, SLUG ) and lacked stemness marker expression. Upon xenografting, both OVCAR-3 and OVCAR-3 CP cells demonstrated phenotypic plasticity, with parental OVCAR-3 xenografts acquiring EMT-like features resembling to those observed in cisplatin-tolerant tumours. These findings suggest a decoupling of EMT from cisplatin-tolerance and instead underscore a stronger association between stemness traits and cisplatin tolerance. Our data further indicate that xenografting can induce significant cellular reprogramming. Comprehensive characterization of ovarian cancer cell-derived xenograft is therefore essential, as they represent a valuable translational platform for investigating therapy adapted ovarian cancer cells.

Changes in genital Human Papillomavirus (HPV) prevalence among urban females a decade after the Malaysian HPV vaccination program

To increase the coverage of HPV vaccination, Malaysia implemented a national school-based vaccination program for all 13-year-old girls in 2010. Two years later, a clinic-based catch-up program was started for 16 to 21-year-old girls. We assessed the prevalence of a range of HPV genotypes, among a sample of urban women within the age groups of 18–24 and 35–45 years in 2019–2020, a decade into the national vaccination program. The HPV prevalence was then compared to that reported in an unvaccinated population in 2013–2015. We sampled a total of 1134 participants, comprising of 277 women aged 18–24 years and 857 women aged 35–45 years, from several urban clinics in the state of Selangor. Participants provided a self-acquired vaginal sample for HPV genotyping. Comprehensive sociodemographic and vaccination history were collected. The HPV vaccination coverage among women in the younger age group increased from 9.3% in 2013–2015 to 75.5% in 2019–2020. The prevalence of vaccine-targeted HPV16/18 decreased 91% (CI: 14.5%–99.0%) among the younger women, from 4.0% in 2013–2015 to 0.4% in 2019–2020. There was also an 87% (CI: 27.5%–97.5%) reduction in HPV6/11/16/18. There was no difference in the prevalence of non-vaccine targeted HPV genotypes among younger women. The HPV prevalence among older women, for both vaccine targeted and non-vaccine targeted genotypes in 2019–2020, did not differ from 2013–2015. The observed decline in prevalence of vaccine-targeted HPV genotype among younger women a decade after the national HPV vaccination program is an early indication of its effectiveness in reducing the burden of cervical cancer.

Factors influencing human papillomavirus school-based immunization in Alberta: A mixed-methods study protocol

More than 1,300 Canadians are diagnosed with cervical cancer annually, which is nearly preventable through human papillomavirus (HPV) immunization. Across Canada, coverage rates remain below the 90% target set out by the Action Plan for the Elimination of Cervical Cancer in Canada (2020–2030). To support this Plan, the Canadian Partnership Against Cancer has commissioned the Urban Public Health Network (UPHN) to coordinate a quality improvement project with Canada’s school-based HPV immunization programs. In Alberta, the UPHN partnered with Alberta Health Services (AHS) for this work. This study has one overarching research question: what are parent/guardian and program stakeholder perceived barriers, enablers and opportunities to immunization for youth as part of the school-based HPV immunization program in Alberta? This study uses a mixed-methods sequential explanatory design. A survey will be emailed to a sample of Albertans with children aged 11–17 years. Questions will be based on a Conceptual Framework of Access to Health Care. Subsequent qualitative work will explore the survey’s findings. Parents/guardians identifying as vaccine hesitant in the survey will be invited to participate in virtual, semi-structured, in-depth interviews. Stakeholders of the school-based immunization program will be purposively sampled from AHS’ five health zones for virtual focus groups. Quantitative data will be analyzed using SAS Studio 3.6 to carry out descriptive statistics and, using logistic regression, investigate if Framework constructs are associated with parents’/guardians’ decision to immunize their children. Qualitative data will be analyzed using NVivo 12 to conduct template thematic analysis guided by the Framework. Study results will provide insights for Alberta’s public health practitioners to make evidence-informed decisions when tailoring the school-based HPV immunization program to increase uptake in vaccine hesitant populations. Findings will contribute to the national study, which will culminate in recommendations to increase HPV immunization uptake nationally and progress towards the 90% coverage target.

Clinical implementation of a cervical cancer screening program via co-testing at a university hospital

The Human Papillomavirus (HPV) test is a crucial technology for cervical cancer prevention because it enables programs to identify women with high-risk HPV infection who are at risk of developing cervical cancer. Current U.S. Preventive Services Task Force recommendations include cervical cancer screening every three years with cervical cytology alone or every five years with either high-risk HPV testing alone or high-risk HPV testing combined with cytology (co-testing). In Argentina, 7,548 new cervical cancer cases are diagnosed each year with 3,932 deaths attributed to this cause. Our study aims to show the clinical implementation of a cervical cancer screening program by concurrent HPV testing and cervical cytology (co-testing); and to evaluate the possible cervical cancer screening scenarios for Latin America, focusing on their performance and average cost. A cervical cancer screening five year program via co-testing algorithm (Hybrid-2-Capture/cytology) was performed on women aged 30–65 years old at a university hospital. Statistical analysis included a multinomial logistic regression, and two cancer screening classification alternatives were tested (cytology-reflex and HPV-reflex). A total of 2,273 women were included, 91.11% of the participants were double-negative, 2.55% double-positive, 5.90% positive-Hybrid-2-Capture-/negative-cytology, and 0.44% negative-Hybrid-2-Capture/positive-cytology. A thorough follow-up was performed in the positive-Hybrid-2-Capture group. Despite our efforts, 21 (10.93%) were lost, mainly because of changes on their health insurance coverage which excluded them from our screening algorithm. Of the 171 women with positive-Hybrid-2-Capture results and follow-up, 68 (39.77%) cleared the virus infection, 64 (37.43%) showed viral persistence, and 39 (22.81%) were adequately treated after detection via colposcopy/biopsy of histological HSIL (High-Grade Squamous Intraepithelial Lesion). The prevalence of high-risk HPV in this population was 192 women (8.45%), with HSIL histology detection rates of 17 per 1,000 screened women. A multinomial logistic regression analysis was performed over the women with positive-Hybrid-2-Capture considering the follow up (clearance, persistence and HSIL) as dependent variable, and the cytology test results (positive- or negative-cytology and Atypical Squamous Cells of Undetermined Significance, ASC-US) as independent variable. The model supported a direct association between cytology test results and follow up: negative-cytology/clearance, ASC-US/persistence, and positive-cytology/HSIL with the following probabilities of occurrence for these pairs 0.5, 0.647 and 0.647, respectively. Cytology could be considered a prognostic-factor in women with a positive-Hybrid-2-Capture. These findings suggest that the introduction of co-testing could diminish the burden of cervical cancer in low-and middle-income-countries, acting as a tool against inequity in healthcare.

A Drosophila model of HPV16-induced cancer reveals conserved disease mechanism

High-risk human papillomaviruses (HR-HPVs) cause almost all cervical cancers and a significant number of vaginal, vulvar, penile, anal, and oropharyngeal cancers. HPV16 and 18 are the most prevalent types among HR-HPVs and together cause more than 70% of all cervical cancers. Low vaccination rate and lack of molecularly-targeted therapeutics for primary therapy have led to a slow reduction in cervical cancer incidence and high mortality rate. Hence, creating new models of HPV-induced cancer that can facilitate understanding of the disease mechanism and identification of key cellular targets of HPV oncogenes are important for development of new interventions. Here in this study, we used the tissue-specific expression technique, Gal4-UAS, to establish the first Drosophila model of HPV16-induced cancer. Using this technique, we expressed HPV16 oncogenes E5, E6, E7 and the human E3 ligase (hUBE3A) specifically in the epithelia of Drosophila eye, which allows simple phenotype scoring without affecting the viability of the organism. We found that, as in human cells, hUBE3A is essential for cellular abnormalities caused by HPV16 oncogenes in flies. Several proteins targeted for degradation by HPV16 oncoproteins in human cells were also reduced in the Drosophila epithelial cells. Cell polarity and adhesion were compromised, resulting in impaired epithelial integrity. Cells did not differentiate to the specific cell types of ommatidia, but instead were transformed into neuron-like cells. These cells extended axon-like structures to connect to each other and exhibited malignant behavior, migrating away to distant sites. Our findings suggest that given the high conservation of genes and signaling pathways between humans and flies, the Drosophila model of HPV16- induced cancer could serve as an excellent model for understanding the disease mechanism and discovery of novel molecularly-targeted therapeutics.

Association of red cell distribution width/albumin ratio with intraoperative blood transfusion in cervical cancer patients

Background Although minimally invasive surgical techniques have reduced intraoperative bleeding, the risk of transfusion exists. However, few studies have evaluated risk factors for transfusion in radical hysterectomy. We aimed to evaluate the association between preoperative red cell distribution width/albumin ratio (RDW/albumin) and transfusion in cervical cancer patients. Methods We analyzed 907 patients who underwent radical hysterectomy between June 2006 and February 2015. Logistic regression and Cox regression analyses were performed to determine the risk factors for transfusion and mortality at 5-year and overall. Net reclassification improvement (NRI) and integrated identification improvement (IDI) analyses were performed to verify the improvement of the intraoperative transfusion model upon the addition of RDW/albumin. Results RDW/albumin was an independent risk factor for transfusion (odds ratio [OR]: 1.34, 95% confidence interval [CI]: 1.02–1.77, p = 0.035). Additionally, body mass index, operation time, laparoscopic surgery, total fluids, and synthetic colloid were risk factors for transfusion. RDW/albumin was an independent risk factor for 5-year mortality (hazard ratio [HR]: 1.51, 95% CI: 1.07–2.14, p = 0.020), and overall mortality (HR: 1.48, 95% CI: 1.06–2.07, p = 0.021). NRI and IDI analyses showed the discriminatory power of RDW/albumin for transfusion (p&lt;0.001 and p = 0.046, respectively). Conclusions RDW/albumin might be a significant factor in transfusion and mortality in cervical cancer patients.

