Journal

Asian Pacific Journal of Cancer Prevention

Papers (348)

Knowledge, Attitudes and Practices of Cervical Cancer Screening among Women Attending Gynecology Clinics at Tertiary Care Hospitals in the Capital City of Pakistan: A Cross-Sectional Survey

This study aimed to assess the current level of knowledge, attitudes, and perceptions regarding cervical cancer (CC) screening among women visiting gynecology clinics in tertiary care hospitals of Pakistan, and to identify preferred health promotion methods to enhance access to CC screening and vaccination services. A descriptive cross-sectional survey was conducted among women aged 21-55 years attending outpatient departments of obstetrics and gynecology. The study employed purposive sampling and utilized a pre-validated questionnaire. Data were analyzed using SPSS 21, with bivariate analysis and binary logistic regression to identify predictors of good knowledge. The survey involved 370 women, revealing profound gaps in knowledge about CC, with 84.7% demonstrating poor understanding. A significant association was found between education, occupation, income, and knowledge of CC. Furthermore, nearly all respondents expressed a desire for more information on CC and preventive measures, with electronic social media identified as the preferred awareness-raising channel. Encouragingly, 99.7% of women showed willingness towards receiving HPV vaccination if provided free or at low cost. The findings underscore a critical need for enhanced awareness and educational interventions to bridge the knowledge gap on CC screening and prevention among Pakistani women. Despite high willingness to engage in preventive practices, barriers such as lack of awareness, limited healthcare access, and socioeconomic factors hinder effective screening uptake. Advocacy and tailored health campaigns are crucial for mobilizing resources and political support to combat CC in Pakistan.

Effect of NQO1 Downregulation on the Migration and Invasion of HPV16-Positive Cervical Cancer Cells

This study aimed to identify upregulated genes in HPV16-positive cervical cancer cells and investigate the impact of downregulating NAD(P) H:quinone oxidoreductase 1 (NQO1) on the survival of these cells. Transcriptomic sequencing (RNA-seq) was utilized to pinpoint upregulated genes and associated cancer-related pathways in HPV16-positive cervical cancer cells, comparing them to HPV-negative cervical cancer cells. NQO1 gene knockdown was performed in HPV16-positive cervical cancer cell lines to assess its effect on cell survival, including parameters such as cell proliferation, migration, invasion, cell cycle progression, apoptosis, and the expression of key proteins in the PI3K/AKT pathway, p53, and RECK. Genes with a fold change ≥4.0 in HPV16-positive cervical cancer cell lines were predominantly localized to the extracellular region and plasma membrane. These genes were involved in protein binding and cell adhesion, influencing cellular responses to stimuli and tissue development. KEGG pathway analysis identified the most significant pathways, including metabolic pathways, cancer pathways, MAPK signaling, and PI3K-AKT signaling. Knockdown of NQO1 significantly decreased cell proliferation, migration, and invasion, while increasing apoptosis in HPV16-positive cervical cancer cells (p ≤ 0.01). Additionally, proteins associated with the PI3K-AKT pathway were downregulated, while p53 and RECK protein levels were elevated. Our findings suggest that NQO1 plays a crucial role in promoting migration and invasion in HPV16-positive cervical cancer cells, highlighting its potential as a therapeutic target.

A Prospective Randomized Trial to Compare Safety, Acceptability and Efficacy of Thermal Ablation and Cryotherapy in a Screen and Treat Setting

The prospective randomized study aimed to compare the safety, acceptability and efficacy of thermal ablation (TA) to that of cryotherapy in screen and treat setting. The participants were recruited prospectively in a community-based screening clinic in India. Women positive on visual inspection with acetic acid (VIA) test and/or Human Papillomavirus (HPV) test were assessed for eligibility for ablative treatment. Total 286 eligible women were randomized to receive either cryotherapy (N=150) or TA (N=136) performed by health workers. Colposcopy and cervical biopsy were performed on all, prior to treatment. Post-treatment follow-up was after one year with colposcopy and biopsy. Both the treatment methods had high acceptability. Significantly higher proportion of women treated by cryotherapy reported pain compared to women treated by TA, though intensity was mild in vast majority of them. Approximately 30% of women in both arms had histologic abnormalities, mainly CIN 1, and among those who attended follow-up 74.1% and 81.0% didn't have any CIN after cryotherapy and TA respectively. TA is as acceptable and safe as cryotherapy in screen and treat setting. TA has the logistic advantages for the low-resourced settings as the machines are more portable, do not require costly refrigerant gas and battery-driven models are available. The cure rates for CIN 1+ lesions in our study were comparable between cryotherapy and TA.

A Meta-Analysis for Association of XRCC3 rs861539, MTHFR rs1801133, IL-6 rs1800795, IL-12B rs3212227, TNF-α rs1800629, and TLR9 rs352140 Polymorphisms with Susceptibility to Cervical Carcinoma

In spite of substantial declines in both incidence and mortality rates in the past 50 years, cervical cancer remains one of the leading causes of cancer associated mortality among women globally. We performed this meta-analysis to explore the role of XRCC3 rs861539, MTHFR rs1801133, IL-6 rs1800795, IL-12B rs3212227, TNF-α rs1800629 and TLR9 rs352140 polymorphism with susceptibility to cervical carcinoma. The search databases include PubMed, SciELO, MedRxiv, Web of Science, Scopus, Cochrane Library, China National Knowledge Infrastructure, and China Biology Medicine disc up to 30 June 2021. The language is limited to English and Chinese. The comparison between the polymorphisms and cervical cancer was assessed using pooled odds ratio (OR) and 95% confidence interval (CI). The data are statistically analyzed by Comprehensive Meta-Analysis (CMA) 2.0 software. A total of 59 studies including seven studies with 1,112 cases and 1,233 controls on XRCC3 rs861539, 14 studies with 2,694 cases and 3349 controls MTHFR rs1801133, four studies with 1,121 cases and 1,109 controls on IL-12B rs3212227, seven studies with 1,452 cases and 2,186 controls on IL-6 rs1800795, 20 studies with 4,781 cases and 4909 controls on TNF-α rs1800629, and seven studies with 1743 cases and 2292 controls on TLR9 rs352140 were included. There was a significant association between XRCC3 RS861539, TNF-α rs1800629, and IL-6 rs1800795 polymorphisms and an increased risk of cervical carcinoma in overall population. However, the MTHFR rs1801133, IL-12B rs3212227 and TLR9 rs352140 polymorphisms were not associated. The pooled analysis showed that XRCC3 RS861539, TNF-α rs1800629, and IL-6 rs1800795 were associated with cervical carcinoma susceptibility, but not MTHFR rs1801133, IL-12B rs3212227 and TLR9 rs352140 polymorphisms.

Health Literacy, Knowledge on Cervical Cancer and Pap Smear and Its Influence on Pre-Marital Malay Muslim Women Attitude towards Pap Smear

Cervical cancer is preventable. In Malaysia, women are found to have good awareness of the disease and yet, the Pap smear uptake is still poor. Measuring health literacy level could explain this discrepancy. This study aims to determine the relationship between health literacy, level of knowledge of cervical cancer and Pap smear with attitude towards Pap smear among women attending pre-marital course. A cross sectional study was performed in three randomly selected centres that organised pre-marital courses. All Malay Muslim women participants aged 18 to 40 years old were recruited while non-Malaysian, illiterate, and had hysterectomy were excluded. Validated self-administered questionnaires used were European Health Literacy Questionnaire (HLS-EU-Q16 Malay) and Knowledge and attitude towards Cervical Cancer and Pap Smear Questionnaire. The mean percentage score (mean± SD) was calculated, with higher scores showed better outcomes. Multiple linear regression was used to measure the relationship of independent variables with attitude towards Pap smear. A total of 417 participants were recruited with a mean age of 24.9 ± 3.56 years old. Prevalence of awareness of cervical cancer was 91.6% (n=382, 95% CI: 89.0%, 94.2%) and mean percentage score was 74.7%±7.6. Prevalence of awareness of Pap smear was 59.0% (n=246, 95% CI: 54.2%, 63.8%) and mean percentage score was 80.2% ± 6.5. The health literacy mean score was 13.3±3.6, with minimum score 0 and maximum score 16. The mean percentage score of attitudes towards Pap smear was 64.8%±9.3. Multiple linear regression analysis demonstrated significant relationship between health literacy (p=0.047) and knowledge of Pap smear (p<0.001) with attitude towards Pap smear. A higher health literacy with high knowledge of Pap smear improves the attitude towards Pap smear. Pre-marital course is an opportunistic platform to disseminate information to improve health literacy and knowledge of cervical cancer and Pap smear screening.

Mismatch Repair Gene Deficiency in Ovarian Cancer: A Clinicopathological Analysis of MLH1, PMS2, MSH2, and MSH6 Mutations Across Histological Subtypes

Mismatch repair (MMR) deficiency is a prognostic biomarker in multiple malignancies, but its clinical significance in ovarian cancer (OC) remains poorly defined. This study investigates the prevalence of MMR gene defects (MLH1, PMS2, MSH2, MSH6) across OC histotypes and their clinicopathological associations. A retrospective cohort of 38 OC patients treated at Azerbaijan Medical University (2018-2023) underwent immunohistochemical (IHC) analysis of MMR protein expression. Clinicopathological data, including survival, recurrence, tumor characteristics, and biomarker status (Ki67, p53), were analyzed using SPSS v26.0. MMR deficiency was defined as loss of nuclear expression in ≥1 protein. MMR deficiency was identified in 5.2% of cases (2/38), restricted to endometrioid carcinomas (33.3% of endometrioid cases, 2/6). No deficiencies occurred in serous (n=27), clear cell (n=2), or mixed subtypes (n=3). Endometrioid tumors exhibited larger mean tumor size (13.7 ±5.2 cm vs. 10.0 ±3.7 cm in serous; p=0.01) and distinct Ki67/p53 expression patterns (p0.05). MMR deficiency in OC is histotype-dependent, occurring exclusively in endometrioid carcinomas. While not prognostic in this cohort, dMMR screening may guide surveillance for synchronous malignancies and identify candidates for immunotherapy. Multicenter studies with expanded cohorts are needed to validate clinical utility.

Impact of Olaparib, Niraparib, Rucaparib therapies on Newly Diagnosed and Relapsed Ovarian Cancer -Systematic Review and Meta-Analysis

This review aims to examine the effect of PARP inhibitors on PFS, OS, and adverse events in women with advanced ovarian cancer (OC). The PRISMA 2020 guidelines are followed while conducting this comprehensive review. Data from 17 randomized control trails (RCT) published between 2014 and June 2024 were included. These trials compared PARPi maintenance therapy to placebo women with newly diagnosed and recurrent advanced OC. The specific keywords were used to search relevant studies in databases including PubMed, SCOPUS, Cochrane library, and WoS. The main outcomes were the Progression free survival (PFS), overall survival (OS), or adverse events (AEs). The combined hazard ratios (HRs) and risk ratios (RRs) were determined, together with 95% confidence intervals (CIs). Each of the analyses were conducted using a model with random effects. Despite high heterogeneity, the meta-analysis found that poly (ADP-ribose) polymerase inhibitors (PARPi) maintenance therapy ominously improved PFS compared to placebo, with a combined HR of 1.33 (95% CI: 1.10-1.61) in newly diagnosed cases and 0.88 (95% CI: 0.59-1.30) in relapsed cases. However, the OS improvement was not significantly substantial, with a collective HR of 1.06 (95% CI: 0.99-1.13). AEs are considerably higher in the PARPi groups, notably hematologic toxicities including anaemia, thrombocytopenia, and neutropenia. However, these adverse effects may be controlled with dosage modifications, and therapy was discontinued only in few cases. PARPi are an effective therapy in both newly discovered and relapsed. Although there is a modest rise in the frequency of severe adverse reactions, they are usually handled well.

Association of P53 Codon 72 Polymorphism with Ovarian Cancer: An Institutional Study

Polymorphism of P53 gene has been explored worldwide to know the genetic predisposition of ovarian cancer, however.literature reports inconsistent association between codon 72 polymorphism and ovarian cancer risk.Several studies have reported a higher incidence of ovarian cancer associated with the Pro variant, while others found non-significant association. Present study has been conducted to investigate the association of codon 72 polymorphism of p53 gene with ovarian cancer risk in Asian population and to correlate them with clinicopathological characteristics of patients. The study was conducted on 60 ovarian cancer patients and  60 healthy women..Single-nucleotide polymorphism (SNP) G>C (Arg>Pro) transition at codon 72 of exon 4 (rs1042522) in the P53 gene Has been analysed.DNA was extracted by using the DNA Sure Blood Mini Kit (GeNei TM).The genetic polymorphism in P53 genes was assessed by Allele-specific polymerase chain reaction(ASO-PCR).X2,Fisher exact test and odds ratio[0R] at 95% confidence interval [CI]) were used for statistical analysis. The distribution of Arg/Arg, Arg/Pro and Pro/Pro genotype of codon 72 of theP53 gene was 30%,50%, and 20% in the ovarian cancer patients and 60%,31.6%, and 8.3%, respectively in healthy individuals. Increased frequency of Pro/Pro allele.  was associated with the risk of ovarian cancer as revealed by statistically significant values at p-0.003.(OR=4.8;95%CI 1.46-15.72). Patients who expressed P53 proline allele might be at higher risk of developing ovarian cancer as compared with those who expressed P53 Arg allele (p= 0.003).However small sample size is the limitation of present study.Analysis of bigger group of ovarian cancer patients may robust the genetic predisposition of P53 codon 72 in ovarian carcinogenesis. Genetic predisposition of proline allele of P53 gene in ovarian carcinoma might be explored as early diagnostic marker of ovarian cancer and to go ahead towards gene-targeted drug therapy for better clinical outcome as well as to reduce mortality.

Ovarian Tumors during Pregnancy and Adverse Pregnancy Outcome: A Retrospective Analysis

To determine the prevalence of ovarian tumor in pregnancy. A retrospective descriptive study was conducted using electronic data from Obstetrics and Gynecology Department at Bhumibol Adulyadej Hospital (BAH), Royal Thai Air Force, Thailand recorded between January 2012 and December 2022. The participants were patients diagnosed with ovarian tumors during pregnancy (OTP) within the study period. Demographic characteristics, histopathological findings, ultrasonography results and pregnancy outcomes were recorded. A total of 190 OTP cases were identified among 41,842 pregnant women. One hundred twenty-six OTP cases underwent surgery during pregnancy. The mean age of the participants was 29.6 years. The prevalence of ovarian tumors was 4.5(190/41,842) in 1000 pregnancies. Malignant ovarian tumors accounted for 0.14% (2/126). Histopathological analysis revealed that germ cell ovarian tumors and common epithelial ovarian tumors were found in 50.79% (64/126) and 49.2% (62/126) of cases, respectively. Most germ cell ovarian tumors were mature cystic teratomas, which were found in 98% (63/64) of cases. One-third (32/126) of the OTP cases underwent surgery during the second and early third trimesters. Fetal loss following surgery occurred in 18.75% (6/32) of cases. Adnexectomy performed with cesarean delivery and after vaginal delivery occurred in 93 and 1 cases, respectively. Symptomatic OTP leading to emergency surgery was observed in 6.84% (13/190) of cases. The prevalence of OTP was 4.5 per 1,000 pregnant women. Fetal loss during surgery in pregnancy occurred in 18.75%. Mature cystic teratoma was the common histopathological finding.

Prognostic Value of The Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Platelet Count for Platinum-Sensitive Recurrent Epithelial Ovarian Cancer

To study the prognostic value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and platelet count in patients with platinum-sensitive recurrent epithelial ovarian cancer (PS-ROC). This was a retrospective study on a database of platinum-sensitive recurrent epithelial ovarian cancer patients who received treatment at HRH Princess Maha Chakri Sirindhorn Medical Center (MSMC) between January 2010 and December 2020. The patients' demographic data, surgical factors, pathological factors, laboratory findings, and response to treatment were reviewed from the patients' medical records. Survival analysis was conducted using the Kaplan-Meier survival estimate and Cox regression model. In total, 56 patients were recruited in this study. The median overall survival (OS) and progression-free survival (PFS) were 33 (95%CI 23-43) and 11 (95%CI 8-16) months, respectively. Survival analysis showed a high PLR was associated with decreased OS compared with low value but no significant difference in PFS. High NLR was associated with poor OS and PFS. There was no association between the platelet count and survival outcome (OS and PFS). In the multivariable Cox regression analysis, the NLR, PLR, and platelet count were not significant prognostic factors for survival outcome. However, low hemoglobin and a decreased disease-free interval were significantly associated with poor PFS. A white blood cell count (WBC) ≥ 8,000 cells/mm3 was a poor prognostic factor for overall survival (Adjusted HR 7.64; 95%CI: 2.21-26.42; p-value = 0.001). The NLR, PLR, and platelet count were not associated with both the OS or PFS in patients with PS-ROC. However, the WBC level is an easy, readily available, and economical way to predict survival outcomes in PS-ROC patients and may help physicians to tailor therapeutic interventions in the future.

Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio as an Early Prognostic Marker in Patients with Ovarian Cancer: A Systematic Review and Meta-Analysis

Presently, ovarian cancer remains the leading cause of death in gynecological malignancies. The survival rate of these patients is low, which might be caused by early metastases and delayed diagnosis. Therefore, it is crucial to investigate novel practical markers that provide early prognostic value which helps construct individualized treatment. A thorough investigation of the neutrophil-lymphocyte ratio (NLR) and lymphocyte ratio (PLR) in ovarian cancer patients was conducted using article selection from PubMed, Cochrane, Science Direct, and Google Scholar databases. The outcomes and hazard ratio (HR) were obtained using Review Manager 5.4, and the 95% Confidence Interval (CI) result was calculated. The chief endpoints of interest in this study include overall survival (OS) and progression-free survival (PFS). Sixteen studies with 3,862 patients were included with a mean age of 50.6 years and a mean follow-up of 45.84 months. Multivariate studies demonstrated that a higher NLR is associated with worse PFS and OS, HR 1.35;95% CI [1.05-1.74] and HR 1.46; 95% CI [1.16-1.83] respectively. Similar results are observed with PLR and poorer PFS and OS, HR 1.62; 95% CI [1.09-2.43] and HR 1.66; 95% CI [1.12-2.46]. Pre-treatment PLR and NLR were found to be prognostic factors in determining PFS and OS in ovarian cancer. High values in pre-treatment PLR and NLR may indicate worse clinical outcomes.

Comparison of Tissue Mismatch Repair Protein Deficiency between Early- and Advanced-Stage Endometrial Cancer

ESGO/ESTRO/ESP guidelines recommend that DNA mismatch repair (MMR) proteins or microsatellite instability tests should be performed in all cases of endometrial cancer. This study aims to clarify the relationship of MMR protein deficiency (dMMR) between early and advanced stages of endometrial cancer. Secondary objective is to identify dMMR affecting factors in endometrial cancer. This cross-sectional study was conducted on endometrial cancer patients who underwent surgery at HRH Princess Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University, between May 2013 and April 2021. Patients with endometrial cancer whose tumor tissue was available for analysis were identified. The expression of MMR proteins was assessed by immunohistochemistry, including MLH1, MSH2, MSH6, and PMS2. Then, the pathological specimens were reviewed. A total of 207 patients with endometrial cancer were assessed for data analysis. MMR deficiency was observed in 92 cases (44.4%). We found patients with dMMR in both the early and advanced stages of endometrial cancer-68/155 cases (43.9%) and 24/52 cases (46.2%), respectively (P = 0.774).  Statistically significant differences were found only in myometrial invasion (adjusted prevalence odds ratio 2.35, 95% CI 1.21 to 4.57, P = 0.012). Our study showed no difference in tissue dMMR between early- and advanced-stage endometrial cancer. The dMMR was not associated with improved outcomes in patients with endometrial cancer. Even though ESGO/ESTRO/ESP guidelines recommend the performance of MMR IHC or MSI tests in all endometrial cancer cases, we can select the appropriate patients those categorized as "advanced stage" or "recurrent"-who may gain the most benefits from the immunotherapy modality of treatment.

Evaluation of the Cutoff Point and Diagnostic Value of the Neutrophil-to-Lymphocyte Ratio in Predicting Ovarian Cancer Compared to Pathological Findings

This research aims to establish a neutrophil-to-lymphocyte ratio (NLR) threshold and evaluate its diagnostic accuracy compared to pathological criteria for diagnosing Epithelial Ovarian Cancer (EOC). We conducted a cross-sectional study at Imam Hossein Hospital involving 204 women aged 18 and older with confirmed ovarian mass based on pathology. We recorded clinical, pathological, and preoperative blood count data, including neutrophil-to-lymphocyte ratio (NLR). Patients were categorized into malignant and benign ovarian mass groups based on postoperative pathology. The power of NLR to diagnosis of EOC was evaluated using ROC curve. At total, 204 patients (Benign 75.5% vs. Malignant 24.5%) were included in the analysis with mean age of 54.26 ±12.04 yrs in malignant and 46.31±13.21 in benign. In all cases, the proportion of patients with the following tumor markers HE4 (>140 Pm), CA 125 (> 35U/Ml) and CEA (>5 ng/Ml) were 52.45%, 41.67% and 3.43%, respectively, and proportion of abnormal tumor markers was statistically higher in malignant group compared to benign mass (p <0.05).  Odds of having higher NLR levels in the malignancy group was higher than benign group (e.g., OR of 4.45 for NLR in quartile 4 vs. quartile 1).  According to model selection criteria, the full model with including NLR level and age, BMI and tumor markers has best performance for diagnosis of malignancy (AUC =0.87). High NLR in combination with tumor markers including CA125, HE4 and CEA were associated with malignancy in patients with ovarian mass. More attention and further examinations should be devoted for patients with ovarian mass having high NLR and abnormal tumor markers levels to detect the probable malignancy as soon as possible.

Longitudinal Analysis of the Overall Survival Rates and Transitional Probabilities of Endometrial Cancer Patients: A Comprehensive Retrospective Study in Thailand

This investigation delineated the survival rates and transitional probability trends of patients with endometrial cancer. This information is pivotal for optimizing patient management and counseling strategies. We conducted a retrospective cohort analysis of patients diagnosed with stage I or II endometrial cancer between November 2006 and October 2012 and those diagnosed with stage III or IV endometrial cancer between January 2012 and May 2017 at Siriraj Hospital, Bangkok, Thailand. Our examination included baseline demographics, clinical characteristics, and adjuvant therapy data. Survival rates and transitional probabilities were assessed using the Kaplan-Meier method for survival curve construction and Markov models, respectively. After exclusions, 229 individuals with early-stage endometrial cancer and 119 with advanced-stage histologically verified endometrial cancer were included in the final cohort. Throughout a median follow-up duration of 12.8 years, the 5-year overall survival rates were 89.05% for the early-stage cohort and 50.42% for the advanced-stage cohort. The transitional probability analysis revealed an elevated likelihood of achieving a curative state in early-stage patients, contrasting with a greater propensity for disease progression or distant metastasis in advanced-stage patients. The findings from this study offer critical insights into the overall survival rates and transitional probabilities of endometrial cancer patients. These insights underscore the importance of strategies focused on preventing recurrence and enhancing treatment. Moreover, the results serve as a cornerstone for clinicians in devising individualized treatment plans and facilitating cost-effective analyses in the context of endometrial cancer care.

CD133, CD47, and PD-L1 Expression in Ovarian High-grade Serous Carcinoma and Its Association with Metastatic Disease: A Cross-sectional Study

Ovarian cancer is a primary cause of cancer-related death in women. At the time of diagnosis, the majority of ovarian malignancies had metastasized. It is believed that cancer stem cells (CSCs) and immune evasion play a crucial role in the metastatic process. The objective of this study was to describe the expression profiles of cluster of differentiation (CD)133, CD47, and programmed death ligand 1 (PD-L1) in high-grade serous ovarian cancer (HGSC) as commonly utilized markers for CSCs and immune evasion. Using an immunohistochemical procedure, 51 HGSC tissue samples were stained with anti-CD133, anti-CD47, and anti-PDL1 antibodies. The samples contained 31 HGSC with metastases and 20 HGSC absent metastases. The expression of CD133, CD47, and PD-L1 was compared between groups. Strong expression of CD133 and CD47 was seen in 52% and 66% of tissue samples, respectively. Twenty of the thirty-one patients with metastases had a significant level of CD133 expression, with a p-value of 0.039. CD47 expression was increased in 26 of 31 samples with metastatic disease. A 62.7 percent of samples were negative for PD-L1 expression, significantly inversely correlated with HGSC metastatic disease (p=0.023). Although there was no significant association between CD133, CD47, or PD-L1 expression and age, Tumor Infiltrating Lymphocytes demonstrated a significantly varied relationship. Our findings suggested that expression of CD133, CD47, and PD-L1 may have dynamically increased as the primary lesion progressed to the metastatic lesion, implying that these proteins may be involved in the progression of high-grade serous ovarian cancer from the primary to the metastatic stage.

The Prevalence of Depression and Anxiety in Women with Ovarian Cancer: An Updated Systematic Review and Meta-Analysis of Cross-Sectional Studies

The results of this study included the prevalence of anxiety and depression in women with ovarian cancer. A thorough search of numerous databases, including PubMed (Medline), Scopus, Web of Science, Embase, and PsycoInfo, was conducted to identify relevant cross-sectional studies published between July 2013 and October 2021. STATA 16 was used to analyses the data, and a random effects model was used to determine the pooled prevalence and a 95% confidence interval (95%CI). Of the 18 cross-sectional studies reviewed, 17 reported the prevalence of anxiety and 16 reported the prevalence of depression in patients with ovarian cancer. There was a moderate degree of heterogeneity between studies, as the pooled prevalence of depression was 27% (95%CI: 14%-41%; I2=69.44%). Similarly, there was a greater degree of heterogeneity in the pooled prevalence of anxiety, which was found to be 33% (95%CI: 21%-44%; I2=78.55%). The findings of this study show that, compared to the overall female population, ovarian cancer patients have much greater rates of sadness and anxiety. These results highlight the necessity for healthcare policymakers to prioritize the provision of resources and support for carrying out additional research, such as longitudinal studies or cohorts, to ascertain the efficacy of various treatments or interventions intended to lessen mental health disorders in women diagnosed with ovarian cancer. Healthcare practitioners can enhance the general wellbeing and quality of life for women with this disease by addressing the psychological components of care.

The Impact of Waiting Time-to-Surgery on Survival in Endometrial Cancer Patients

Endometrial cancer (EC) is the most common gynecological cancer in developed countries and a standard treatment of surgery should be performed as expediently as possible. Delay time to surgery and survival was debated. The aim of this investigation was to evaluate the effect of time-interval between diagnosis and surgery (TDS) in EC patients with regards to prognosis and mortality rates. This retrospective study was conducted between January 2009 and May 2021 at Bhumibol Adulyadej Hospital, Thailand. Subjects were EC cases who underwent primary surgery during the study period. Cases with partial treatment were disqualified from the study. Subjects who underwent surgery before and after 6 weeks were classified as early and delayed surgery groups. Baseline and clinical characteristics were collected and analyzed. During the study period, 419 EC cases were recruited. The mean age of participants was 56.8 years. Two-thirds (338/491) of subjects were menopausal. Endometrioid histology (406/491) was the most common histology subtype. Five years disease free survival (DFS) of early and delayed surgery groups were comparable at a percentage of 82.5 and 83.0, respectively. Among advanced stage and non-endometrioid EC cases, the delayed surgery group had significantly shorter DFS than the early group. Advanced stage, high grade and positive lympho-vascular space invasion (LVSI) were independent factors for poor DFS. Predictive factors for mortality were advanced stage and tumor recurrence. The TDS was not a prognostic factor for disease recurrence or overall mortality. Time to surgery equal to or more than 6 weeks gave worse prognosis for DFS among advanced stage or non-endometrioid histology EC.

PD-L1 Immunohistochemical Expression in Endometrial Carcinoma: Egyptian Cross-Sectional Study

Endometrial carcinoma (EC) is the most common cancer of the female genital tract. According to the recently evolved strategies of cancer immunotherapy, immune checkpoints inhibitors are one of the most crucial strategies. Programmed Death Ligand 1 (PD-L1) is an important immune checkpoint regulator. PD-L1 antibodies have shown efficacy in clinical trials of some malignancies. Some of these antibodies have been approved for clinical usage by the Food and Drug Administration (FDA). This retrospective study included a total of 100 ECs, collected from archived, formalin-fixed, paraffin-embedded tissue blocks of hysterectomy specimens of Egyptian females. The samples were immunohistochemically analyzed for PD-L1 expression (in both tumor cells; TCs and tumor infiltrating leucocytes; TILs) by a semiquantitative score (0 to 4), with cutoff points of (0: <1% of the cells, 1: 1% to 4%, 2: 5% to 9%, 3: 10% to 49%, and 4: ≥ 50%). Membranous staining only was considered positive. PD-L1 was highly expressed in ECs (67% TCs+ and 61% TILs+), with statistically significant relationships with age, lympho-vascular space invasion (LVSI) and TILs score (P = 0.006, 0.016 and <0.005 respectively).  However, no statistically significant relationships were detected between PD-L1 expression and the following parameters: histological type, histological grade, pathological stage (pT) or FIGO stage, myometrial, cervical, adnexal/serosal, parametrial involvements and nodal metastasis, as well as ESMO risk stratification system. Moreover, statistically significant relationships were achieved when correlating TILs score with tumor grade and LVSI (P = 0.034 and 0.012 respectively). Also, comparing endometrial hyperplasia (EH) PD-L1 and TCs PDL1 median scores achieved statistically significant relationship (P = 0.001). Our results concluded that PD-L1 expression was greater in both TCs and TILs in a subgroup of patients that have advanced age, LVSI and are TILs-rich, identifying them as potential candidates for anti-PD-1/PD-L1 immunotherapy.

Retrospective Analysis of All Types of Adjuvant Radiotherapy in Endometrial Cancer: Single-Center Experiences in a Middle-Income Country

We retrospectively analyzed the efficacy, focusing on overall survival (OS) and the patterns of failure, along with the toxicities of adjuvant radiotherapy (RT) in endometrial cancer patients. Two-hundred and nineteen patients with endometrial cancer patients who received adjuvant radiotherapy ± adjuvant chemotherapy (ACT) from January 2014 to December 2018 were investigated for overall survival (OS), local recurrence-free survival rate (LRFS), regional recurrence-free survival rate (RRFS), and distant metastasis-free survival rate (DMFS). Two-hundred and fourteen patients were evaluated. The numbers of VBT alone, EBRT plus VBT, and adjuvant chemotherapy (ACT) plus EBRT plus VBT were 65 (30.4%), 80 (37.4%), and 69 (32.2%) patients, respectively. Stage I (107 patients) was the most common followed by stage III (87 patients). With a median follow-up time of 67 months (IQR 56-78), the 5-year overall survival rates for VBT alone, EBRT plus VBT, and EBRT plus VBT plus ACT were 84.4%, 65%, and 57.4%, respectively. The most common severe (grade 3-4) acute toxicity was neutropenia (4.6%), followed by diarrhea (3.7%). Grade 3-4 late proctitis was found in only 1.9%. On multivariate analysis, advanced age (HR 6.15, p: 0.015), lymph node involvement (HR 6.66, p: 0.039), cervical involvement (HR 10.60, p: 0.029), and substantial LVSI (HR 21.46, p: 0.005) were associated with a higher risk of death. Advanced age (>65), substantial LVSI, lymph node involvement, and cervical stromal involvement were associated with poor overall survival. These findings here will help identifying high-risk patients and would make it possible to avoid unnecessary adjuvant treatment among patients with a good prognosis.

Dosimetric Comparison of Isodose Surface Volume and Total Reference Air Kerma (TRAK) based Volume in Cervical Cancer Brachytherapy

We aim to compare TRAK & TPS based isodose volumes in cervical cancer brachytherapy and assess the feasibility, accuracy and potential future implications of TRAK in this regard and as a newer emerging tool to assess treatment intensity in cervical cancer brachytherapy. one hundred patients with histologically proven squamous cell carcinoma of cervix uteri were assessed for brachytherapy (after completion of external radiation) and prospectively enrolled for the study. 60 Gy, 75 Gy, and 85 Gy isodose volumes were obtained from the TPS (VTPS) for 50, 25 & 25 patients with Manchester, Fletcher & interstitial implant respectively, receiving various fractionation schedules by Ir192 HDR remote after-loading system. Using the formula Vpred=4965(TRAK/dref)3/2+170(TRAK/dref)-1.5 the TRAK based isodose surface volumes (Vpred) were derived. Reference doses (dref) were calculated based on accumulated EBRT and brachytherapy doses. The two sets of volume were compared with respect to applicator type, standard, and optimised plan. Surrogate point A dose was also correlated. VTPS - Vpred were 5.24 ± 2.7%, all volumes being predicted within 10%. Correlation of TRAK vs VTPS60/ VTPS75/ VTPS85 showed R2 of 0.994, 0.987 and 0.971 respectively. There was no significant difference in predicted volumes with respect to applicator type. The surrogate point A showed mean volume and standard deviation of 7.44 ± 13.4%, 17.63 ± 16.38 and 3.5 ± 0.95 for Manchester optimised, Fletcher optimised and standard plans respectively. TRAK with point A (R2=0.5632), bladder (R2=0.2015) and rectal doses (R2=0.121) yielded no correlation. Volumes calculated by TRAK correlate with TPS obtained volumes significantly and the formula predicting isodose surface volumes within 10% accuracy for ICBT applications and not for pure interstitial implants. However, TRAK fails to correlate with surrogate point A, bladder and rectal doses hence has questionable utility as a marker for biological response & treatment intensity.