Disease progression role as well as the diagnostic and prognostic value of microRNA-21 in patients with cervical cancer: A systematic review and meta-analysis

IntroductionCervical cancer is the fourth commonest and the fourth leading cause of cancer death in females globally. The upregulated expression of microRNA-21 in cervical cancer has been investigated in numerous studies, yet given the inconsistency on some of the findings, a systematic review and meta-analysis is needed. Therefore, the aim of this systematic review and meta-analysis is to investigate the role in disease progression as well as the diagnostic and prognostic value of microRNA-21 in patients with cervical cancer.MethodsLiterature search was carried out through visiting several electronic databases including PubMed/MEDLINE/ PubMed Central, Web of Science, Embase, WorldCat, DOAJ, ScienceDirect, and Google Scholar. After extraction, data analysis was carried out using Rev-Man 5.3, STATA 15.0 and Meta-disk 1.4. I2 and meta-bias statistics assessed heterogeneity and publication bias of the included studies, respectively. The area under summary receiver operating characteristic curve and other diagnostic indexes were used to estimate diagnostic accuracy.ResultA total of 53 studies were included for this systematic review and meta-analysis. This study summarized that microRNA-21 targets the expression of numerous genes that regulate their subsequent downstream signaling pathways which promote cervical carcinogenesis. The targets addressed in this study included TNF-α, CCL20, PTEN RasA1, TIMP3, PDCD-4, TPM-1, FASL, BTG-2, GAS-5, and VHL. In addition, the meta-analysis of reports from 6 eligible studies has demonstrated that the overall area under the curve (AUC) of summary receiver operating characteristic (SROC) of microRNA-21 as a diagnostic accuracy index for cervical cancer was 0.80 (95% CI: 0.75, 0.86). In addition, evidence from studies revealed that upregulated microRNA-21 led to worsening progression and poor prognosis in cervical cancer patients.ConclusionmicroRNA-21 is an oncogenic microRNA molecule playing a key role in the development and progression of cervical malignancy. It has good diagnostic accuracy in the diagnosis of cervical cancer. In addition, the upregulation of microRNA-21 could predict a worse outcome in terms of prognosis in cervical cancer patients.

Feasibility of a novel non-invasive swab technique for serial whole-exome sequencing of cervical tumors during chemoradiation therapy

Background Clinically relevant genetic predictors of radiation response for cervical cancer are understudied due to the morbidity of repeat invasive biopsies required to obtain genetic material. Thus, we aimed to demonstrate the feasibility of a novel noninvasive cervical swab technique to (1) collect tumor DNA with adequate throughput to (2) perform whole-exome sequencing (WES) at serial time points over the course of chemoradiation therapy (CRT). Methods Cervical cancer tumor samples from patients undergoing chemoradiation were collected at baseline, at week 1, week 3, and at the completion of CRT (week 5) using a noninvasive swab-based biopsy technique. Swab samples were analyzed with whole-exome sequencing (WES) with mutation calling using a custom pipeline optimized for shallow whole-exome sequencing with low tumor purity (TP). Tumor mutation changes over the course of treatment were profiled. Results 216 samples were collected and successfully sequenced for 70 patients (94% of total number of tumor samples collected). A total of 33 patients had a complete set of samples at all four time points. The mean mapping rate was 98% for all samples, and the mean target coverage was 180. Estimated TP was greater than 5% for all samples. Overall mutation frequency decreased during CRT but mapping rate and mean target coverage remained at &gt;98% and &gt;180 reads at week 5. Conclusion This study demonstrates the feasibility and application of a noninvasive swab-based technique for WES analysis which may be applied to investigate dynamic tumor mutational changes during treatment to identify novel genes which confer radiation resistance.

Individual and intimate-partner factors associated with cervical cancer screening in Central Uganda

Intimate-partner factors have a significant effect on the uptake of services that affect maternal reproductive health outcomes. There is limited research on intimate-partner factors associated with cervical cancer screening. Therefore, this article examines the intimate-partner correlates of cervical cancer screening among married women in Central Uganda. We conducted a cross-sectional survey in Wakiso and Nakasongola districts in Central Uganda. A total of 656 married women aged 25–49 participated in the study. Frequency distributions for descriptive statistics and Pearson chi-squared tests were done to identify the association of selected individual explanatory variables and intimate-partner factors with cervical cancer screening. Finally, multivariable complementary log-log regressions were used to estimate intimate-partner factors associated with women’s cervical cancer screening uptake in Central Uganda. About 2 in 10 (20%) of the participants had been screened for cervical cancer. The following characteristics when examined separately in relation to the uptake of cervical cancer screening service and were significant: woman’s age, education attainment, occupation, wealth index, parity, male partner’s age, and male partner’s emotional support. After adjusting for independent factors, cervical cancer screening was significantly associated with women who had; attained secondary (AOR = 2.19; CI 1.18–4.06) compared to none/ primary education, and received partner’s emotional support (AOR = 30.06; CI 13.44–67.20) compared to those who did not receive partner’s emotional support. In Central Uganda, cervical cancer screening among married women was significantly associated with women’s education, and partner’s emotional support. These factors point to the importance of intimate-partner factors. Therefore, more effort should be directed at encouraging men’s participation. This should be supplemented with empowering women through education to increase uptake of screening services.

Cervical cancer management in Zimbabwe (2019–2020)

Background Globally, cervical cancer is the fourth most commonly diagnosed cancer amongst women, and it is especially common in low- and middle-income countries (LMICs). The aim of the study was to determine the current patterns and characteristics of CC management in Zimbabwe in the HIV pandemic era, including the knowledge, attitude and practice of patience. Methods The study was a mixed method which incorporated a cross-sectional survey of 408 CC patients which was conducted from October 2019 to September 2020 using an interviewer administered paper questionnaire. The study was conducted at Parirenyatwa hospital, the only cancer treating public health facility in Harare, Zimbabwe. Differences in study outcome by categorical variables were assessed using the Person Chi-square (χ2) test. Odds ratios (unadjusted and adjusted) and 95%CIs for potential risk factors associated with the outcome were estimated using logistic regression model. Results From a total of 408 CC patients recruited into the study no prevention mechanism was available or known to these patients and only 13% knew that CC is caused by Human papillomavirus. Only 87 (21%) had ever been screened for CC and 83 (97%) of those who had been screened had the visual inspection with acetic acid procedure done. Prevention (screening uptake) is statistically high among the educated (with secondary education OR = 9.497, 95%CI: 2.349–38.390; with tertiary OR = 59.381, 95%CI: 11.937–295.380). Late presentation varied statistically significantly with marital status (high among the divorced, OR = 2.866; 95% CI: 1.549–5.305 and widowed OR = 1.997; 95% CI: 1.112–3.587), was low among the educated (Tertiary OR = .393; 95% CI: .166-.934), low among those living in the rural (OR = .613; 95% CI: .375-.987), high among those with higher parity OR = 1.294; 95% CI: 1.163–1.439). Less than 1% of the patients had surgery done as a means of treatment. Radiotherapy was administered to 350 (86%) of the patients compared to chemotherapy administered to 155 (38%). A total of 350 (86%) have failed to take medication due to its unavailability, while 344 (85%) missed taking medication due to unaffordability. Complementary and alternative medicines were utilized by 235 (58%). Majority, 278 (68%) were HIV positive, mainly pronounced within age (36–49 years OR = 12.673; 95% CI: 2.110–76.137), among those with higher education (secondary education OR = 4.981; 95%CI: 1.394–17.802 and in those with no co-morbidities (893.956; 95%CI: 129.611–6165.810). Conclusion CC management was inadequate from prevention, screening, diagnosis, treatment and palliative care hence there is need to improve CC management in Zimbabwe if morbidity and mortality are to be reduced to acceptable levels. Education helped improve prevention, but reduces chances of diagnosis, working as a doubled edged sword in CC management Prevention was high among the educated. Those in rural areas experience poor CC management. It should be noted that general education is good; however it must be complimented by CC awareness to improve CC management outcomes holistically. Cervical cancer management services need to be decentralized so that those in rural areas have easy access. Given that those with co-morbidities and high parity have better CC management, CC services need to be tied to co-morbidity and antenatal/post-natal care and management services.

Reproductive health needs of Human papillomavirus (HPV) positive women: A systematic review

Objectives Human papillomavirus is one of the most important causes of cervical cancer. Participating in an HPV test and receiving an HPV diagnosis can create questions about the needs and preferences. The present systematic review was conducted to determine the reproductive health needs of women with HPV. Methods We searched PubMed, Scopus, Web of Science, Google Scholar and Magiran, SID and Iranmedex. Without language restrictions and time constraints. We also searched the grey literature and carried out forward/backward citation searches. Results In the first, 1056 articles were retrieved, and, after removing them, 13 articles published were entered. The studies were qualitative (N = 9), quantitative (N = 3), and one was unclear. Most qualitative studies collected data using individual interviews (N = 7), two qualitative studies, narratives of HPV patients from a website of patient experiences and questions. Women wanted further information on different HPV viral types, transmission, implications for sexual partners, prevalence, latency and regression of HPV, their management options and the implications of infection for cancer risk and fertility. Women’s experience of searching the Internet for further information about HPV was reported as difficult, anxiety provoking and contributing to the stigma of the infection because information was often located in the context of other sexually transmitted infections, with multiple sexual partners highlighted as a risk factor for infection. Conclusion Surveys showed that the majority of women had unanswered questions about their HPV test results. The information that women thought was helpful in interpreting their test results included having a high-risk type of HPV, and cancer survival statistics for the virus. Women also needed information about sexual transmission, how HPV tested positive in a long-term relationship, and the potential consequences for their partners and the risk of re-infection. Younger women had questions about whether HPV could affect fertility.

Full genotyping and FAM19A4/miR124-2 methylation analysis in high-risk human papillomavirus–positive samples from women over 30 years participating in cervical cancer screening in Örebro, Sweden

Currently, cervical cancer prevention is undergoing comprehensive development regarding human papillomavirus (HPV) vaccination and cervical cancer screening. In Sweden and many other countries, high coverage vaccinated cohorts are entering screening within the next few years. This entails demands for baseline HPV genotype data across the screening age range for surveillance and a basis for screening program adjustment. In 2016, Örebro County, Sweden, changed to primary HPV screening using HPV mRNA testing followed by cytology triage. An alternative triage method to cytology could allow for a fully molecular screening algorithm and be implemented in a screening program where self-sampling is included. Hypermethylation analysis of the human genes FAM19A4/miR124-2 has been suggested as a promising triage method. HPV mRNA-positive screening samples (n = 529) were included and subjected to genotyping targeting a broad range of both low-risk and high-risk genotypes in addition to hypermethylation analysis of the two human genes FAM19A4/miR124-2. Data were connected to cytological and histological status and age. The most commonly detected genotypes were HPV31, 16, and 52. In addition, HPV18 was one of the most common genotypes in high-grade squamous intraepithelial lesions (HSILs) samples. In relation to available vaccines, 26% of the women with histological HSIL or cancer (≥HSIL) tested positive for only hrHPV included in the quadrivalent vaccine and 77% of the genotypes in the nonavalent vaccine. According to these figures, a relatively large proportion of the HSILs will probably remain, even after age cohorts vaccinated with the quadrivalent vaccine enter the screening program. Hypermethylation positivity was associated with increasing age, but no HPV-related independently predictive factors were found. Accordingly, age needs to be considered in development of future screening algorithms including triage with hypermethylation methodology.

Empirical investigation of e-health intervention in cervical cancer screening: A systematic literature review

Cervical cancer (CC) screening can detect the cancer early but is underutilized, especially among the developing countries and low- to middle-income countries. Electronic health (e-health) has the potential for disseminating health education and is widely used in the developed countries. This systematic literature review investigates the effectiveness of e-health intervention for improving knowledge of CC and the intention or uptake for CC screening. We followed the PRISMA 2020 guideline and registered with PROSPERO (registration ID CRD42021276036). We searched the Web of Science, Scopus and EBSCO Medline Complete databases for eligible studies. Studies that conveyed informational material through e-health intervention were selected. The results were analyzed using narrative synthesis, and the pooled estimates were calculated using meta-analysis. A total of six studies involving 1886 women were included in this review. The use of e-health aids alone led to increased knowledge. The meta-analysis demonstrated that the mixed-education method of e-health movies and video education with didactic sessions increased CC screening uptake. A random-effects model revealed that CC screening uptake following e-health interventions were almost double of that of their comparison (odds ratio = 2.29, 95% confidence interval: 1.28–4.10, p &lt; 0.05). Various areas of study demonstrated e-health intervention effectiveness (minority communities, urban areas, rural areas). Health education through e-health intervention has huge potential for promoting CC screening in the community. Nevertheless, the use of appropriate frameworks, user engagement and culturally tailored e-health need to be prioritized.

Histopathological profile of cervical punch biopsies and risk factors associated with high-grade cervical precancerous lesions and cancer in northwest Ethiopia

Introduction Cervical cancer is an important public health problem in Ethiopia. However, the disease is not well characterized and studied in various parts of the country. This study was designed to describe the histopathological profile of cervical biopsies and to identify risk factors associated with high-grade cervical lesions and cancer (CIN2+C). Methods A cross-sectional study was conducted at Felege Hiwot Compressive Specialized Hospital (FHCSH) between 1 March 2019 and 30 October 2021. A structured questionnaire was used to collect data on the participants’ demographic, reproductive and gynecologic history. From women presented with different degrees of cervical lesions, a senior gynecologist collected cervical swabs using (Digene HC2 DNA collection device: Qiagen, Hilden, Germany) for detection of high-risk Human papillomaviruses (HR-HPV) and punch biopsy for histopathological examinations. HR-HPVs were detected using the Abbott Alinity m system following the manufacturer protocol at the Institute of Virology, Leipzig University Hospital, Germany. Collected data entered and analyzed using SPSS version 25. A logistic regression model was used for both bivariable &amp; multivariable analysis in order to determine the association between independent variables and CIN2+C. Statistical significance was set at a p-value &lt;0.05. Results In this study, 335 women were included; the mean age was at 46.5±11.4 years. Most were living in rural settings, 221(66%) and had no formal education, 259 (77.3%). More than half of the participants, 193(57.6%) were unaware of cervical cancer. The prevalence of HIV infection and previous history of cervical screening were 44(13.1%) and 93(27.8%), respectively. HR-HPVs were detected in 178(54.3%) of the participants. The majority of biopsies, 140(41.8%; 95%CI: 36.6–47.1%), were diagnosed as cervical carcinoma. Normal histology, cervicitis, cervical intraepithelial neoplasia (CIN)-1, CIN-2, and CIN-3 accounted for 74(22.1%), 30(9.0%), 40(11.9%), 12(3.6%), and 12(3.6%), respectively. High-grade lesions and cancer (CIN2+C) together accounted 164(49.0%; 95%CI: 43.6–54.2). Cervical cancer increased steadily with the age of the participants (p&lt;0.001) in which women above the age of fifty were approximately four times more likely to develop CIN2+C than the younger ones (AOR: 3.73; 95%CI: 1.80–7.82; p&lt;0.001). Likewise, no screening history in the last five years (AOR: 2.03; 95%CI: 1.05–3.92; p = 0.035) and being infected with HR-HPVs (AOR: 14.23; 95%CI: 7.9–25.64; p&lt;0.001) were found significantly associated with CIN2+C. Conclusions The findings of this study revealed that cervical cancer continues to be an important women’s health challenge in northwest Ethiopia. Postmenopausal women, who had no screening history within a five-year period and those women who tested positive for HR-HPV need special attention. It is important to increase the awareness of women about cervical cancer and actions for early detection of precancerous lesions should be expanded.

Implementation strategies to increase human papillomavirus vaccination uptake for adolescent girls in sub-Saharan Africa: A scoping review protocol

Introduction The human papillomavirus (HPV) is sexually transmitted and infects approximately 75% of sexually active people early in their sexual life. Persistent infection with oncogenic HPV types can lead to malignant conditions such as cervical cancer. In 2006, the World Health Organisation approved the use of an efficacious HPV vaccine for girls aged 9 to 14 to prevent HPV-related conditions. Despite the HPV vaccine being available for about 15 years, dose completion remains as low as 20% in sub-Saharan African (SSA) countries implementing the vaccination program compared to 77% in Australia and New Zealand. A fraught of barriers to implementation exist which prevent adequate coverage. Achieving success for HPV vaccination in real-world settings requires strategies to overcome implementation bottlenecks. Therefore, a better understanding and mapping of the implementation strategies used in sub-Saharan Africa to increase HPV vaccination uptake is critical. This review aims to identify implementation strategies to increase HPV vaccination uptake for adolescent girls in sub-Saharan Africa and provide a basis for policy and future research, including systematic reviews to evaluate effective strategies as we accelerate the elimination of cervical cancer. Materials and methods This scoping review will consider studies pertaining to implementation strategies to increase HPV vaccination uptake for adolescent girls in sub-Saharan Africa. Studies targeted at different stakeholders to increase adolescent vaccine uptake will be included. Studies using interventions not fitting the definition of implementation strategies as defined by the refined compilation of implementation strategies from the Expert Recommendations for Implementing Change project will be excluded. MEDLINE (via PubMed), Embase, CINAHL (via EBSCO), Scopus and Google Scholar will be searched. Two independent reviewers will screen titles and abstracts for studies that meet the review’s inclusion criteria, and the full text of eligible studies will be reviewed. Data will be extracted from eligible studies using a structured data charting table developed by this team for inclusion by two independent reviewers and presented in a table and graphical form with a narrative summary.

Vaginal microbiota and personal risk factors associated with HPV status conversion—A new approach to reduce the risk of cervical cancer?