Mismatch Repair Protein Deficiency Does Not Affect Disease Free Survival in Type I Endometrial Carcinoma

This study aimed to analyze the correlation between the 3-year disease-free survival (DFS) and mismatch repair (MMR) protein levels in patients with type 1 endometrial carcinoma. Many studies have reported different results regarding the role of MMR in the prognosis of endometrial carcinoma; therefore, we aimed to identify this association in our hospital. This observational study employed a historical cohort design and included patients with type 1 endometrial carcinoma who underwent surgery at Dr. Soetomo Hospital between January 2017 and December 2019. Medical records and paraffin blocks meeting these criteria were obtained. MMR proteins (MLH1 and MSH2) were assessed using immunohistochemistry. A total of 46 patients with type 1 endometrial carcinoma were analyzed. We observed MMR deficiency (dMMR) in 12 patients (26.1%) and MMR proficiency (pMMR) in 34 patients (73.9%). Of the 12 patients with dMMR, nine cases (75%) were diagnosed as stage I and 7 (58.33%) as low grade. The 3-year DFS in patients with dMMR and pMMR was 83.3% and 67.6%, respectively (Hazard Ratio 2.31, 95% CI 0.5135-10.475, p=0.27). Higher stages had a 5.42 times increased risk of recurrence (95% CI 1.3378-21.9358, p=0.018). Higher histopathological grades were also associated with 8.65 times increased risk of recurrence (95% CI 2.5020-29.8738, p=0.001). Patients with dMMR had a better DFS compared to those with pMMR; however, the difference was not statistically significant. The tumor stage and histopathological grade were independent risk factors for recurrence.

Simplifying Mismatch Repair Deficiency Screening in Endometrial Adenocarcinoma: Immunohistochemistry with Two-Antibody Panel (PMS2 and MSH6)

Mismatch repair deficiency (dMMR) is a well-established characteristic of endometrial adenocarcinoma and is crucial in screening for Lynch syndrome, guiding adjuvant treatment decisions, and identifying candidates for immune checkpoint inhibitors. The traditional approach to dMMR screening involves a four-antibody panel, but a simplified two-antibody method utilizing PMS2 and MSH6 has shown promise. This study aims to compare the diagnostic performance of the simplified two-antibody method with the traditional four-antibody panel in endometrial cancer samples. We conducted a retrospective cohort study on endometrial carcinoma cases diagnosed between 2013 and 2022. We compared the diagnostic performance of the two-antibody panel with the traditional four-antibody panel in detecting dMMR. Clinical data and immunohistochemistry results were collected, and agreement between the two methods was evaluated using Cohen's kappa coefficient. 304 endometrial cancer cases were included, with 27% demonstrating loss of at least one MMR protein using the four-antibody panel. The two-antibody method detected MMR deficiency in 26.6% of cases, with a high agreement rate of 98.8% between the two methods. Only one case showed discordant results, prompting further investigation. The simplified two-antibody MMR IHC screening approach using PMS2 and MSH6 showed high concordance with the traditional four-antibody panel. This suggests its potential as an alternative method for reflex MMR status testing in endometrial adenocarcinoma. The implementation of this approach could streamline the diagnostic process, reduce costs, and improve the detection of Lynch syndrome in affected individuals and their families. Further studies with larger cohorts and long-term follow-up are needed to validate these findings and assess the clinical implications of this approach in routine practice.

Study on Preoperative Neutrophil/Lymphocyte (NLR) and Platelet/Lymphocyte Ratio (PLR) as a Predictive Factor in Endometrial Cancer

To evaluate predictive factors between serum inflammatory markers and malignancy potential of endometrium. This retrospective study was conducted at the gynecological oncology unit, department of obstetrics and gynecology, at the faculty of medicine of Thammasat University. The study period was from 2017 to 2020. Endometrial cancer and benign gynecologic disease cases who underwent hysterectomy (with or without adnexectomy) during the study period were recruited. Demographic characteristics, histopathology reports and serum markers were also collected. The study included a study group of 49 participants with endometrial cancer and a control group consisting of 119 cases of benign uterine disease. The study group had statistically significantly higher mean ages, proportional menopausal status and instances of underlying diseases when compared with the control group. Neutrophil/Lymphocyte ratios (NLR) and Platelet/Lymphocyte ratios (PLR) could not meaningfully predict the malignant potential of endometrium in hysterectomy specimens. NLR and PLR were statistically associated with depth of myometrial invasion (MI) in endometrial cancer cases. NLR equal to or greater than 1.93 predicted MI more than half thickness with sensitivity, specificity, accuracy, positive (PPV) and negative predictive value (NPV) at a percentage of 83.3, 52.8, 37.0, 90.5 and 60.4, respectively. PLR equal to or greater than 134.95 predicted MI of greater than fifty percent thickness with sensitivity, specificity, accuracy, PPV and NPV at 75.0, 55.6, 36.0, 87.0 and 60.4 percent, respectively. NLR and PLR have positive associations with myometrial invasion of endometrial cancer.

Immunohistochemical Expression of Programmed Death Ligand 1(PDL1) in Endometrial Carcinoma and Its Relation to CD4 and CD8 Positive Immune Cells

Endometrial cancer (EC) is the most common cancer of the female genital tract. Egypt showed a significant increase in incidence lately of which 25% were premenopausal. Advanced or recurrent disease are mostly unresectable and the traditional adjuvant therapy give modest results with devastating side effects. Late discoveries of immune checkpoint inhibitors have produced promising results. Programmed cell death 1 (PD1) is an immune inhibiting receptor on surface of lymphocytes, which plays critical roles in maintaining immunological self-tolerance. There are two ligands for this receptor, PDL1 and PDL2. PD-L1 is expressed on tumor cells; attaches to PD1, allowing tumor cells to escape from the host immune response. Its prognostic significance in various tumors is controversial and its significance in ECs has just begun to be investigated. Therefore, we investigated the relationship between PDL1 expression and different clinicopathologic parameters in EC cases and its correlation with CD4 and CD8 immune cells, in order to identify the predictive biomarkers for the outcome by immune therapy. Hundred, paraffin tissue blocks of EC cases were collected and stained with antibodies against PDL1,CD4 and CD8. PDL1 was positive in 67% of cases in tumor cells and in 61% of cases in immune cells. CD4 and CD8 were expressed in 79% of cases. Statistically significant correlations were observed between PDL1 expression and patients mean age, LVSI, TILS score and CD4+/CD8+ expression. Those variables can stratify candidates who can benefit most from immunotherapy, or can be chosen for further high cost molecular investigations application.

Human Papillomavirus (HPV) Vaccination and Cervical Cancer Prevention: Ghanaian Adolescent Students’ Perspectives Through Focus Group Discussion

The Human Papillomavirus (HPV) vaccine is effective in reducing HPV-related cancers. However, little is known about Ghanaian adolescents' attitudes toward HPV vaccination. We examined the perspectives of Ghanaian adolescent students on HPV vaccination. We conducted four focus group discussions with students from School A (n=15), School B (n=20), School C (n=10), and School D (n=14) in the Ashanti Region of Ghana. Ten open-ended questions guided the discussions. Two independent coders transcribed and analyzed the data thematically using NVivo software. Fifty-nine students (mean age: 14.97 years, SD = 1.55) participated. Thematic analysis revealed: (a) low knowledge of HPV and HPV vaccines, but strong general belief in vaccine benefits; (b) barriers such as fear of side effects (e.g., pain, death), misconceptions (e.g., infertility, "destroying the womb"), and vaccine cost; (c) facilitators including perceived vaccine effectiveness, social influences (parents, doctors, friends), school-based education, and altruistic motives; and (d) lack of adolescent-parent communication, though students expressed willingness to initiate conversations when informed. These insights highlight the socio-cultural and informational gaps that may impact vaccine uptake. Findings highlight the urgent need for culturally relevant, school-based HPV education programs in Ghana. Interventions should address common misconceptions, promote adolescent-parent communication, and leverage trusted influencers such as healthcare providers and teachers to improve HPV vaccine acceptance.

Effects of Gallic Acid on Endometrial Cancer Cells in Two and Three Dimensional Cell Culture Models

Cell culture studies are an indispensable tools used to understand basic physiological, biophysical and biomolecular mechanisms. Although traditional two-dimensional (2D) cell culture models are more preferred in experimental studies, three-dimensional (3D) cell culture models, attract more attention due to several advantages including mimicking tumor physiology, biochemistry and biomechanics. We aimed to investigate the effects of Gallic Acid, an antimutagenic, antioxidant and anticarcinogenic agent, on both 2D and 3D cultured endometrial cancer cells for the first time. IC50 values were determined in 2D and 3D cultured endometrial cancer cells exposed to different doses of GA. In the 2D culture model exposed to GA, Caspase 3 expression levels were analyzed. In addition, the effect of GA on the migration of 2D cultured endometrium cancer cells was investigated. IC50 value in the 3D model was found significantly higher than the 2D model. In 2D culture model, Caspase 3 expression and apoptosis was increased significantly in cells of GA exposed group compared to the control group. GA did not have a significant effect on the migration profile of cells. Gallic Acid is shown to induce apoptosis in Ishikawa cells via Caspase 3 activation. We demonstrated a significantly higher  IC50 level in 3D model which provide evidence to prefer 3D models in drug-test trials. The data obtained in the current study will provide a basis for further experiments to analyze the effects of GA on endometrial cancer and to develop strategies for clinical treatment.

Lynch Syndrome in Thai Endometrial Cancer Patients

Lynch syndrome increases lifetime risk of endometrial cancer to 40-60%. Screening with molecular tumor testing for mismatch repair (MMR) proteins have been recommended. This study aims to evaluate the incidence of MMR deficiency and germline mutation in endometrial cancer Thai patients. Immunohistochemistry for MMR proteins, including MLH1, MSH2, MSH6 and PMS2 were tested in 166 surgical specimens. Patients who had MMR deficiencies were offered genetic counseling and a germline testing using gene-panel next generation sequencing. Fifty-eight of 166 patients (34.9%) had one or more MMR deficiencies which were: MLH1 and PMS2 in 42 patients (25.3%), MSH2 and MSH6 in 11 patients (6.6%), and MSH6 in 5 patients (3.0%). Of the 40 patients (24.1%) who met the revised Bethesda guidelines, 19 patients (47.5%) had MMR deficiency. In contrast, MMR deficiency was found in 39 of the 126 patients (31.0%) who did not meet the revised Bethesda guidelines. A total of 27 patients with MMR deficiencies agreed to have germline genetic testing. Germline MMR mutations were detected in 5 patients (18.5%) including MSH6 (n=2), PMS2 (n=2), and MLH1 mutations (n=1). Incidental germline mutations in other genes were detected in 3 patients (1 BRCA1, 1 PTEN, and 1 BARD1). Among 5 Lynch syndrome patients, 2 patients (40%) did not meet the revised Bethesda guidelines. Eight patients who met the revised Bethesda Guidelines but having MMR proficiency had genetic testing, but no germline mutation was detected. MMR deficiencies were detected in 34.9% of the endometrial cancer patients. Germline mutations were diagnosed in 3.0% of this cohort (5/166 patients). Lynch syndrome screening with MMR immunohistochemistry should be considered in all patients regardless of personal or family history of Lynch syndrome-related cancers.

Curcumin-Galactomannoside Complex inhibits the Proliferation of Human Cervical Cancer Cells: Possible Role in Cell Cycle Arrest and Apoptosis

Cervical cancer is the most common cancer and has the highest morbidity rate of gynaecological malignancies in women worldwide. So, the development of effective anti-cancer agents to treat this condition is vital. Considering the recent interest in free (unconjugated) curcuminoids delivery, the present study investigated the efficacy of a novel food-grade, free-curcuminoids (curcumin-galactomannoside complex; CGM) on cervical cancer cells (HeLa) of human origin. In this study, we examined the anticancer potential of CGM as well as its effects on the cell cycle and the apoptosis of HeLa cancer cell. Determination of anti-proliferative and apoptosis validation of CGM on HeLa cells was performed by 3-(4,5-Dimethylthiazol-2-yl)-2, 5,-diphenyltetrazolium bromide (MTT), acridine orange/propidium iodide and annexin-V-fluorescein isothiocyanate assays. Measurement of Reactive Oxygen Species (ROS) production, Caspase activities and protein expression experiments were performed to investigate the potential mechanisms of action in the apoptotic process. The cytotoxic assays revealed that the CGM showed inhibition of cell survival and exhibited high cytotoxic activity against HeLa cells at 25 μg/mL. Further studies on morphological changes were done in CGM-treated cervical cancer cells contributing to apoptosis. Flow cytometry analysis with Annexin V-FITC and PI staining precisely indicated that CGM induced apoptosis in HeLa cell lines at 25 μg/mL. By the supplementation of CGM showed an increase in Bax and cleaved caspase-8 protein in HeLa cells after 48 h exposure. The evidence obtained from this study suggests that CGM is a potent and promising natural formulation against cervical cancer cells via induction of apoptosis through ROS mediated mitochondrial damage in HeLa cells. Hence, CGM could be further explored as a potential lead in treating cancer..

Evaluation of Twenty Genes in Prognosis of Patients with Ovarian Cancer Using Four Different Clustering Methods

Comparison of gene expression algorithms may be beneficial for obtaining disease pattern or grouping patients based on the gene expression profile. The current study aimed to investigate whether the knowledge within these data is able to group the ovarian cancer patients with similar disease pattern. Four different clustering methods were applied on 20 genes expression data of 37 women with ovarian cancer. All selected genes in this study had prominent roles in the control of the activity of the immune system, as well as the chemotaxis, angiogenesis, apoptosis, and etc. Comparison of different clustering methods such as K-means, Hierarchical, Density-Based Spatial Clustering of Applications with Noise (DBSCAN) and Expectation-Maximization (EM) algorithm was the other aim of the present study. In addition, the percentage of correct prediction, Robustness-Performance Trade-off (RPT), and Silhouette criteria were used to evaluate the performance of clustering methods. Six out of 20 genes (IFN-γ, Foxp3, IL-4, BCL-2, Oct4 and survivin) selected by the Laplacian score showed key roles in the development of ovarian cancer and their prognostic values were clinically and statistically confirmed. The results indicated proper capability of the expression pattern of these genes in grouping the patients with similar prognosis, i.e. patients alive after 5 years or dead (62.12%). The results revealed the better performance for k-means and hierarchical clustering methods, and confirmed the fact that by using the expression profile of these genes, patients with similar behavior can be grouped in the same cluster with acceptable accuracy level. Certainly, the useful information from these data may contribute to the prediction of prognosis in ovarian cancer patients along with other features of patients..

Impact of Esomeprazole, Ciprofloxacin and Their Combination on Cervical Cancer Cell Line Proliferation: A Focus on Heat Shock Protein 70 Modulation

This investigation aimed to evaluate the combined efficacy of ciprofloxacin and esomeprazole in inhibiting cervical cancer proliferation and their capacity to target heat shock protein 70 in vitro. The MTT assay was utilized to assess the anticancer properties of the ciprofloxacin-esomeprazole combination on the HeLa cervical cancer cell line. The human fibroblast cell line (HFF) is employed to assess the combination's safety. The assay was performed within 24 and 72 hours of incubation. Ciprofloxacin, esomeprazole, and their combination concentrations ranged from 0.1 to 1000 µg/ml, with the mixture containing 50% of the individual concentration of each medication when assessed individually. The study employed the selective toxicity index to assess the selectivity of the mixture for cancer cells. The combination index was utilized to evaluate the potential synergistic effects of ciprofloxacin and esomeprazole. This study utilizes computational molecular docking simulations to assess the binding affinity of Ciprofloxacin and esomeprazole to heat shock protein 70 (PDB code: 1hjo). The MTT assay and selective toxicity index results indicated that the combination of ciprofloxacin and esomeprazole selectively inhibited the proliferation of cervical cancer cells. The inhibitory effect depended on the concentration of the mixture and the incubation duration, with a diminished impact on the viability of the HFF cell line. The combination index study indicates that the interaction between ciprofloxacin and esomeprazole shows a synergistic effect at each incubation period. The computational molecular docking simulation indicated that ciprofloxacin and esomeprazole target Hsp 70, with docking scores of -7.4 kcal/mol and -7.3 kcal/mol, respectively. Our findings from the MTT assay, selective toxicity index, combination index, and computational docking simulations suggest that the combination of ciprofloxacin and esomeprazole is a promising option for treating cervical cancer, given their set adverse effects and pharmacokinetic profiles.

Comparative Study in Quality of Life between Thai Endometrial Cancer Survivors and Healthy Women in Thammasat University Hospital

This study aimed to survey quality of life (QoL) in endometrial cancer survivors between surgery with adjuvant therapy (radiation with or without chemotherapy) and surgery alone in Thammasat University Hospital, Thailand. This cross-sectional study was conducted at the Gynecologic Oncology clinic, Thammasat University hospital, Thailand between March 2011 and May 2019. Participants were endometrial cancer cases who underwent surgical staging with or without adjuvant treatment (study) and healthy women who came to gynecologic department for annual cervical screening (control). Assessment of QoL was investigated via the structural questionnaire designed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (Thai version). During the period of the study, 94 participants who were diagnosed with endometrial cancer and underwent surgical staging were enrolled. There were 51, 43 and 51 cases in group A (surgery with adjuvant therapy), group B (surgery only) and group C (control), respectively. Control cases were participants who had comparable demographic characteristics and underwent gynecological checkup during the period of study. In part of physical functioning, group B had statistically better scores than group A. Participant in group B and C reported significantly better QoL in part of social functioning than group A. Symptom severity; appetite loss and constipation in group B was statistically less than in group A. Constipation problems in group A and C were comparable. Participants in group C had worse global health status than group A/B. Adjuvant treatment with either radiation or chemotherapy had negative impacts on QoL in endometrial cancer survivors. It impacted physical health, social function, appetite loss, and constipation. All endometrial cancer survivors had global health scores better than healthy peers. Thoroughly counseling to endometrial cancer survivors remains an important tool for increasing awareness of treatment complications and lowering psychological emotional stress..

Analysis of In-Vivo Dose Measurement of Urethra Using Array MOSFET Detectors and TPS-Calculated Dose in High-Dose-Rate Interstitial Brachytherapy in Gynaecological Malignancies

The urinary sub-structures, which lie in close proximity to the target, are often not contoured or evaluated during cervical cancer brachytherapy planning. This study aims to investigate the in vivo urethral dose during High-Dose-Rate Interstitial Brachytherapy applications using an array of Metal-Oxide-Semiconductor Field-Effect-Transistor detectors, and to compare the urethral dose recorded during brachytherapy planning with that calculated by the treatment planning system. Twenty patients with cancer of the cervix, vagina, or vault, from Stage IB to Stage IV, who were treated with external beam radiotherapy (EBRT) and interstitial brachytherapy, were included in the study. The high-risk clinical target volume and organs at risk, such as the urinary bladder, rectum, sigmoid colon, urethra, and periurethra, were delineated. The commercially available linear array MOSFET detector, with each detector and its reader module, was characterized and used in this study. The detector channel was inserted into the Foley's catheter until it reached the neck of the bladder. The maximum and mean doses received by the urethra were 486.32 ± 105.88 cGy and 246.73 ± 101.43 cGy per fraction, respectively, for the prescription dose of 700 cGy/fraction. The maximum dose received by the periurethra per fraction of brachytherapy was 697.43 ± 165.26 cGy, and the cumulative dose, in terms of Equivalent Dose at 200 cGy (EQD2) received by the periurethral region, including the EBRT dose, was found to be 13,406.1 ± 2,909.17 cGy. The urethral doses calculated by the Treatment Planning System (TPS) were compared with the doses measured by the detector per fraction of brachytherapy during treatment. The urethral doses calculated by the Treatment Planning System (TPS) were comparable to the doses measured by the MOSFET detector. Urethral dose measurement using an array of MOSFET detectors in patients treated with the Interstitial Brachytherapy (ISBT) technique proved its suitability and ease for measuring urethral dose. A good correlation was observed between the MOSFET-measured dose and the TPS-calculated dose, with a P-value > 0.05.

Standardizing Cost-Effectiveness Evidence for Cancer Prevention: A Case Study Analysis of HPV Vaccination

Cervical cancer remains a leading cause of cancer mortality worldwide, with over 85% of deaths occurring in low- and middle-income countries (LMICs) where resources are scarce. A fundamental challenge in global health policy is comparing economic evaluations across these diverse settings, as traditional Incremental Cost-Effectiveness Ratios (ICERs) are constrained by different currencies, price levels, and willingness-to-pay (WTP) thresholds. To address this, we propose a standardized Cost-Effectiveness Ratio (CER), calculated as the ICER divided by the country-specific WTP threshold, creating a unitless, income-adjusted metric. We conducted a rapid review of HPV vaccination economic evaluations published between 2022 and 2025. Employing a case study approach, we extracted original ICERs and WTP thresholds from diverse countries. All monetary values were converted to 2024 US Dollars using transparent exchange rates, with a critical handling of the Thailand WTP threshold to ensure it was based on the original Thai Baht value from the publication before conversion to USD to ensure analytical integrity. The CER was then calculated to facilitate direct comparison. The CER provides a powerful lens for interpreting value. Our case study reveals that a vaccination strategy in China (CER=0.0002) is dramatically more favourable than one in Japan (CER=0.20), a finding obscured by absolute costs. Furthermore, the CER shows that programs in Thailand and the Philippines offer over twice the relative economic value of Japan's program. It also enables nuanced comparisons, such as between single-dose and two-dose regimens, revealing comparable value for money in lower-middle-income settings. The CER is a simple yet powerful tool that transforms incomparable data into a standardized metric. For international funders like Gavi and national policymakers, it provides robust evidence to prioritize investments in LMICs, where the return on investment is highest. By reframing the economic question from "can we afford it?" to "how can we afford not to?", the CER promotes health equity and strengthens the case for accelerating global HPV vaccination efforts.

Knowledge Attitude and Determinants of Cervical Cancer Screening Uptake Among Age-Eligible Women and Male Partners in Makurdi North-Central Nigeria

To inform effective intervention strategies, this study aimed to assess the knowledge, attitude, and determinants of cervical cancer screening (CCS) among women and their male partners in Makurdi, North-Central Nigeria. A convergent parallel mixed-methods study involving a cross-sectional descriptive study of 288 women aged 25 to 65 years and key informant interviews (KIIs) with 10 women and 10 male partners across five primary health care centers in Makurdi, North-Central Nigeria. Data were collected using an interviewer-guided online questionnaire (KoboToolbox) and a semi-structured interview guide. Quantitative data were analyzed with SPSS version 20 (Armonk, NY: IBM Corporation). Qualitative data were transcribed verbatim and analyzed thematically. Participants were primarily traders (41.0%) with secondary education (46.2%) and a monthly income below 30,000 Naira (19.44 USD) (50.7%). Cervical cancer (CC) awareness was low (28.8%), with limited knowledge of HPV vaccination (15.6%). Despite high willingness to screen (94.8%), screening rates were minimal (3.1%). Support for CCS and HPV vaccination was high (94.4% and 92.7%, respectively). Key determinants of CCS uptake included age (≥40 years), family history of CC, and knowledge of HPV vaccination. The key informant interviews corroborated these findings. Poor knowledge of CC and CCS as well as low uptake of CCS were observed among the respondents. They however expressed positive intentions towards CCS. The study underscores inadequate knowledge of CC and its prevention, highlighting the necessity for targeted awareness campaigns and enhanced involvement of male partners to boost CCS uptake and reduce cervical cancer incidence among Nigerian women.

Outcomes and Prognostic Factors of Patients with Platinum- Resistant or Refractory Epithelial Ovarian Cancer, Fallopian Tube Cancer and Peritoneal Cancer

To determine the survival outcomes and prognostic factors of the patients with recurrent platinumresistant and refractory epithelial ovarian cancer (EOC), tubal, and peritoneal cancer. Women with recurrent platinum-resistant and refractory EOC, tubal and peritoneal cancer who received treatment at the HRH Princess Maha Chakri Sirindhorn Medical Center (MSMC) between January 2010 and December 2019 were included. Demographic data, serum marker, surgical factors, pathological factors and response of treatment were reviewed. Kaplan-Meier was used to calculate survival outcome. Forty patients were recruited in this study (platinum-resistant 24 patients and refractory 16 patients). The median survival times were 19 and 21 months in and platinum-resistant and platinumrefractory patients, respectively. There were no significant differences in overall survival according to age, comorbidity, tumor grading, primary treatment, and secondary surgery. However, histology of clear cell carcinoma may associate with increased risk of death. The median overall survival of patients with clear cell carcinoma, serous carcinoma, and others were 14.4, 22.9, and 32.2, respectively (p = 0.003). Almost 10 years, the survival rate of the patients in these group has not increased despite new treatments option. Novel strategies should be considered in National policy of the treatment for ovarian cancer in our country.

Exploring Knowledge, Attitudes, Practices, and Information-Seeking on HPV Infection and Cervical Cancer Prevention in Rural Indonesia

Cervical cancer remains a leading public health problem in Indonesia, with low screening and HPV vaccination coverage, particularly in rural areas where knowledge gaps and limited healthcare access persist. This study aims to assess the knowledge, attitudes, and practices (KAP) regarding HPV infection and cervical cancer, and the role of information-seeking behavior in identifying effective channels for raising awareness on these issues. A cross-sectional study was conducted between 20 March 2023 and 20 January 2024, involving 220 women from two rural districts in North Moluccas, selected via convenience sampling. Data were collected using a validated questionnaire administered through face-to-face interviews. Data were analyzed using SPSS version 25.0 with descriptive statistics, normality testing (Kolmogorov-Smirnov), bivariate analyses (Chi-square, Fisher's Exact, Pearson's or Spearman's tests), and multivariate logistic regression (backward LR, p < 0.05), with model performance assessed using ROC curves and AUC values. Most participants demonstrated poor KAP, with 18.7% showing good knowledge, 22.7% expressing a positive attitude, and 44.5% engaging in favorable practices. KAP were found to be positively correlated (p<0.001). Key predictors of good knowledge included higher education (AOR = 7.07), family history of cancer (AOR = 15.20), private vehicle use (AOR = 4.15), and active health-information seeking behavior (HISB) (AOR = 3.41). Determinants for a positive attitude included higher education (AOR = 3.79), family history of cancer (AOR = 4.42), active HISB (AOR = 3.88), and good knowledge (OR = 10.29). Favorable practices were influenced by private vehicle use (AOR = 2.66) and positive attitude (AOR = 20.62). In conclusion, KAP are influenced by HISB, and involving healthcare workers in providing information, particularly through digital platforms, has the potential to improve KAP in rural communities.

Evaluation of the Diagnostic Accuracy of Cervical Cell Morphologies from Android Device-Captured Cytopathological Microscopic Images through Artificial Intelligence in Mainly Rural or Resource-Constraint Areas of India

This study aims at develop and evaluate an artificial intelligence programming software, an integrated system that automatically detects and classifies cells from microscopic Pap smear slide images taken on Android phones or tabs to diagnose the cervical cell morphology in a time-efficient and cost-effective manner. This study presents an integrated system designed to automatically detect and classify cells in Pap smear slide images, differentiating cellular morphologies. The system leverages three deep learning (DL) and one machine learning (ML) models, each tailored to specific tasks in the image analysis pipeline. The analysis of 292 hospital in-house microscopic Pap smear images was conducted from July 2023 to December 2024 at CliniMed LifeSciences, Kolkata, India. The following article describes the datasets used, the training procedures and the performance metrics for each model.  Results: Pap smear images have been validated and standardized by using SipakMed, Herlev (public datasets) and hospital in-house data. A total of 292 in-house Pap smear images have been analysed through the newly developed AI software. Standardization and validation include an Intersection-over-Union score of cell-nuclei boundary extraction model of 71.14%, the accuracy of cell classification model and morphological feature based ML model are 99.213% and 91.23% respectively. The custom AI model could successfully classify 98.09% and 80.49%  of normal and abnormal cells in hospital in-house samples respectively. Also a significant meaningful correlation is observed between biopsy (gold standard) and AI reports. AI offers a lot of promise for diagnosing cervical cancer, and its uses in cervical cytology screening are particularly well-established. Manual screening of cervical cytology smears is a time-tested method, but AI is set to revolutionize the process by improving outreach, availability, accuracy and economy. A total of 292 hospital in-house Pap smear images have been validated and examined in this study with significant accuracy percentages between AI and expert eyes.

An Altered Ratio of CD4+ and CD8+ T Lymphocytes in Cervical Cancer Tissue and Peripheral Blood as a Predictor of Prognostic Outcome: A Clinicopathological Study

The aim of our study is to compare CD4+ & CD8+ T lymphocytes in the cervical tumor tissue with those in peripheral blood in patients with carcinoma cervix and to access thier association with known prognostic factors. The study also aims to investigate the association between tumor infiltrating lymphocytes (TILs) and the HPV status of the patients. In this prospective study, 42 patients with locally advanced squamous cell carcinoma of cervix were included. Percentages of CD4+ and CD8+ T lymphocytes were obtained using flow cytometry-based method from single-cell suspension prepared from simultaneously collected tumor tissue and peripheral blood samples. DNA extracted from tumor tissue was analysed to detect HPV16 (Human Papillomavirus 16) and HPV18 infection. T lymphocyte subsets in blood and tumor tissue were compared. The association of T lymphocytes with known prognostic factors and HPV status of the tumor was examined. Both CD4+ and CD8+ T cells were significantly higher in peripheral blood compared to tumor tissue (p < 0.001). The CD4/CD8 ratio was reversed in tumor tissue compared to peripheral blood due to relatively lower reduction of CD8+ cells compared to CD4+ cells in tumor tissue. No significant association of T lymphocyte subpopulation was found with known prognostic parameters of cervical cancer. CD4+ and CD8+ T lymphocyte infiltration was significantly higher in tumor with HPV16 infection (p < 0.05). A significant alteration of CD4/CD8 ratio was observed for HPV18 positive tumors (p < 0.05). Our study demonstrates that both CD4+ and CD8+ T lymphocyte, which are major component of TILs, are significantly lower in tumor tissue compared to peripheral blood in locally advanced cervical cancer. No association was observed between T lymphocyte subpopulations and major prognostic factors of cervical cancer. The enhanced TILs observed in HPV-associated cervical cancer represents a significant alteration with promising therapeutic applications.

Performance of a New Brazilian Self-Sampling Device for High-Risk Human Papillomavirus Screening

To evaluate the performance of a new Brazilian self-sampling device (COARI®) compared with clinician-collected samples for high-risk human papillomavirus (hrHPV) detection and partial typing. This diagnostic agreement study included 57 women who underwent routine cervical screening or follow-up at a private health center in Maringá, Brazil, between May and October 2023. Each participant provided two samples: a self-collected vaginal sample using the COARI® device (Kolplast, Brazil) and a clinician-collected cervical sample. Both were tested using the Cobas® HPV 4800 assay (Roche, USA), which detects HPV16, HPV18, and a pooled group of 12 other hrHPV types. hrHPV detection was significantly higher in self-collected samples than in clinician-collected ones (52.9% vs. 37.2%; P = 0.008). The Overall agreement between sampling methods was 84.3%. All discordant cases (15.7%) were hrHPV-positive in self-collected samples and negative in clinician-collected specimens, suggesting potentially greater sensitivity for self-sampling. The COARI® device showed 100% sensitivity and a 100% negative predictive value, with an overall accuracy of 84.3%. The COARI® self-sampling device demonstrated reliable and effective performance for hrHPV detection and partial typing, showing strong potential to increase access to and coverage of cervical cancer screening in Brazil. Further studies with larger and more diverse populations are needed to validate these findings and inform public health implementation.

Schlafen 11 (SLFN11) And Tumor-Infiltrating Lymphocytes (TILs): Dual Predictive Biomarkers In Ovarian Serous Carcinoma

This study aims to investigate the clinicopathological significance and prognostic impact of SLFN11 expression and tumor-infiltrating lymphocytes (TILs) in high-grade and low-grade ovarian serous carcinoma. A total of 70 patients diagnosed with high-grade and low-grade serous carcinoma were retrospectively analyzed. Clinical data, including age, Karnofsky Performance Status (KPS), CA125 levels, treatment details, and survival outcomes, were collected. Immunohistochemistry was used to assess SLFN11 expression in tumor cells and TILs. Statistical correlations were performed with chemotherapy response, recurrence, progression-free survival (PFS), and overall survival (OS). High SLFN11 expression was significantly associated with better response to neoadjuvant chemotherapy (p = 0.003), higher histopathologic chemotherapy response score (p = 0.026), lower recurrence rate (p = 0.037), and improved survival outcomes (p < 0.001). High SLFN11 expression had significantly longer PFS (median= 33.05 months) and OS (median= 66.91 months), compared to those with low SLFN11 expression (median PFS =7.60 and median OS = 31.50, p<0.001). Similarly, high TILs count was associated with improved response to neoadjuvant chemotherapy (p = 0.008) and higher response score (p = 0.007). TILs-high patients had longer median PFS (25.52 months) and median OS (68.24 months) than TILs-low patients (median PFS = 10.30 and median OS = 30.63 months, p<0.001). Our findings highlight that immunohistochemical expression of SLFN11 and the density of TILs may serve as predictive biomarkers for chemotherapy response and survival in ovarian serous carcinoma, with potential implications for personalized treatment strategies.