Vaginal microbiota (VMB) is associated with changes in Human papilloma virus (HPV) status, which consequently influences the risk of cervical cancer. This association was often confounded by personal risk factors. This pilot research aimed to explore the relationship between vaginal microbiota, personal risk factors and their interactions with HPV status conversion to identify the vaginal microbiota that was associated with HPV clearance under heterogeneous personal risk factors. A total of 38 women participated by self-collecting a cervicovaginal mucus (CVM) sample that was sent for metagenomics sequencing. Most of the participants also filled in personal risk factors questionnaire through an eHealth platform and authorized the use of their previous HPV genotyping results stored in this eHealth platform. Based on the two HPV results, the participants were grouped into three cohorts, namely HPV negative, HPV persistent infection, and HPV status conversion. The relative abundance of VMB and personal factors were compared among these three cohorts. A correlation investigation was performed between VMB and the significant personal factors to characterize a robustness of the panel for HPV status change using R programming. At baseline, 12 participants were HPV-negative, and 22 were HPV-positive. Within one year, 18 women remained HPV-positive, 12 were HPV-negative and 4 participants showed HPV clearance. The factors in the eHealth questionnaire were systematically evaluated which identified several factors significantly associated with persistent HPV infection, including age, salary, history of reproductive tract infection, and the total number of sexual partners. Concurrent vaginal microbiome samples suggest that a candidate biomarker panel consisting of Lactobacillus gasseri, Streptococcus agalactiae, and Timona prevotella bacteria, which may be associated with HPV clearance. This pilot study indicates a stable HPV status-related vaginal microbe environment. To establish a robust biomarker panel for clinical use, larger cohorts will be recruited into follow-up studies.

Incidence of cervical, breast and colorectal cancers between 2010 and 2015 in people living with HIV in France

Background We aimed to evaluate the incidence rates between 2010 and 2015 for invasive cervical cancer (ICC), breast cancer (BC), and colorectal cancer (CRC) in people living with HIV (PLWH) in France, and to compare them with those in the French general population. These cancers are targeted by the national cancer-screening program. Setting This is a retrospective study based on the longitudinal data of the French Dat’AIDS cohort. Methods Standardized incidence ratios (SIR) for ICC and BC, and incidence rates for all three cancers were calculated overall and for specific sub-populations according to nadir CD4 cell count, HIV transmission category, HIV diagnosis period, and HCV coinfection. Results The 2010–2015 CRC incidence rate was 25.0 [95% confidence interval (CI): 18.6–33.4] per 100,000 person-years, in 44,642 PLWH (both men and women). Compared with the general population, the ICC incidence rate was significantly higher in HIV-infected women both overall (SIR = 1.93, 95% CI: 1.18–3.14) and in the following sub-populations: nadir CD4 ≤ 200 cells/mm3 (SIR = 2.62, 95% CI: 1.45–4.74), HIV transmission through intravenous drug use (SIR = 5.14, 95% CI: 1.93–13.70), HCV coinfection (SIR = 3.52, 95% CI: 1.47–8.47) and HIV diagnosis before 2000 (SIR = 2.06, 95% CI: 1.07–3.97). Conversely, the BC incidence rate was significantly lower in the study sample than in the general population (SIR = 0.56, 95% CI: 0.42–0.73). Conclusion The present study showed no significant linear trend between 2010 and 2015 in the incidence rates of the three cancers explored in the PLWH study sample. Specific recommendations for ICC screening are still required for HIV-infected women and should focus on sub-populations at greatest risk.

Human papillomavirus vaccination uptake and its associated factors among adolescent school girls in Ambo town, Oromia region, Ethiopia, 2020

Background The Human Papillomavirus (HPV) vaccine has offered a great promise to reduce the cervical cancer burden; its utilization (uptake) however has been lagging. However, the levels and factors associated with the uptake of the vaccine have not been well investigated, especially in the local context. Objective To assess the uptake of human papillomavirus vaccination and its associated factors among adolescent school girls in ambo town, Oromia, Ethiopia, 2020. Methods An institution-based cross-sectional quantitative study design supplemented with the qualitative inquiry was employed to assess Human Papillomavirus vaccination uptake and its associated factors among 422 adolescent school girls in Ambo town, central Ethiopia from December 1–30, 2020. The collected data were coded, entered, and cleaned by using Epi info 7.2.3 and exported to SPSS version 25 for analysis. Descriptive statistics were used to compute summary statistics and proportions. Both bivariate and multivariable logistic regression was employed to identify factors associated with HPV vaccine uptake. Adjusted odds ratio and 95% confidence interval were used for the strength and directions of association. A P-value of &lt; 0.05 was used to declare statistical significance. Qualitative findings have been analyzed with manual thematic analysis. Result The proportion of HPV vaccination uptake among school girls in this study was 44.4%. Hearing about HPV vaccine [AOR = 2.50, 95%CI: (1.045–5.959)], availability of awareness creation [AOR = 2.53, 95%CI: (1.507–4.258)], and favorable attitude [AOR = 2.049, 95%CI: (1.153–3.64)] were the key identified factors associated with vaccination uptake. In addition, poor perception, fear of side effects, and misunderstanding were among the major factors identified by qualitative findings. Conclusion There was low uptake of HPV vaccination among the school Adolescents in the study area. Availability of awareness creation programs, favorable attitude towards HPV vaccine, and hearing about HPV vaccine was significantly associated with the uptake of the HPV vaccination. Therefore, awareness creation and behavior change education are mandatory to scale up the vaccination.

Determinants of utilization of cervical cancer screening among women in the age group of 30–49 years in Ambo Town, Central Ethiopia: A case-control study

Background Globally, cervical cancer is the second most common and the leading cause of death in women in low-income countries. It is one of the potentially preventable cancers, and an effective screening program can result in a significant reduction in the morbidity and mortality associated with this cancer; however, evidence showed that only a small percentage of the women were screened. As a result, predictors of cervical cancer screening usage among women in Ambo town, central Ethiopia, were identified in this study. Method Unmatched, a community-based case-control study was conducted among 195 randomly sampled women in the age group of 30–49 years in Ambo town from February 1 to March 30, 2020. Data was collected using an interviewer-administered questionnaire. Descriptive, bivariate, and multivariable binary logistic regression analysis was done using SPSS. Results A total of 195 study participants, sixty-five cases and one hundred thirty controls, participated in this study, making a response rate of 100%. Being in the age group of 30–34 years old (AOR = 0.2; 95% CI: 0.06–0.7), being Para five and above (AOR = 4.5; 95% CI: 1.4–14.1), modern contraceptive utilization (AOR = 5.4; 95% CI: 1.8–16.3) and having high-level knowledge regarding cervical cancer screening and its predisposing factors (AOR = 5.9; 95% CI: 2–17) were significantly associated with the utilization of cervical cancer screening. Conclusion The age of women, parity, use of modern contraception, and level of knowledge regarding cervical cancer screening and its predisposing factors were the determinants of the utilization of cervical cancer screening among women. As a result, the media, the health bureau, and health professionals should advocate raising awareness about cervical cancer and its preventative methods, which are primarily focused on screening.

Diagnose earlier, live longer? The impact of cervical and breast cancer screening on life span

Cancer has become a leading cause of death and aroused the cancer scare. Breast and cervical cancer are two main health threats for women. In order to reduce mortality through early detection and early treatment, cancer screening has been widely recommended and applied for breast and cervical cancer detection and prevention. However, the benefit of cancer screening has been a controversial issue for the recent decades. The Chinese government has launched a free screening program on breast and cervical cancer for women since 2009. There is lack of strong data and sufficient information, however, to examine the effect of breast and cervical cancer screening. A Difference-in-Difference model estimated by Cox proportional hazard estimation was applied to evaluate the effects of breast and cervical cancer screening using data from Nown County Cancer Registry between the year 2009 and 2013. Based on the case study in a county of central China, this study found that the screening program reduced the risk of death, but found the lion’s share for the benefit has been mainly due to the cervical cancer screening rather breast cancer screening, which may be related to the difference between early detection screening and preventive screening. Our results suggest sufficient funding and better education of related cancer knowledge will be meaningful measures for the prevention and treatment of breast and cervical cancer.

Association between delayed initiation of treatment indications and survival in patients with cervical cancer: A systematic review and meta-analysis protocol

Background Cervical cancer is a growing public health problem globally. Despite the availability of management options, the progression of the disease as a function of waiting time may challenge the effort to attain a desired outcome. There is a conflicting report on the role of waiting time to initiate an appropriate treatment in improving patients’ survival. Objective This review aims to evaluate the association between delayed time to initiate any treatment indication with survival in patients with cervical cancer. Methods An internet-based literature search will be performed using text words, MESH terms and truncated words in databases, namely MEDLINE, Cochrane CENTRAL, EMBASE, Web of Science and Scopus. Grey literature searches in Google Scholar, Networked Digital Library of Theses and Dissertations (NDLTD) and Dissertations and Theses Global will be made. All articles published until 30th of December 2021 on human subjects will be searched without a language restriction. Studies which fulfil the inclusion criteria will be screened in full reading, selected, appraised and assessed for methodological quality by two independent reviewers. Data on participants, study methods, interventions, and outcomes will be abstracted. Included studies will be pooled for meta-analysis. Microsoft-Excel and R packages will be employed to carry out the statistical analysis. Heterogeneity will be assessed using Cochrane Q statistic, Tau2, and I2. Results will be reported as a function of 4-week delay in treatment initiation and the corresponding hazard ratio (HR) at 95% confidence interval. Statistical significance will be considered at P&lt;0.05. Trial registration PROSPERO registration number: CRD42022299689.

Effectiveness of couple education and counseling on knowledge, attitude and uptake of cervical cancer screening service among women of child bearing age in Southern Ethiopia: A cluster randomized trial protocol

Background Cervical cancer occurred nearly in 570 000 women and 311 000 women died from the disease worldwide in 2018. Of the new cases diagnosed globally in 2012, approximately 85% of the burden took place in low- and middle-income countries. Human Papilloma virus is the necessary cause for the development of cervical cancer and the majority of these infections resolves naturally but progress to precancerous lesions whenever there is persistence and delay in treatment. Majority of the cervical cancer cases, over 80% in sub-Saharan Africa including Ethiopia, have been detected at a late stage mainly due to poor early preventive measures. Therefore, utilization of early preventive measures could increase timely detection and treatment of precancerous changes and significantly reduce morbidity &amp; mortality due to advanced disease. Methods In this interventional study we will randomly assign 16 clusters (kebeles) in to the intervention and the control arm using block randomization. The study will employ a cluster randomized controlled trial. Women are eligible to participate in this study when they satisfy certain eligibility criteria; being in the age range of 30–49 years, no history of hysterectomy, did not receive cervical cancer or pre-cancer treatment and non-pregnant. Home based couple education and counseling will be provided to the eligible participants within the intervention group, while the control group receives standard of care. Base line and end line surveys will be completed by interviewing 288 eligible women to evaluate the effect of couple education and counseling on the knowledge, attitude and cervical cancer screening uptake. Generally the intervention lasts for six months. The results of baseline &amp; end line surveys will be compared between the groups to determine the effectiveness of the intervention. Blinding is not possible due to the clustering of the trial arms. Discussion Findings of the study will inform the regional or national scale up of the intervention modality to achieve the screening targets set by the Ethiopian government and world health organization. Trial registration PACTR, PACTR202108529472385. Registered on 05 August 2021, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=16037

Understanding no-show behaviour for cervical cancer screening appointments among hard-to-reach women in Bogotá, Colombia: A mixed-methods approach

The global burden of cervical cancer remains a concern and higher early mortality rates are associated with poverty and limited health education. However, screening programs continue to face implementation challenges, especially in developing country contexts. In this study, we use a mixed-methods approach to understand the reasons for no-show behaviour for cervical cancer screening appointments among hard-to-reach low-income women in Bogotá, Colombia. In the quantitative phase, individual attendance probabilities are predicted using administrative records from an outreach program (N = 23384) using both LASSO regression and Random Forest methods. In the qualitative phase, semi-structured interviews are analysed to understand patient perspectives (N = 60). Both inductive and deductive coding are used to identify first-order categories and content analysis is facilitated using the Framework method. Quantitative analysis shows that younger patients and those living in zones of poverty are more likely to miss their appointments. Likewise, appointments scheduled on Saturdays, during the school vacation periods or with lead times longer than 10 days have higher no-show risk. Qualitative data shows that patients find it hard to navigate the service delivery process, face barriers accessing the health system and hold negative beliefs about cervical cytology.

Awareness and knowledge associated to Human papillomavirus infection among university students in Morocco: A cross-sectional study

Worldwide, cervical cancer is a real health issue, however, gaps exist in the public’s awareness of the causal role of Human papillomavirus (HPV) in the development of this disease. This study aims to determine the level of awareness, knowledge and the associated factors on HPV among university students in Morocco. A cross-sectional study was conducted with a descriptive and analytical aim, among students attending Ibn Zohr University, in Agadir, Morocco. An interview questionnaire was used to collect information about the participants: demographic data, awareness and level of knowledge on HPV infection, and awareness of cervical cancer. Logistic regression analyses were used to determine the associated factors with awareness and level of knowledge on HPV. A total of 479 students participated in this study (mean age 21.82 ± 2.091). Most participants n = 391 (81.6%) were aware of cervical cancer, while only n = 7 (1.5%) identified HPV as a sexually transmitted infection. Among students, 10.0% (n = 48) were aware of HPV but only half of them n = 23 (47.9%) confirmed that HPV is associated with cervical cancer, and n = 29 (60.4%) showed low knowledge on HPV. Multivariate analysis revealed that HPV awareness has a strong association with a higher level of education (OR 4.04; 95% CI: 1.92–8.52), and with being a biology student (OR 5.20; 95% CI: 2.12–12.73), while high HPV knowledge was only associated with the female gender (OR 3.76; 95% CI: 1.01–13.92). The data suggest that university students in Morocco did not show sufficient knowledge of HPV infection and its consequences. This supports that earlier incorporation of sexual health education programs, especially related to HPV and cervical cancer, must be implemented in the university to reduce the burden of HPV-associated diseases among the population at risk.

Comparison of Seegene Anyplex II HPV28 assay with BD Onclarity HPV assay for human papillomavirus genotyping

Presently, human papillomavirus (HPV)-based cervical cancer screening is commonly used and is replacing conventional cytology screening tests. The HPV genotyping assay is useful for triage in cervical cancer screening and the evaluation of HPV vaccination effects. In this study, we evaluated the clinical performance of two HPV genotyping assays, BD Onclarity HPV (Onclarity) and Seegene Anyplex II HPV28 (Anyplex) in the detection of relevant cervical lesions and for HPV genotyping concordance. Anyplex and Onclarity assays were performed on 920 consecutive liquid-based specimens. Anyplex, sensitivity, specificity, and genotyping concordance with Onclarity were optimal when restricted to ≥2+ (medium) viral loads. HPV genotyping agreement between the two assays ranged between 0.75 and 0.9 (excellent), except for HPV 33/58, which was 0.73 (good). With Onclarity as a reference, the relative sensitivity of Anyplex for the detection of ≥CIN 2 was 1.05 (95% CI: 0.99–1.1) and the relative specificity for detection of negative for intraepithelial lesion and malignancy (NILM) was 0.89 (95% CI: 0.85–0.93). For most ≥CIN 2 lesions, high-risk HPV was detected by Onclarity (66/72) and Anyplex (69/72) assays. For high-risk HPV negative ≥CIN 2 lesions, possible high-risk HPV genotypes were detected by Anyplex. In conclusion, the genotyping agreement between the tests was good to excellent. Full genotyping with Anyplex might confer additional benefits to patients with ≥CIN 2, although the difference is small. We also suggest an optimal cutoff value when reporting HPV infections using the Anyplex assay (≥2+; medium viral loads).

Time to death from cervical cancer and predictors among cervical cancer patients in Felege Hiwot Comprehensive Specialized Hospital, North West Ethiopia: Facility-based retrospective follow-up study

Introduction A sexually transmitted virus called the Human Papillomavirus is responsible for more than 99% of cervical cancer cases and its precursors. In 2019, the median survival time of cervical cancer patients at 5 years was 37 months. The survival time and predictors of death from cervical cancer vary in different study settings. This study was aimed to assess the time to death and to identify the major predictors of death of cervical cancer patients in Felege Hiwot Comprehensive Specialized Hospital. Methods A facility-based retrospective follow-up study was conducted among 422 randomly selected cervical cancer patients in Felege Hiwot Comprehensive Specialized Hospital from 25th June 2017 to 31st March 2021. Data were extracted from the sampled patient charts by using a structured checklist which was prepared in an English version. Data were coded and then entered, edited, and cleaned using EPI-data 3.1 and exported to STATA14.2 statistical software for analysis. Frequencies and proportions were used to describe the study population with relevant variables and were presented using tables, pie charts, and graphs. Kaplan Meier and life table were used to describe the restricted mean survival time and the overall survival rates. Differences in survival among different variables were compared using the log-rank test. The assumption of proportional hazard was checked using Schoenfeld residual test. Variables having a P-value &gt; 0.05 were considered as fulfilling the assumption. Variables with a significance level below 0.2 in the bivariable Cox regression model were included in a multivariable Cox regression model analysis, where Variables with a p-value &lt; 0.05 were considered to be statistically significant at a 95% confidence interval. Model fitness was checked by Cox-Snell residual. Results The mean follow up time of this cohort was 27.66 (CI: 26.96, 28.36) months, and the restricted mean survival time of cervical cancer patients in this study was 40.21 (95% CI: 38.95, 41.47) months. Being FIGO stage IV [AHR = 6.10, 95% CI: 2.18, 16.90)], having adenocarcinoma [AHR = 3.12, 95% CI: 1.34, 7.28)], having co-morbidity [AHR = 2.57, 95% CI: 1.29, 5.11)], and being initiated with radiotherapy [AHR = 4.57, 95% CI: 1.60, 13.06)] were a significant predictors of death from cervical cancer. Conclusion The restricted mean survival time of cervical cancer patients in this study was 40.21 months. Marital status, type of tumor histology, stage of disease, type of treatment initiated, and presence of co-morbidity were significant predictors of death for cervical cancer. Treatment of comorbidities in the early stage of cervical cancer plays a key role in maximizing the survival time of cervical cancer patients.