Exploring Women’s Attitudes Towards Cervical Cancer Screening and Their Association with Life Satisfaction and General Life Attitudes: A Systematic Review

Cervical cancer is a serious public health issue worldwide, with screening playing a critical role in the prevention and early diagnosis of the disease. Despite its proven effectiveness, women's participation rates in screening remain insufficient. This systematic review aims to investigate the degree of compliance among women with cervical cancer screening and the factors associated with these attitudes. It also aims to examine the association between life satisfaction and general attitudes towards life with women's compliance with this screening. The PRISMA 2020 methodology was followed. The PICO framework was used to identify relevant studies in the PubMed and Scopus databases. The search was performed in November 2024. Five studies with quantitative design met the inclusion criteria. The methodological quality of the studies was assessed using the Newcastle-Ottawa scale adapted for cross-sectional studies. Data were synthesized narratively presented in summary tables. Life satisfaction emerged as a positive predictor of participation in cervical cancer screening. In addition, factors such as high educational level, active employment status, and religiosity were associated with positive attitudes towards screening. Conversely, smoking habits, low health literacy, and fatalism beliefs about cancer were associated with reduced participation in screening. The small number of included studies (n=5), sample and variable heterogeneity, and the inability to do a meta-analysis, however, constituted important limitations of the review. In addition, restricting the search to English-language published studies may have excluded relevant evidence. Life satisfaction is an important predictor of preventive health behaviors. Interventions that aim to enhance life satisfaction and psychological well-being in general may improve compliance with cervical cancer screening and, by extension, prevent the disease.

Knowledge and Attitudes of Pregnant Women toward Cervical Cancer Screening during Pregnancy

To assess the knowledge and attitudes towards cervical cancer screening (CCS) during pregnancy among pregnant women. This prospective cohort study was conducted at the antenatal clinic of Thammasat University Hospital, Pathum Thani, Thailand from February to September 2024. Participants were pregnant women aged 18 to 45 years old who attended their first antenatal visit at a gestational age of less than 20 weeks. After counseling, written informed consent was signed after well understood of the study. A self-administered questionnaire consisting of knowledge about cervical cancer, attitudes towards screening and interest in undergoing screening during pregnancy was used. A total of 384 participants were recruited. The average maternal age was 30 years. Two-thirds (254/384) of the participants had at least a bachelor's degree, and over half (197/384) had a high salary. Only 42.7 (164/384) percent had previously undergone CCS with 70 (115/164) percent screened in the past 3 years. Knowledge scores averaged 8.9 out of 15 with many participants unaware of key facts, including the use of the Pap smear for screening. Although most participants (85.2-97.4%) had a positive attitude towards CCS during pregnancy, only 57(219/384) percent were interested in undergoing CCS during pregnancy. Factors such as prior screening and knowledge level were significant determinants of interest in CCS. Pregnant women had moderate knowledge and a good attitude towards cervical cancer and CCS. Less than half of pregnant women uninterested in CCS during pregnancy with the reason of prior CCS before pregnancy and inconvenience.

Introduction of the HPV Vaccine among Young Girls to Reduce the Long-Term Risk of Cervical Cancer in Eswatini: Programmatic Decision and Roll Out

Cervical cancer is a significant public health concern in Eswatini. In June 2023, the Eswatini government launched a national school based vaccination program aimed at administering two doses of the human papillomavirus (HPV) vaccine to adolescent girls, with the second dose administered six months after the first. This study seeks to assess the feasibility of school based HPV vaccination introduction campaign for prevention of cervical cancer among women in the Kingdom of Eswatini in Africa. The lessons learned, and challenges faced during the implementation of the national HPV vaccination program designed to prevent HPV infection are documented to improve HPV vaccination campaign in Africa. The review study details the planning and execution of the HPV vaccination initiative within Eswatini's school based campaign, targeting 82,400 girls aged 9-14 years from 12 to 23 June 2023 schooldays. The national goal was to vaccinate 82,400 girls. The campaign achieved a national coverage rate of 55.9%, with 46,512 girls successfully vaccinated. The Manzini region recorded the highest coverage at 60.1%, while the Shiselweni region had the lowest at 48.2%. The introduction of the large-scale HPV vaccination campaign in schools proved successful. However, challenges such as misconceptions about eligibility criteria and misinformation persisted, impacting vaccine uptake and coverage. Continued efforts in community mobilization, public education on eligibility, and integration with healthcare services are essential for sustaining the program. Strengthening partnerships and mobilizing resources will also be critical for its long-term success.

Radical Trachelectomy Using A Titanium-Nickelide Metal Tricotage Implant to Preserve Fertility in Cervical Cancer Patients

Among malignant neoplasms of the female reproductive system, cervical cancer traditionally occupies a leading position in terms of both morbidity and mortality. Traditional surgical treatment of early-stage cervical cancer leads to satisfactory oncological results, but irreversibly reduces the fertility in this category of patients. The aim of this work was to evaluate the applicability of a metal-ceramic implant with shape memory made of titanium nickelide for the purpose of forming uterine closure and strengthening the anastomosis zone. A total of 168 untreated patients with cervical cancer underwent radical trachelectomy with reinforcement of the utero-vaginal anastomosis using a titanium-nickelide shape memory implant. The fertility of women after organ-preserving treatment was evaluated. Thirty-nine pregnancies were registered. Currently, 28 healthy children have been born. Two patients gave birth twice, one woman gave birth to twins. In addition, 2 miscarriages were registered at 7 and 19 weeks, 7 patients terminated pregnancy for social reasons at early stages, 2 patients are currently pregnant, at 24 and 32 weeks. The median follow-up for this category of patients is 89±9.6 months. Eight relapses were registered at various follow-up periods with the localization of the relapse mainly in the area of the anastomosis and iliac vessels. Analysis of menstrual function showed that the duration of the menstrual cycle after surgical treatment in the volume of radical trachelectomy was 29±4.7 days and did not differ significantly from the indicators before the operation. The duration of menstruation also did not differ significantly before and after surgical treatment. Improvement of the method of organ-preserving surgical treatment by radical trachelectomy with the formation of the uterine locking apparatus using titanium-nickelide metal tricotage contributes to the improvement of reproductive results without compromising oncological effectiveness.

Determinants of Female Cancer Screening Awareness in Alabama’s Black Belt Region

Breast and cervical cancers represent significant health challenges in Alabama's Black Belt region, where they are leading causes of mortality among women. This study aims to investigate the factors influencing awareness levels of three critical female cancer screening methods: mammograms, clinical breast exams, and Pap tests. A cross-sectional survey was conducted with 257 participants in Alabama's Black Belt region, utilizing self-administered questionnaires to gather data on awareness of female cancer screening methods. To identify significant predictors of awareness for each screening method, logistic regression analysis was employed. The study revealed high levels of awareness regarding mammograms, clinical breast exams, and Pap tests among participants. Women demonstrated significantly greater awareness of mammograms and Pap tests compared to men. Employment status and family history of cancer were identified as key predictors of awareness. Specifically, participants with a family history of cancer and those who were employed were more likely to be aware about mammograms, clinical breast exams, and Pap tests. Furthermore, self-reported health status was positively associated with awareness of clinical breast exams and Pap tests. Notably, the perception of racial impact on healthcare quality significantly influenced awareness of mammograms. Although this study highlights relatively high levels of female cancer screening awareness among women in Alabama's Black Belt region, there is a pressing need for concerted efforts to further enhance this awareness. Implementing comprehensive educational initiatives and improving healthcare resource provision are critical steps toward augmenting knowledge and achieving optimal cancer screening rates in this underserved community. Such measures are essential to mitigate cancer risks and improve health outcomes for women in this region.

Health Literacy and Factors Associated with HPV Vaccination among Adolescent Students: A Cross-Sectional Analytic Study

Human papillomavirus (HPV) vaccination is a key strategy for cervical cancer prevention. Health literacy may influence vaccine uptake, but evidence among adolescents remains limited in Thailand. This study aimed to examine the association between health literacy, social support, and HPV vaccination among female secondary school students. A cross-sectional analytical study was conducted between November 2024 and January 2025 in Chalerm Phrakiat District, Nakhon Si Thammarat Province, Thailand. A total of 296 female students aged 13-18 years were included, comprising 148 unvaccinated participants and 148 vaccinated controls. Data were collected using a validated questionnaire covering demographic characteristics, health literacy (six subscales), and perceived social support and role modeling (two subscales). Logistic regression analyses were performed to identify factors associated with HPV vaccination. Approximately one-third of both groups had fair overall health literacy (33.11% and 37.84%, respectively). Participants in senior high school were significantly less likely to be vaccinated (AOR = 2.27, 95% CI: 1.37-3.76). Interestingly, participants with low knowledge and understanding were more likely to be vaccinated (AOR = 0.34, 95% CI: 0.16-0.69), while those with low communication skills were more likely to be unvaccinated (AOR = 1.91, 95% CI: 1.05-3.48). Overall health literacy was not significantly associated with vaccination status. Specific dimensions of health literacy, particularly knowledge and communication skills, were significantly associated with HPV vaccination. These findings highlight the need for targeted health education interventions focusing on improving communication and reinforcing key knowledge to increase vaccine uptake among adolescents.

Synergistic Chemopreventive Effects of Curcumin, Gingerol, and Shogaol on HeLa Cervical Cancer Cells

Bioactive compounds including curcumin, gingerols, and shogaols possess strong anti-inflammatory and anti-tumour properties. However, their combined efficacy has yet to be fully explored. This study aimed to investigate the chemopreventive potential of individual and combined treatments of 6-/10-gingerols (6-/10-G), 6-/10-shogaols (6-/10-S), and curcumin (Cur) in HeLa cervical cancer cells. HeLa cell viability was evaluated using the MTT assay following a 24-hour treatment with a wide range of concentrations and ratios of the bioactive compounds. The combination index was analysed using the Chou-Talalay method, and apoptotic cells were assessed via flow cytometry with Annexin V/FITC-PI staining. We found that the optimal formulation of Cur in combination with all ginger bioactive compounds demonstrated synergistic inhibition of HeLa cancer cell growth at a 3:1 ratio of Cur to ginger bioactive compounds. Furthermore, treatment with the Cur:6-G (45µM: 40µM) and Cur:10-S (45µM: 20µM) combination formulations at a ratio of 3:1 significantly (p < 0.005) inhibited cell growth (72-77%) and induced apoptosis (60-87%). These findings highlight the potent anticancer properties of the combined formulations on HeLa cells, surpassing the efficacy of individual compounds which require relatively high concentrations. The combination of Cur and ginger bioactive compounds enhances anti-proliferative effects and induces apoptosis in HeLa cell lines.

Disparities in Human Papillomavirus Vaccination and Cervical Cancer Prevention and Screening Strategies: A Meta-Analysis

Sociodemographic disparities continue to impact access to cervical cancer screening and treatment outcomes. Although advancements in preventive and therapeutic strategies have contributed to reductions in cervical cancer incidence and mortality, inequities in healthcare access remain largely influenced by social gradients and limited health literacy. This study aimed to investigate the influence of factors such as age, race, socioeconomic status, educational attainment, and insurance coverage on cervical cancer mortality and participation in preventive measures, including HPV vaccination and cervical cancer screening. A systematic search of the MEDLINE, EMBASE, and Cochrane databases was conducted through January 2024. Eligible studies examined associations between disparities, defined as differences in race, social determinants of health, treatment modalities, and cervical cancer prevention or mortality. Data were synthesized using a random-effects meta-analysis, supplemented by subgroup analyses and multiple meta-regression models. A total of 69 studies met the inclusion criteria. Screening participation was higher among individuals who were non-Black, had attained higher education levels, were publicly insured, were married, and had a higher income. In contrast, higher cervical cancer mortality rates were observed among individuals who were Black, uninsured, less educated, unmarried, or those who either did not receive treatment or underwent surgery alone. Significant disparities persist in access to cervical cancer prevention services and in mortality outcomes. These findings highlight the urgent need for policy interventions aimed at addressing economic, social, and racial barriers to equitable healthcare access.

Factors Associated with Suboptimal Screening for Cervical Cancer among Ethnic Women in Thailand-Myanmar Border Area

Suboptimal screening for cervical cancer is found in remote areas. This study aims to evaluate the suboptimal screening prevalence and determine the factors associated with suboptimal cervical cancer screening among  ethnic women in the Thailand-Myanmar border area. This is a cross-sectional study conducted from July to December 2023. The eligible criteria were ethnic women aged 30-60 in Pai district, Mae Hong Son province in northern Thailand. Descriptive statistics were used to describe the characteristics, accessibility to health care service, knowledge, attitude and perceptions about Human Papillomavirus (HPV), cervical cancer and screening, and support for cervical cancer screening. The factors associated with suboptimal screening were determined using binary logistic regression. Among 354 ethnic women, one-fourth had suboptimal screening for cervical cancer. The positive attitude towards cervical cancer screening and the perceived risk of cervical cancer were high. Most of the participants had a medium level of knowledge about HPV and cervical cancer. Factors associated with suboptimal screening were younger age (adjusted Odds Ratios(aOR) = 1.48, 95% confidence interval (CI): 1.06-2.07), being Hmong ethnic group (aOR = 2.63, 95%CI: 1.30-5.34) compared to Karen ethnic group, and lack of information support from health care personnel (aOR = 1.88, 95%CI: 1.08-3.29) . Positive attitude toward the screening was associated with less suboptimal screening (aOR=0.56, 95%CI: 0.32-0.96). Information support from local health personnel plays an important role in health promotion and health literacy for cervical cancer screening in ethnic women as information and support to accommodate the languages and cultural can enhance engagement and trust.

The Adoption of Cancer Screening and Prevention in Hawaiian Homestead Communities

This study examined screening behaviors for breast, prostate, and cervical cancers among residents on several Native Hawaiian Homesteads. From 2016 to 2020, a cross-sectional survey was administered to identify the most relevant and modifiable factors associated with participants' health behaviors. The participating Homestead communities are located on the Islands of O'okinaahu and Hawai'i. A mailed invitation letter was sent to 1,582 lessees and/or the listed resident in each Homestead community. Respondents were identified as the Homestead lessee, lessees' successor, and/or designee who were over age 18. Sociodemographic and economic variables, as well as cancer-related and cancer screening behaviors, were assessed using items derived from the Behavioral Risk Factor Surveillance Survey (BRFSS). Four items assessing the ability to perform daily activities were also included. Descriptive statistics were calculated, followed by frequencies and percentages for categorical variables, and means and standard deviations for continuous variables. A p-value of < .05 (two-tailed) was used to determine statistical significance. Out of 1,582 surveys sent, a total of 459 surveys (29%) were collected. Screening rates for several cancer sites (colon 72%, cervical 97%, breast 99%) were well-above average for Hawai'i and the U.S. These results may be a direct reflection of the strong engagement efforts cultivated by community-based researchers and their longstanding university-community partnership that utilizes community-based participatory research approaches for health promotion.

Effective Anti-Cancer Activity of Red Rice Bran Extract on Cervical Cancer and Breast Cancer Cells

Many researchers have shown that red rice bran is a rich source of antioxidants and has potential anticancer properties. This research aims to evaluate the cytotoxicity and inhibitory effects of Red Rice Bran Extract (RRBE) on the growth and migration of human cervical and breast cancer cells. HeLa and MCF-7 cancer cells were treated with various concentrations of RRBE for 24 and 48 h. Cytotoxicity was assessed using the MTT assay. Then, the half-inhibitory concentration (IC50) value was determined. The anti-proliferative effects were evaluated using the MTS assay, and the anti-cell migration activity was assessed using the wound healing assay. It was found that the RRBE exhibited cytotoxicity to both HeLa and MCF-7 cancer cells. As the concentration level increased (100 - 1000 µg/ml), the survival rate of the cells significantly decreased, especially at 48 h, corresponding to the IC50 values of 818.67 µg/ml and >1000 µg/ml for HeLa and MCF-7, respectively. Then, concentrations of RRBE with lower cytotoxic effects were selected for further experiments, which revealed that treatment with RRBE at concentrations of 100, 250, 500, and 1000 µg/ml significantly suppressed the proliferation and reduced the migration of those cancer cells. These results demonstrate that RRBE has potent anti-cancer activity in HeLa and MCF-7 cancer cells, making it a suitable candidate for in vivo studies and development as an anti-cancer agent.

Barriers to HPV Vaccination in Brazil: A Systematic Review

Cervical cancer is the third most common cancer worldwide. Expanding HPV (Human papillomavirus) vaccination coverage to 90% of all adolescent girls by 2030 is the World Health Organization's (WHO) primary vaccination strategy to eliminate cervical cancer by the end of the century. To identify the main challenges associated with HPV vaccination in Brazil. A systematic review in accordance with the PRISMA reporting guidelines was conducted using PubMed, EMBASE Lilacs, Cochrane Library, SCOPUS, and Web of Science databases, which included prospective and cross-sectional studies. Different term combinations were used: ((("HPV vaccination"[TITLE]) OR ("HPV vaccine"[TITLE]) OR ("HPV immunization"[TITLE]))) AND (Brazil); HPV vaccination AND Brazil; Barriers AND vaccination AND HPV AND Brazil; Barriers AND HPV vaccination AND Brazil. This study included published articles with no language or date restrictions. A total of 179 articles were identified. After deleting 50 duplicates, 78 articles were excluded based on their title or abstract, while 28 were excluded after full reading, thus leaving only 23 articles. Seven studies were carried out in the southeast region, one in the southern region, one in the midwest region, and two in the north region. Knowledge was the biggest problem detected among parents and guardians, health caregivers, health students, and general users of the Brazilian Unified Health System (SUS). All studies indicated that knowledge is essential for adherence. For students and health professionals, a more comprehensive approach to the topic would be beneficial in advancing their knowledge.

Prevalence of Human Papillomavirus Infection in Nakhon Ratchasima, Northeastern Thailand

To assess the prevalence of high-risk human papillomavirus (hrHPV) in Nakhon Ratchasima province, Thailand, which might lead to the formulation of effective HPV vaccination strategies in the region. This study analyzed hrHPV DNA test results, liquid-based cytology findings, and available histological data. The data came from women aged 18 to 62 years who underwent cervical cancer screening in six Nakhon Ratchasima districts: Khon Buri, Soeng Sang, Pak Thong Chai, Nong Bun Mak, Wang Nam Khiao, and Mueang Nakhon Ratchasima. The screening occurred between March 2021 and August 2023. We determined the prevalence of hrHPV infection and performed statistical analysis using chi-square tests and multiple logistic regression. A total of 16,209 hrHPV DNA test results were included in the analysis, revealing an overall hrHPV prevalence of 8.03% (1,301/16,209). The most frequently detected category was other hrHPV types (5.62%), followed by HPV type 16 (1.78%) and type 18 (0.62%). A single case of co-infection involving HPV type 16 and another hrHPV type was identified. A significant association between age and hrHPV infection was found (p<0.001), with the highest prevalence occurring in women aged 30-39 years. Additionally, increasing age was significantly linked to a decline in hrHPV infection rates. This study identifies age as a significant risk factor for hrHPV infection. To enhance hrHPV surveillance, we recommend using tests that detect specific HPV types, which will enable a more detailed assessment of prevalence. Furthermore, conducting similar prevalence studies across different regions in Thailand will provide essential data to guide future HPV vaccination policies.

The Utilization of Human Papillomavirus Testing for Cervical Cancer Screening in Thailand: A Comparison of Screening with and without Self-sampling Samples

Cervical cancer (CC) screening shifted from Pap-smear to human papillomavirus (HPV) testing HPV with and without a self-sampling HPV-test in Thailand. Few studies have reported the initial outcomes of such a transition. This study aims to explore CC screening rate, CC detection and compare the CC detection rate by HPV with and without self-sampling methods in Krabi, province. A retrospective study was conducted from 1st October 2023 to 30th September 2024. A total of 11,925 women's records were retrieved. Information on demographic, screening results and cancer diagnosis was retrieved from the Krabi provincial hospital. Different proportions of CC detections and self-test collection based on demographic features were tested using chi-square and Fisher's exact tests.  Result: CC screening rate was 42.4%: 10,619 (89%) of women had an HPV test and 1,306 (11%) had a Pap-smear test. The screening rate was 30.2% in 2023 and 52.1% in 2024. With regard to age, occupation, and health insurance schemes there was a significant difference in the proportion of those taking the self- collection test. Religion showed non-significance difference in the proportion of self-sampling test in relation to religion. CC detection was 3% among women who underwent the Pap-smear test and 0.12% for those who performed the HPV test. There is a significant difference in CC detection between the HPV with and without a self-sampling test. CC screening with HPV testing, especially with self-sampling, showed a promising approach to increasing CC screening uptake in the population. The rate of CC detection through self-sampling was lower in the early years of implementation compared to non-self-sampling methods. Ensuring the correct performance of self-sampling should be carefully considered and monitored in the future.

The Role of lncRNAs in the Epithelial-Mesenchymal Transition in Cervical Cancer: A Narrative Review

In this context, the aim of this study was to compile the main works that address the relationship between lncRNAs and Epithelial-Mesenchymal Transition (EMT) in cervical cancer. Data extraction was conducted using the PubMed database, where a search for selected studies on lncRNAs involved in EMT in cervical cancer was performed. The search was based on the following keywords: "Epithelial-Mesenchymal Transition" AND "Uterine Cervical Neoplasms" and "lncRNA and EMT and cervical cancer." Included in this study were 16 lncRNAs, which encompass expression level, microRNAs, targets, clinical significance, and references. Among the 16 lncRNAs observed, it was found that 5 of them can regulate EMT by modulating microRNAs. It was also noted that these biomolecules are capable of regulating the expression of important EMT genes, such as SNAIL, SLUG, and TWIST, thus influencing cancer invasion and metastasis. In addition to these, 11 lncRNAs were found, which can regulate biological pathways such as Wnt/β-catenin and AKT/mTOR, playing fundamental roles in EMT. In conclusion, the future prospects of lncRNAs in therapy and inhibition of EMT are promising. Considering the relevance of EMT to cancer progression and the involvement of lncRNAs in this biological process, it becomes important to better understand their role and the possibility of targeting them therapeutically, which can represent significant advancements in the treatment not only of cancer but also of other diseases.

Incidence and Survival Trends of Cervical Cancer in Khon Kaen, Thailand

To evaluate and report the incidence and survival trends of cervical cancer in Khon Kaen, Thailand, during 1991-2020. A retrospective study was conducted by using the electronic cancer registry database of Khon Kaen province population. Joinpoint regression model was used to analyze the Age-Standardized Incidence Rate (ASR) and the incidence trend graph was built. Overall Observed Survival (OS) was analyzed by Kaplan Meier method and the survival trend graph was built similarly. During 1991-2020, 3,071 cervical cancer patients were found in Khon Kaen. Their mean age was 51.7 year-old. The ASR had decreased from 13.51 (95%CI: 10.67-16.35) per 100,000 women-year in 1991 to 7.63 (95%CI: 5.93-9.33) per 100,000 women-year in 2020. This trend was consistent with the country's and international trends. The highest incidence was found in 1993, which was 17.73 (95%CI: 14.65-20.81), and the lowest incidence was found in 2016, which was 5.7 (95%CI: 4.30-7.10) per 100,000 women-year. However, the 5-year OS was 48.37% (95%CI: 46.49-50.22), which was a constant trend. At the beginning in 1991-1995, the OS was 40.31% (95%CI: 35.43-45.12), and at the end in 2016-2020, the OS was 40.46% (95%CI: 34.59-46.23). These were very similar. In Khon Kaen, Thailand, during 1991-2020, the cervical cancer incidence (ASR) trend was decreasing, while the cervical cancer survival (OS) trend was constant. WHO elimination of cervical cancer initiative target should be reached by 2030.

Efficacy and Safety of Neoadjuvant Chemotherapy Plus Concurrent Chemoradiotherapy Compared to Concurrent Chemoradiotherapy Alone in Locally Advanced Cervical Cancer: A Systematic Review and Meta-Analysis

This systematic review and meta-analysis assessed the efficacy and safety of neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy (CCRT) compared to CCRT alone in locally advanced cervical cancer (LACC). We systematically searched PubMed, ScienceDirect, Cochrane Library, EBSCOHost, ProQuest, and grey literature (Google Scholar, OpenGrey, WorldCat) up to April 26, 2024 (PROSPERO: [CRD42024540599]). Seven studies were included (stages IB2-IVA, FIGO 2018), involving 446 participants. Outcomes included complete response (CR), progression-free survival (PFS), overall survival (OS), and adverse effects. Seven studies were included (n = 1,638), with 825 patients receiving NACT+CCRT and 813 receiving CCRT alone. The NACT+CCRT group showed higher CR rates (77% vs. 70.9%), but the difference was not statistically significant (OR 1.23, 95% CI 0.40-3.83). No significant differences were found in PFS (HR 0.94, 95% CI 0.53-1.69) or OS (HR 1.07, 95% CI 0.56-2.03). Adverse effects, including anemia, neutropenia, thrombocytopenia, nausea, vomiting, fatigue, and creatinine elevation, showed no significant differences between the groups. In patients with locally advanced cervical cancer, NACT followed by CCRT is associated with comparable survival outcomes and a similar safety profile to standard CCRT, with a non-significant trend toward improved CR.

Interventions to Improve the Uptake of Cervical Cancer Screening with Visual Inspection with Acetic Acid: A Scoping Review

Cervical cancer is a leading cause of death worldwide. Early detection and management are essential. In this case, you can use screening methods such as pap smear, visual acetic acid inspection, and HPV DNA test. Healthcare professionals recommend the Visual Inspection with Acetic Acid (VIA) test for finding precancerous lesions. This is especially useful in resource-limited settings. This scoping review explored methods to increase cervical cancer screening for women. It focused on the use of the VIA test. We did a systematic search in PubMed, Scopus, Science Direct, and ProQuest. We used these keywords: (uptake OR participation) AND ("visual inspection acetic acid" OR VIA) AND ("cervical cancer" OR "uterine cervical neoplasm"). We used the EndNote app to manage data. First, we screened titles and abstracts. Then, we identified potential articles and checked the full text. We looked for non-relevant outcomes, insufficient data, and duplicate publications. We followed the Prisma framework throughout the process. Two reviewers selected and extracted the data. A total of 39 studies were found to be assessing methods to increase VIA. Research reveals 6 ways to enhance cervical cancer screening using the VIA method worldwide. The six emerging themes for these intervention types include: health education and counselling (n=53%), cancer screening programs (n=12%), technology-driven interventions (n=10%), community and peer-based approaches (n=16%), cultural and language-specific approaches (n=4%), as well as training and capacity building (n=4%). Health education and counseling increase awareness about cervical cancer screening for women. This is especially true in countries with limited resources. The main interventions obtained from this study were health education and counseling. Future screening should use digital health tools like mHealth. It should also boost community-based methods. Finally, interventions need to fit cultural and language needs. This way, we can increase participation rates.

Unveiling The Impact of Prophylactic Para-Aortic Lymph Nodes Irradiation in Cervical Cancer: Meta-Analysis of Randomized Controlled Trials

This study assessed the impact of prophylactic para-aortic lymph node (PALN) irradiation with extended-field radiotherapy (EF-RT) in individuals with locally advanced cervical cancer. The principal objective was overall survival (OS), whereas the secondary outcomes included PALN metastases, full remission, pelvic recurrence, distant metastasis, and mortality attributable to cervical cancer. A thorough search was performed in Pubmed, Cochrane Central Register of Controlled Trials, and Science Direct in November 2023, following PRISMA procedures. Randomized trials comparing EF-RT to pelvic-only radiation for locally advanced cervical cancer without PALN involvement were incorporated. A meta-analysis was conducted using RevMan software to evaluate the Hazard Ratio (HR) for overall survival (OS) and the Odds Ratio (OR) for additional outcomes. Six Randomized Controlled Trials involving 1,028 patients (508 in EF-RT group and 520 in pelvic-only radiotherapy group) were analyzed. EF-RT significantly reduced para-aortic lymph node metastases compared to standard pelvic radiotherapy (OR = 0.23, 95% CI [0.12;0.44], p-value0.05, 6 studies) nor other outcomes. EF-RT was also associated with increased gastrointestinal but not urological or gynecological complications. EF-RT as a prophylactic treatment for cervical cancer patients with negative PALN metastasis significantly reduces para-aortic lymph node metastatic events, nonetheless, it is improbable to offer any advantages regarding overall survival, managed pelvic illness, or distant metastatic sites. Furthermore, its adverse effects on gastrointestinal problems were observed to exceed those of conventional pelvic irradiation, necessitating further consideration.

Antiproliferative Potential of Linagliptin-Rivaroxaban Mixture in Cervical Cancer: Mechanistic Insights into Targeting Mutant MAPK, RAS kinase Signal Protein

Repositioning existing marketed drugs represents a viable strategy for identifying new anticancer agents. This study employed an approach that combined these drugs and examined their molecular mechanisms of action against cancer. This study evaluated the anticancer properties of the linagliptin-rivaroxaban mixture and its molecular anticancer mechanism by screening its ability to target the mutant MAPK-RAS kinase signal proteins. Following 24 and 72 hours of incubation, HeLa and human-derived adipose tissue (NHF) cell lines were utilized to investigate the anticancer and safety properties of a linagliptin-rivaroxaban mixture and cisplatin at concentrations between 0.1 and 1,000 µg/ml. A combination and selectivity index study assessed the potential synergistic effects between mixture ingredients and selective toxicity. Computational molecular docking simulations were employed to investigate the binding affinity of linagliptin and rivaroxaban to various mutant kinase signal proteins within the MAPK-RAS kinase pathway. The study results indicated that the combination of linagliptin and rivaroxaban significantly suppressed the growth of cervical cancer cells compared to the inhibitory effects of cisplatin, linagliptin, and rivaroxaban individually. Furthermore, the mixture cytotoxicity on the NHF cell line was significantly lower than that of cisplatin. The interaction between linagliptin and rivaroxaban exhibited synergistic cytotoxicity, as evidenced by the combination index score. The mixture exhibited selective cytotoxicity against cancer cells, suggesting a favorable toxicity index score. The outcomes of the molecular docking pilot study of diverse mutant MAPK-RAS kinase signal proteins with the mixture's ingredients are indicated. Linagliptin and rivaroxaban's best interactions were with mutant P38 MAPK and RAS kinase signal proteins, with docking scores of -7.9 kcal/mol and -8.7 kcal/mol, respectively. Regarding the study findings and the established pharmacokinetic and safety profiles of mixture drugs. The linagliptin-rivaroxaban mixture offers an attractive and safer alternative for cervical cancer treatment.

Development of a Predictive Model for Therapy Response in Advanced-Stage Cervical Cancer Using Apparent Diffusion Coefficient (ADC) Value and Quantitative T2 Tumor on MRI: Correlation with Survivin Expression

The aims of this study are to optimize Magnetic Resonance Imaging (MRI) as a predictive modality for therapy response in advanced-stage cervical cancer and to identify predictors of this response in relation to survivin expression. This case-control study was conducted from January 2023 to May 2024, with total 35 subjects. The target population comprised patients with stages IIB to IIIC2 (FIGO 2018) cervical cancer. MR examination was performed three times: pre therapy, in the mid cycle of external radiation (20-30Gy), and 2 months after complete therapy. The study analyzed relations between age, tumor size, nodal metastasis, ADC and T2 parameters on MR, and survivin levels, with final therapeutic response. The predictive model for final therapy response was developed using four variables: patient age, tumor size, nodal metastasis, and the T2 tumor-to-muscle ratio on MRI #2. The scoring system showed the minimum total score was 0 and the maximum total score was 6. The cut-off score on this predictive model is score 3 to differentiate between the prediction of good or poor response with the sensitivity of 92,86% and a specificity of 85,71%. This study found that T2 tumor-to-muscle ratio (T2 t/m ratio) on MR in the mid-cycle external radiation is a potential predictive factor of final therapy response on advanced-stage cervical cancer. A predictive model for assessing the final response could effectively incorporate clinical and MR parameters, including patient age, tumor size, nodal metastasis findings on MR, and Ratio T2 t/m on MR in the mid-cycle external radiation.

Synergistic Cytotoxic Impact of Linagliptin - Ciprofloxacin Combination on Cervical Cancer Cell Line: Insights into Targeting Heat Shock Protein 60

This study aimed to assess the combined impact of linagliptin and ciprofloxacin on inhibiting cervical cancer cell line proliferation and their ability to target heat shock protein 60. The anticancer properties of the linagliptin-ciprofloxacin combination were assessed employing the HeLa cervical cancer cell line, with incubation periods of 24 and 72 hours. The human fibroblast cell line (HFF) was utilized to evaluate the mixture's safety. The concentrations of linagliptin, ciprofloxacin, and their combination varied between 0.1 and 1000 µg/ml. combination index value was estimated to assess the potential synergistic impact of linagliptin and ciprofloxacin. The study also employs computational molecular docking simulations to evaluate the affinity of linagliptin and ciprofloxacin for binding to heat shock protein 60. The study's findings demonstrated that the combination of linagliptin and ciprofloxacin markedly inhibited the proliferation of cervical cancer cells. The inhibitory effect depended on the concentration of the mixture and the incubation duration. It concurrently exhibits a diminished impact on the viability of the HFF cell line. The combination index study indicates that the interaction between linagliptin and ciprofloxacin shows a synergistic effect across all concentrations, particularly after 24 hours of incubation. The computational molecular docking simulation demonstrated that linagliptin and ciprofloxacin can bind with Hsp 60. The docking scores for linagliptin and ciprofloxacin were recorded at -7.6 kcal/mol and -8.1 kcal/mol, respectively. Our study findings from the MTT assay, combination index, and computational docking simulations indicate that the combination of linagliptin and ciprofloxacin presents a promising option for treating cervical cancer, considering their defined adverse effects and pharmacokinetic profiles.