Geographical risk pattern and temporal trends in incidence of HPV-related cancers in northern Thailand: A population-based study

Background The burden of HPV-related cancers in different regions worldwide varies according to several factors. This study aims to measure inequality in the risk of incidence of HPV-related cancers in term of geographical risk patterns in northern Thailand using a population-based cancer registry data. Methods Trends in age-standardized HPV-related cancer incidence were calculated for the 2008–2017 time period. The Besag-York-Molli´e model was used to explore the spatial distribution of the relative risk (RR) of HPV-related cancers at the district level. A higher RR reflects a larger disparity. The geographical risk pattern of the diseases in two periods, 2008–2012 and 2013–2017 were described and compared. Results From 2008 to 2017, the incidence of oropharyngeal and anal cancers showed a slightly increased trend in males but remained stable in females, the incidence of vulvar, vaginal and penile cancers were stable while the incidence of cervical cancer decreased. The RR range was closer to 1 in the second period compared to the first period. This suggests a decrease in the disparities of incidence of cervical cancer. However, in some areas near the Thai-Myanmar border, the RR values remained high. Conclusion The incidence rate of most HPV-related cancers remained low and stable over the study period in northern Thailand. For the most common HPV-related malignancy, cervical cancer, the incidence rate steadily decreased but with marked geographic disparities, possibly reflecting health inequity especially in the border areas.

Identification and validation of a prognostic signature related to hypoxic tumor microenvironment in cervical cancer

BackgroundHypoxia is a common microenvironment condition in most malignant tumors and has been shown to be associated with adverse outcomes of cervical cancer patients. In this study, we investigated the effects of hypoxia-related genes on tumor progress to characterize the tumor hypoxic microenvironment.MethodsWe retrieved a set of hypoxia-related genes from the Molecular Signatures Database and evaluated their prognostic value for cervical cancer. A hypoxia-based prognostic signature for cervical cancer was then developed and validated using tumor samples from two independent cohorts (TCGA-CESC and CGCI-HTMCP-CC cohorts). Finally, we validated the hypoxia prediction of ccHPS score in eight human cervical cancer cell lines treated with the hypoxic and normoxic conditions, and 286 tumor samples with hypoxic category (more or less) from Gene Expression Omnibus (GEO) database with accession GSE72723.ResultsA risk signature model containing nine hypoxia-related genes was developed and validated in cervical cancer. Further analysis showed that this risk model could be an independent prognosis factor of cervical cancer, which reflects the condition of the hypoxic tumor microenvironment and its remodeling of cell metabolism and tumor immunity. Furthermore, a nomogram integrating the novel risk model and lymphovascular invasion status was developed, accurately predicting the 1-, 3- and 5-year prognosis with AUC values of 0.928, 0.916 and 0.831, respectively. These findings provided a better understanding of the hypoxic tumor microenvironment in cervical cancer and insights into potential new therapeutic strategies in improving cancer therapy.

Knowledge, attitudes, and practices among Indonesian urban communities regarding HPV infection, cervical cancer, and HPV vaccination

Background Few studies explored Indonesian understanding of cervical cancer (CC) and the human papillomavirus (HPV) vaccination. We aimed to investigate the association between knowledge, attitudes, and practices (KAP) and socio-demographical influences related to HPV, CC, and vaccination among Indonesian urban citizens. Methods We conducted an online survey during March 2020-August 2021 using the Snowball sampling technique. The socio-demographic characteristic and KAP responses were collected via Google Forms from 400 respondents in Jakarta. The knowledge and attitudes were divided into HPV and CC (aspect 1) and HPV vaccination (aspect 2). Correlation between KAP scores was performed using Spearman’s test, and multiple logistic regression analyses were conducted to determine KAP predictors. Results Indonesian urban citizens in Jakarta were found to have poor knowledge in individual aspects of the inquiry but moderate knowledge overall, good attitude in inquiry both in each aspect and overall, and unsatisfying practices. Overall, in the general population, men, and women respectively: 50.8%, 32.4%, and 53.6% had good knowledge; 82.0%, 75.2%, and 84.4% expressed positive attitude; and 30.3%, 15.2%, and 35.6% applied favorable practice regarding questions inquired. Knowledge was weakly correlated towards attitude (ρ = 0.385) but moderately correlated with practice (ρ = 0.485); attitude was moderately correlated with practice (ρ = 0.577), all results: p&lt;0.001. Significant odds ratio (OR) for predictors to good knowledge were female sex (OR = 2.99), higher education (OR = 2.91), and higher mother’s education (OR = 2.15). Factors related to positive attitudes were higher mother’s education (OR = 4.13), younger age (OR = 1.86), and better results in the knowledge inquiries (OR = 2.96). Factors that suggested better practices were female sex (OR = 2.33), being employed (OR = 1.68), excellent knowledge scores (OR = 4.56), and positive attitudes expressions (OR = 8.05). Having done one vaccination dose and intention to receive vaccines were significantly influenced by good KAP. Conclusions KAP had inter-association to successful CC and HPV prevention programs, and socio-demographical characteristics are critical to influencing better KAP.

Sociodemographic correlates of cervix, breast and oral cancer screening among Indian women

Introduction Cervix, breast and oral cancers account for about one-third of all cancers in India which as a group is a major contributor to all non-communicable disease-related morbidity and mortality among women. Existing evidence suggests that early diagnosis plays a pivotal role in the prevention and intervention of these cancers, and many community-based early screening and awareness programs have been in place in developed countries. Currently, there is not enough research evidence regarding the sociodemographic correlates of cervix, breast and oral cancer screening among Indian women. In the present study, we aimed to assess the self-reported percentage and sociodemographic factors associated with the use of these three types of cancer screening services among Indian women aged 15–49 years. Methods Data were collected from National Family Health Survey conducted during 2015–16. Sample population was 699,686 women aged 15–49 years. Associations between self-reported cervical, breast and oral cancer screening status and the associated sociodemographic factors were analyzed using multivariable logistic regression methods. Results The percentage of screening for cervical (21%), breast (8.95%), and oral cancers (13.45%) varied significantly across the population sub-groups. Higher age, urban residence, higher education, having employment, health insurance, use of electronic media, higher household wealth quintile, having healthcare autonomy, showed a positive effect on taking screening services. Further analyses revealed that the strength of the associations varied considerably between urban and rural residents, denoting the need for region-specific intervention strategies. Sex of household head, age, watching TV, using radio, and having health insurance were the most significant contributors to the outcome effects. Conclusions The present study provides important insights regarding the current scenario of seeking cancer screening services among women in India. These findings could inform policy analysis and make an avenue for further in-depth analysis for future studies. Our findings conclude that cancer prevention policies should focus on leveraging the positive effects of better socioeconomic status, employment, health insurance ownership, exposure to electronic media, and better healthcare autonomy to improve the cancer screening service uptake among Indian women.

Addition of digital VIA/VILI to conventional naked-eye examination for triage of HPV-positive women: A study conducted in a low-resource setting

Background World Health Organization guidelines for cervical cancer screening recommend HPV testing followed by visual inspection with acetic acid (VIA) for triage if HPV positive. In order to improve visual assessment and identification of cervical intraepithelial neoplasia grade 2 and worse (CIN2+), providers may use visual aids such as digital cameras. Objectives To determine whether combined examination by naked-eye and digital VIA (D-VIA) and VILI (D-VILI) improves detection of CIN2+ as compared to the conventional evaluation. Materials and methods Women (30–49 years) living in Dschang (West Cameroon) were prospectively invited to a cervical cancer screening campaign. Primary HPV-based screening was followed by VIA/VILI and D-VIA/VILI if HPV-positive. Health care providers independently defined diagnosis (pathological or non-pathological) based on naked-eye VIA/VILI and D-VIA/VILI. Decision to treat was based on combined examination (VIA/VILI and D-VIA/VILI). Cervical biopsy and endocervical curettage were performed in all HPV-positive participants and considered as reference standard. Diagnostic performance of individual and combined naked-eye VIA/VILI and D-VIA/VILI was evaluated. A sample size of 1,500 women was calculated assuming a prevalence of 20% HPV positivity and 10% CIN2+ in HPV-positive women. Results Due to the COVID-19 pandemic, the study had to terminate prematurely. A total of 1,081 women with a median age of 40 (IQR 35.5–45) were recruited. HPV positivity was 17.4% (n = 188) and 26 (14.4%) had CIN2+. Naked-eye VIA and D-VIA sensitivities were 80.8% (95% CI 60.6–93.4) and 92.0% (95% CI 74.0–99.0), and specificities were 31.2% (95% CI 24–39.1) and 31.6% (95% CI 24.4–39.6), respectively. The combination of both methods yielded a sensitivity of 92.3% (95% CI 74.9–99.1) and specificity of 23.2% (95% CI 16.8–30.7). A trend towards improved sensitivity was observed, but did not reach statistical significance. Conclusion Addition of D-VIA/VILI to conventional naked-eye examination may be associated with improved CIN2+ identification. Further studies including a larger sample size are needed to confirm these results.

Prevalence and determinants of late-stage presentation among cervical cancer patients, a systematic review and meta-analysis

Background An estimated 570,000 women were diagnosed with cervical cancer worldwide, and about 311,000 women died from the disease. Cervical cancer is possibly the most curable human cancer; if detected at the precancerous stage. Additionally, early diagnosis and management other factors are essential to decrease mortality rate among those patients. So this review was aimed to identify the prevalence and determinants of late-stage presentation among cervical cancer patients. Methods A systematic search had carried out on PubMed, EMBASE, MEDLINE, Cochrane, Scopus, Web of Science CINAHL, and manually on Google Scholar. This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The modified Newcastle-Ottawa Scale (NOS) was used to assess the quality of each study. A meta-analysis was done using a random-effects method using the STATA™ Version 14 software. Result Twenty-five studies from 3 world regions with 53,233 participants were enrolled in this meta-analysis. The overall estimated global pooled prevalence of late-stage presentation among cervical cancer patients with a random-effects model was 60.66% (95% CI: 56.27, 65.06). The subgroup analysis revealed that the prevalence of late-stage presentation was 62.60% in Africa, 69.30% in Asia, 46.51% in Europe, and 50.16% in North America. Educational status (p = 0.031) and place of residence (p = 0.004) are determinants of late-stage presentation. Conclusion The results of this meta-analysis indicated that the prevalence of late-stage presentation of cervical cancer is substantially high. Place of residence and educational status were significantly associated with late-stage presentation. Health care organizations should work on early screening, management, and on increasing community awareness to minimize late stage at presentation among those patients.