Analysis of the Effectiveness and Coverage of Breast, Cervical, and Colorectal Cancer Screening Programs in Kazakhstan for the Period 2021-2023: Regional Disparities and Coverage Dynamics

Cancer screening is a crucial component in the fight to reduce cancer incidence and mortality. Currently, the WHO recommends highly effective cancer screening programs, including screening for cervical cancer (CC), breast cancer (BC), and colorectal cancer (CRC). Despite the implementation of a cancer screening program since 2014, an evaluation of the effectiveness of BC, CC, and CRC screening in the Kazakhstan has not yet been conducted. Study aimed to assess the effectiveness and coverage of BC, CC, and CRC screening in the Republic of Kazakhstan during the period from 2021 to 2023. Data for the retrospective analysis were extracted from the "Healthcare Statistics" database. Data on participants eligible for screening (n=8,167,184) for BC, CC, and CRC were included in the analysis. In 2023, there was a noticeable decrease in the number of detected cases of CC (1.7) compared to previous years. The detection rates for BC (14) and CRC (around 1) per 100,000 population in 2023 remained almost at the same level as in previous years. The detection rate for BC was 0.74% in 2021, followed by a decline to 0.59% in 2022. In 2023, there was an increase to 1.69%. As for CC, the detection rate was 0.70% in 2021, it increased to 0.77% in 2022, but then decreased again to 0.53% in 2023. CRC shows a steady decline in detection rates. In 2021, the detection rate was 4.23%, then it dropped to 3.64% in 2022, and continued to decrease to 3.28% in 2023. The data for 2021-2023 underscore the necessity for continuous monitoring, analysis, and adaptation of screening strategies, taking into account regional peculiarities and new challenges, such as the pandemic. Ensuring high screening coverage for BC, CC, and CRC is a key factor for the early detection and effective treatment of these diseases.

Sexual Dysfunction in Patient’s Diagnosed with Cervical Cancer in Comparison to the Healthy Female Population

Aim of the study was to evaluate and compare the prevalence female sexual dysfunction (FSD) in cervical cancer (CC) survivors to a healthy female population. This observational prospective trial was conducted at Thammasat University Hospital, Thailand, between April 2023 and February 2024. Participants were CC survival who attended an outpatient cancer clinic. Subject with age between 30 and 60 years old and engaged in sexual intercourse at least once within the last 4 weeks were recruited. The control group was women who attended outpatient gynecologic clinic for routine pelvic examination with no serious medical diseases and no malignancy. The female sexual function index (FSFI) was applied to all the participants during the survey. Other demographic data of the participants were collected. A total of 116 cases were enrolled in the study. Participants were equally divided into the study and control groups. The mean age and BMI of participants were 49.4 years and 24.7 kg/m², respectively without statistical significance. The FSD's prevalence of the CC survival was significantly higher than control group (34.5 and 10.4 percent, respectively). CC survivors reported significantly poorer outcomes in the domains of lubrication, sexual satisfaction, and pain compared to the control group. The prevalence rates of CC survival and control group was 34.5 and 10.4 percent, respectively. Three out of six FSFI domains namely lubrication, satisfaction, and pain showed more problematic for CC survivors compared to control group.

Health Related Quality of Life and Religiosity of Women with Cervical Cancer in the Souss-Massa Region, Morocco: A Cross-Sectional Study

Cervical cancer is a highly prevalent cancer among women, especially in low- and middle-income countries. This disease affects women in various ways and consequently impacts the quality of life of those diagnosed with this type of cancer. The aim of this study is to assess the quality of life and the degree of religiosity among women with cervical cancer in Morocco. This is a cross-sectional study conducted at the Regional Oncology Center in the Souss-Massa region of Morocco during the period from January to May 2024. A total of 80 patients with cervical cancer were surveyed using the two validated Moroccan versions of the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) module and the BIAC (Belief Into Action Scale). Mean scores were calculated, and the ANOVA test was used to examine the significance of the mean difference between variables. A stepwise multivariable logistic regression analysis was used to explore the predictive factors of health-related quality of life. The average age of the patients was 56.1 ± 9.21 years. The mean overall quality of life score was 51.78 ± 30.06. Social functioning had the highest score (92.19 ± 21.90), while emotional functioning had the lowest score (62.55 ± 42). Pain (AOR= 6.98, 95% CI: 1.18-41.16) was associated with the patients' health-related quality of life. Regarding religiosity, the mean overall score on the BIAC scale was 54.17 ± 23.72. The patients' faith in God remained intact, but religious practice was significantly impaired. Cervical cancer significantly affects the health-related quality of life of patients. Consequently, efforts to improve quality of life should be undertaken, particularly in terms of emotional functioning, pain, and financial difficulties.

Effect of a Nurse-Led Educational Intervention on the Knowledge, Perceptions and Uptake of Cervical Cancer Screening among HIV-Infected Women in Kenya

Health education influences the sociocultural health beliefs and enhances the decision making of women resulting in a change in their screening behavior. This study evaluated the impact of a nurse-led health education based on the Health Belief Model constructs on improving the knowledge, perceptions and the uptake of cervical cancer screening among HIV-infected women in Kisii County, Kenya. A 2-arm quasi-experimental design was employed in the HIV care clinics at Keumbu and Gucha sub-County hospitals in Kisii County, Kenya. The study population comprised of HIV-infected women aged between 15 and 49 years attending the two HIV care clinics. A sample size of 306 for each arm of the study was used. Systematic random sampling was used to select the 306 participants enrolled in each of the study arms. Socio-demographic and clinical characteristics, knowledge, perceptions and uptake of cervical cancer screening data among the HIV-infected women was collected at pre-test and post-test surveys. We analyzed 566 participants (response rate 566/612, 92%) with 287 participants in the control arm and 279 participants in the intervention arm. There was a statistically significant difference in the mean scores of knowledge (p=0.001), perceived susceptibility (p=0.003), perceived severity (p=0.001), perceived barriers (p=0.001) and perceived self-efficacy (p=0.001) in the intervention arm compared to the control arm after the intervention. The proportion of participants screened significantly (p<0.001) increased from 16% to 57% in the intervention arm versus 7% to 9% in the control arm after the intervention. A nurse-led educational intervention in a hospital setting was effective in improving the knowledge and uptake of cervical cancer screening among HIV-infected women. The intervention partially improved their perceptions of cervical cancer and screening. Targeted health education can influence the uptake of cervical cancer screening among HIV-infected women.

Knowledge and Behaviors toward Human Papillomavirus and Cervical Cancer in the Women of Reproductive Age in Thailand-Myanmar Border Areas

Infectious disease is an important health problem in border areas as there is a possibility that the migrants may carry the disease into the area. The purpose of this study is to evaluate the knowledge and behaviors toward human papillomavirus (HPV) and cervical cancer in the women of reproductive age in the Thailand-Myanmar border area. A survey study in a population of 418 women of reproductive age in Mae Hong Son Province in the Thailand-Myanmar border area. Knowledge and risk behaviors of HPV and cervical cancer were described using descriptive statistics. Fifty percent of the participants had sexual debut at age less than 20 years, 27% had more than one lifetime sexual partner and only 3% had sex outside a monogamous relationship during the past 12 months. In term of knowledge, 62.5% knew about HPV. The proportion of correct answers about HPV and cervical cancer questions ranged from 14-95% and 52-94%, respectively. Among the cervical cancer screening target, 69.4% accessed the screening. The factors associated with better knowledge about HPV and cervical cancer were education level higher than high school and sexual debut. The women of reproductive age in the Thailand-Myanmar border areas showed relatively low sexually risk behaviors for HPV infection. More than one-third of the participants did not know about HPV. The percentage of correct answer to questions about cervical cancer were low.  We encourage the Thai Ministry of Public Health to increase health promotion and health literacy on prevention of HPV and cervical cancer in the women of pre- and reproductive age in the Thailand-Myanmar border area.

Experience of Cervical Cytology and High-Risk HPV Testing (Physician vs Self-Collected) for Primary Cervical Cancer Screening in an Urban Hospital of Thailand

To explore the experience of conventional Pap smear (CPS), physician-collected HPV (pHPV) and self-collected HPV test (sHPV) for cervical cancer (CC) screening in the general population in the north-eastern region of Thailand. A retrospective study was conducted among women who visited the gynecology and colposcopy clinic in Kuchinarai Crown Prince Hospital for CC screening between January 2020 and December 2023. Participants received counselling before choosing between CPS, pHPV, and sHPV testing. Data reviewed from medical records included age, parity, CC screening results, colposcopy results, and treatment. A total of 5,984 women were enrolled in the study. There were 1,727, 2,962 and 1,295 cases in the CPS, pHPV, and sHPV, respectively. The average age of participants was 40.6, 49.5 and 47.6 years old in the CPS, pHPV, and sHPV, respectively. Percentage of multiparous participants were 86.3, 94.4 and 93.8 in CPS, pHPV and sHPV, respectively. Positive test results from the CPS, pHPV, and sHPV were 1.4, 5.7, and 6.8 percent, respectively with statistical significance. Return to colposcopy of CPS (62.5%) was highest and followed by pHPV (35.3%) and sHPV (18.2%) groups with statistical significance. Detection rate of CIN2+/CIN 3+ were 0.1/0.1, 0.5/0.4 and 0.2/0.2 percent from CPS, sHPV, and sHPV groups, respectively with statistical significance. Primary HPV and CPS testing had comparable reliability and acceptability for CC screening among Thai women. High missing rate for reflexed cytology or colposcopy of sHPV was a major issue.

Scrutiny of the Co-Cytotoxic Impact of Metformin-Omeprazole on the Cervical Cancer Cell Line and Their Aptitude to Target Heat Shock 60

This study aimed to assess the simultaneous effect of the metformin-omeprazole combination on inhibiting cervical cancer proliferation. Their ability to target heat shock protein 60. The anticancer properties of the metformin-omeprazole combination in cancer treatment were evaluated by employing a cervical cancer cell line (HeLa cell line). The assessment included two incubation periods: one of 24 hours and another of 72 hours. The concentrations of metformin, omeprazole, and their combination varied from 0.1 to 1000 µg/ml. The study encompassed an estimated combination index value to assess the potential synergistic effect of metronidazole and linagliptin. The study employs computational molecular docking simulation to determine the affinity of metformin and omeprazole for binding with heat shock protein 60. The study concluded that the metformin-omeprazole combination significantly reduced the proliferation of cervical cancer cells. The inhibitory effect was demonstrated to depend on the mixture's concentration and the treatment duration. The combination index indicates that metformin and omeprazole synergistically interacted. furthermore, the computational molecular docking simulation indicated that metformin and omeprazole exhibited a propensity to associate with Hsp 60. The docking scores for metformin and omeprazole were measured at -7.3 kcal/mol and -6.2 kcal/mol, respectively. Study indicates that the simultaneous use of metformin and omeprazole synergistically suppresses the growth of cervical cancer cells via both cell cycle-specific and cell cycle-nonspecific pathways. The findings, corroborated by molecular docking studies, demonstrated that metformin and omeprazole can bind to Heat Shock Protein 60. Furthermore, the molecular docking data elucidate the synergistic interactions among the combination components since every drug occupies a distinct binding site on Hsp 60, indicating a complementary binding mode with Hsp 60. Regarding the expected adverse impact and the known pharmacokinetic profile of the mixture's components, the mixture offered an attractive alternative treatment for cervical cancer.

Comparison of Sexual Function after Thermal Ablation Versus Loop Electrosurgical Excision Procedure (LEEP) for Cervical Intraepithelial Neoplasia (CIN 2 and 3): A Randomized Controlled Trial

The prevention of cervical cancer can be achieved by treating high-grade cervical precancerous lesions. Treatment options for cervical precancer include excisional procedures, and ablation treatments. Despite the long pre-invasive course of the disease, literature addressing sexual function post-treatment for cervical pre-invasive lesions is scarce. This study aims to bridge this gap and assess the sexual function and the acceptability, efficacy, safety, and complications of loop electrosurgical excision procedure (LEEP) versus thermal ablation. The prospective open-label randomized controlled trial recruited women aged 22-55 with histologically confirmed Cervical Intraepithelial Neoplasia (CIN) 2 and 3 lesions. Participants were randomly allocated to either thermal ablation or LEEP. All cases were followed up with a Pap smear at three- and six-months post treatment. Sexual health assessments were conducted using a questionnaire at baseline and 3 months post-procedure. Secondary outcome measures included comparison of acceptability, pain, and side effects between the two treatment measures. Out of 1356 screened cases, 60 were included in the study and randomized in two groups. The groups had similar baseline characteristics. Duration of LEEP was longer than thermal ablation (25.33 vs. 20.67 minutes), with higher pain reported 10 minutes post-procedure in the LEEP group. Three months post-procedure, both groups showed comparable acceptability and symptom relief. Sexual function parameters significantly improved in the thermal ablation group compared to LEEP, including satisfaction, desire, lubrication, flexibility, and ability to reach climax. LEEP and thermal ablation are effective treatments for CIN with similar efficacy at 6 months. Thermal ablation demonstrated advantages in procedure time and post-procedural pain but exhibited varying effects on sexual function, improving satisfaction and desire. In contrast, LEEP showed a decrease in satisfaction and potential alterations in lubrication and flexibility. Larger-sample, longer-term studies are recommended for further insights.

Inflammatory Markers in Prior Loop Electrosurgical Excision Procedure (LEEP) as a Prognosis Factor in the Recurrence of Cervical Intraepithelial Neoplasia

To investigate the relationship between preoperative inflammatory markers and recurrence of CIN after loop electrosurgical excision procedure (LEEP). A retrospective historical cohort study was conducted at gynecologic oncology unit, Bhumibol Adulyadej Hospital, Royal Thai Air Force, Thailand. Data was collected from medical records of CIN cases from year 2016 to 2021. Inclusion criteria were subjects who were diagnosed of CIN and underwent LEEP with pathologic confirmation and followed up for two years (at 6 months, 1 year, and 2 years). Preoperative complete blood count (CBC) was obtained within one month for calculation as systemic inflammatory values. One hundred and ten cases of CIN were enrolled. Mean age of participants was 48.1 years old. Three-fourths (83/110) of the participants had histological confirmation as CIN2/3. Sixteen (18/110) and twenty (22/110) percentage of cases had recurrence of disease at 1 and 2 years, respectively. Monocytes /lymphocytes ratio (MLR) and systemic inflammation response index (SIRI) could predict recurrence of CIN within 2 years. MLR more than 0.16 and SIRI more than 0.57 gave the sensitivity and negative predictive value (NPV) at percentage of 77.3/ 81.8 and 91.8/ 90.2, respectively. Combination of MLR and SIRI had sensitivity and NPV at 90.5 and 95.4 percent, respectively. MLR and SIRI could not predict marginal involvement, glandular involvement, and LEEP confirmed CIN 2/3. Pretreatment MLR and SIRI were statistically significant in predicting the recurrence in CIN after post LEEP procedure within 2 years follow up.

Role of Cyclooxygenase-2 (COX-2) Expression as a Prediction of Persistent Cervical Low Grade Squamous Intraepithelial Lesion (LSIL)

Cervical cancer rates have been decreasing due to improved screening programs targeting HPV infections. Cervical Intraepithelial Neoplasia (CIN), including CIN 1, can regress, persist, or progress, leading to patient anxiety. The expression of Cyclooxygenase-2 (COX-2) may serve as an indicator of poor cancer outcomes and could potentially predict the persistence of CIN 1. To assess the relationship between COX-2 expression and the persistence of low-grade squamous intraepithelial lesions (LSIL) or CIN 1. Additionally, to compare baseline characteristics between patients with persistent and regressive LSIL/CIN 1. This case-control study included patients diagnosed with CIN 1 at least 12 months prior to the study started and followed up between May 2019 and April 2020. Pelvic examination and liquid-based cytology collection were performed. Participants were divided into two groups: regressive and persistent, based on current examination results. Previous cervical biopsy slides were reviewed by two gynecologic pathologists to confirm the CIN 1 diagnosis. Paraffin blocks from selected samples underwent immunohistochemistry staining to evaluate COX-2 expression, which was assessed using the Allred score. Clinical risk factors, cervical cytology, HPV genotype, and Allred scores were analyzed. Of the 161 patients recruited, 132 were in the regressive group and 29 in the persistent group, yielding a regression rate of 81.99%. COX-2 expression was observed in 83.8% of the patients. In the regressive group, 110 out of 132 patients tested positive for COX-2, while 25 out of 29 patients in the persistent group were COX-2 positive. Median Allred scores were similar between the groups, with no significant correlation between COX-2 expression and persistent LSIL/CIN 1 (p = 0.663). Furthermore, there was no significant correlation between Allred scores, high-risk HPV infection, and high-risk HPV status (p = 0.66 and p = 0.80). Persistent detection of high-risk HPV was found to be a significant risk factor for persistent LSIL in univariate analysis (p = 0.001), but not in multivariate analysis. COX-2 expression and HPV status do not appear to predict persistent LSIL/CIN 1. Further research is needed to identify reliable predictors for the persistence of LSIL/CIN 1.

Disparities in the Uptake of Cervical Cancer Screening in Kuwait: A Cross-Sectional Analysis of the Nationwide WHO STEPS Survey

Cervical cancer is projected to increase by 48% in Kuwait by 2035. Detecting cervical cancer early can prevent its progression. Given the paucity of prior research in Kuwait, we aimed to investigate cervical cancer screening (CCS) prevalence using a representative sample and assess disparities in CCS uptake among Kuwaiti women. We obtained a representative Kuwaiti sample (n=3915) through WHO's STEPwise approach to noncommunicable disease risk factor surveillance (STEPS). Demographic, socioeconomic, and health data were analyzed for women aged 18-69 (n=2292) with available CCS information. Results were age-weighted, and analysis included descriptive statistics, bivariate analysis, and multivariable logistic regression adjusted for sociodemographics and health status. Weighted CCS prevalence was 15.2% (95% CI [13.7-16.7]). Older women had higher odds of CCS; 60-69 age group was four times more likely to be screened than the 18-29 group (OR 4.0 [2.6-9.4]). Married (OR 5.0 [2.6-9.4]), divorced/widowed (OR 5.2 [2.6-11.3]) women, retirees (OR 2.1 [1.3-3.5]), those with high school degree or higher (OR 2.7-2.8 [1.1-7.0]), and those with hypertension (OR 1.7 [1.1-2.4]) had higher odds of screening. Overweight/diabetic women had 40% lower odds of CCS (OR 0.6 [0.4-0.9]), and non-Capital residents had 60% lower odds (OR 0.4 [0.3-0.6]). CCS uptake among Kuwaiti women is minimal, with disparities in age, education, residence, marital status, employment, and health issues. Efforts are needed for organized, widely promoted, physician-endorsed screening programs  addressing such disparities and Kuwait's cultural norms.

Counselling to Screening: Honing an Institutional Cervical Cancer Screening Program

Cervical cancer screening is an important tool in WHO's global strategy for cervical cancer elimination. The objective of the study was to suggest and study the impact of capacity building interventions to increase cervical cancer screening rates in women aged 30-49 years attending the gynecological OPD. As part of a multicentric study, qualitative research was carried out at a tertiary care institute (from September 2021 to June 2022) to gather information regarding the existing cervical cancer screening practices, analyze factors preventing universal screening, and develop troubleshooting strategies. A fishbone analysis was done to identify barriers to cervical cancer screening. Stepwise sequential implementation of seven Plan-Do-Study-Act (PDSA) cycles which included; doctors training, policy formation, dedicated counsellor and reminders on social network groups, OPD card stamps, reading and educational material, screening in all OPD rooms and finally establishment of dedicated screening room. The effect of each on counselling and screening of eligible women was noted. With the implementation of these PDSA cycles, the rates of eligible women being screened increased from 10.6% at baseline to 44.8% at the end of the study period. The percentage of counselled women increased to 70% and it was observed that counselled women were more likely to get screened. Educating women about the importance of cervical cancer screening and the creation of a dedicated screening room were the two most important quality improvement interventions.

HPV Vaccination Program in Indonesia: Effectiveness, Dose, Scale-Up Costs, Future Prospects, and Policy Recommendations

Among females, Cervical cancer affects more frequently than any other type of cancer in Indonesia. Cervical cancer and illnesses linked to HPV infection are potentially preventable through vaccination.  The aim of his study was to describe the characteristics of the available vaccines, the  policy, and the implementation of HPV vaccination in Indonesia. A scoping review was performed by collecting information from previous studies, including general information about vaccines, vaccine efficacy, effectiveness, and safety. Approved HPV vaccine products in Indonesia have proven efficacy, effectiveness, and safety. Procuring vaccines through GAVI/UNICEF and the government has both advantages and disadvantages. Alongside the limited supply, numerous research studies show that dosage reduction to a single dose provides equal protection compared to 2-3 doses. The benchmark implementation of the single dose has been done in many countries, ranging from high-income to low-middle-income countries. Therefore, considering other countries and Indonesia's high population and vaccination burden, proposed updates for vaccination programs are recommended to achieve the cancer elimination target by 2030. Improvement of vaccination programs using single-dose HPV vaccine to prevent cervical cancer requires a coherent framework, sufficient funds, effective management of stakeholder interests, and sensitivity to contextual factors.

Breaking Barriers in Cancer Screening: Understanding Participant Dropout in Breast and Cervical Programs in Morocco

This study aimed to investigate loss to follow-up (LFU) rates within breast and cervical cancer screening programs in Kenitra-Morocco, identifying contributing factors from both patient and healthcare worker perspectives to enhance care continuity. The study was a non-experimental, mixed-methods design conducted in three-phases. We started by identifying LFU women and their characteristics from medical records, interviewing LFU women to ascertain reasons for discontinuation, and surveying healthcare workers for perceived determinants of LFU through semi-structured questionnaires. The study covered primary healthcare centers, the Reproductive Health Reference Center (RCRH) in Kenitra, and the National Institute of Oncology (NIO) in Rabat. Of 1,225 women studied, 94 cancer cases were diagnosed, with LFU rates varying across care stages. Key factors associated with LFU included age (p<0.005, OR=1.67, CI[1.2-2.4]), marital status (p<0.03, OR=0.8, CI[0.65-0.98]), distance from healthcare facilities (p<0.00, OR=2, CI[1.3-4.0]), and medical coverage (p<0.03, OR=2.3, CI[1.3-4.0]). Healthcare workers cited poor communication, organizational issues, and staffing shortages as barriers to follow-up. The study underscores LFU's multifaceted reasons in Kenitra's cancer screening programs, suggesting improvements in communication after a positive screening test, re-engagement strategies, and financial accessibility. Addressing these issues is essential for reducing LFU rates, enhancing cancer care outcomes, and decreasing breast and cervical cancer mortality in Morocco.

Antiproliferative Impact of Linagliptin on the Cervical Cancer Cell Line

This study aimed to assess linagliptin's inhibitory effects on the proliferation of cervical cancer cell lines and investigate its potential for targeting human heat shock protein 90. Linagliptin's cytotoxicity was assessed on a cervical cancer cell line (Hela cancer cell line) at two different incubation periods, 24 and 72 hours. The molecular docking between linagliptin and the receptor protein human Hsp 90 (PDB code: 5XRE) was performed using the Biovia Discovery Studio and AutoDock tool software. The Discovery Studio visualizer generated three-dimensional (3D) and two-dimensional (2D) interactive images. The study's cytotoxicity results demonstrated that linagliptin can inhibit the proliferation of cervical cancer cells. The cytotoxicity exhibited a time-dependent pattern (cell cycle specific). The molecular docking study was conducted to investigate the interaction between linagliptin and human Hsp90. The study identified 11 sites where linagliptin can bind to Hsp90 amino acid residues. The total docking score for this interaction was -10.3 kcal/mol. The most potent binding occurred through conventional hydrogen bonds with the ASP:54 amino acid residues at a distance of 2.93 Å. The docking scores for linagliptin were comparable to those of the reference drug geldanamycin, indicating a strong interaction between linagliptin and Hsp90. The study has found that linagliptin successfully reduces the growth of cervical cancer cells with a time-dependent cytotoxic pattern. The potential anticancer mechanism of linagliptin can be inferred by analyzing the docking score and docking pattern between linagliptin and Hsp90, suggesting that linagliptin targets human Hsp 90.

A Comprehensive Integration of Data Regarding the Correlation of TNF-α rs1800629 Polymorphism with Susceptibility to Cervical Cancer

Cervical cancer, globally, ranks as the runner-up among the most prevalent forms of cancer affecting women. The role of the tumor necrosis factor alpha (TNF-α) polymorphism in the susceptibility to cervical cancer has been a subject of interest. However, the current evidence regarding this association remains inconclusive. To address this uncertainty, eligible studies were systematically searched and retrieved from various databases including Cochrane Library, EMBASE, PubMed, Web of Science, CNKI, and Wanfang database. The search was conducted until September 01, 2023. The collected literature was then subjected to independent analysis by two authors. The pooled odds ratio along with the corresponding 95% confidence interval was calculated using different genetic models. Additionally, sensitivity and cumulative analyses were performed to assess the stability of the obtained results. A total of 29 case-control studies involving 8850 cases and 9286 controls were included in the present analysis. The findings revealed that the TNF-α rs1800629 polymorphism increased the risk of cervical cancer under the allele genetic model (A vs. G: OR = 1.277, 95% CI = 1.104-1.477, P = 0.001) in the general population. Subgroup analysis based on ethnicity demonstrated that this polymorphism was associated with an increased risk of cervical cancer in Caucasian and African women, but not in Asians. Furthermore, subgroup analysis based on country of origin indicated a significant correlation between the TNF-α rs1800629 polymorphism and an increased risk of cervical cancer in American and Chinese women, but not in Iranian women. The findings from this meta-analysis suggest that the TNF-α rs1800629 polymorphism is a risk factor for cervical cancer in the general population, particularly in Caucasian and African women. However, further well-designed studies are warranted to validate these findings.

In vitro Evaluation of Anti-Cancer Potential of Different Solvent Extracts Derived from Clerodendrum Infortunatum Linn against Cervical Cancer

Cervical cancer is a prevalent and deadly malignancy in females, with chemotherapy often proving ineffective due to significant side effects and the development of chemo-resistance. This study investigates the medicinal potential of Clerodendrum infortunatum linn. , a genus with approximately 500 species in the Lamiaceae family. Limited research exists on the species of Clerodendrum infortunatum and its various solvent extracts. The study aims to assess the anti-cancer properties of different solvent extracts from this plant on human cervical cancer cells. The study examines the plant's phytochemical components and their potential to inhibit cancer growth. Aerial parts of the plant were extracted using the Soxhlet method, and the presence of Rutin, Quercetin, and Gallic Acid in specific solvent extracts was validated through High-Performance Thin Layer Chromatography (HPTLC). In vitro assays, including MTT, Apoptosis, Cell Cycle analysis, Intracellular Reactive Oxygen Species assessment, and Gene expression PCR, were conducted to investigate the plant's anti-cancer properties further. The outcomes of the phytochemical assessment indicated that Rutin was predominantly present in the water extract, with quercetin being more concentrated in the decoction, and the hydro-alcoholic extract showing elevated levels of gallic acid. Notably, the decoction extract demonstrated the highest cytotoxic activity, primarily through early apoptosis and arrests in the S-phase and G2M phases. Clerodendrum infortunatum exhibited a reduction in Intracellular Reactive Oxygen Species. The gene expression analysis disclosed an impact on the BCL-2 gene. Notably, Clerodendrum infortunatum exhibited the ability to initiate early apoptosis, halt the cell cycle at the S and G2M phases, and diminish levels of reactive oxygen species significantly. The gene expression analysis revealed an influence on the BCL-2 gene. To sum up, this research underscores the encouraging cytotoxic and antioxidant attributes of Clerodendrum infortunatum, implying its potential for cervical cancer treatment.

Effectiveness of Group Cognitive-Behavioral Therapy for Managing Anxiety and Depression in Women Following Hysterectomy for Uterine Cancer

Hysterectomy as well as uterine cancer could be associated with a long-term risk of mental disorders. The purpose of this study is to investigate the effectiveness of group cognitive-behavioral therapy (GCBT) in reducing anxiety and depression in women who have undergone hysterectomy for uterine cancer. This experimental, pretest-post-test study was conducted in an academic hospital. 26 women with uterine cancer who underwent hysterectomy were recruited and randomly divided into two equal groups as the experimental and control groups. The experimental group was treated by GCBT for eight 1-hour sessions (by a senior psychology expert) every week until 8 weeks. Otherwise, no intervention was performed for the control group. The anxiety and depression scores of all participants were assessed and compared before and after the therapy sessions by Beck Anxiety (BAI) and Beck Depression-second version (BDI-II) questionnaires. The mean±SD age of the participants was 33.6±4.1. Our result found significant different after GCBT in both anxiety (p=0.000) and depression (p=0.000) scores in the experimental group. However, no differences between pre and post-test scores in the control group were observed. Compared to the control group the rate of depression (p=0.000) and anxiety (p=0.000) in the case group was significantly decreased after therapy. GCBT is effective in reducing anxiety and depression in women after hysterectomy. The use of GCBT in oncology centers along with medical treatments to reduce mental distress, improve mental health, and accelerate the recovery process of patients with uterine cancer and other cancers seems necessary.

Co-existing of HSV1/2 or EBV Infection with the Presence of High-Risk HPV DNA in Cervical Lesions in the Southwest of Iran

While the vast majority of the cervical lesions have been attributed to the HPVs, the role of EBV and HSV1/2 as co-factors in the progression of these abnormalities needs more investigation. In this study, we aimed to determine the co-existence of EBV or HSV in cervical lesions infected with high-risk HPVs. Totally, 102 formaline-fixed cervical lesions with different pathological grades (LSIL, HSIL, and SCC) were enrolled in this study. DNA was extracted, and its integrity was examined by PCR assay. Two conventional PCRs were performed for the detection of EBV and HSV1/2 genomes in the tissue specimens. Besides, an in-house Real-Time PCR, as well as a nested PCR assays following sequencing, was performed to detect HPV genotypes in EBV or HSV positive samples.  Results: The mean age of the participants was 42.8±13 years. Out of 102 samples, 32% (n=33) were confirmed to be LSIL, 42.2% (n=43) were HSIL, 22.5% (n=23) were SCC and 2.9% (n=3) were adenocarcinoma.  EBV genome was detected in 13(12.7%) samples including 2 of LSIL, 8 of HSIL and 3 of SCC. All EBV positive samples harbored high risk HPV types 16,18 and/or 31 co-infections. However, the HSV genome was not found in any of the samples. Our result revealed that the frequency of EBV infection is higher in HISL than LSIL.  Moreover, the amount of HPV load showed an elevated level among co-infected patients, which indicates that EBV might be an enhancing factor of disease progression. In contrast, HSV may not has a role as a co-factor in cervical lesions pathogenesis.

Dynamic Changes in Body Composition and Protein Intake in Epithelial Ovarian Cancer Patients Undergoing Chemotherapy: A Preliminary Study

Ovarian cancer patients often face poor nutritional status, with body composition (BC) serving as a significant prognostic indicator. Skeletal muscle mass (SMM) and fat-free mass (FFM) are crucial predictors of both survival and hospitalization duration. Increasing protein intake has been linked to improvements in SMM and FFM. This study aimed to document the alterations in BC parameters among ovarian cancer patients undergoing chemotherapy and correlate these changes with their nutrient intake. Twelve female patients with stage III ovarian cancer who received first-line chemotherapy were categorized based on their body mass indices (BMI). BC parameters were assessed using an 8-point bioelectrical impedance analysis with a frequency of 50 Hz-60 Hz and measurement impedance range of 10 Ω-1000 Ω. Nutrient intake (energy, protein, fat, and carbohydrate) was assessed before (T0), during the 3rd (T3), and 6th cycle of chemotherapy (T6) through 24-hour food recall. Significant increases in body weight (BW)were observed in the underweight group (from 40.9 to 46.8 kg, p=0.001), concomitant with enhancements in all BC parameters. While changes were noted in SMM, they were not statistically significant (p=0.105).Among the underweight group, a protein intake above 1.2 g/kg BW led to an uptrend trend in SMM. Conversely, FFM in overweight/obese patients decreased significantly (from 37.6 to 36.4 kg, p=0.005) due to a a reduction in body water. Throughout chemotherapy, fat mass (FM), visceral fat (VAT), and phase angle (PhA) increased in all patient groups, reflecting heightened fat and carbohydrate intake. Among stage III ovarian cancer patients, BC undergoes dynamic changes dynamically during the course of chemotherapy, with more pronounced enhancements observed in FFM among underweight patients. Notably, improvements in PhA, SMM or FFM were particularly evident among underweight patients with a protein intake above 1.2 g/kg BW.

Prediction Score of Cervical Intraepithelial Neoplasia Grade II or Higher (CIN2+) in Patients with Low-Grade Cytology (ASC-US, LSIL) and HPV- Negative or Non-type 16/18 High-Risk HPV-Positive Results

The aim of this study was to identify and quantify the risk factors with the greatest impact on the development of CIN2+ in patients with low-grade cytology and either HPV-negative or high-risk HPV-positive (non-16/18) results. The secondary aim was to develop and validate a multiparameter, risk-based prediction system. This retrospective cohort study was conducted in the Department of Obstetrics and Gynecology at Thammasat University Hospital between January 2021 and December 2024. Women who underwent cervical cancer screening and had a report of low-grade cytological abnormalities (ASC-US or LSIL), with either non-16/18 high-risk HPV infection or a negative HPV test, were included. A total of 480 participants were included. The mean age of participants was 40.7 years. The prevalence of CIN2+ was 15.6% (75/480). The predictive model was developed by incorporating six factors: having three or more deliveries, six or more lifetime sexual partners, smoking, no cervical screening within five years, lack of HPV vaccination, and high-risk HPV positivity (non-16/18). Subjects with a score of 5 or more out of 14 points were classified as high-risk and recommended to undergo colposcopy within four weeks. The model demonstrated a sensitivity of 97.3% and a negative predictive value (NPV) of 98.6%. The risk factors for CIN2+ included having three or more deliveries, six or more lifetime sexual partners, smoking, no cervical screening within the past five years, lack of HPV vaccination, and high-risk HPV positivity (non-16/18). The predictive model demonstrated a sensitivity of 97.3% and a negative predictive value (NPV) of 98.6%.

Enhancing Cervical Cancer Screening Among Northern Thai Women: Satisfaction with Self-Collected HPV DNA Testing under the National Program

Cervical cancer is a leading cause of cancer-related morbidity and mortality among women in Thailand. Despite the availability of national cervical cancer screening programs, participation rates remain low in Northern Thailand due to barriers such as limited accessibility and discomfort with clinical sample collection. Self-collected HPV DNA testing offers a promising alternative to traditional screening methods by addressing these barriers and improving access to care. Cervical cancer is a major health burden in Thailand, yet participation in national screening programs remains low, particularly in Northern Thailand. This study evaluated satisfaction with self-collected HPV DNA testing and examined factors influencing screening acceptance to inform strategies for increasing uptake. A cross-sectional study was conducted among 299 women aged 30-60 years attending the national cervical cancer screening program at Maharaj Nakorn Chiang Mai Hospital. Participants performed self-collection following a demonstration and completed a five-point Likert scale satisfaction survey. Descriptive statistics and logistic regression were used to assess satisfaction and identify predictors of screening intention. Most participants (85.95%) strongly agreed that self-collected HPV DNA testing improved screening accessibility, and 100% found the process easy to follow. Mean satisfaction scores were high for accessibility (4.85/5), effectiveness (4.82/5), and reliability (4.81/5). No invalid samples were reported, and beta-globin Ct values confirmed high-quality sample collection (mean Ct = 29.00 ± 1.70). Education level significantly influenced screening intention (OR = 17.61, p = 0.039). Self-collected HPV DNA testing was highly satisfactory and could enhance national screening programs, especially in underserved populations.

Bioinformatics Analysis Reveals Distinct Oncogenic Profiles of HPV-16 and HPT-18 to Other Subtypes in Cervical Cancer

HPV types 16 and 18 are associated with 70% of invasive cervical cancers. Between these two types of HPV, HPV type 16 is more commonly found in cervical cancer patients, whereas HPV type 18 is less frequently reported. Currently, the molecular mechanism underlying the increased cancer risk in HPV type 16, compared to HPV type 18, has not yet been fully elucidated. This paper aims to identify the factors that make HPV type 16 the primary contributor to cervical cancer by comparing gene expression profiles with those of HPV type 18. The examination began after obtaining the RNA sequencing dataset (GSE192897). The dataset's genes were then analyzed to identify differentially expressed genes (DEGs) using the GEO2R tool. With the help of Enrichr and SRplot tools, the DEGs were first enriched and analyzed through Gene Ontology (GO), GeDiPNet, and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, a protein-protein interaction (PPI) network was constructed using Cytoscape, and the top ten hub genes were ranked with the help of CytoHubba. DEG analysis revealed 128 differentially expressed genes (DEGs), including 14 upregulated and 114 downregulated genes. The upregulated genes were associated with positive regulation of interferon-beta production, vesicle-related processes, endopeptidase inhibitor activity, and interferon-gamma signaling. The downregulated genes were linked to positive regulation of cell motility, the endoplasmic reticulum lumen, cytokine activity, and signal transduction. There are several differentially expressed genes (DEGs) in HPV type 16 compared to type 18; these upregulated genes may potentially play a role in promoting cervical cancer development more significantly than HPV type 18. These DEGs underscore the urgency of implementing HPV genotyping tests to identify HPV types with higher cervical cancer prevalence. This analysis identified BUB1, DLGAP5, and ASPM as key genes specifically expressed in HPV-16/18-related cervical cancer, suggesting their potential as biomarkers for prognosis and disease progression.

Pesticide Exposure and the Risk of Ovarian Cancer among Postmenopausal Women in Rural Punjab, India

Punjab, a state in Northern India, has reported an alarming rise in cancer cases, which has been linked to the extensive use of pesticides in agriculture. Ovarian cancer, often diagnosed at late stages, lacks systematic screening within the population under the national program. The present study aimed to screen postmenopausal women for ovarian cancer and to evaluate pesticide exposure as a potential risk factor. A total of 1,327 postmenopausal women, residing in 48 villages for at least ten years, were screened annually for CA-125 levels. Women with CA-125 levels >35 U/mL were referred for transvaginal ultrasound. Demographic data were collected through a semi-structured questionnaire. For pesticide profiling, a case-control design was adopted. Blood samples were collected and analyzed for organochlorine and organophosphate residues using gas chromatography. Among 1,327 postmenopausal women screened, 30 (2.3%) had elevated CA-125 levels (>35 U/ml); no ovarian cancers were detected during follow-up imaging and specialist evaluation. In the case-control analysis (24 cases; 42 controls), detectable pesticide residues were associated with a crude 6.7-fold increased odds of ovarian cancer (95% CI: 1.4-32.7). After multivariable adjustment for parity and education, Ethion (aOR = 6.29, 95% CI: 1.37-28.8) and DDE (aOR = 6.39, 95% CI: 1.35-30.3) remained associated, though confidence intervals were wide, reflecting small sample size. In agricultural participants, chlorpyrifos detections were more frequent among controls (OR = 0.12, p = 0.008). Although no ovarian cancer cases were detected during screening, the study highlights the prevalence of pesticide exposure among women in Punjab's Malwa region and its possible association with ovarian cancer risk. Routine population screening using CA-125 is not supported in light of current evidence and guidelines. Instead, strengthening diagnostic and registry systems in rural areas, reducing harmful exposures through safer agricultural practices, and conducting well-powered prospective studies with repeated exposure assessments are essential to clarify risks and inform targeted strategies in high-exposure settings.

Missed Opportunities in Cervical Cancer Prevention: Knowledge and Screening Practices Among Women with Hemoglobinopathies in Greece

Women with hemoglobinopathies represent a chronically ill population with frequent healthcare contact, yet limited integration into preventive health programs. Despite the proven effectiveness of HPV vaccination and screening, cervical cancer remains a preventable cause of both morbidity and mortality. To assess the levels of knowledge, awareness, and adherence to cervical cancer prevention and screening practices among women with hemoglobinopathies in Greece. A cross-sectional study was conducted among 202 women with thalassemia or sickle cell disease, attending a tertiary hospital's Hemoglobinopathy Unit in Athens between December 2023 and March 2024. Data were collected using the validated Cervical Cancer Knowledge and Prevention Questionnaire (CCKP-64) and analyzed with SPSS 25, using descriptive and inferential statistics. Nearly all participants were aware of cervical cancer (98.5%), the Pap test (99.0%), and the HPV vaccine (96.5%). However, only 6.5% were vaccinated against HPV, while 75.2% underwent annual Pap screening. Higher adherence to screening was associated with younger age (p = 0.009), employment status (p = 0.032), and higher income (p = 0.049). Knowledge regarding risk factors was moderate, with 58.4% recognizing HPV infection as the main cause. The most frequent reason for non-compliance was negligence (14.8%). Despite adequate awareness of cervical cancer and good adherence to Pap testing, HPV vaccination rates remain strikingly low among women with hemoglobinopathies. This highlights missed opportunities to integrate HPV vaccination and education into chronic disease management. Tailored preventive strategies and continuous awareness campaigns are essential to achieving the WHO's 2030 cervical cancer elimination goals.

HPV Self-Sampling for Cervical Cancer Screening in Morocco: A Cross-Sectional Study

Morocco is currently planning to introduce HPV testing as the primary screening method in routine cervical cancer screening. Accordingly, HPV self-sampling offers a potential solution to increase participation rates, particularly in underserved regions. Therefore, this study was designed to assess the feasibility and acceptability of HPV self-sampling using the GeneXpert assay as an alternative to clinician-administered screenings in Morocco. A cross-sectional study was conducted among 997 women aged 30 or 40 years from four Moroccan provinces. Participants were offered the choice of clinician-collected sampling, supervised self-sampling, or unsupervised self-sampling. Socioeconomic and clinical data were collected using structured questionnaires, and HPV detection and genotyping were performed using the GeneXpert HPV assay. Overall, 13% of participants opted for self-sampling, including 4.8% who chose unsupervised, and 8.2% supervised self-sampling. Women living in urban areas, younger participants (30 years old), and those with higher education and income levels were more likely to select self-sampling. Satisfaction was high: 92.2% found the procedure easy to perform, all participants reported comfort using the cytobrush, and all indicated willingness to recommend the test to relatives or friends. Additionally, the diagnostic performance of high-risk HPV (hrHPV) testing was comparable between self-collected and clinician-collected samples, demonstrating no effect of sampling method on HPV detection. HPV self-sampling is feasible and highly acceptable among Moroccan women. However, the low uptake, particularly in rural settings, highlights the need for targeted education and awareness efforts. Integrating self-sampling into national screening programs may improve participation and contribute to reducing cervical cancer incidence in Morocco.

Phytochemical Analysis and Apoptosis-Inducing Anticancer Activity of Buddleja polystachia Leaf Extract against HeLa Cell Lines

Cervical cancer is the second leading cause of mortality in women globally, with its incidence increasing due to multidrug resistance (MDR) and adverse side effects associated with chemotherapeutic agents. Hence, this study was carried out to investigate the selective cytotoxicity and apoptotic induction potential of Buddleja polystachya leaf diethyl ether (BPL-DE) extract on cervical cancer HeLa cell lines. The selective cytotoxicity of leaf extracts of B. polystachya was assessed by the MTT assay. The apoptotic induction potential of BPL-DE extract at IC₅₀ (20 µg/mL) was assessed by Acridine Orange/Ethidium Bromide (AO/EB) dual staining. Furthermore, qRT-PCR analysis was performed to study mRNA gene expression of pro-apoptotic (Bax, p53) and anti-apoptotic genes (Bcl-2, survivin), as well as caspase-9 and caspase-3 gene expression levels. The BPL-DE extract showed the highest selective cytotoxic effect against HeLa cells, with an IC₅₀ of 20 µg/mL, resulting in a selective index of 25.31. AO/EB dual-staining analysis revealed that the BPL-DE extract at IC₅₀ (20 µg/mL) significantly induced late apoptosis (p≤0.001). qRT-PCR results showed that the mRNA expression levels of Bax and p53 increased by 3.96-fold (p≤0.01) and 5-fold (p≤0.001), respectively. In contrast, Bcl-2 and survivin mRNA expression levels were significantly downregulated by 1.02-fold (p≤0.01) and 1.13-fold (p≤0.001), respectively, at two-fold IC50 (40 µg/mL). The BPL-DE extract also upregulated the mRNA expression of caspase-9 and caspase-3 by 32.07-fold (p≤0.001) and 15.06-fold (p≤0.01), respectively, at two-fold IC50. The findings of this study demonstrate that the BPL-DE extract significantly induced the p53-mediated intrinsic apoptotic pathway in HeLa cell lines and provides a potential alternative therapeutic agent for cervical cancer treatment by minimizing damage to normal cells.

Tumor Budding Significance as a Biomarker for Clinicopathology and Prognostic Evaluation in Gynecological Malignancy: A Bayesian Meta-Analysis

Tumor budding (TB) has been recommended as a marker for prognosis and therapeutic decision-making in various types of cancer, yet it has not been comprehensively studied in gynecological malignancies. This study aimed to evaluate the relationship between TB and clinicopathological features, as well as prognosis, in patients with gynecological malignancies, using a Bayesian meta-analysis design. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 protocol was followed. A systematic literature search was conducted using PubMed, ScienceDirect, and Cochrane databases. A meta-analysis was performed to assess the relationship between TB and clinicopathological parameters using odds ratios (ORs). Prognostic outcomes were analyzed using hazard ratios (HRs). Specific Bayesian priors were applied to each variable. Data analysis was conducted using R (version 4.4.0). Eighteen cohort studies (n = 3,320) involving patients with cervical and endometrial cancer were included. Bayesian meta-analysis showed that TB was significantly associated with clinicopathological parameters, specifically cancer stage (OR=2.91; 95%CrI: 1.86-4.41; prediction interval (PI) OR=2.92; 95%CrI: 0.82-9.92; τ2=0.53), grading (OR=5.00; 95%CrI: 2.83-8.76; PI OR=5.00; 95% CrI: 0.89-27.87; τ2=0.77), nodal involvement (OR=3.63; 95%CrI: 2.41-5.47; PI OR=3.63; 95%CrI: 0.85-15.52; τ2=0.66), and lymphovascular invasion (LVI) (OR=4.22; 95%CrI: 2.52-6.92; PI OR=4.22; 95%CrI: 0.63-27.80; τ2=0.89). Overall survival (OS) showed an HR of 2.14 (95%CrI: 1.27-3.63; PI HR=2.14; 95%CrI: 0.83-5.58; τ2=0.25) and DFS showed an HR of 1.20 (95%CrI: 0.77-1.59; PI HR=1.21; 95%CrI: 0.14-2.20; τ2=0.42). Tumor budding is significantly associated with clinicopathological features and prognosis in patients with gynecological malignancies.

Moesin and Ezrin as New Promising Markers for Early Detection of Endometrial Carcinoma: An Immunohistochemical Study

the aim of this study is to evaluate immunohistochemically the expression of ezrin, and moesin, in endometrial lesion cases in order to detect EC at early stages which will have an important implication on the patients' outcome. 100 stored, formalin-fixed, paraffin-embedded tissue blocks of endometrial curettage obtained due to abnormal uterine bleeding or postmenopausal bleeding were collected. Each paraffin block was re-cut by rotatory microtome at 4 μm thickness then mounted on a glass slide and stained by hematoxylin and eosin for routine histopathological examination and on charged slides for immunohistochemistry using an automated staining system (Dako autostainer link 48) with antibodies against Moesin and Ezrin. Cytoplasmic staining was evaluated for both Moesin and Ezrin based on the intensity and extent of staining and scored for each sample. Both Moesin and Ezrin were significantly higher in atypical endometrial hyperplasia compared to benign hyperplasia and significantly higher in endometrial carcinoma compared to atypical hyperplasia. Moesin also significantly correlated with higher tumor grades while Ezrin was significantly higher in postmenopausal women denoting their role in tumor progression and poor prognosis. Both Moesin and Ezrin could be potentially used as predictive markers for endometrial carcinoma screening programmes as well as indicators for cancer progression.

Awareness about Cervical Cancer and HPV Vaccine among Undergraduate College Students in Purba Barddhaman District, West Bengal: A Cross-Sectional StudyVelentur

Cervical cancer is a leading cause of mortality among women worldwide. Human Papillomavirus (HPV) plays a definite role in its causation. This study was conducted to assess the level of awareness about cervical cancer and HPV vaccine among urban and rural undergraduate college students in Purba Barddhaman District, West Bengal. The study was conducted among 420 undergraduate students in two co-educational colleges, one urban and one rural. The data was collected using pre-designed pre-tested open-ended questionnaire and analysed using SPSS (version 23.0). A Chi square test and multiple logistic regression analysis was done to assess the association between variables of interest. Majority of the study subjects,53.8%, were males from urban college and females,52.8%, from rural college and the mean age was 20.09±2.53 and 19.91±2.24 years in urban and rural college respectively. Regarding the knowledge of cervical cancer, only 33.3% from urban and 28.9% from rural college had heard about cervical cancer and 19.5% from urban and 16.1% from rural college had knowledge about its prevention. Regarding HPV infection, 21.3% from urban and 23.3% from rural college had heard about HPV with 13.8% from urban and 12.7% from rural college had heard about the HPV vaccine. Multiple logistic regression analysis revealed that gender retained its statistical significance with risk factors (p=0.007), signs and symptoms (p=0.007) and modes of prevention (p=0.012) of cervical cancer in urban college. In rural college gender was statistically significant with risk factors (p=0.019) and mother's occupation was statistically significant with risk factors (p=0.011) and signs and symptoms (p=0.004) of cervical cancer. Only one-third of the study population had knowledge about cervical cancer and HPV vaccine. Generation of widespread awareness through community participation, mass media involvement and health education is need of the hour.

A Comparative Study of Clinical Outcomes in Locally Advanced Cervical Cancer: External Beam Radiotherapy (EBRT) and Sequential High Dose Rate Intracavitary Brachytherapy (HDRICBT) with or without Concurrent Cisplatin on the Day of ICBT Insertion - A Tertiary Care Center Randomized Controlled Trial in India

The current study aimed to delve into the comparative clinical outcomes between external beam radiation therapy (EBRT) and sequential High Dose Rate Intracavitary Brachytherapy (HDRICBT) with or without concurrent cisplatin administration on the day of intracavitary brachytherapy (ICBT) insertion in women with locally advanced cervical cancer. In this study, conducted between January 2017 and July 2018 at a leading institute in India, diagnosed and untreated patients of locally advanced carcinoma cervix were randomized into two groups. Arm 1 received concurrent cisplatin before each course of brachytherapy, while Arm 2 underwent brachytherapy alone. The outcomes were compared in terms of acute and late toxicities, treatment response, and follow-up. Data analysis was performed using SPSS 16, with statistical significance set at p < 0.05. Both study arms showed similar complete response (CR) rates of 73.3%, with no significant advantage of concurrent cisplatin before brachytherapy. However, a noteworthy trend emerged during follow-up. In the concurrent cisplatin group, the CR rate increased from 73.3% post 1 month of brachytherapy to 86.7% at 3 months and 83.3% at 6 months. Contrastingly, the control group showed CR rates of 73.3% post 1 month, 80% at 3 months, and 76.6% at 6 months. While not statistically significant, this observation suggests a possible enhancement in response rates with concurrent cisplatin and ICBT. Future studies focusing on the optimal drug, dosage, scheduling, and combining cisplatin with other agents are recommended to further explore the potential benefits observed in this study.

Short Course Brachytherapy in Locally Advanced Cervical Cancer; Safety and Response Rate

Overall treatment time (OTT) is an important index for local control in patients with locally advanced‌ cervical cancer treated with definitive chemoradiation (External Beam Radiation Therapy (EBRT), Brachytherapy (BT) and concomittant chemotherapy). This study aimed to evaluate the efficiency and safety of reducing OTT by shortening the brachytherapy duration to one week in the intervention group copared to three weeks in the control group. The study was a non-randomized open-label phase II clinical trial, carried out on 49 cervical cancer patients (26 in intervention grouop and 23 in control group) who received EBRT concomitant with Cisplatin, followed by brachytherap in order to deliver 60 Gy  equivalent total doses in 2-Gy fractions (EQD2) to Intermediate Risk-Clinical Tumor Volume (IR-CTV) and 85-90 Gy EQD2 to High Risk-Clinical Tumor Volume (HR-CTV). In the intervention group, all brachytherapy sessions were performed in 1 week, while for the control group, it was administrated in 3 consecutive weeks. The participants were followed (Minimum follow up time was 6 month and median follow up time was 10 month) to assess response and toxicity of the treatment. Overall, more than 95% of study participants had a complete response and more than 4.0% reported partial response, and no treatment failure was observed. The complete response in intervention and control groups was 96.1% and 95.6%, respectively (P value > 0.05). There was no difference in acute toxicity between the two groups. considering that short course brachytherapy was non inferior to conventional course from point of  Response Rate and Side Effects during follow up time; so this strategy can be  considered as an option for reducing the OTT which can at least cause decreasing the costs. Studies with larger sample size and phase 3 are recommended.

Comparative Analysis of VMAT and IMRT Techniques: Evaluation of Dose Constraints and Bone Marrow Sparing in Cervical Cancer Patients Undergoing Chemoradiotherapy

Carcinoma of the cervix is a globally significant cause of morbidity and mortality among women. Concurrent chemoradiotherapy, a standard approach for locally advanced cervical cancer, invariably involves pelvic irradiation. Although this strategy is effective, it inevitably affects the pelvic bone marrow, a crucial hematopoietic site, and leads to hematological toxicity The potential of IMRT to spare bone marrow in pelvic irradiation settings has been an area of significant interest, with the aim to mitigate the hematological toxicity associated with pelvic radiotherapy. Radiotherapy techniques have evolved in terms of conformity and normal tissue sparing. Our study intends to explore the use of BM sparing techniques among patients of carcinoma cervix. Twenty patients of carcinoma cervix FIGO Stage IIIB treated with concurrent chemoradiotherapy were selected for this study. The external contour of bones was delineated on planning CT as a surrogate for BM. We generated three plans on a single patient:1. without BM as the dose constraint, namely N-IMRT plan; 2. with BM constraint, namely BMS-IMRT plan; 3. VMAT plan in which BM constraint was given. The dose volume histogram (DVH) for planning target volume (PTV) and organs at risk (OAR) were analyzed. BM parameters: V10, V20, V30, V40, mean, maximum and minimum dose were compared.  Results: PTV coverage was comparable in all techniques. VMAT plans resulted in superior BM sparing compared with N-IMRT plan (P-<0.001) and BMS-IMRT plan (P-<0.001, 0.021 and 0.001 respectively for V20, V30 and V40). VMAT plans had better CI compared with BMS-IMRT (P-0.002) and N-IMRT (P-0.001) plans. Our study adds to the growing evidence that VMAT might be the preferred technique for patients with carcinoma of the cervix undergoing concurrent chemoradiotherapy, as it provides comparable target coverage and better sparing of bone marrow compared to IMRT.

Clinical Performance of Self-collected Specimen HPV-DNA vs Clinician- collected Specimen HPV-mRNA to Detect High-risk HPV and High-grade Cervical Lesions and Cancer

Self- collected specimens to detect high-risk (hr) HPV and high-grade cervical lesions (CIN2+) has been introduced aiming to increase cervical cancer screening coverage. The performance of self- collected specimen  compared to clinician collected specimen is one major concern. This study aimed to compare self-sampling HPV-DNA and clinician-sampling HPV-mRNA to detect hr-HPV and high-grade cervical lesions. Women with abnormal cervical cytology and/ or positive hr-HPV who attended the colposcopy clinics in 10 tertiary hospitals in Bangkok were enrolled. Self-collected specimens were evaluated for  HPV DNA using Cobas® 4800 HPV test prior to the clinician-collected specimens which were tested for HPV mRNA with APTIMA® HPV Assay. Subsequent colposcopy with biopsy was performed. The detection rates of hr-HPV from both HPV tests and their performance to detect high-grade lesions pathology were compared. Data from 497 women's specimens were analyzed. Both samplings had 86.8% concordance rate in detecting hr-HPV (Kappa 0.670; 95% confidence interval [CI] 0.599-0.746, P value < 0.001). The sensitivity (95% CI) of self-collected specimen HPV DNA and clinician- collected specimen HPV-mRNA to detect high-grade lesions were 91.8% (85.4%-96.0%) and 90.2% (83.6%-94.9%) respectively. The corresponding negative predictive values (95% CI) were 91.9% (85.6%-96.0%) and 91.7% (86.0%-95.7%) respectively. HPV DNA testing from self-collected specimen to detect HR-HPV demonstrates high concordance with HPV mRNA testing from clinician-collected specimen. The sensitivity and negative predictive value of both tests to detect high-grade lesions are comparable.

Genetic Characterization of Ovarian Tumor Tissues from Patients with Epithelial Ovarian Cancer in a Philippine Tertiary Hospital: A Descriptive Study

This study identified genetic variations in ovarian tumor specimens from Filipino epithelial ovarian cancer (EOC) patients using next-generation sequencing. Genomic DNA was isolated from formalin-fixed paraffin-embedded ovarian specimens from 8 chemosensitive and 8 chemoresistant EOC patients. Targeted next-generation sequencing was done to identify mutations in hotspot regions of common oncogenes and tumor-suppressor genes. The mutations were cross-referenced with dbSNP and ClinVar databases to identify previously reported alterations, and potentially damaging variants were predicted using PolyPhen-2. Our study has identified 85 unique variants, 35 in chemosensitive EOC, 22 in chemoresistant EOC, and 28 in both. Chemosensitive EOC specimens had more exonic single nucleotide variants than chemoresistant EOC specimens. Of the 50 oncogenes and tumor suppressor genes, KDR gene had the most frequent variations in EOC patients. Two of the unique KDR variants identified were novel mutations. Thirty-nine unique protein-modifying genetic variants were identified in all specimens, the majority of which have been previously reported in dbSNP and ClinVar. This study was the first non-BRCA genetic analysis done on ovarian cancer in Filipino patients. Next-generation sequencing was able to identify previously reported alterations with known therapeutic implications which may benefit from targeted therapy instead of standard chemotherapy regimen.

Establishment of Epithelial Cell Culture from Ovarian Cancer Tissues: A Method Comparison Study

This study aimed to determine the most effective method in establishing primary cell culture from epithelial serous ovarian cancer tissues with the highest yield of cells and percentage of epithelial cells. Primary and metastasis tissues from three serous ovarian cancer patients were processed using 18 different combinations of methods based on different factors: the source of tissue (primary site or metastasis site), the cell suspension method (explant method, enzymatic methods, or the addition of Percoll), and the alternatives of three different media. We compared the total count of cells, the percentage of epithelial cells, and the estimated number of epithelial cells per observation field. The calculation of cells from primary tissues were compared to metastasis tissues, and the difference was statistically analyzed using Mann Whitney-U test on SPSS software. The groups that were processed using dispase and trypsin resulted higher number of cells and higher percentage of epithelial cells when compared to the explant method. Among all media, we found that DMEM:F12 and McCoy's 5A media as equally useful in isolating and culturing epithelial cells. Statistically, the metastasis tissue derived more epithelial cells when compared to the primary tissue (102.32±82.65 vs 22.6±23.81, p=0.001). The use of metastasis tissue processed with trypsin or dispase and cultured in DMEM:F12 or McCoy's 5A media was found to be the most efficient way to produce the highest amount of cells with high percentage of epithelial cells.

Cervical Cancer Screening Coverage at Tertiary Care Institutes Across India

The 70% screening coverage target proposed in the global cervical cancer elimination strategy is not achieved even at tertiary centres in India. A situational analysis was done to assess the currently existing facilities and barriers in tertiary care institutes. This cross sectional multicentric study was conducted from August to September 2021 in six tertiary care institutes across India. Women aged 30-49 years attending outpatient services (OPD) were invited for cervical screening. Women and health care professionals (HCPs) were administered structured questionnaires to assess knowledge, attitude and practices regarding cervical cancer screening services. Out of 6709 eligible women who attended OPD, 1666 (24.8%; range:19-57%) received screening. Availability of screening kits was limited to 10-25 Pap/HPV tests per day. Visual inspection with acetic acid (VIA) and HPV testing were offered only at certain centres. Colposcopy and treatment facilities were optimal at all centres. Knowledge, attitude and practices were analysed for 1800 women: 45.7% had heard of cervical cancer, 78.0% did not know that it is preventable, 75.8% never heard about screening. Common symptoms correctly identified included postmenopausal bleeding (4.8%), postcoital bleeding (5.7%), intermenstrual bleeding (5.8%) and vaginal discharge (12.4%). Risk factors were identified by minority: poor menstrual hygiene (6.6%), oral contraceptive pill use (6.4%), multiparity (4.4%), and HPV infection (3.0%). Out of 21, mean total knowledge score (MTKS) was 2.07± 2.67. Out of 317 HCPs, 96.5% knew that cervical cancer is caused by HPV infection, is preceded by premalignant stage, and that it is preventable by screening and treatment (80.1%). Knowledge about screening modalities was present in 87.4% for cytology, 75.1% for VIA, 68.8% for HPV test. MTKS of HCPs was 20.88±6.61 out of 32. Even at tertiary centres, limited availability of HPV tests, reluctance to implement VIA and lack of awareness among women remain the major barriers.

Novel Complex of Zinc (II) Dichloroethylenediamine: Synthesis, Characterization, In-silico, and In-vitro Evaluation against Cervical Cancer Cells

Cervical cancer is a malignancy originating from the cervix and often caused by oncogenic Human Papilloma Virus (HPV), specifically subtypes 16 and 18. Anticancer drugs are chemotherapeutic compounds used for cancer treatment. Therefore, this research aims to synthesize and characterize Zinc (II) dichloroethylenediamine (Zn(en)Cl2) complex, as well as determine its antiproliferative activity against HeLa cells. The Zn(en)Cl2 complex was successfully synthesized, and the antiproliferative activity was tested. The synthesis involved reacting ethylenediamine and KCl with Zn metal. The complex formed was characterized using a conductometer, UV-Vis spectroscopy, FT-IR spectroscopy, and XRD, while the activity was measured against HeLa cells. The synthesis yielded a 56.12% conversion with a melting point of 198-200 oC and a conductivity value of 2.02 mS/cm. The Zn(en)Cl2 complex showed potential activity against HeLa cells with an IC50 value of 898.35 µg/mL, which was evidenced by changes in the morphological structure of HeLa cells. Its interaction with DNA targets was investigated by employing molecular docking. The observed data indicated that the Zn(en)Cl2 complex bound to DNA at the nitrogenous base Guanine (DG) by coordinate covalent bonds. Interestingly, DG maintained interaction with the complex until the end of the docking simulation. Additionally, molecular dynamics (MD) simulation was conducted, and the results showed that Zn(en)Cl2 remained bound to the DNA binding pocket all through the process.

Exploring Parents’ Decisions Regarding HPV Vaccination for Their Daughters in Jakarta, Indonesia: A Qualitative Study

Cervical cancer, caused by the human papillomavirus (HPV), is the fourth most common cancer among women worldwide. Although many countries have introduced national HPV vaccination programs, many girls worldwide remain unprotected. As part of a demonstration project in 2016, the Indonesian government provided the HPV vaccination for free to all year five and six female students in Jakarta and several other cities, with a plan to roll out the program nationally in the future. Understanding parents' decision-making regarding whether they will allow their daughters to receive the HPV vaccine is important to ensure optimum uptake. Methods: Twenty-four parents in Jakarta were interviewed. Data were analysed thematically using The Theory of Planned Behaviour constructs of attitudes, subjective norms and perceived behavioural control. Result: Some parents had limited knowledge about cervical cancer and the HPV vaccine; others did not even realise that the free HPV vaccination program had been offered in their daughter's schools. Those who had better knowledge and positive attitudes trusted their health professionals as a source of information. Peer approval, trust in the government and having the vaccine through a school-based program was important for trust, eliminated cost barriers, and increased access.Conclusion: Parents' attitudes towards cervical cancer and HPV vaccination are influenced in part by their knowledge. Shaping positive initial attitudes is important, as once formed, attitudes are often difficult to change. Our findings suggest that a free school-based vaccine accompanied by sufficient and non-ambiguous information from trusted sources is vital to uptake.

A Systematic Review of Cervical Cancer Mobile Applications and a Future Directions for Developers

The objective of this study is to evaluate the quality of mobile health (mHealth) applications that promote cervical cancer awareness and provide screening assistance, with an emphasis on apps available on the Google Play Store and iOS. From December 2023 to February 2024, we assessed mobile applications focused on cervical cancer screening that are available on Google Play and Apple iTunes. The "Cervical Cancer," "Mobile Application," "Pap Test," "Cervical Cancer Guide," "Human Papillomavirus," plus "Cervical Screening are the keywords used to search the applications." Data collection includes features such as application name, pricing, download metrics, invention date, last update, affiliation, online access, login requirements, and notification functionality, which were gathered in Excel. Interrater reliability based on four reviewers' independent judgments, varied from 0.75 to 0.83. In our research, we found 25 apps (16 on the Google Play Store and 9 on iOS). After a thorough review, only 14 relevant apps were included. According to the MARS rating, Rise Against Cancer received the highest score (3.9), followed by FightHPV and Cervical Cancer Forum (3.8). Rise Against Cancer (29), HPV Vaccine (28), and CDC STI Tx Guidelines (28) scored highest in the APPLICATIONS rating system. Hope 4 All and OCI Cervibreast closely matched the statements, meeting seven of the thirteen requirements each. Future app developers should produce user-friendly, often updated mHealth applications that include high-quality cervical cancer awareness and screening content. These apps should provide validated information and pleasant graphic effects.

A Study of the Impact and Restitutive Efforts of Cervical Cancer Screening during the COVID-19 Pandemic in a Regionsl Cancer Centre in Eastern India

To evaluate the feasibility and efficacy of switching to a self-sampling based screening as compared to ongoing provider-collection based screening using HPV DNA test and assess the compliance of HPV positive women for further treatment during the COVID 19 pandemic. The study participants were women aged 30-60 years from rural and semi-urban communities around Kolkata, who underwent screening followed by HPV testing by Hybrid Capture II test. In the pre pandemic era, the women who attended the health centres where trained health workers that collected cervical samples. Following lockdown, the health workers distributed the self-sampling device to the women during home visits and counselled them to collect their samples by themselves. Thereafter the self collected screened positive women were brought to the hospital for further treatment instead of community clinics. From April 2018 to March 2020, 12,718 women underwent screening using either HPV DNA test or visual inspection with acetic acid. HPV samples were either provider collected (62.7%) or self-collected (37.2%). The HPV positivity and CIN2+ detection rate were 5.4% and 2%. From April 2020 to February 2022, 10,792 women underwent screening using self-sampling only. The HPV positivity rate and CIN2+ detection rate were found to be 5.1% and 1.9 % . Cervical cancer screening by HPV self-sampling advocates participation of more women especially in rural areas, while accelerating progress towards elimination of cervical cancer.