Fused toes homolog, a potential molecular regulator of human papillomavirus type 16 E6 and E7 oncoproteins in cervical cancer

Human papillomavirus type 16 (HPV16) plays a major role in the development of cervical cancer. The oncogenic potential of HPV16 is attributed to E6 and E7 oncoproteins. Here, we investigated the relationship between fused toes homolog (FTS) and HPV16 E6 and E7 in cervical cancer cells. HPV16-positive CaSki and SiHa cell lines were used for in vitro studies. FTS silencing was performed using a small interfering RNA (siRNA)-based approach, and western blotting was performed to determine the protein expression of tumor suppressors and cell survival markers. Immunoprecipitation, immunofluorescence, in silico analysis, and immunohistochemistry were performed to determine the interaction between, and intracellular co-localization of, FTS and both the E6 and E7 proteins. Silencing of FTS reduced the expression of the E6 and E7 proteins in cervical cancer cell lines and conversely increased the expression of the tumor suppressor proteins p53 and retinoblastoma protein. However, the primary transcripts of HPV16 E6 and E7 were unaffected by FTS silencing; furthermore, FTS transcription was unaffected by silencing of either E6 or E7, suggesting their interaction occurs post-translationally. Immunofluorescence and immunohistochemistry analysis demonstrated co-localization of FTS with the HPV16 E6 and E7 proteins, while immunoprecipitation results suggested that FTS interacts with both E6 and E7. Furthermore, in silico structural analysis identified putative residues involved in the binding of FTS with E6 and E7. Taken together, these results show that FTS affects both HPV16 E6 and E7 oncogenes in cervical cancer. We propose FTS as a target for the prevention of cervical cancer development and progression.

Determination of human papillomavirus type in archival tissue specimens of invasive cervical cancer using molecular mapping and E6/E7-based polymerase chain reaction

In our previous study, an L1-based human papillomavirus (HPV) test using liquid-based cytology revealed that some invasive cervical cancers (ICC) exhibited multiple HPV types or harbored no HPV DNA. Here, molecular mapping of formalin-fixed paraffin-embedded cancer tissue specimens from the same patients were conducted to confirm these observations. Among 377 ICC cases, 73 eligible specimens (9 positive for multiple HPV types, 16 negative for HPV, and 48 positive for a single HPV type from the previous study) were reexamined by manual microdissection of cancer lesions, then subjected to HPV genotyping using the uniplex E6/E7 polymerase-chain-reaction method to detect all high-risk and potentially high-risk HPV types. The HPV typing results were confirmed in 52 of 73 cancer cases; among the 21 remaining cases, 15 were discordant and 6 were partially concordant. In total, 8 of 16 (50%) HPV-negative samples became positive; 6 were positive for HPV16 and 2 were positive for HPV67. Moreover, two samples previously positive for HPV6 and HPV53 were negative for HPV. All nine cancers with multiple HPV types were found to harbor only a single HPV type. In total, 63 cancer tissues exhibited a single HPV type. HPV16 and HPV18 were detected in squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Alpha-5 (HPV82), -6 (HPV56), and -9 (HPV31/52/67) HPV types were detected in SCC, whereas Alpha-7 (HPV59/68) types were detected in ADC and adenosquamous carcinoma (ADSCC). These findings suggested that the different HPV types induced different histological cancers. Furthermore, all SCCs and 10 of 11 usual-type ADCs were positive for high-risk HPV types, supporting the use of HPV screening for the detection of these cancers and associated premalignant lesions. HPV16 is likely to remain undetected in some cervical cancer tissues because of low viral-copy-numbers. Putative high-risk HPV types (e.g., HPV67 and HPV82) might be high risk in Japan.

Clinical outcome of FIGO 2018 stage IB3/IIA2 cervical cancer treated by neoadjuvant chemotherapy followed by radical surgery due to lack of radiotherapy equipment: A retrospective comparison with concurrent chemoradiotherapy

This study aimed to assess neoadjuvant chemotherapy’s clinical outcomes such as efficacy, toxicity, and survival outcomes followed by radical hysterectomy ((NACT-RS) among women with cervical cancer stage IB3 and IIA2, by comparing concurrent chemoradiotherapy (CCRT) and NACT-RS. The study retrospectively reviewed patients with (2018 FIGO) stage IB3 and IIA2 cervical cancer who received preoperative neoadjuvant chemotherapy followed by NACT-RS or concurrent chemoradiotherapy (CCRT). The outcome measures were the 5-year survival and complication rates between the two groups. The median follow-up was 75 months. In total, 218 patients had stage IIA2, 136 patients had stage IB3, 201 patients received CCRT, and 153 patients received preoperative NACT-RS. In the CCRT group, the incidence of early complications (myelosuppression, gastrointestinal and urinary) was higher compared with that in the NACT-RS group (76.1 vs. 26.1%; p &lt; 0.001, respectively). There was no significant difference between the two study groups concerning late complications. Five-year PFS was 79.9% and 85.5% in the NACT-RS and CCRT groups, respectively (p = 0.093). Five-year OS was 86.9% and 85.5% in the NACT-RS and CCRT groups, respectively (p = 0.97). In the multivariate clinicopathologic characteristics analysis for OS, initial tumor size &gt; 4.3 cm (HR 5.11; p &lt; 0.001), AC/ASC (HR 1.89; p = 0.02), histologic grade 2–3 (HR 2.25; p = 0.04), and 2018 FIGO stage IIA2 (HR 8.67; p &lt; 0.001) were independent risk factors. The survival of patients with stage IB3 and IIA2 cervical cancer treated with NACT-RS was similar to that of patients treated with CCRT without increasing side effects.

High human papillomavirus (HPV)-35 prevalence among South African women with cervical intraepithelial neoplasia warrants attention

Human papillomavirus (HPV) prevalence and genotype distribution data is important for HPV vaccine monitoring. This study investigated the prevalence and distribution of HPV genotypes in cervical lesions of unvaccinated women referred to Nelson Mandela Academic Hospital Gynaecology Department due to different abnormal cervical conditions. A total of 459 women referred to the Nelson Mandela Academic Hospital Gynaecology department were recruited. When the cervical biopsy was collected for histopathology, an adjacent biopsy was provided for HPV detection. Roche Linear Array HPV genotyping assay that detects 37 HPV genotypes was used to detect HPV infection in cervical biopsies. HPV infection was detected in 84.2% (383/455) of participants. The six most dominant HPV types were HPV-16 (34.7%), followed by HPV-35 (17.4%), HPV-58 (12.1%), HPV-45 (11.6%), HPV-18 (11.4%) and HPV-52 (9.7%). HPV-35 was the third most dominant type among women with cervical intraepithelial lesion (CIN)-2 (12.6%; single infection: 5.7% and multiple infection: 6.9%), the second most dominant type among women with CIN3 (22.2%; single infection: 8.0% and multiple infection: 14.2%); and the fourth most dominant type among women with cervical cancer (12.5%; single infection: 7.1% and multiple infection: 5.4%). A proportion of 41.1% (187/455) was positive for HPV types targeted by the Cervarix®, 42.4% (193/455) by Gardasil®4, and 66.6% (303/455) by Gardasil®9. There was a statistically significant increase when the prevalence of women infected with HPV-35 only or with other HPV types other than Gardasil®9 types was included to those infected with Gardasil®9 HPV types (66.6%, 303/455 increase to 76.0%, 346/455, p = 0.002). High HPV-35 prevalence in this population, especially among women with CIN3 warrants attention since it is not included in current commercially available HPV vaccines.

Phytoconstituents of traditional Himalayan Herbs as potential inhibitors of Human Papillomavirus (HPV-18) for cervical cancer treatment: An In silico Approach

Human papillomavirus (HPV) induced cervical cancer is becoming a major cause of mortality in women. The present research aimed to identify the natural inhibitors of HPV-18 E1 protein (1R9W) from Himalayan herbs with lesser toxicity and higher potency. In this study, one hundred nineteen phytoconstituents of twenty important traditional medicinal plants of Northwest Himalayas were selected for molecular docking with the target protein 1R9W of HPV-18 E1 Molecular docking was performed by AutoDock vina software. ADME/T screening of the bioactive phytoconstituents was done by SwissADME, admetSAR, and Protox II. A couple of best protein-ligand complexes were selected for 100 ns MD simulation. Molecular docking results revealed that among all the selected phytoconstituents only thirty-five phytoconstituents showed the binding affinity similar or more than the standard anti-cancer drugs viz. imiquimod (-6.1 kJ/mol) and podofilox (-6.9 kJ/mol). Among all the selected thirty-five phytoconstituents, eriodictyol-7-glucuronide, stigmasterol, clicoemodin and thalirugidine showed the best interactions with a docking score of -9.1, -8.7, -8.4, and -8.4 kJ/mol. Based on the ADME screening, only two phytoconstituents namely stigmasterol and clicoemodin selected as the best inhibitor of HPV protein. MD simulation study also revealed that stigmasterol and clicoemodin were stable inside the binding pocket of 1R9W, Stigmasterol and clicoemodin can be used as a potential investigational drug to cure HPV infections.