Correlation between Knowledge, Attitude, and Partner Support Towards Visual Inspection with Acetic Acid Test among Women in Denpasar City, Indonesia

Cervical cancer is the fourth most common cancer in women worldwide. Thus a high mortality rate is unavoidable. Visual Inspection with Acetic Acid (VIA) is a practical and inexpensive screening test for detecting cervical cancer. We aim to show the association between knowledge, attitude, and partner support towards VIA practice in women in Denpasar, Bali. The study design was a cross-sectional and analytical observational study conducted at the Public Health Center Denpasar in July-August 2022. The respondents consisted of 90 child-bearing-age women who met the inclusion criteria. The questionnaire consisted of informed consent, demographic characteristics (26 questions), knowledge (20 questions), attitude (22 questions), partner support (11 questions), and practice of VIA (2 questions). The data analysis used the Chi-square test using SPSS ver26. The median age of all respondents was 33 (10) years. The majority of respondents were monogamous (93.03%), had no history of miscarriage (80%), used contraception (56.07%), and the mean age of first sexual intercourse was 20.6 years. Up to 69 women (76.7%) had the VIA Test in the past five years, and 42 women (46.7%) took the test regularly every three years. There is a correlation between knowledge (p=0.001, r =0.334), attitude (p<0.001, r=0.367), and partner supports (p=0.03, r=0.197) toward practicing VIA. The practice of VIA is influenced by the level of knowledge, attitudes, and partner support of the child-bearing-age women in Denpasar. All healthcare professionals and the environment should support and encourage women to perform VIA regularly.

Factors Affecting Non-Histologically Proven Invasive Cancer of the Uterine Cervix that Had an Abnormal Pap Smear: Results of the CCS Program

Cervical cancer (CC) ranks fourth among cancers diagnosed around the world, but early detection and treatment can reduce invasive cervical cancer and mortality. Screening programs (CCSP), such as the one covering Thailand's 75 provinces, use histology to confirm cases. The study determined the incidence rate (IR) and investigated the factors associated with non-histologically proven invasive cancer of the uterine cervix (non-HPICUC) with an abnormal pap smear from the CCSP at Mahasarakham Hospital, Thailand. The CCSP was used to analyse a retrospective cohort of 288 women between 30 and 60 years of age. All abnormal pap smears were followed up until April 30, 2022. We estimated the IR and assessed the relationship between various independent variables and non-HPICUC using the generalised linear model (GLM) for testing association data. We reported the adjusted RR and 95% confidence intervals (95%CI). 260 non-HPICUC cases had abnormal CCSP pap smears for an overall IR of 90.0 (95% CI: 86.3 - 93.2). After adjusting the model for all variables, age at recruitment and pregnancy had a statistically significant association with non-HPICUC (p-value < 0.05). We found that the risk of non-HPICUC increased 1.02 times for every 20-year increment in age compared to below that age (adjusted RR=1.02, 95% CI: 1.01 - 1.04). Pregnancy at risk for non-HPICUC was 0.89 times compared to non-pregnancy (adjusted RR=0.89, 95% CI: 0.80 - 0.99). Pathological vaginal discharge (PVD) did not have a statistically significant association with non-HPICUC (p-value = 0.094); notwithstanding, women with PVD had 1.08 times the risk of non-HPICUC compared to women without PVD (adjusted RR=1.08, 95% CI: 0.97 - 1.20). Based on an abnormal pap smear from the CCS Program at Mahasarakham Hospital Thailand, age and pregnancy are associated with an increased risk of non-HPICUC. High-risk groups with abnormal pap smears should be targeted for CC campaigns.

Midwives as the Primary Care Providers: Knowledge, Attitude, Practice, and Skill of Early Detection of Cervical Cancer Using Visual Inspection with Acetic Acid

Cervical cancer is the third most common malignancy in women globally. It is also the leading cause of death for women in Indonesia. When detected at an early precancerous stage, cervical cancer is largely preventable. Early detection with Visual Inspection with Acetic Acid (VIA) is an acceptable, affordable, and safe alternative method in developing countries. Midwives, as primary health care providers, can perform VIA at various health center levels. This study evaluated the knowledge, attitude, practice, and skill of cervical cancer screening with VIA among midwives in Denpasar. A cross-sectional study was conducted among 70 midwives at Public Health Centers in Denpasar, Bali, Indonesia, from July-August 2022. The data were collected using a structured knowledge, attitude, and practice questionnaire. An obstetrician-gynecologist assessed the skills with a standardized checklist. Data were analyzed using univariate, bivariate, and multivariate analysis on SPSS version 26. A level of p<0.05 was considered significant with a prevalence ratio (PR) and 95% confidence interval (CI). Out of all midwives, 42 (60.0%) were knowledgeable, 42 (60.0%) had a favorable attitude, 36 (51.4%) had good practice of VIA, and 54 (77.1%) had competent skills. Knowledge (PR=5.00, 95%CI=1.76-14.16), attitude (PR=2.92, 95%CI=1.08-7.89), and skill (PR=11.90, 95%CI=2.44-57.84) were associated with the practice of VIA. Age group and work experience were strongly associated with the training and skill of VIA. Most midwives in Denpasar were knowledgeable, had a favorable attitude, good practice, and competent skills to perform cervical cancer screening using VIA.

A Comprehensive Review of Cervical Cancer Screening Devices: The Pros and the Cons

The low screening coverage and reluctance of women in participation lead to low uptake in cervical screening tests. Hence the majority of cervical cancer patients visiting the hospitals are diagnosed at advanced stage, often leading to poor survival rate. This paper aims to review and compile available cancer screening devices so that more people in this field will adopt suitable devices in cervical cancer screening routine depending on requirements which may encourage the uptake in cervical screening tests. This paper reviews devices invented for different cervical cancer screening methods, which are Pap smear test, visual inspection with acetic acid (VIA) or Lugol's iodine (VILI), and HPV (human papillomavirus)-DNA (deoxyribonucleic acid) self-test in terms of functionality, performance in solving the limitations of screening procedure and additionally where applicable, the cervical cell collection efficacy and abnormality detection accuracy. The devices are either available in the market, published in research articles or published in international patent databases. The reviewed devices either simplified the screening procedure to improve the clinical efficiency and accuracy in screening, reduced the pain and discomfort experienced by women during screening procedures, or achieved both outcomes. Many devices have been invented to improve the screening procedures which may potentially improve the uptake in cervical screening tests and encourage the organization of screening campaigns to reduce cervical cancer incidence.

Development and Evaluation of p16 based Double Antibody Sandwich ELISA for Detection of Cervical Precancer and Cancer

Cervical cancer is the third most common cancer in women, worldwide. This study was designed to develop an affordable, accurate and simpler screening test like Enzyme-linked immunosorbent assay (ELISA) which is low cost and will help in bringing down the disease burden in resource poor countries. In this study, we have raised and evaluated monoclonal antibodies against recombinant p16 using immunohistochemistry (IHC), western blot, immunoprecipitation and ELISA. Double antibody sandwich ELISA (DAS-ELISA) and cytokeratin ELISA was designed for screening women with cervical dysplasia and cancer. Cloned, expressed and purified recombinant p16 were used for generation of monoclonal antibodies. After initial screening, six clones were selected, and affinity purified. Except 155D11G10, which was isotype Immunoglobulin (Ig) G1 all the others were found to be IgG2b. 133A6G5 and 151A7B9 were found to be best for p16 IHC, both showed 70 - 80% and 80 - 90% of nuclear staining respectively. All the antibodies positively detected p16 from the HeLa lysates in western blot except 133A6G5. Studies using immunoprecipitation showed 133A6G5, specifically detected p16. DAS-ELISA developed using a combination of our p16 monoclonal antibodies showed sensitivity of up to 2pg. A pilot study using DAS-ELISA and cytokeratin ELISA in cervical samples revealed the assay sensitivity and specificity as 100% and 80%, respectively. Using combination of DAS-ELISA and cytokeratin ELISA we have developed an accurate and reliable method for the early detection of cervical cancer in a subject, with minimal false results. In the future after large scale validation, p16 ELISA could be used as a reliable tool for diagnostic purposes.

Analysis of E-cadherin (CDH1) Gene Polymorphism and Its Association with Cervical Cancer Risk in Bangladeshi Women

E-cadherin (CDH1), a tumor suppressor gene, encodes a transmembrane glycoprotein that helps in maintaining squamous epithelium integrity of the cervix. We aimed to investigate the association between -160C/A genetic polymorphism in CDH1 and the risk of cervical cancer in Bangladeshi females. The present case-control study included 117 cervical cancer cases and 147 age-matched controls. The genomic DNA was extracted from peripheral blood and genotyped by using PCR-RFLP analysis. Genotyping results demonstrated that the occurrences of normal homozygous (-160C/C), heterozygous (-160C/A) and variant homozygous (-160A/A) genotypes were 64.10, 27.35 and 8.55% in cases, and 77.55, 19.73 and 2.72% in controls, respectively. Compared to normal C/C genotype, variant A/A and combined (C/A+A/A) or 'any A' genotypes exhibited 3.80-fold (95% CI=1.150-12.561, P=0.029) and 1.93-fold (95% CI=1.126-3.323, P=0.017) increased risk of cervical cancer development. The -160C allele was found to be positively linked to cervical cancer incidence and raised the risk by 1.81-fold (OR= 1.814, 95% CI=1.152-2.857, p=0.01). Moreover, women carrying -160A/A variant homozygosity along with an early marital history (<18 years) were more susceptible to cervical cancer development (χ2 =6.605, p=0.037). The study suggests that the (A/A) and combined (C/A +A/A) genotypes are associated with greater risk of cervical cancer in Bangladeshi women.

Screening for Breast, Cervical and Prostate Cancers in Kazakhstan: Key Factors and Psychological Aspects

Screening is the main method for early detection and reduction of cancer mortality in all countries, including Central Asia and Kazakhstan. However, there is no official data on the awareness of the population about cancer screening in Kazakhstan. In addition, there were no studies on the psycho-emotional state of the patients during the screening procedure conducted yet. The purpose of the study was to assess the potential factors of awareness and psycho-emotional state during screening for breast (BC), cervical (CC), and prostate cancers (PC) in Kazakhstan (using the example of Almaty city). This cross-sectional study was conducted in the period from 01/01/2017 to 05/31/2017. The study was carried out at six polyclinics in Almaty (Kazakhstan). 1 625 volunteers took part in the study. The special questionnaires were employed to assess awareness of the screening procedure and subjective feelings during screening. The survey was conducted on patients who were screened for BC (n=674  or 41.5%), CC (n=565  or 34.8%) and PC (n=386 or 23.8%). Demographic data (age, education, marital status, preferred language of communication, etc.) were collected from participants using in-depth interviews. The internal consistency of the questionnaires was analysed by determining the reliability index (Cronbach's alpha). The mean age of screening participants was 54.6 ± 3.3 years (BC), 49.2 ± 7.3 years (CC), and 56.6 ± 5.1 years (PC) (p = 0.001). Participants in BC and CC screening had a general knowledge of the procedure (45.1 % and 59.8 % of cases, respectively). Men had no information about PC screening (76.4 % of cases, p = 0.001). On the other hand, women had no sufficient knowledge about mammography (46.4 %) and Papanicolaou (Pap)  test (51.2% of cases). In 40.1 % (BC) and 41.1 % (CC) of cases, the fact of having the test was an unpleasant circumstance. However, in 59.6 % (PC) of cases, men did not have any discomfort associated with undertaking the test (p = 0.001). PC screening participants experienced no discomfort in 58.3 % of cases. At the same time, participants in BC and CC screenings experienced discomfort in 38.1 % and 42.5 % of cases, respectively (p = 0.001). Analysis of internal consistency on the questionnaire on awareness of the screening procedure showed the value of Cronbach's Alpha 0.693. The scores of subjective feelings during screening were 0.702. The study's results revealed the reliability and applicability of the questionnaires on awareness of the screening procedure and assessment of subjective feelings. Knowledge of general information about the screening program differed depending on the type of screening. Participants in BC and CC screening were more likely to be aware of the screening program than participants in PC screening. An unpleasant circumstance associated with screening test is most often considered the very fact of having the test, especially for participants in BC and CC screening. The results of this study highlight the importance of providing an information campaign to raise awareness about screening tests. In addition, the results indicate the need to provide patients with full information about the screening process, and possible risks and benefits.

High ALDH-1 Expression Predicts Non-Complete Response of Radiotherapy in Stage III Squamous Cell Cervical Carcinoma Patients

ALDH1 is a cervical cancer stem cell marker that has radioresistance profile. Recurrence and metastasis following radiotherapy are still being problems of most patients. This study aimed to determine the correlation between ALDH1 and radiotherapy response in stage III squamous cell cervical carcinoma (SCCC) of the cervix. A total 58 of 360 patients of stage III SCCC who received external beem radiation and brachytherapy (2016-2021) at Cipto Mangunkusumo Hospital met the eligibility criteria of this study. Pre- and post-irradiation MRI examinations and ALDH expression with immunohistochemistry (Santa Cruz®) were performed on formalin-fixed paraffin-embedded of pre-treatment cervical tissue biopsy taken from RSCM pathological anatomy laboratory. Patients were divided into two groups, complete responders vs non-complete responders. ALDH-1 scores were compared between two groups to assess ALDH-1 expression. The statistical analyses were carried out by SPSS 24. The optimal ALDH-1 score cut-off point on the radiation response was 166.05 pg/mL which was obtained from the analysis of the ROC curve. The AUC value was 0.682 with sensitivity and specificity, 63,6% and 64%, respectively. ALDH score ≥166.05 increased the risk by 3.127 times for not achieving complete response (adj OR 3.127, 95% CI 1.034 - 9.456, p = 0.043). Pre-radiation tumor size (p = 0.593), degree of differentiation (p = 0.161), renal abnormalities (p = 0.114), and keratinization (p = 0.477) were not associated with radiation response. High ALDH expression was associated with non-complete radiation response in stage III squamous cell cervical carcinoma. .

HPV Vaccination and Cervical Cancer Screening Policies and Practices in 18 Countries, Territories and Entities across Eastern Europe and Central Asia

To assess readiness to achieve the WHO Global Strategy targets for HPV vaccination and cervical screening and to guide capacity building, the current status of these services in 18 Eastern European and Central Asian countries, territories and entities (CTEs) was evaluated. In order to assess the current status of HPV vaccination and cervical cancer screening in these 18 CTEs, a 30 question survey tool was developed, covering: national policies, strategies and plans for cervical cancer prevention; status of cancer registration; status of HPV vaccination; and current practices for cervical cancer screening and treatment of precancerous lesions. As cervical cancer prevention comes within the mandate of the United Nations Fund for Population Development (UNFPA), the UNFPA offices in the 18 CTEs have regular contact with national experts who are directly involved in cervical cancer prevention actions and are well placed to provide the data required for this survey. Working through the UNFPA offices, the questionnaires were sent to these national experts in April 2021, with data collected from April to July 2021. All CTEs returned completed questionnaires. Only Armenia, Georgia, Moldova, North Macedonia, Turkmenistan and Uzbekistan have implemented national HPV vaccination programmes, with only the last 2 of these reaching the WHO target of 90% of girls fully vaccinated by age 15, while rates in the other 4 range from 8%-40%. Cervical screening is available in all CTEs but only Belarus and Turkmenistan have reached the WHO target of 70% of women screened once by age 35 and again by age 45, while rates elsewhere range from 2%-66%. Only Albania and Turkey follow the WHO recommendation to use a high-performance screening test, while the majority use cervical cytology as the main screening test and Kyrgyzstan, Tajikistan, Turkmenistan and Uzbekistan use visual inspection. No CTEs currently operate systems to coordinate, monitor and quality assure (QA) the entire cervical screening process. Cervical cancer prevention services in this region are very limited. Achieving the WHO Global Strategy targets by 2030 will require substantial investments in capacity building by international development organisations.

Survival after Diagnosis of Cervical Cancer Patients at a Tertiary Referral Hospital in Northeast Thailand

Cervical cancer (CC) is the third most common cancer in women globally, including Thailand, where the incidence rate was 16.2 cases per 100,000 individuals in 2018. Survival rates for patients with this condition have not improved over recent years. This study evaluated the survival rate and median survival time after diagnosis among CC patients, and investigated factors associated with survival in Northeast Thailand. This study included CC patients admitted to the gynecological ward at Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand from 2010 to 2019. Survival rates and median survival time since the date of diagnosis and 95% confidence intervals (CIs) were calculated. Multiple cox regression was performed to investigate factors associated with survival which were quantified by adjusted hazard ratios (AHR) and their 95% CIs. Of 2,027 CC patients, the overall mortality incidence rate was 12.44 per 100 person-years (95% CI: 11.7 - 13.22), median survival time was 4.82 years (95% CI: 3.92 - 5.72), and 10-year survival rate was 43.16% (95% CI: 40.71 - 45.59). The highest 10-year survival rate was 87.85% (95% CI: 82.23 - 91.78) found among those with stage I CC, followed by those who received surgical treatment, which was 81.22% (95% CI: 74.47 - 86.35). Factors that were associated with decreased survival included age ≥60 years (AHR = 1.25; 95% CI: 1.07 - 1.46), health insurance with the Universal Health Coverage Scheme (UCS) (AHR = 6.26; 95% CI: 5.13 - 7.64), malignant neoplasms histopathology (AHR = 1.36; 95% CI: 1.07 - 1.74), and treatment with supportive care (AHR = 7.48; 95% CI: 5.22 - 10.71). Among patients diagnosed with CC, those with stage I had the highest 10-year survival rate. CC patients with older age, UCS, malignant neoplasms histopathology, and received supportive care showed the highest survival association.

Prognostic Outcome of Mesenchymal Transition Biomarkers in Correlation with EGFR Expression in Epithelial Ovarian Carcinoma Patients

CD44 is an epithelial-mesenchymal transition (EMT) surface receptor that regulates the interactivity between the cells and the extracellular matrix, thereby promoting cell migration. The epidermal growth factor receptor (EGFR) family is a trans-membrane kinase-related protein. It regulates cell adhesion proteins, which may promote cell proliferation and invasiveness. Mesenchymal epithelial transition (MET) is another EMT receptor that stimulates cell proliferation, invasion, survival, and angiogenesis. This study aimed to evaluate the prognostic impact of CD44, EGFR expressions, and MET gene amplification in epithelial ovarian cancer (EOC). This is a retrospective cohort study, including 85 cases of EOC. CD44 and EGFR expressions were evaluated in both epithelial and stromal cells by immunohistochemistry. Tumor cells also underwent a cytogenetic analysis using fluorescent in situ hybridization (FISH) to detect MET gene amplification. High CD44 expression in tumors was significantly associated with serous subtypes (P=0.001), peritoneal deposits (P=0.002), and advanced stage (P=0.002). EGFR high tumor expression demonstrated a significant association with lymph node metastasis (P=0.038) and the advanced stage of EOC (P=0.016). Increased copy number of the MET gene was significantly associated with partial therapy response (P=0.030).  CD44 and EGFR tumor high expression was associated with poor overall survival (OS). In addition, MET gene gain in tumors was associated with a shorter OS (P=0.000). EMT biomarkers (CD44 and MET) and EGFR expression in EOC are independent prognostic factors for OS. MET gene increase copy number was detected in cases of serous neoplasm and associated with poor survival and minimal therapy response.

Effects of Mefenamic Acid in Pain Control during Loop Electrical Excision Procedure:A Prospective Double-Blind Randomized Control Trial

To investigate the effectiveness of pre-procedural oral mefenamic acid compared with placebo in women undergoing Loop Electrosurgical Excision Procedure (LEEP) with intracervical lidocaine injection. A prospective double-blinded randomized control trial. Materials, Setting, Methods: Women undergoing LEEP for any indications were asked to participate in the study. The participants were randomly allocated into two groups. In group 1 (oral mefenamic acid), the participants were offered oral mefenamic acid (500 mg) for 30 minutes before procedures. In group 2 (placebo), the patients were given oral placebo (identical tablet) for 30 minutes before operation. All participants received immediate 10 mL of 2% lidocaine with 1:100,000 of epinephrine intracervical injection before undergoing the LEEP. All participants were excised in one piece of LEEP. No top-hat excision in this study.  The patients graded their pain on a 10-cm visual analog scale (VAS) at different points during the procedure, including speculum insertion, at starting excision, and 30 minutes post excision. Primary outcomes revealed the difference of VAS during all steps of LEEP by generalized estimating equations procedure. Sixty participants (30 in mefenamic group and 30 in placebo group) participated in this study. The study did not find differences of VAS during all steps of LEEP and analgesic drug requirement at 30 minutes after LEEP procedure. All patients reported no immediate complications and no intervention-related adverse events were observed. Using pre-procedural oral mefenamic acid before LEEP procedure was not associated with pain reduction during all steps of excision..

Higher Level of Fatty Acid Synthase Enzyme Predicts Lower Rate of Completing Debulking Surgery in Epithelial Ovarian Cancer

The most dominant histopathologic type of ovarian cancer is epithelial ovarian cancer (EOC). Primary debulking surgery determines the treatment success and prognosis of advanced stage EOC. To maintain survival and progression, cancer cells need fatty acid synthase enzyme (FASN). The aim of this study was to evaluate preoperative serum FASN and CA 125 as predictors of primary debulking surgery results in patients with EOC. An observational cross-sectional study was performed on consecutive patients who underwent debulking surgery for suspected ovarian cancer at Dr. Hasan Sadikin Hospital Bandung from 2017 to 2019. Before debulking surgery, blood samples were examined for the serum levels of FASN and CA 125 using ELISA. There were 53 patients enrolled in this study. Compared with the optimal debulking surgery group, the significant suboptimal debulking surgery group had significantly lower mean serum levels of FASN (0.46 ± 0.144 vs. 0.36 ± 0.128, p = 0.012) and CA 125 (964.22 ± 1722.5 vs. 264.98 ± 251.8, p = 0.002). The cutoff value was highest for the combination of FASN and CA 125 [410.06, area under the curve (AUC) = 77.5% (95% CI 65.5% to 81.9%, p = 0.001)] than for FASN alone [0.375, AUC = 71.3% (95% CI 56.8% to 85.8%, p = 0.009)] and CA 125 alone [222.5, AUC = 75.3% (95% CI 62.5% to 88.1%, p =0.002)]. The serum levelof FASN was correlated with suboptimal debulking surgery.

Time from Self-Detection of Symptoms to Seeking Definitive Care among Cervical Cancer Patients

India had the burden of 97,000 new cases of cervical cancer with 60,000 deaths accounting nearly one-third of global cervical cancer deaths during the year 2018. Cervical cancer is the leading cause of cancer mortality in India. The present study aims to estimate the time interval between self-detection of cervical cancer symptoms and seeking care and different barriers for the possible time lag in seeking care. A cross-sectional study was undertaken from April 2017 to September 2017 in a regional cancer centre in the south of India. The centre has both a population and a hospital-based cancer registry. Cervical cancer cases (N= 210) with histological confirmation were interviewed at the hospital using a pre-tested semi-structured questionnaire. The median time interval between the self-detection of cervical cancer symptoms and first contact with the general physician was 80 [IQR 45-150] days. The overall median time interval between the self-detection of symptoms to the initiation of primary treatment was 123[IQR 83-205] days. The major perceived reason for not seeking medical care was a lack of awareness in identifying cervical cancer symptoms in 183(92.9%) women. The median time of 80 days was observed from the self-detection of cervical cancer symptoms to the first contact with a general physician. Lack of awareness of patients pertaining to cancer symptoms was the major concern in seeking cancer care..

Prevalence of Cervical Cancer Screening in Asia: A Systematic Review and Meta-Analysis

Cervical cancer is one of the most common causes of cancer-related mortality among female, especially in the low-and-middle income countries. This systematic review and meta-analysis aimed to identifying the prevalence and trend of cervical cancer screening among 21member countries of the Asian National Cancer Centres Alliance (ANCCA)/ regions in Asia. We conducted a search on three databases including: PubMed, Web of Science and Scopus, using our search terms. Two independent reviewers screened titles and abstracts based on inclusion and exclusion criteria, and any conflicts were resolved through discussion. Full-text screening was also completed by two independent reviewers, and conflicts were resolved accordingly. Relevant information was extracted into an Excel sheet, and random-effects meta-analysis was performed to identify the pooled estimate of cervical cancer screening in Asia using Stata 17. The review has been registered in PROSPERO (registration ID: CRD42023401516). We identified 54 studies from 19 ANCCA member countries/ regions in Asia reporting cervical cancer screening rates between 2012-2023. The pooled estimate of eight countries (Bangladesh, China, India, Iran, Japan, Korea, Nepal, and Thailand) that had more than three data points and were rated as satisfactory to very good in the quality assessment showed that cervical cancer screening rate was around 28% (95% CI: 0.25 - 0.32) in the last ten years. Most of countries/regions in Asia do not have sufficient data on cervical cancer screening due to lack of nationally representative surveys or national level cancer registries. Hence, it is crucial to encourage governments and private sector to strengthen their capacities and work in collaboration to enhance the cervical cancer screening rate in their respective countries.

Association between miR-196a-2 Gene Polymorphism and Ovarian Cancer Prognosis in Egyptian Females

Ovarian cancer is the fifth leading cause of cancer-related deaths among women worldwide. Unfortunately, early detection tests are relatively lacking. Diagnosis in the late stages of the disease carries a poor prognosis. To evaluate the relationship between miR-196a-2 rs11614913 polymorphism and ovarian cancer risk and prognosis in Egyptian females. In this case-control study, the participants were classified into 2 groups. Group A is the control group which included 50 healthy females. Group B included 50 patients newly diagnosed with ovarian carcinoma confirmed by histopathological analysis. Immunohistochemistry for P53 and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for miR-196a-2 genotypes detection were performed.   Results: There was a statistically significant difference among ovarian cancer cases and controls regarding genotypes (P = 0.003). However, the distribution of the T and C alleles in both studied groups showed no significant difference (P = 0.17). There was a statistically significant increase of CA 125 levels among CT and CC genotypes carriers of ovarian cancer cases (p = 0.04). Besides, there was a statistically significant correlation between miR-196a-2 polymorphism and each of tumor grade (P <0.001), p53 immunohistochemical expression (P= 0.002), and Figo classification (P <0.001). There was a statistically significant increase of CA 125 levels among C allele carriers of ovarian cancer cases. Besides, there was a statistically significant association between the miR-196a-2 polymorphism and each of tumor grade, p53 immunohistochemical expression, and Figo classification. So, miR-196a-2 polymorphism can be a possible prognostic factor in ovarian cancer.

Anti-Proliferative and Apoptosis-Inducing Activity of Acacia Modesta and Opuntia Monocantha Extracts on HeLa Cells

Cancer is one of the leading causes of death in the world. Numerous phytochemicals from plants have shown antineoplastic effects via programmed cell death (apoptosis). The aim of this study was to evaluate the effect of anti-proliferative and apoptosis-inducing activity of Acacia modesta and Opuntia monocantha against HeLa cells. To estimate anti-proliferative activity of the plants against HeLa cells, ethanol solvent was used for the extraction. For the evaluation of anti-proliferative effects, MTT assay was performed with 100, 200, and 400 µg/mL dose. The antioxidant assays including glutathione reductase (GSH), superoxide dismutase (SOD) and catalase were performed. Moreover, enzyme linked immunosorbent assay (ELISA) was performed. Furthermore, immunocytometry P53 and flow cytometry were also carried out to assess the apoptosis in HeLa cell. MTT assay showed that the groups treated with Opuntia monocantha and Acacia modest have less level of toxicity as compared to untreated groups. Antioxidant assays confirmed that GSH, SPD and, catalase activities were quite decreased in treated groups as compared to untreated groups. Similarly, ELISA and apoptosis p53 have shown more pronounced apoptosis effect in treated groups as compared to untreated groups. Based on above findings, treatment of HeLa cells with these plant extracts induced apoptosis, restricts proliferation, and enhances the anti-oxidative index in post treated cells..

Survival Outcome of Urinary Diversion in Advanced Cervical Cancer Patients with Hydronephrosis

Urinary diversion is the treatment of choice for cervical cancer patients with urinary tract obstruction. The aim of this study is to determine the survival rate among advanced cervical cancer patients with hydronephrosis who undergo urinary diversion and factors that affect patient survival. Clinical data of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) Stage-IIIB or advanced cervical cancer were not surgical candidates admitted to Saiful Anwar Hospital, Malang from May 2016 to August 2022 were retrospectively analyzed. The parameters including age, cancer stage, comorbidity, cancer treatment at diagnosis, hydronephrosis treatment, grade, site, and survival, were analyzed using the IBM SPSS Statistics version 21. The significance level was set up to 0.05. One hundred eighteen patients were included in this study. Most patients were under 60 (84.75%) and presented with stage IIIB (79.66%). Diabetes mellitus type 2 (8.47%), hypertension (7.63%), acute kidney injury (16.10%), and chronic kidney disease (36.78%) were comorbidities discovered in patients. More than half of patients received chemotherapy (54.24%). Ureteral stents were inserted in 85.59% of patients. Patients with moderate hydronephrosis were the most common, accounting for 67.80% of all cases. Patients with bilateral hydronephrosis outnumber those with unilateral by 91.53% to 8.47%. The survival rate did not differ significantly between ureteral stents (median survival was 11.00 months) and percutaneous nephrostomies (median survival was 15.00 months), p=0.749. In univariate analysis, age, cancer stage, and hydronephrosis stage were associated with worse 1-year survival. In multivariate analysis, age, DM type 2, cancer staging and hydronephrosis staging were associated with worse 1-year survival. In advanced cervical cancer patients, urinary diversion techniques such as ureteral stents and percutaneous nephrostomy offer similar survival rates. In addition, age, cancer stage, DM type 2, and hydronephrosis site are strong predictors of a worsening survival rate in patients.

Awareness, Knowledge and Attitude Regarding Cervical Cancer among Women Living with HIV in the Souss-Massa Region, Southern Morocco: A Cross-Sectional Study

Human immunodeficiency virus- positive women have an increased risk of precancerous lesions and invasive cervical cancer. This study aims to identify the level of awareness/knowledge and attitudes toward cervical cancer among women living with Human immunodeficiency virus in the region of Souss-Massa in southern Morocco.  Methods: This is a multicenter cross-sectional study conducted in the Souss-Massa region (southern Morocco) among women attending Human immunodeficiency virus treatment and care centers between March 2022 and September 2022. A questionnaire was used for data collection. The Chi-square test and logistic regression were deployed to identify factors associated with cervical cancer awareness among the target population. A total of 494 respondents to the questionnaire, 440 (89.1%) are aware of cervical cancer. Nevertheless, 405 (82.0%) and 369 (74.7%) were unaware of cervical cancer risk factors and symptoms, respectively. Only 125 (25.3%) knew the exact frequency of cervical cancer screening among Human immunodeficiency virus positive women, whereas 221 (44.7%) had ever been tested for cervical cancer. Factors associated with women's awareness of cervical cancer are as follows:  level of education (adjusted Odds Ratio = 3.78 with 95% CI, 1.23-11.65), time since diagnosis of Human immunodeficiency virus (adjusted Odds Ratio = 4.31 with 95% CI, 1.12- 16.52), knowledge of women with cervical cancer (adjusted Odds Ratio = 6.30 with 95% CI, 1.87-21.18) and heard the pap- smear/visual inspection with acetic acid (adjusted Odds Ratio = 4.92 with 95% CI, 2.35-10.33). The general knowledge of seropositive women regarding cervical cancer remains very low, which justifies the integration of cervical cancer prevention services with Human immunodeficiency virus care, and pinpoints the crucial role of patient education.

Genetic Polymorphisms of the Human Cytochrome P450 1A1 (CYP1A1) and Cervical Cancer Susceptibility among Northeast Thai Women

CYP1A1 is an enzyme in phase I of the cytochrome P450 (CYP) superfamily, and plays a key role in detoxification of carcinogens. Host genetic predisposition in the CYP1A1 may be associated with an increased susceptibility to cervical cancer.The study aimed to evaluate four common polymorphisms of the CYP1A1 and cervical cancer susceptibility among Northeast Thai women. A case-control study was conducted involving 204 patients with squamous cell cervical cancer (SCCA) and 204 age-matched healthy controls. DNA was extracted from peripheral blood leucocytes. CYP1A1 m1, m3, and m4 genotypes were detected using PCR-RFLP, whereas the CYP1A1 m2 genotype was investigated using real-time PCR. Haplotype analysis was performed using PHASE algorithm version 2.1.1. CYP1A1 m3 was monomorphic. Association between the common CYP1A1 polymorphisms, m1 and m2, and cervical cancer risk was not observed (p>0.05), nor was any association found between the m1-m2-m4 haplotype and cervical cancer risk (p>0.05). Interestingly, the CA genotype of CYP1A1 m4 was observed in 30.88% of the cervical cancer patients but was absent in healthy controls. Our results demonstrated a possible involvement of the CYP1A1 m4 polymorphism but no other common polymorphisms (viz., m1, m2, and m3) in the risk for cervical cancer.This finding may be useful when screening for risk of cervical cancer among Northeast Thai women..

Cytotoxic Effects of Mangosteen Pericarp Extracts on Oral Cancer and Cervical Cancer Cells

Despite immense advancements in treatment modalities, cancer remains a dreadful disease until the present. The major influencing factors behind the increased mortality rate of cancer are increased drug resistance and severe adverse effects caused by conventional cancer therapies. To overcome these limitations, the current medical field is focusing more on natural phyto-derived molecules to mitigate cancer. Mangosteen is a phytotherapeutic with potent anti-inflammatory and antioxidant properties. In the present study, we investigated the anticancer potential of the crude ethanolic extract of mangosteen against two dreadful forms of cancers, namely, oral cancer and cervical cancer, in vitro. The pericarp of Garcinia mangostana or mangosteen was removed, air-dried, ground to fine powder, and macerated with ethanol. The extract obtained was then filtered and extracted with water for 48 h. The aqueous fraction thus obtained was then concentrated with a rotary evaporator at 40°C and dried with a freeze dryer. The anticancer efficacy of these extracts was investigated in human tongue squamous cell carcinoma (H357) cells and cervical cancer cells (HeLa) using the MTT assay, TUNEL assay, western blotting, and flow cytometry techniques. The crude mangosteen pericarp extract (MPE) significantly inhibited the growth of  H357 and HeLa cells in a dose-dependent manner. Moreover, mangosteen induced early apoptosis in these cells after 48 h of incubation. Mangosteen also upregulated the expression of pro-apoptotic proteins, including caspases and Bax, and downregulated the expression of anti-apoptotic protein Bcl-2. The MPE exerted significant cytotoxicity against the H357 and HeLa cells in a dose-dependent manner and promoted their apoptosis. Hence, this natural phytoextract can be considered a potent anticancer agent for treating oral cancer and cervical cancer.

Anticancer Activity of Solvent Extracts of Hexogonia glabra against Cervical Cancer Cell Lines

In this study, we aimed to harness some solvent extracts of one wild mushroom Hexagonia glabra and test their anti-cancer activity against cervical human cell lines, namelyHeLa, SiHa, and CaSki. It includes cell morphological study by microscope, nuclear morphology by DAPI staining under fluorescence microscopy, apoptosis assay by fluorescence technique, anti-proliferation by MTT assay and expression of apoptotic and anti-apoptotic genes by Western blotting and cell cycle analysis was done. The selected cervical cancer cells were treated separately with 150 µg/mL of three extracts, namely of ethanolic (EE), ethyl acetate (EAE), and water extract (WE) and exhibited features like round, shrink and dead. All extracts caused apoptosis in cell lines and EE had the highest effect in this regard. The percentages of apoptotic cells in HeLa, SiHa and CaSki, at the same concentration of EE were 79.23, 75.42, and 76.36% respectively. Cytotoxicity assay showed that all three extracts (50 - 250 μg/mL) were potent for inhibition of cell growth of three cell lines and again EE had the highest effect. The percentages of cell growth inhibition in HeLa, SiHa, and CaSki cells treated with EE at 24 h at 50 µg/mL were 45.79±4.11, 41.66±4.03, and 36.72±2.67, while they were 74.23±7.45, 62.31±5.97, and 54.23±5.04 at 150 µg/mL concentration. At 250 µg/mL concentration, the percentages of cell growth inhibition were 94.25 ±8.11, 90.02 ±8.67, and 85.43±6.21, respectively. The expression of apoptotic gene (Caspase 3, 9) and tumor guard gene (p53), as their proteins in Western blotting increased . However, anti-apoptotic BcL2 gene of all cell lines was decreased following treatment with extracts. In addition, the cell cycle analysis (CaSki cell) showed that treatment (EE) arrested at G2/M check point cell cycle. All extracts of this mushroom were active in arresting growth of three cell lines and EE had the highest effect, indicating that this mushroom can be a valuable source of anticancer agents.

Association of DNA Repair Genes XRCC1 and APE-1 with the Risk of Cervical Cancer in North Indian population

Cervical cancer (CC) is one of the leading cause of death in women worldwide, HPV infection is the major risk factor in the disease development, 0and however other risk factor such as chemical carcinogens, genetic susceptibility and altered immune system are also a cause of the disease progression. In the light of the above statement we studied the base excision repair pathway (BER). We identified and studied the association of Single Nucleotide polymorphisms in the DNA repair genes of XRCC1 (Arg194Trp, Arg399G,) and APE-1Asp/148Glu to the susceptibility of cervical cancer (CC) in North Indian population. In our study of cases (n=102). Controls (n=109) were recruited from among women without cervical abnormalities. Genotypes were determined by PCR-CTPP method, Taking DNA from peripheral blood in a case control study. A positive association was observed between the polymorphisms of XRCC1 genes, that is, in codons 194 (P=0.03, odds ratio (OR) =2.39, 95% confidence interval (CI)=5.2-1.1), 280 (P=0.01, OR=4.1, 95% CI=11.5-1.3) and 399 (P=0.01, OR=3.4, 95% CI=8.6-1.3) while APE-1 genotype GG (p=0.03,odds ratio(OR)=0.2,95% confidence interval (CI)=0.97-0.004) we observed a statistically significant protective role in developing cervical cancer. Our results suggested that, XRCC1 gene is an important candidate gene for susceptibility to cervical cancer. Although the sample size was small, the present study indicate a statistical association between cervical cancer and XRCC1 SNPs. Future studies are needed that may provide a better understanding of the association between gene polymorphism and cervical carcinoma risk..

Influence of Demographic and Reproductive Factors on Cervical Pre-Cancer and Cancer in Bangladesh

In Bangladesh, cervical cancer (CC) is the 2nd most common cancer with estimated 8068 new cases and 5,214 deaths every year. It is also revealed that different socio-demographic factors have association with CC. This study was performed to evaluate the colposcopy outcomes and the association of different demographic and reproductive risk factors with cervical pre-cancer and cancer. This retrospective cross-sectional study was carried out at the colposcopy clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU) between January 2010 and December 2016. A total 16147 women attended the colposcopy clinic of BSMMU with VIA positive reports. Among them, 65.73% women were referred from different VIA centers of Dhaka district. Mean age of marriage of the subjects was 16. 93 (± 1) and mean age of 1st delivery was 18.45 years (± 4.10). Almost three-fourth of them were married before 18 years and had their 1st delivery by 20 years. Colposcopy examination of the VIA positive women revealed that 36.7% had CINI, 10.6% had CINII/ III and 7.1% had carcinoma of cervix. Considering CIN as disease the Sensitivity, Specificity, PPV and NPV of colposcopy were found 99.7%, 75.3%, 70.3% and 99.8% respectively. On other hand considering CIN2+ as disease the Sensitivity, Specificity, PPV and NPV of colposcopy were found 73.8%, 92.7%, 64.4% and 95.2% respectively. Statistical analysis revealed that higher age (p=0.000), lower level of education (p=0.007), lower socioeconomic status (p=0.014), higher parity (p=0.001) had individual influence on cervical pre-cancer and cancer. This study indicated higher age, low level of education, lower socio-economic condition and higher parity as most important socio-demographic factors for developing cervical pre-cancer and cancer in Bangladesh.

Association of IL-12B rs3212227 and IL-6 rs1800795 Polymorphisms with Susceptibility to Cervical Cancer: A Systematic Review and Meta-Analysis

Primary studies have shown that the IL-12B rs3212227 and IL-6 rs1800795 polymorphisms are associated with an increased risk of cervical cancer. However, conflicting results warrant a meta-analysis to obtain more precise estimates. A comprehensive literate search on PubMed, Web of Science, Scopus, CNKI, and SciELO was performed to collect all eligible studies up to November 10, 2019. The pooled odds ratios (OR) and 95% confidence intervals (CI) were used to calculate the risk. This meta-analysis was carried out by utilizing CMA software. A total of eleven case-control studies including four studies on IL-12B rs3212227 and seven studies on IL-6 rs1800795 were selected. Pooled ORs revealed that the IL-6 rs1800795 polymorphism was significantly associated with an increased risk of cervical cancer (C vs. G: OR = 1.294, 95% CI 1.071-1.564, p= 0.007; CC vs. GG: OR = 1.633, 95% CI 1.059-2.520, p= 0.027; CC+CG vs. GG: OR = 1.312, 95% CI 1.048-1.643, p= 0.018; and CC vs. CG+GG: OR = 1.592, 95% CI 1.268-1.999, p≤0.001), but not IL-12B rs3212227 polymorphism. Stratified analysis by ethnicity revealed that both IL-12B rs3212227 and IL-6 rs1800795 polymorphisms were associated with risk of cervical cancer in Asian women. Our pooled data revealed that the IL-12B rs3212227 and IL-6 rs1800795 polymorphisms may be used to identify individuals at high risk of cervical cancer in Asian women..

Epidemiologic and Health Economic Evaluation of Cervical Cancer Screening in Rural China

Cervical cancer is preventable and curable by detected early and managed effectively. To explore the most economical and effective cervical cancer screening strategies would lay a solid foundation for reducing the health and economic burden of cervical cancer. A Markov model was established for a cohort of 100,000 female to simulate the natural history of cervical cancer. 18 screening strategies were estimated including careHPV, Thin prep cytologic (TCT), Visual inspection with acetic acid/ Lugol's iodine (VIA / VILI), careHPV in series with VIA / VILI, careHPV in series with TCT, three methods parallel connection every 1, 3, 5 years respectively. Model outcomes included cumulative risk of incidence and death of cervical cancer, quality-adjusted life years (QALYs), cost-effectiveness ratios (CERs), incremental cost-effectiveness ratios (ICERs), cost-utility ratios (CURs) and benefits. According to the results of epidemiological analysis, careHPV similar to the parallel connection every 1 year achieved highest epidemiological effects via reducing the cumulative risk of onset and death by more than 98 %. In health-economic terms, CER among all the screening strategies ranged from -756.34 to 113040.3 Yuan per year and CUR ranged from -169.91 to 11968.27 Yuan per QALY. The benefit ranged from -1629 to 996 Yuan. The incremental cost-effectiveness analysis showed that three methods in parallel every 1 year, TCT every 1 year, VIA/VILI every 1, 3, 5 years and careHPV every 5 years were dominant strategies. Considering the economic and health benefits of all the strategies, our results suggested careHPV every 3 or 5 years and VIA/VILI every 1 or 3 years eventually were more appropriate as screening methods in rural China.

Sexual Dysfunction in Carcinoma Cervix: Assessment in Post Treated Cases by LENTSOMA Scale

Treatment for cervical cancer consists of hysterectomy, radiotherapy, chemotherapy and targeted therapy in different combination based on stage at presentation. However, late consequences of such radical treatments are known but not many Indian studies have reported it. Quality of life and impact on sexual health has become an important issue in view of long survival of cervical cancer patients. LENTSOMA scale is one such scale validated for scoring radiotherapy related morbidity. However, there is need for a comprehensive scale covering all aspects of physical and psychological disruptions to provide complete recovery and rehabilitation. The study was prospective and patients who were treated for cervical cancer on follow up were included in this study. A total of 85 patients, who were treated with surgery, radiotherapy, chemotherapy alone or in combination, comprising of stage I to stage IV disease, participated in this study. Findings of this study showed that pain during intercourse and altered sexual life were reported by 32.9% and 25.9% patients respectively whereas 24.7% found it problematic and in 22.3% patients, alteration in interest in sex were reported. Vaginal stenosis was seen in 75.29% of patients after treatment with decreased frequency of intercourse after treatment was seen in 16.4 % of patients. Combination of surgery and radiotherapy in cervical cancer patients caused more sexual dysfunction and dissatisfaction, especially in lower age group. Treatment morbidity in term of sexual function was more with advanced stage disease and with the patients on longer follow up. Sexual function is an important aspect of quality of life but there is no single self-report measure in routine clinical follow up use which is brief, easy to complete and incorporates all (physical, psychological, emotional) aspects of sexual health for people affected by cancer..

Trends in Cervical Cancer Mortality in Brazilian Women who are Screened and Not Screened

This study aimed to analyze the trend in cervical cancer (ICD C53) mortality in Brazilian regions in women who are who are screened and not screened from 1996 to 2015. An epidemiological study, of time series of mortality from cervical cancer performed in 90,856 women under 24 years old (343 women), between 25 and 64 years old (32,703 women), and over 65 years old (10,909 women). The data from this research were collected from the DATASUS, from the SIM Health Surveillance Secretariat files, captured through TABNET selecting the resident population by gender and age group and ICD 10 C53 from 1996 to 2015. Among women, 43.8% were white, and 76% had less than eight years of formal education. Polynomial regression showed an increasing trend in cervical cancer mortality in Brazil for women aged 15 - 24 years (p=0.01). Between 25 - 64 and 65 years or older it remained constant, but high (p=0.07; 0.99). The Northeast region pointed a growing trend in women aged 15 to 24 (p=0.01), 25 to 64 years (p=0.01) and 65 or older (p=0.001). The Northeast presented the highest average growth per year. In the Southeast, South and Midwest regions, decreasing trends were observed despite the high rates. The Joinpoint regression showed a 95% confidence interval, and that mortality from cervical cancer in the North region increased throughout the period analyzed. an increasing trend was observed from 1996 to 1998, whereas in the Midwest region, the trend remained stable throughout the period analyzed. The Federal District presented an upward trend from 1996 to 2015. In Brazil, an upward trend was observed throughout the whole period analyzed. Cervical cancer mortality in younger women is becoming more predominant, in addition to the high rate observed for women aged 65 or older. .

Pap Smear miR-92a-5p and miR-155-5p as potential diagnostic biomarkers of squamous intraepithelial cervical cancer

one of the female-specific diseases with a high incidence and mortality is cervical cancer. The main cause of cervical cancer is infection with Human papilloma virus (HPV). Low-grade squamous intraepithelial lesions (LSIL) and High-grade squamous intraepithelial lesions (HSIL) usually is caused by an HPV infection. Considering the role of microRNAs (miRNAs) as diagnostic biomarkers for a variety of cancers, the aim of this study was to determine miR-92a-5p and miR-155-5p expression levels in LSIL and HSIL Pap Smear samples. After initial bioinformatic studies, A total of 75 samples (25 samples of patients with LSIL, 25 patients with HSIL and 25 healthy individuals) were subjected to RNA extraction and cDNA synthesis. The expressions levels of confirmed miRNAs in samples of patients with LSIL, HSIL and healthy individuals were evaluated by Real time PCR analysis. To demonstration the role of predicted miRNAs as novel biomarkers in diagnosis of LSIL and HSIL, ROC curve analysis was done. Bioinformatics results showed that miR-92a-5p and miR-155-5p target the HPV E6 and E7 genes. The expression levels of these miRNAs were strikingly higher in Pap smear of patients with LSIL than in the healthy individuals (35.36, P = 0.001) (62.23, P = 0.001). Similarity, expression levels of miR-92a-5p and miR-155-5p were amazingly higher in patients with HSIL than in the healthy individuals (33.62, P= 0.001) (69.07, P= 0.001). Although, the levels of miR-92a-5p (0.95, P = 0. 85) and miR-155-5p (1.11, P = 0.84) exhibited no statistical differences between patients with LSIL and HSIL. Also, ROC curve analyses verified that miR-92a-5p and miR-155-5p are specific and sensitive and may serve as new biomarkers for the early detection of cervical cancer. These data suggest miR-92a-5p and miR-155-5p, which are upregulated in LSIL and HSIL, can be consider as predictive biomarkers for the prognosis of cervical cancer patients..

A Case Study on PPM1D and 9 Other Shared Germline Alterations in a Family

The use of high-throughput genotyping techniques has enabled us to identify the rare germline genetic variants with different pathogenicity and penetrance, and understand their role in cancer predisposition. We report here a familial cancer case, a study from Western Indian. NGS-WES was carried out in a lung cancer patient who has a family history of multiple cancers across generations, including tongue, lung, brain, cervical, urothelial, and esophageal cancer. The results were validated by data mining from available data bases. I-TASSER, RasMol and PyMol were used for protein structure modelling. The sequencing by NGS-WES revealed PPM1D c.1654C>T (p.Arg552Ter) mutation in hotspot region exon 6 leading to sudden protein truncation and loss of the C-terminal, due to the substitution of C>T. This mutation was classified as a variant of uncertain significance (VUS), due to limited data on lung cancer, The three unaffected siblings of proband did not show any pathogenic variants and comparative analysis of the four siblings indicate 9 shared genetic variants, classified as benign as per ClinVar. PPM1D constitutional genetic alterations are rare and uncommon in different ethnic populations. This gene encodes a phosphatase playing role in regulating the P53 tumor suppressor pathway and DNA damage response. Genetic alterations in the PPM1D gene maybe linked to history of gliomas, breast cancer, and ovarian cancer onset in the proband's family..

Out-reach Colposcopy Clinics and HPV Self-Sampling Decreases Loss to Follow up in a Community based Cervical Cancer Screening Programme

To introduce HPV self-sampling and out-reach colposcopy clinic as interventions to improve the follow-up of HPV positive women in a community based cervical cancer screening programme. This was a prospective observational study conducted during October 2017 to August 2019 and 2977 women underwent cervical cancer screening using CareHPV test. Follow up colposcopy for HPV positive women were conducted at the rural health center and alternatively as out-reach clinics in their own villages and default rates were compared. HPV positive women were followed up at one-year. They were given an option of either having a follow-up HPV test performed by a health care worker (HCW) or by self-sampling. Compliance to follow up in these two modalities were compared. A validated questionnaire was given to women who had given an HPV self-sample to assess their awareness about HPV and cervical cancer. During our initial round of cervical cancer screening using HPV as a primary screening modality, our HPV screen positive rate was 7.05% (210 out of 2977 women screened).  Our colposcopy rates following an initial invitation at the rural health centre was only 28.5%. Following this, we initiated out-reach colposcopy clinics at their own villages for HPV positive women and this increased colposcopy rates from 28.5% to 45.2%. The participation rate at one-year follow-up was increased from 40.5% to 60% by the introduction of self-sampling as a follow up option and 16.2% of women who were initially positive remained HPV positive at 12-14 months follow up. All women who were offered the option of self-sampling preferred it over a HCW collected sample. Our study showed that self-sampling could also be used effectively in the follow up of HPV positive women in the community. Outreach colposcopy clinics in their own villages enabled better follow up of HPV positive women.

Evaluation of HPV 16 and HPV 18 Oncoprotein Expression as Alternative Diagnostic Tools in Cervical Lesion

The study aimed to evaluate E6 and E7 oncoproteins of HPV16 and HPV18 expression in formalin - fixed paraffin embedded (FFPE) tissue in different grades of the cervical lesion and evaluate the potential use of E6 and E7 oncoproteins derived from HPV 16 and 18 as diagnostic protein biomarkers for triaging cervical lesions. A total of 102 FFPE cervical tissues were collected from 2 tertiary hospitals and immunohistochemical reactivity staining of E6 and E7 oncoproteins of HPV16 and HPV18 were evaluated using immunoreactive scoring (IRS) system and analysed statistically. The result showed an increased oncoprotein expression with the progression of cervical lesions. There is a statistically significant association between histology grade and HPV16/18-E6 expression (p = 0.028). However, there are no significant association of histological grade to HPV16-E7 immunoreactivity score (p = 0.264) and HPV18-E7 (p=0.080). The immunohistochemical expression of HPV oncoproteins is a potential alternative diagnostic tool applicable in a low-resource laboratory setting. The advantage of the histochemical evaluation is that this method is simpler to apply and less expensive in comparison to in situ mRNA hybridization. Nevertheless, our study also found that antibodies against HPV that are commercially available suffer quite substantial specificity issues such as background staining and inconsistency between different batches. Hence, the utilization of antibody-based staining warrants stringent quality control.

Predicting Factors for Pelvic Lymph Node Metastasis in Patients with Apparently Early-Stage Endometrial Cancer

Performing lymphadenectomy in all patients with early-stage endometrial cancer (EC) is debatable because the procedure may expose patients to unnecessary risks of postoperative complications. Aim of this study was to evaluate the prevalence and risk factors of pelvic lymph node metastasis (PLNM) in patients with apparently early-stage EC. Two hundred and two patients with apparently early-stage EC who underwent surgical staging at Thammasat University Hospital between the years 2013 and 2020 were included in this retrospective study. Clinicopathological data and preoperative laboratory results were obtained from computer-based medical records. All data were statistically analyzed to determine the prevalence of PLNM and risk factors for developing PLNM. PLNM was detected in 22 (10.9%) patients. Univariate analysis demonstrated that having grade 3 tumor, myometrial invasion of 50% or greater, vaginal involvement, cervical involvement, adnexal involvement, lower uterine segment involvement, lymphovascular space invasion (LVSI), and positive peritoneal cytology were associated with higher risk for developing PLNM. In addition, lower preoperative hemoglobin level and higher preoperative white blood cell count were significantly associated with PLNM. Multivariate analysis demonstrated that myometrial invasion of 50% or greater and LVSI were independent risk factors for developing PLNM (odds ratio (OR) 9.31, 95% confidence interval (CI) 2.58-33.55, p = 0.001, and OR 3.73, 95%CI 1.39-10.02, p = 0.009, respectively). Myometrial invasion of 50% or greater and LVSI were independent risk factors for developing PLNM in patients with apparently early-stage EC and thus lymphadenectomy in these patients should be provided.

Evaluating The Feasibility and Acceptability of Cervical Cancer Screening in an Urban Slum Community by HPV Self-Sampling With the Aid of Telecounselling: Lessons Learnt

HPV testing is the most sensitive method of secondary cervical cancer prevention and the preferred method recommended by the World Health Organization. To increase cervical cancer screening, self-sampling has been introduced, which has shown significant results in improving access and simplifying screening for large and remote populations in low- and middle-income countries. This study aims to evaluate the feasibility and acceptability of HPV self-sampling in an urban slum community using tele-counselling, which is a niche population for HPV positivity and HPV-related diseases. This study is a community-based, prospective, single-arm design. Women were counselled telephonically about the methods of self-sampling, and HPV self-sampling kits were couriered to them. The collected kits were returned via courier and tested at the study site. In the case of a positive test result, the individual was linked to treatment at the study center. Test positives were offered either a 'see and treat' approach or colposcopy triage. In the community, 982 women were enrolled in the study, but only 600 (61%) women consented to screening by HPV self-sampling. Ninety-six (15.6%) out of 600 women tested positive for Hr-HPV. Age, educational status, locality, occupation, menopausal status, and smoking status were similar in both screen-negative and screen-positive groups. Among the 600 women, 570 (95%) found it easy to take a self-sample, and 588 (98%) were satisfied with the overall experience. CIN I was found in 6 (6.4%), and CIN II was found in 4 (4.3%) cases. LEEP was performed in patients diagnosed with CIN II. HPV self-sampling is an acceptable method of cervical cancer screening, with an acceptance rate of 61% among urban slum women. It demonstrates that HPV self-sampling is feasible when supported by tele-counselling.

HPV Screening in Women Living with HIV (WLHIV) in Karnataka, India: Can it be Integrated into ART Centres?

Women living with HIV (WLHIV) face a six-to-tenfold increased risk of cervical cancer due to higher HPV prevalence and persistence. Despite an estimated 1.05 million WLHIV in India and a vast National AIDS Control Programme (NACP) network, no organized cervical screening exists within this infrastructure. This pilot implementation project aimed to demonstrate a feasible and efficacious model for integrating cervical cancer prevention services, including HPV screening and a 'see and treat' approach, for WLHIV within or near ART centres in hard-to-reach Indian settings. A total of 368 WLHIV aged >21 years on ART from three centres were invited. 314 (85.3%) were screened using the COBAS 6800 high-risk HPV test. HPV-positive women were recalled for colposcopy using a portable digital device. A 'see and treat' approach was applied, using thermal ablation or LLETZ for minor/major lesions suggestive of precancer in field clinics. 76 of 314 screened women (24.2%) tested positive for high-risk HPV. 65 of 76 HPV positive women (85.5%) complied with colposcopy and treatment. Histology from these 65 women showed 17 high-grade squamous intraepithelial lesions (HSIL), 23 low-grade SIL (LSIL), and 2 invasive cancers. The overall prevalence of HSIL or worse lesions was 5.7% among screened WLHIV. High participation was observed despite logistical challenges. The study confirms the significant burden of cervical neoplasia in WLHIV and demonstrates the feasibility and importance of integrating HPV screening and 'see and treat' services within or near existing ART centres using portable technologies. Leveraging the extensive NACP network offers a strategic opportunity for nationwide implementation, crucial for cervical cancer elimination efforts in this high-risk population.

Recurrent BRCA1 Mutation, but no BRCA2 Mutation, in Vietnamese Patients with Ovarian Carcinoma Detected with Next Generation Sequencing

Identification of germline and somatic BRCA1/2 mutations in ovarian cancer is important for genetic counseling and treatment decision making with poly ADP ribose polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 mutations in Vietnamese patients are scare. We aim to explore the occurrence of BRCA1/2 mutations in 101 Vietnamese patients with ovarian cancer including serous (n = 58), endometrioid (n = 14), mucinous (n = 24), and clear cell (n = 5) carcinomas. BRCA1/2 mutations were detected from formalin-fixed parafin-embedded tumor samples using the OncomineTM BRCA Research Assay on Personal Genome Machine Platform with Ion Reporter Software for sequencing data analysis. The presence of pathogenic mutations was confirmed by Sanger sequencing. We found no BRCA2 mutation in the entire cohort. Four types of pathogenic mutations in BRCA1 (Ser454Ter, Gln541Ter, Arg1751Ter, and Gln1779AsnfsTer14) were detected in 8 unrelated patients (7.9%) belonging to serous and endometrioid carcinoma groups. Except for the c.1360_1361delAG (Ser454Ter) mutation in BRCA1 exon 11 that was somatic, the other mutations in exons 11, 20, and 22 were germline.  Interestingly, the recurrent Arg1751Ter mutation in BRCA1 exon 20 appeared in 4 patients, suggesting that this is a founder mutation in Vietnamese patients. Mutational analysis of tumor tissue using next generation sequencing allowed the detection of both germline and somatic BRCA1/2 mutations..

Women’s Knowledge, Attitude and Practice on Cervical Cancer and Its Screening in Dhaka, Bangladesh

Background: Cervical cancer is the fourth most common cancer among women in the world. Visual Inspection with Acetic Acid (VIA) is a common screening test for cervical cancer in Bangladesh. This study will assess the knowledge, attitude and practice towards cervical cancer and screening among women residing in Dhaka district. Methods: A cross-sectional survey was conducted among 956 women aged 30 years and above in Dhaka. The women’s score on knowledge, attitude and practice were categorized as sufficient or insufficient. We calculated frequencies and used binary logistic regression to describe and assess the association between scores and socio-demographic characteristics of respondents. Results: Most (87%) respondent knew about cervical cancer and 13% knew that HPV is a risk factor for cervical cancer. Women who had sufficient knowledge were more likely to test VIA than those who had insufficient knowledge (39%, OR: 2.5; CI: 1.6, 2.8). Most (92%) would advise other women to have a VIA test. However, only 26% had a VIA test and 2% were vaccinated in private health care facilities for Human Papilloma Virus (HPV). Women who had sufficient attitude were equally likely to test VIA than those who had insufficient attitude. The VIA was underutilized because of low privacy during examination, unaware that VIA screened for cervical cancer, belief that they must pay for the test, and nurses performed examination. Conclusion: Women were knowledgeable about cervical cancer and likely to have a VIA test. However, the VIA test in underutilized and HPV vaccine coverage was low.

Sequential Chemoradiotherapy Compared to Radiotherapy in Endometrial Carcinoma

The role of combined modality in the adjuvant treatment of Endometrial Cancer has not been established. This study aims to assess the benefits of Sequential Chemoradiotherapy (SCRT) compared to Radiotherapy (RT) alone in the treatment of patients with Endometrial Cancer. Retrospective analysis of patients with Endometrial Cancer stage I to stage III C at King Abdullah Medical city, Makkah. Each group of patients was assigned to receive External pelvic RT, brachytherapy or both. While a second group received SCRT consisting of six cycles of Carboplatin (AUC 5) and Paclitaxel 175 mg/m2 followed by radiotherapy. Fifty-six women were treated of which 26 received SCRT and 30 received RT. The two groups had a median age of 58 years old ranging from 34 - 84 years old with no other statistically significant difference. Patients who received SCRT had poorer prognostic tumor characteris-tics. Median follow-up was 29.6 months (95% CI: 19.6-39.5 months). All deaths (n=5) were exclusively in the RT group. The 2 and 4-year OS rates were 100% and 100% in SCRT group versus 87.3% and 64.9% in RT group (hazard ratio [HR] 0.018 [95% CI: 0-24.4; p= 0.038); The 2- and 4-year DFS were 100% and 100% in SCRT group versus 78.1% and 43.9% in RT group (HR 0.102 [95% CI: 0.103-0.805; p= 0.008). Adjuvant chemotherapy given before radiotherapy for Endometrial Cancer may lessen the effect of high-risk features on the DFS and OS. Randomized clinical trials are needed to determine the benefits of early Systemic Therapy.

Effect of Metformin For Decreasing Proliferative Marker in Women with Endometrial Cancer: A Randomized Double-blind Placebo-Controlled Trial

To compare the Ki-67 index of endometrial cancer cells before and after treatment between the metformin and placebo group in women with endometrial cancer (EC). This study was a randomized, double-blind, placebo-controlled trial conducting in non-diabetic women who diagnosed with endometrioid EC and had a schedule for elective surgical staging at Rajavithi Hospital between August 2018 and June 2019. Tissue specimens were obtained via endometrial curettage at the time of initial diagnosis (pre-treatment) and hysterectomy (post-treatment) to assess the value of the Ki-67 index by immunochemistry. Patients were randomly assigned into 2 groups: metformin and placebo group. Metformin 850 mg or placebo 1 tab were administered once daily for at least 7 days, starting on the first morning after recruitment until one day before surgery. Baseline characteristics (e.g., age, body mass index, co-morbidities) including surgical and pathological characteristics were recorded. The metabolic effect of metformin was also evaluated by a recording of fasting blood sugar, HbA1C and potential adverse events including nausea, vomiting, dizziness, and hypoglycemic symptom. A total of 49 EC patients were included in this study. Twenty-five patients were assigned to the metformin group and 24 patients were assigned to the placebo group. Baseline demographic, surgical, and pathological characteristics between the 2 groups were similar. Metformin significantly changed the Ki-67 index relative to placebo, with a mean decrease of 23.3% (p=0.001) and a mean proportional decrease of 39.1% (p=0.006) before and after treatment. Additionally, no significant differences were detected in metabolic effects and adverse events between the metformin and the placebo groups. Short-term treatment with an oral metformin significantly reduced a proliferative marker Ki-67 index in women with endometrioid EC awaiting surgical staging. This study supports the biological effect of metformin in EC and potential applications in the adjuvant treatment in EC patients.

New Surgical Techniques for Early Stage Cervical Cancer Under 2 cm : Is There Enough Evidence?

Cervical cancer is the fourth most common malignancy in women worldwide and the second leading cause of cancer related mortality globally, making it a significant public health problem. Half of the women diagnosed are at an early stage; these women are typically young, mainly nulliparous, and have a long life expectancy. Less radical surgery is an attractive option for this selected group. In this narrative review, we aim to summarize the data regarding less radical surgery for early cervical cancer. Studies regarding less radical surgery including, conisation, simple trachelectomy and simple hysterectomy were searched in PUBMED database  in English and included from January 1995 to September 2024.Retrospective studies with a significant number of patients and  randomised controlled studies in this subject were included and discussed in detail as well. Retrospective studies have identified a low rate of parametrial involvement in specific subsets of patients with early cervical cancer, such as those with small tumor sizes (less than 2 cm), cervical stromal invasion less than 10 mm, no lymph node involvement, and no distant disease on imaging. In these patients, the incidence of parametrial involvement is less than 1%, which may render radical surgery unjustifiable. For this selected group, less radical surgery options, such as conization or simple hysterectomy, become attractive alternatives. When fertility preservation is desired, conization is an option; when fertility is not a concern, simple hysterectomy is the standard approach. Strict patient selection and preoperative evaluation are critical.

PIK3CA Polymorphisms in Cervical Cancer: Differential Impact of rs6443624 and rs141178472

Cervical cancer remains a major cause of mortality in low- and middle-income settings. We assessed whether two PIK3CA single-nucleotide polymorphisms (SNPs) rs6443624 (A/C) and rs141178472 (C/T) are associated with disease risk, clinicopathological features, and survival. In a prospective case control study at a tertiary center, 154 participants were enrolled (77 cases, 77 controls). Genomic DNA was isolated from FFPE cervical tumors (QIAamp DNA FFPE Tissue Kit) and genotyped using TaqMan allelic discrimination. Clinicopathological variables (FIGO stage, histology, grade, treatment, tumor-infiltrating lymphocytes [TILs]) were abstracted from records. Genotype distributions were compared by Pearson chi-square. Associations with clinicopathological features used chi-square/Fisher's exact as appropriate; ANOVA compared age across genotypes. Overall survival (OS) was estimated by Kaplan-Meier and compared with the log-rank test; mean OS with SE and 95% CI is reported. Cases were predominantly locally advanced at presentation and squamous histology; most were moderately differentiated. rs6443624 differed significantly between cases and controls (χ²=21.1, p<0.001), with CC over-represented in cases and CA less frequent. rs141178472 showed no significant case control difference (χ²=2.9, p=0.086). For OS, rs6443624 showed a significant genotype effect (log-rank χ²=23.45, p=0.001): AA had the poorest survival, CA the longest, CC intermediate. rs141178472 was not associated with OS (χ²=1.06, p=0.588). Genotype clinicopathological correlations for stage group, grade, TILs, and treatment were non-significant or inconsistent, with some comparisons limited by small sample sizes. The PIK3CA rs6443624 variant appears to influence both susceptibility and prognosis in cervical cancer, highlighting its potential as a biomarker for molecular risk stratification. Validation in larger, multi-center cohorts incorporating HPV/p16 assessment and extended follow-up is warranted to confirm its clinical relevance.