Cervical cancer screening programme attendance and compliance predictors regarding Colombia’s Amazon region

Background Cervical cancer (CC) promotion and prevention (P&amp;P) programmes’ challenge lies in guaranteeing that follow-up strategies have a real impact on reducing CC-related mortality rates. CC P&amp;P programme compliance and coverage rates are relevant indicators for evaluating their success and good performance; however, such indicators’ frequency rates are considerably lower among women living in rural and border areas. This study was aimed at identifying factors associated with CC screening programme attendance for women living in Colombia’s Amazon region. Methods This study (qualitative and quantitative phases) was carried out between September 2015 and November 2016; women residing in the border towns of Leticia and Puerto Nariño participated in it. The first phase (qualitative) involved interviews and focus group discussions; this led to establishing factors related to CC P&amp;P programme attendance which were used in the quantitative phase for designing a survey for determining the strength of association in a logistic regression model. The terms attendance and compliance were considered to apply to women who had followed the 1–1–3 scheme throughout their lives, i.e. a cytology examination every 3 years after receiving two consecutive negative annual cytology results. Results Inclusion criteria were met by 309 women (≥18-year-olds having an active sexual life, having resided in the target community for at least one year); 15.2% had suitable P&amp;P programme follow-up. Screening programme attendance was positively associated with first intercourse after becoming 20 years-old (aOR: 3.87; 1.03–9.50 95%CI; p = 0.045), frequent contraceptive use (aOR: 3.11; 1.16–8.33 95%CI; p = 0.023), awareness of the age to participate in P&amp;P programmes (aOR: 2.69; 1.08–6.68 95%CI; p = 0.032), awareness of cytology’s usefulness in identifying cervical abnormalities (aOR: 2.43; 1.02–5.77 95%CI; p = 0.043) and considering cytology important (aOR: 2.64; 1.12–6.19 95%CI; p = 0.025). Women living in rural areas had a lower probability (aOR 0.43: 0.24–0.79 95%CI; p = 0.006) of adhering to CC P&amp;P programmes. Conclusions This study’s findings suggested the need for including novel strategies in screening programmes which will promote CC P&amp;P activities going beyond hospital outpatient attendance to reach the most remote or widely scattered communities, having the same guarantees regarding access, opportunity and quality. Including education-related activities and stimulating the population’s awareness regarding knowledge about CC prevention could be one of the main tools for furthering the impact of attendance at and compliance with P&amp;P programmes.

Association of HIV status and treatment characteristics with VIA screening outcomes in Malawi: A retrospective analysis

BackgroundAlthough evidence from high-resource settings indicates that women with HIV are at higher risk of acquiring high-risk HPV and developing cervical cancer, data from cervical cancer “screen and treat” programs using visual inspection with acetic acid (VIA) in lower-income countries have found mixed evidence about the association between HIV status and screening outcomes. Moreover, there is limited evidence regarding the effect of HIV-related characteristics (e.g., viral suppression, treatment factors) on screening outcomes in these high HIV burden settings.MethodsThis study aimed to evaluate the relationship between HIV status, HIV treatment, and viral suppression with cervical cancer screening outcomes. Data from a “screen and treat” program based at a large, free antiretroviral therapy (ART) clinic in Lilongwe, Malawi was retrospectively analyzed to determine rates of abnormal VIA results and suspected cancer, and coverage of same-day treatment. Multivariate logistic regression assessed associations between screening outcomes and HIV status, and among women living with HIV, viremia, ART treatment duration and BMI.ResultsOf 1405 women receiving first-time VIA screening between 2017–2019, 13 (0.9%) had suspected cancer and 68 (4.8%) had pre-cancerous lesions, of whom 50 (73.5%) received same-day lesion treatment. There was no significant association found between HIV status and screening outcomes. Among HIV+ women, abnormal VIA was positively associated with viral load ≥ 1000 copies/mL (aOR 3.02, 95% CI: 1.22, 7.49) and negatively associated with ART treatment duration (aOR 0.88 per additional year, 95% CI: 0.80, 0.98).ConclusionIn this population of women living with HIV with high rates of ART coverage and viral suppression, HIV status was not significantly associated with abnormal cervical cancer screening results. We hypothesize that ART treatment and viral suppression may mitigate the elevated risk of cervical cancer for women living with HIV, and we encourage further study on this relationship in high HIV burden settings.

Global cervical cancer research: A scientometric density equalizing mapping and socioeconomic analysis

Cervical cancer has caused substantial morbidity and mortality for millions of women over the past decades. While enormous progress has been made in diagnosis, prevention and therapy, the disease is still fatal for many women—especially in low-income countries. Since no detailed studies are available on the worldwide research landscape, we here investigated the global scientific output related to this cancer type by an established protocol. The “New Quality and Quantity Indices in Science” platform assessed all relevant cervical cancer research published in the Web of Science since 1900. A detailed analysis was conducted including country-specific research productivity, indicators for scientific quality, and relation of research activity to socioeconomic and epidemiologic figures. Visualization of data was generated by the use of density equalizing map projections. Our approach identified 22,185 articles specifically related to cervical cancer. From a global viewpoint, the United States of America was the dominating country in absolute numbers, being followed by China and Japan. By contrast, the European countries Sweden, Austria, and Norway were positioned first when the research activity was related to the population number. When the scientific productivity was related to annual cervical cancer cases, Scandinavian countries (Finland #1, Sweden #4, Norway #5, Denmark #7), the Alpine countries Austria (#2) and Switzerland (#6), and the Netherlands (#3) were leading the field. Density equalizing mapping visualized that large parts of Africa and South America were almost invisible regarding the global participation in cervical cancer research. Our data documented that worldwide cervical cancer research activity is continuously increasing but is imbalanced from a global viewpoint. Also, the study indicated that global and public health aspects should be strengthened in cervical carcinoma research in order to empower more countries to take part in international research activities.

Communities’ perceptions towards cervical cancer and its screening in Wolaita zone, southern Ethiopia: A qualitative study

Background Cervical cancer is a malignant neoplasm from cells originating in the cervix uteri. Any woman who is sexually active is at risk of getting HPV. Women in sub-Saharan Africa region have higher chance of developing the disease. There are nearly 26 million Ethiopian women who are over the age of 15 and believed to be at risk of getting HPV. Regrettably, Ethiopian women typically present for cervical cancer care at a late stage in the disease, where treatment is most ineffective. Objectives To explore communities’ perceptions of cervical cancer and screening among women in Wolaita zone, southern Ethiopia. Methods A qualitative research using focused group discussions and in-depth interviews was used to explore communities’ perceptions of cervical cancer and screening among women in Wolaita zone, southern Ethiopia from March 2018-November 2019. The study participants were men, women and communities who were residents of the study settings and were not health professionals. All focused group discussions (FGDs) and key informant interviews were transcribed and entered into Microsoft Word and thematic content analysis was done. Results A total of fifty-nine participants participated in both FGD (three with men and six with women) and in-depth interviews (IDIs). Most participants have not heard about cervical cancer but know cancer in general. Participants mentioned that the disease usually relates to many births and unprotected sexual intercourse but none mentioned HPV infection. Most of the participants perceive that cervical cancer is incurable and assume that it could be prevented but they think they are not vulnerable to the disease and screening is not necessary. Conclusion This study indicates that rural communities in the zone had limited knowledge about cervical cancer and even less about risk factors, screening, treatment and prevention. There is a great need for cancer education and prevention in Ethiopia.

The diagnostic value of core needle biopsy in cervical cancer: A retrospective analysis

Cervical carcinoma is a major cause of morbidity and mortality among women worldwide. Histological subtype, lymphovascular space invasion and tumor grade could have a prognostic and predictive value for patients’ outcome and the knowledge of these histologic characteristics may influence clinical decision making. However, studies evaluating the diagnostic value of various biopsy techniques regarding these parameters of cervical cancer are scarce. We reviewed 318 cases of cervical carcinoma with available pathology reports from preoperative core needle biopsy (CNB) assessment and from final postoperative evaluation of the hysterectomy specimen. Setting the postoperative comprehensive pathological evaluation as reference, we analysed CNB assessment of histological tumor characteristics. In addition, we performed multivariable logistic regression to identify factors influencing the accuracy in identifying LVSI and tumor grade. CNB was highly accurate in discriminating histological subtype. Sensitivity and specificity were 98.8% and 89% for squamous cell carcinoma, 92.9% and 96.6% for adenocarcinoma, 33.3% and 100% in adenosquamous carcinoma respectively. Neuroendocrine carcinoma was always recognized correctly. The accuracy of the prediction of LVSI was 61.9% and was positively influenced by tumor size in preoperative magnetic resonance imaging and negatively influenced by strong peritumoral inflammation. High tumor grade (G3) was diagnosed accurately in 73.9% of cases and was influenced by histological tumor type. In conclusion, CNB is an accurate sampling technique for histological classification of cervical cancer and represents a reasonable alternative to other biopsy techniques.

Publisher

Public Library of Science (PLoS)

ISSN

1932-6203