Evaluation of PathTezt™, a Liquid-Based Cytology System

Liquid-based preparation (LBP) cytology is commonly used in most laboratories these days due to its convenience and reliable results for the cervical cancer screening program. The PathTezt™ Liquid-based Pap smear is a second-generation LBP, which uses a filter-based concentration technique in processing the sample. This study was done to evaluate the cellular fixation, morphology, quality of smear in gynae cytology, and diagnostic interpretation of cervical cytological smears produced by the PathTezt liquid-based processor. A total of 400 pap smear samples were taken and processed using the PathTezt 2000 processor. The slides were evaluated in terms of sample adequacy, percentage of the circle covered by epithelial cells, cellular distribution, obscuring factors, and cell fixation. About 95.25% (381) of the samples were satisfactory for the evaluation. In 19 (4.75%) of the samples, epithelial cells covered less than 50% of the circle. A sample with good cellular distribution was seen in 92% of the cases, while 354 (88.5%) samples showed minimal inflammatory background. Almost all the smears (95.75%) had no erythrocytes in the background. All smears showed good quality fixation features toward nuclear, cytoplasm, and microorganisms. The total performance rate was 99%. Although the PathTezt liquid-based processor is still new compared to other first-generation LBP, the smears produced by this method were of high quality and it was cost-effective.

Dual Repurposing Strategy: Rivaroxaban and Ciprofloxacin as a Synergistic Anticancer Therapy in Cervical Cancer: Insight into Inhibition of Metastasis via Targeting the EMT Pathway

This study assessed the anticancer and antimetastatic impact of rivaroxaban-ciprofloxacin mixture and explored its molecular mechanism by examining its ability to target the epithelial-mesenchymal transition (EMT) pathway. Following incubation periods of 24 and 72 hours, HeLa and normal human fibroblast (NHF) cell lines were employed to investigate the anticancer and safety properties of rivaroxaban, ciprofloxacin, rivaroxaban-ciprofloxacin mixture, and carboplatin, with concentrations varying from 0.1 to 1000 µg/ml. The wound healing assay (WHA) of cervical cancer cells was employed to assess the anti-metastatic effects of the mixture at three time points: 0, 12, and 24 hours.. A combination index (CI) and selectivity toxicity index (SI) score were estimated to assess the potential synergistic effects of the mixture's components and their selectivity toxicity. A computational molecular docking simulation was conducted to evaluate the binding affinity of rivaroxaban and ciprofloxacin to different regulatory signals in the EMT pathway. The MTT and WHS assays outcomes revealed that the rivaroxaban-ciprofloxacin mixture possesses anticancer and antimetastatic properties. This combination significantly suppresses the growth of cervical cancer cells more effectively than carboplatin, rivaroxaban, or ciprofloxacin alone. Additionally, the mixture results in a 98% delay of cancer cell migration after 24 hours of incubation. Furthermore, the mixture's cytotoxicity on NHF cells was significantly lower than carboplatin. The combination of rivaroxaban and ciprofloxacin showed synergistic cytotoxic effects, as confirmed by the CI score. Also, it displays a selective cytotoxicity toward cancer cells, as indicated by the SI score. The molecular docking study results revealed that the most favorable interactions for rivaroxaban and ciprofloxacin occurred with the matrix metalloprotease and Tankyrase enzyme, with docking scores of -9 kcal/mol and -8.9 kcal/mol, respectively. The study's findings and the established pharmacokinetic and safety profiles of mixture drugs suggest that the pairing of rivaroxaban and ciprofloxacin offers a promising and safer option for treating cervical cancer.

Barriers to Cervical Cancer Screening in India: Insights from National Family Health Survey-5 Data

Cervical cancer, one of the commonest malignancies, can be prevented and cured through early diagnosis. Screening plays an important role in its control strategy, and India has dedicated strategies to its implementation. However, screening uptake is low in India. We examined how sociocultural and financial factors affect Indian women's cervical cancer-screening uptake behaviour. Cervical cancer screening-uptake and relevant social, cultural, and financial data obtained from round-5 of the National Family Health Survey (NFHS) were used for analysis. We examined 399,039 eligible records to survey cervical cancer screening conduct and assessed the impact of sociocultural barriers on such conduct using logistic regression. Descriptive statistics were used to describe background data. Most participants, aged 30-34 years, were uneducated, homemakers with bank accounts; mobile phone usage was limited, particularly in rural areas. One-third possessed health insurance, and approximately 10% had pre-diagnosed comorbidities. Only 2% underwent cervical cancer screening. Screening uptake was higher among older, educated, employed individuals with bank accounts, phone access, and media exposure. Mothers with more children and perceived constraints against healthcare seeking had lower uptake rates. Tobacco use, insurance, wealth, and media access had contrasting effects in rural and urban settings. Sociocultural and monetary factors have an unmistakable influence on cervical cancer screening uptake. Thus, aside from the continuous strengthening of the health system, our findings call for targeted mediations against misguided judgments and taboos alongside financial and social empowerment for better outcomes in India's cancer-screening policy.

Awareness about Cervical Cancer and Acceptance of Pap Smear for Screening among Women Attending a Tertiary Care Center

Our main objective was to increase the number of pap smears taken amongst women in the age group of 25-60 years (excluding antenatal women) attending the gynecology out-patient department of our hospital. To achieve our outcome goal, process goals were established. The process goals were to improve awareness on cervical cancer prevention and vaccination in both healthcare workers and patients/family attending the gynecology clinic. This study was done using the A3 methodology for quality improvement through the EQuIP India (Enable Quality Improve patient care) program which came about as a collaboration with PC-PAICE (Palliative Care-Promoting Assessment & Improvement of Cancer Experience) program of Stanford. The A3 quality improvement (QI) tool has well defined steps to identify the root cause of any given problem and to derive interventions to solve the stated problem. The steps are as follows(i) Process mapping and Gemba walk for analyzing contributors to the stated problem (ii) Pareto chart- to derive key drivers (iii) Run chart- to measure impact of interventions and sustainability. The progress was monitored biweekly and recorded as run charts for the study period of 9 months. There was an increase in uptake of pap smear rate from 30% to 70% among women in the general gynecology clinic during the study period of 9 months. The application of A3 methodology was very valuable to identify contributors towards a low pap smear rate and to develop interventions to improve cervical cancer awareness and pap smear rates in our hospital..

Phase II Study to Evaluate the Safety and Efficacy of Neoadjuvant Chemotherapy with Weekly Paclitaxel and Carboplatin Followed by Radical Chemoradiation in Locally Advanced Cervical Cancer in Egyptian Population

Since 1999, platinum based chemoradiation (CRT) is the standard treatment for locally advanced cervical cancer patients, but the estimated increase in overall survival (OS) over a 5-year period was only 6% in patients treated with CRT versus radiotherapy alone.There have been no additional developments in the treatment of locally advanced cervical cancer(LACC) patients since CRT introduction and approximately 30-40% of those patients failed to achieve complete response to CRT. Therefore, alternative approaches are needed to improve the outcome for such patients. NACT with Weekly paclitaxel and carboplatin for 4 - 6 weeks as dose-dense chemotherapy prior to CRT could be one such potential approach. A phase II, prospective , non randomized study was conducted at the Clinical Oncology Department of Ain Shams University hospital. 42 patients diagnosed with locally advanced cervical cancer patients (FIGO 2018 stage IIB to IVA ) and were treated by NACT carboplatin (AUC2) and paclitaxel (80 mg/m 2) for 4 - 6 week, then they proceeded to definitive CCRT (with a dose of 45-50.4 Gy) with weekly cisplatin followed by brachytherapy. Response rate and toxicity were the primary endpoints and Survival were the secondary endpoints. Median age at diagnosis - 48 years ; 90% (38/42 ) of cases diagnosed with squamous cell carcinoma and 9% (4/42) diagnosed with other histologies; 38% (16/42) had FIGO stage IIB , 40% (17/42) with stage IIIC, 7% (3/42) stage IIIB, 7% (3/42) with stage IVA, 5% (2 /42) with stage 2A and only 1 case diagnosed with stage 3A. 42 patients were evaluated.The overall response rate post-NACT was 71% and 61% developed complete response rate (CR) at end of all treatment course. Grade 3and 4 adverse events during NACT were most common, with hematological toxicity occurring in 21% of patients. There were no treatment- related deaths. The 9-month and 12-month overall survival rates were 94% and 84% , respectively. NACT with dose dense protocol, followed by CCRT, is a treatment option for locally advanced cervical cancer with controllable adverse events and agood response rate.

Knowledge, Attitude and Practice on Human Papillomavirus Vaccination among Healthcare Providers at a Tertiary Care Centre in North Delhi

In India, majority of cancer-related deaths are attributed to Human Papillomavirus (HPV), which is preventable through vaccines such as Gardasil and Gardasil 9. Despite their efficacy, uptake of these vaccines among healthcare providers (HCPs) remains low. This study aimed to evaluate knowledge, attitudes, and practices (KAP) regarding HPV vaccination among HCPs at a tertiary care center in India. A survey was conducted among 399 HCPs at a tertiary care hospital. Data were collected using an online questionnaire focusing on knowledge of HPV, attitudes towards HPV vaccination, personal vaccine uptake, and perceived barriers to vaccination. Statistical analysis was conducted using chi-squared tests, p-value of <0.05 were considered statistically significant. Significant knowledge gaps were identified, particularly among nurses and paramedical staff. While 95.9% of doctors were aware of HPV, only 66.7% of nurses and 73.4% of paramedical staff had similar knowledge. Awareness of HPV transmission was highest among doctors (98.5%) compared to nurses (87.1%) and paramedical staff (91.7%). Despite 89.34% of doctors expressing confidence in the vaccine's safety, only 11.67% had received it. Fewer than 9% of nurses and paramedical staff reported being vaccinated. The primary barriers to vaccine uptake were affordability and lack of awareness. The study highlights the need for targeted educational efforts to improve knowledge about HPV and its vaccines among HCPs, especially nurses and paramedical staff. Addressing misconceptions and integrating the HPV vaccine into national immunization programs could improve vaccine accessibility and uptake, ultimately reducing cervical cancer burden in India.

High Expression of Vascular Endothelial Growth Factor, Ki-67, and Protein 53 are Risk Factors for Poor Response of Paclitaxel-Carboplatin Neoadjuvant Chemotherapy in Stadium IB3, IIA2, and IIB Cervical Cancer

The therapeutic strategy for stage IB3, IIA2, and IIB cervical cancer is still controversial. The modalities are chemoradiation, radical hysterectomy surgery, or administration of neoadjuvant chemotherapy followed by radical hysterectomy. Response to chemotherapy is determined by tumor vascularization or angiogenesis, proliferative activity, and genetic instability of cervical cancer. The marker of tumor cell proliferation is the Ki-67 protein. In cervical cancer, the p53 gene is suppressed by human papillomavirus (HPV). The HPV E6 protein promotes the degradation of p53 thereby inhibiting stabilization and activation of p53. This study aimed to prove that high expression of VEGF, Ki-67, and p53 are risk factors for a poor response to neoadjuvant chemotherapy. This was a case-control study that was conducted at the Department of Obstetrics and Gynecology in one tertiary hospital in Denpasar from October 2021 to April 2022. There were 56 samples included in this study, which were divided into two equal groups, namely good response and poor response to neoadjuvant chemotherapy. Data were analyzed using the software SPSS-24 including the Kolmogorov-Smirnov normality test, Chi-square, and multiple regression logistics. Data were presented in tables and described narratively. It was found that the risk of a poor response to chemotherapy on the expression of VEGF VEGF, Ki-67, and p53 were 11.5, 15.0, and 8.33 times, respectively. We obtained a formula for calculating chemotherapy response, y = -7.3+ 1.6 VEGF + 1.6 Ki-67 + 1.8 p53. High VEGF, Ki-67, and p53 expressions were scored 1, and low expressions were scored 2. The limit value used is 0.05. The result y 0.05 means good response. This formulation can be used as a parameter to assess the risk of poor response to neoadjuvant chemotherapy in stage IB3, IIA2, and IIB cervical cancer which can be applied in clinical practice in the treatment of cervical cancer.

Clinicopathologic Impact of NANOG, ZEB1, and EpCAM Biomarkers on Prognosis of Serous Ovarian Carcinoma

Serous ovarian carcinoma (SOC) is a biologically heterogeneous with different genomic and molecular profiles, beside clinical response to the chemotherapy with subsequent in obstacles in starting unified, acceptable treatments and so we assess immunoexpression of Nanog, ZEB1, and EpCAM in SOC. In this study, the immunoexpression of Nanog, ZEB1, and EpCAM was studied in 60 cases of SOC. Overall survival (OS), disease-free survival (DFS) data and response to chemotherapy were  analyzed. NANOG was immunostained in 65% of the cases with a significant association with tumor grade, lymph node metastasis, and FIGO stage (p < 0.001 for each). ZEB1 showed moderate- high expression in 58.3% of the cases with significant up-regulation of ZEB1 expression with SOC grade, nodal metastasis, and SOC FIGO stage (p<0.001). EpCAM revealed high expression in 60% of the cases with significant association with higher grade, nodal metastasis, and advanced stage (p < 0.001 for each). Up-regulation of Nanog was significantly associated with response to chemotherapy, relapse, shorter OS and DFS (p < 0.001 for each). ZEB1 overexpression exhibited a significant association with response to chemotherapy (p= 0.012), relapse, shorter OS and DFS (p<0.001 for each). Moreover, the high EpCAM had a significant association with response to chemotherapy (p= 0.043), relapse (p < 0.001) shorter OS (p=0.006) and DFS (p< 0.001). Up-regulation of Nanog and ZEB-1 and EpCAM perhaps promote an aggressive SOC with a high risk of relapse and unfavorable response to standard chemotherapy regimen.

Human Papillomavirus Vaccine Awareness and Acceptability for Primary Prevention of Cervical Cancer in Pakistan: A Cross-Sectional Study

Human papillomavirus (HPV) vaccine is the most effective option for primary prevention HPV, a well-known cause of cervical cancer.  The objective of the study was to assess awareness of HPV, the acceptability of its vaccine and factors associated with the acceptability among the adult population in Pakistan. A cross-sectional survey was conducted among adult population of Pakistan from January 2022 and March 2022. Due to the ongoing COVID-19 pandemic, instead of face-to-face interviews, a self-administered questionnaire was developed and distributed through Google Forms. The questionnaire was available in both English and Urdu languages to cater to a diverse population. Overall, 313 (65.2 %) study participants had heard about HPV infection, while 297 (61.9%) knew HPV as the cause of genital warts and 256 (53.3 %) knew that HPV can cause any type of cancer, with a higher percentage of awareness among those who were in any health care setting compared to those who were in a non-healthcare setting. Regarding the acceptability to get HPV vaccine, 320 (66.7%) of the study participants were willing to get vaccinated, while only 15(3.1%) of the study population had previously received HPV vaccine. The most important factors associated with HPV vaccine acceptability were younger age of 18-25 years (Prevalence Ratio (PR) =1.60, 95% Confidence Interval (CI) =1.11, 2.32), and 26-35 years (PR= 1.65, 95% CI=1.09, 2.50). HPV vaccine acceptability was also associated with working in a healthcare setting due to better awareness of HPV vaccine (PR= 1.29, 95% CI=1.03, 1.62). It is important to address the knowledge gaps existing in the community about HPV vaccine acceptability and barriers against it for the successful rollout of the HPV vaccination program in Pakistan. Mass awareness campaigns about HPV, HPV vaccine, and cervical cancer are needed to increase the acceptability of HPV vaccine among public at the time of reintroducing HPV vaccine.

Syntaxin 6 Enhances the Progression of Epithelial Ovarian Cancer by Promoting Cancer Cell Proliferation

The aim of this study is to evaluate the expression of syntaxin 6 (STX6) in epithelial ovarian cancer (EOC) and assess the effects of STX6 on the prognosis of patient. Using information from the Kaplan-Meier Plotter database, the effects of STX6 expression on overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients were examined. The clinical information of 147 patients with epithelial ovarian cancer was evaluated, and immunohistochemical staining was used to identify STX6 expression in postoperative tumor specimens, and the affection of STX6 expression on patient prognosis was assessed. In addition, the expression of STX6 in tumor tissue, peritoneal metastases (PM) derived from 13 patients with epithelial ovarian cancer and 6 normal ovarian specimens was detected by PCR and Western blot. In order to investigate how STX6 affects the proliferation of tumor cells, STX6 was also over expressed and knock down in ovarian cancer cell lines. Then colony formation assay was used to explore the effect of STX6 regulating on cell proliferation. Kaplan-Meier Plotter enrollment data analysis revealed that patients with overexpressed STX6 had substantially worse OS and PFS than individuals with low STX6 expression. Retrospective study revealed a significant (P<0.05) correlation between the STX6 expression and tumor classifications, tumor stage, peritoneal carcinomatosis index (PCI), and PFS survival of patients. Western blot and PCR findings for fresh samples showed that STX6 was overexpressed in both primary lesions and PM nodules of OC. SKOV3 cell proliferation was shown to be dramatically reduced by STX6 knockdown and promoted by STX6 overexpression, according to the in vitro experiments. STX6 may increase the progression of epithelial OC by encouraging the proliferation of cancer cells, indicating that STX6 was a viable therapeutic target of epithelial OC.

Investigation of in-vitro Anti-Cancer and Apoptotic Potential of Garlic-Derived Nanovesicles against Prostate and Cervical Cancer Cell Lines

Investigate the anti-cancerous potential of garlic-derived nanovesicles (GDNVs), exploring their cytotoxic effects on HeLa and PC-3 cell lines, and elucidate the underlying mechanisms, including apoptosis induction and inhibition of epithelial-mesenchymal transition (EMT). GDNVs were isolated using differential centrifugation and ultracentrifugation. Characterization was performed through dynamic light scattering (DLS), field-emission scanning electron microscopy (FESEM), and Fourier-transform infrared spectroscopy (FTIR). Cytotoxicity assessments on HeLa and PC-3 cell lines using MTT assay. Apoptosis induction was evaluated through nuclear morphology changes and quantification of apoptotic cells using DAPI and PI/annexin V analysis. Western blot of apoptosis-related proteins (bcl-2, bax, caspase-3) was analysed. Anti-metastatic potential was assessed using wound healing assay and EMT transition inhibition. Garlic-derived nanovesicles (GDNVs), characterized by a size of 134.2 nm, demonstrated a substantial and dose- as well as time-dependent anti-proliferative impact on HeLa and PC-3 cell lines. The induction of apoptosis was unequivocally established through discernible modifications in nuclear morphology. The apoptotic cell count in HeLa and PC-3 cells increased by 42.4 ± 4.2% and 38.2 ± 3.2%, respectively. Comprehensive Western blot demonstrated alterations in the expression of key apoptotic regulators, namely bcl-2, bax, and caspase-3, providing robust evidence for the initiation of apoptosis. Furthermore, GDNVs exerted a significant inhibitory effect (p < 0.001) on the migratory potential of both HeLa and PC-3 cells. Moreover, there was a discernible association between GDNVs and the suppression of Epithelial-Mesenchymal Transition (EMT), emphasizing their role in impeding the metastatic potential of these cancer cell lines. This study establishes, for the first time, the anti-cancerous potential of GDNVs. The observed dose- and time-dependent anti-proliferative effects, selective cytotoxicity, apoptosis induction, and anti-migratory potential highlight GDNVs as a promising candidate for cancer treatment.

Vaccination Effectiveness against Human Papillomavirus in Kazakhstan

The purpose was to determine the effectiveness of human papillomavirus immunization and its impact on cervical cancer development in Kazakhstan. The current research is a case-control study with two groups: a main group and a control group. A total of 725 subjects participated in the research. The association between vaccination and cervical cancer development was calculated both for the two groups as a whole and for individual patients, who were selected based on criteria of residence, presence of immunodeficiency or chronic cardiac or renal pathology, as well as analysis of age at which the vaccine dose was received. There was a statistically significant association between the absence of the human papillomavirus vaccine and the risk of cervical cancer in all groups. When considering the entire cohort, the chance of finding a risk factor (lack of vaccination) was almost 7 times higher in the main group than in the control group. Thus, an association between vaccination and cervical cancer risk was found in each of the pairs of subjects. The effectiveness of vaccination in preventing cervical cancer was not observed in patients who were vaccinated after 18 years of age, while most patients in the control group were vaccinated in their teens. The practical significance of the research is not only to further study the problem of human papillomavirus (HPV) vaccination in Kazakhstan but also to popularize HPV immunization to prevent cervical cancer (CC).

Lack of Association between TP73 G4C14-A4T14 Polymorphism and Cervical Cancer Risk in Overall and Asian Women: A Meta-Analysis

Growing studies revealed the association between polymorphisms in Tumor Protein TP73 (TP73) and susceptibility to cancer, especially with gynecological cancers. but, the results remained inconsistent. This meta-analysis was carried out to examine the relationship of the TP73 G4C14-to-A4T14 polymorphism (hereafter, G4C14-to-A4T14) with susceptibility to cervical cancer globally and by ethnicity. Eligible studies were collected by retrieving PubMed, Scopus, Web of Science, Embase, Wan Fang, and CNKI published before 25 October, 2023. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of such association. A total of 10 case-control studies with 1804 cervical cancer cases and 2433 healthy controls were included to this study. The pooled results showed that TP73 G4C14-to-A4T14 polymorphism was not associated with cervical cancer risk in overall. in terms of stratified analyses by ethnicity, this polymorphism was not associated with risk of cervical cancer among East-Asian women. however,  there was a significant association based source of control among hospital-based studies. Inconsistent with previous meta-analyses, our pooled results revealed that TP73 G4C14-to-A4T14 polymorphism might not be a risk factor for development of cervical cancer globally and among East-Asian women. Moreover, further studies examining the effect of gene-gene and gene-environment interactions may eventually provide a better knowledge.

The Predictive Model of Suboptimal Primary Debulking Surgery among Women with Ovarian Cancer Using Pre-Operative Computerized Tomography, Tumor Markers and Comparison with the Intraoperative Findings: An Experience in Tertiary Care Hospital of Pakistan

Ovarian cancer is reported to be one of the most morbid gynecological cancers, often diagnosed at advanced stages. Primary debulking surgery (PDS) along with chemotherapy is the treatment of choice; however, there is a high probability of suboptimal excision. Thus, each patient should be evaluated for the appropriate treatment modality and PDS should be deferred as the risk of surgical complications and delay in chemotherapy consequently impacts survival. It is imperative to formulate a predictive model to select patients for optimal debulking surgery. A prospective observational study was conducted on women with ovarian cancer who underwent PDS at Indus Hospital and Health Network (IHHN), Pakistan from March 1st, 2020 till June 30th, 2024. Data was analyzed using SPSS 20.0. Chi-Square test was used to find the association between the predictors of optimal and sub-optimal debulking surgery using pre-operative computed tomography (CT) scan findings, and serum tumor markers. The sensitivity and specificity of serum cancer antigen 125 (CA-125) levels were measured. A total of 65 women with ovarian tumors were recruited in the study. Around 90.7% of patients had optimal PDS while 9.2% of patients underwent suboptimal PDS. Using pre-operative predictive scoring criteria, 48 (73.8%) patients scored 0-5 and all had optimal PDS while 11 (16.9%) patients scored 6-8, out of which 9 had suboptimal PDS (P value 0.00). A predictive score of 9 or more was reported in 6 (9.2%) patients, out of which 4 had suboptimal PDS. This study proposed a predictive model using pre-operative CT scan criteria and tumor marker serum CA-125 level which will help in scoring the patients with epithelial ovarian cancer. Subsequent treatment options should be decided either in the form of upfront debulking surgery or neoadjuvant chemotherapy. Further prospective studies are required to formulate a better applicable predictive model in all types of ovarian cancer including germ-cell ovarian tumors and sex cord-stromal tumors.

Male Human Papillomavirus Infection and Genotyping in Turkey

High-risk (HR) Human Papillomavirus (HPV) has been shown to play an important role in men in various locations in Turkey. This study aims to screen the male persistent infection with the high-risk human papillomavirus (HPV) genotype status in Turkey to provide a reference basis for formulating prevention strategies for the development of genitourinary tract neoplasia. The HPV QUANT-21 Quantitative RT-PCR Kit® was used to identify and quantify low-risk HPV (HPV 6, 11, 44) and high-risk (HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) from male individuals in Turkey. Of the total 1304 samples, 473 were positive for at least one HPV genotype, with an overall frequency of 36.2%. Two-hundred fifty-four patients were positive only for one or more LR   HPV genotypes (54%), and 219 patients were positive for one or more HR HPV genotypes (46%). The LR HPV genotype frequency was 53.7%, while the HR HPV genotype frequency was 46.3%. Our technology had the positive advantage of being able to calculate concentrations for each genotype. Genotype 51 was second in frequency but had the highest average concentration of 5.38 log (copies/sample). The presence and genotype of the virus before HPV vaccination are also of increasing importance. The data obtained will serve as a guide for prevention strategies, especially vaccination. Based on our findings there is a need of new estimates of the efficacy of currently available HPV vaccines and to develop a screening program to prevent and reduce the incidence of genitourinary tract neoplasias in Turkey. Further studies are planned to measure and define the high levels of infection that may lead to the development of cervical tumors. Using this technique, it may be possible to make clinical decisions about the extent of cytological alterations.

Fas Ligand (FasL) in Association with Tumor-Infiltrating Lymphocytes (TILs) in Early Stage Cervical Cancer

To date, little is known about the roles of FasL and TILs in cervical cancer. This study aims to determine the correlation between FasL expression and TILs presence in cervical cancer. In this study, we analysed the FasL and TIL presence in 32 squamous cell carcinoma or adenocarcinoma that were obtained from early stage (≤ IIA2) cervical cancer patients using immunohistochemistry. The level of FasL and TIL was assessed qualitatively, and then quantified with the H-Score system. Most of the patients were between 30 to 50 years old (59,4%), and had never taken pap smear examination before (96,9%). Based on the Pearson analysis of FasL and TIL presence, we found that FasL was inversely correlated with CD45 or TIL number when the level of FasL is above 140 and the CD45 is below 160. Based on Chi-Square test of FasL and TIL classification, there was a nine-fold odds ratio (OR) of lower TILs classification in high expression of FasL classification (OR 9, p=0.01). An inverse correlation between FasL expression and TILs level, that might indicate FasL-induced TILs apoptosis in tumor tissue, was observed. The strong inverse correlation between FasL and TILs presence showed some insight about the interactions between cancer cells and its surroundings inside of the cervical cancer tissue. This might also be further developed to tailor a prognostic marker that can predict the outcome of therapy in patients, not only in cervical cancer, but generally in all cancer.

A Descriptive Study of Different Methods of Cervical Cancer Screening among Ever-Married Women in 35-Year and 45-Year Cohorts in Kalutara District, Sri Lanka

Screening for cervical cancer in Sri Lankan females with Pap smears (conventional cytology) has shown no marked reduction in cervical cancer incidence over the past two decades. The study aims to compare the efficacy of Pap smear, with other screening tools such as Liquid Based Cytology (LBC) and Human Papilloma Virus/deoxyribonucleic acid (HPV/DNA) (using cobas 4800) in detection of underlying cervical intraepithelial neoplasia (CIN) and cervical cancer among 35 and 45 year old ever married women in Kalutara districtin Sri Lanka. Women from 35-year cohort and 45-year cohort were selected from all Public Health Midwife areas (n=413) in Kalutara district by random sampling. Pap smear, LBC, and HPV/DNA specimen were collected s from women who attended the Well Woman Clinics (WWC) . Women with positive results from any method were confirmed by colposcopy.  Results: Of the, 510 and 502 women in the 35-year cohort and 45-year cohort, respectively, included in the analysis, nine women among 35-year cohort (1.8%) and 7 women among 45-year cohort (1.4%) had cytological abnormality (positive results) with Pap smears. Thirteen women among 35-year cohort (2.5%) and 10 women among 45-year cohort (2%) age groups had cytological abnormality (positive results) with Liquid Based Cytology reports. Total of 32 women among 35-year cohort (6.2%) and 24 women among 45-year cohort (4.8%)  were positive for HPV/DNA test. Of  the women tested positive on screening, colposcopy revealed that HPV/DNA method was superior to Pap and LBC for detecting CIN while the results of latter two were comparable. The CIN detection rate by colposcopy was high with HPV/DNA screening with cobas 4800, whereas the detection rate by LBC was insignificantly higher than Pap smears.

Minilaparotomy, Cyfra21-1, and Other Predicting Factors for Suboptimal Cytoreductive Surgery in Advanced Epithelial Ovarian Cancer: A Pilot Study

Currently, there is no reliable method to predict the result of the primary cytoreduction to decide whether to go on primary cytoreductive surgery or receive neoadjuvant chemotherapy. This study aimed to identify candidate predicting factors from clinical data, serum biomarkers, CT/MRI imaging, and minilaparotomy for suboptimal cytoreduction in women with advanced epithelial ovarian cancer. Women who were clinically suspicious of advanced-stage epithelial ovarian, fallopian tube, and peritoneal cancer undergoing primary cytoreductive surgery were recruited. Clinical data, abdominopelvic CT/MRI, and serum biomarkers, including CA125, HE4, and Cyfra21-1, were collected preoperatively. At the start of the surgery, a minilaparotomy incision was made, the peritoneal cavity was assessed, and the operating surgeons gave the impression of whether the optimal cytoreductive surgery would be attainable. Subsequently, the incision was extended as necessary, and the standard cytoreductive surgery was attempted. After the procedure completion, the surgical outcome (optimal vs. suboptimal cytoreduction) and other operative outcomes were recorded. The association between the potential predicting factors and the surgical outcome was examined. Fourteen patients were included in this pilot study. Twelve patients were diagnosed with primary ovarian or fallopian tube cancer, while two had ovarian metastasis from colorectal cancer. The optimal cytoreduction was achieved in eight women. After minilaparotomy, the surgeons could predict suboptimal surgery correctly in five out of six cases (OR: 24.12, 95%CI: 2.34-Inf., p8 ng/mL) and HE4 (>83 pmol/L) were significantly associated with suboptimal cytoreduction, with OR: 35.00, 95%CI: 1.74-702.99, p=0.02 and OR: 15.00, 95%CI: 1.03-218.30, p=0.05, respectively. The finding of rectosigmoid invasion from abdominal CT, increased serum cyfra21-1 and HE4, and the initial minilaparotomy impression were potentially associated with suboptimal cytoreduction.

Comparative Study of Smart Scope® Visual Screening Test with Naked Eye Visual Screening and Pap Test

Cervical cancer is a major contributor to mortality and morbidity in women. Naked eye visual screening (NE test) and Pap test are commonly used for cervical cancer screening.  Both tests have inherent limitations like low sensitivity (Pap test) and subjectivity in interpretation, lack of permanent record and overestimation (NE test). Here, Smart Scope® visual screening test (SS test) was compared with NE and Pap tests. Smart Scope® is a small, hand-held device that captures cervical images attached to a tablet to store data. To compare SS test with Pap and NE tests. This prospective observational study was conducted at a tertiary care hospital in India, over 16 months. A total of 509 women in the age group of 25 to 65 years were included in the study as per the inclusion criteria. All the participants underwent Pap test, NE test and SS test. Screen positives on any one test were advised colposcopy and biopsy. Out of 154 screen-positive women, 49 visited for follow-up colposcopy-guided biopsy. Nine incidental biopsies of screen-negative women were included in the data.  Thus, statistical analysis was carried out based on 58 available histopathology results. Out of 58 biopsies, 8 were normal, 30 were benign lesions, 18 were precancerous and 2 were cancerous lesions. SS test was found to have a sensitivity and NPV of 100% each, PPV of 45.4% and a specificity of 36.8%. Sensitivity and specificity of NE test was 90% and 39.5% respectively, PPV was 43.9% and NPV was 88.2%. Pap smear had a sensitivity of 25% and specificity of 84.2%, PPV of 45.5% and NPV of 68.08%. SS test has great potential to be a primary screening test in low-resource settings due to its better sensitivity and NPV as compared to NE and Pap tests..

Knowledge of Cervical Cancer and Human Papillomavirus among Japanese Women

The combination of human papillomavirus (HPV) vaccination and cervical cancer tests are globally recommended. Although knowledge regarding cervical cancer and HPV and experience of HPV vaccination are reportedly closely associated, the associations between knowledge and frequency of cervical cancer testing are unclear. We conducted a questionnaire survey regarding the knowledge of cervical cancer and HPV and experience of HPV vaccination and frequency of cervical cancer testing including cervical cytology and HPV testing. Among 99 women who visited Tsuruha Festa, most of the 77 non-medical workers who received information on cervical cancer and HPV through the Internet were not more likely to have knowledge about cervical cancer and HPV than were 12 medical workers who had gotten information in vocational school or university curriculum. The rates of HPV vaccination, cervical cytology, and HPV testing were 4.0%, 14.1%, and 4.0%, respectively, among participants and did not differ significantly according to participant job and age. Knowledge about cervical cancer and HPV was associated with experience of HPV vaccination and frequency of cervical cytology and was not associated with frequency of HPV testing. We observed insufficient knowledge about cervical cancer and HPV among non-medical workers as well as low HPV vaccination, cervical cytology, and HPV testing rates, and knowledge about cervical cancer and HPV to which frequency of cervical cancer testing were partially related. Therefore, the government should take measures to enhance public awareness about cervical cancer and HPV through social media such as the Internet..

Accuracy of the Triple Test Versus Colposcopy for the Diagnosis of Premalignant and Malignant Cervical Lesions

Despite the World Health Organization (WHO) recommendations concerning the use of alternative tests for the detection of cervical cancer precursor lesions in low-income countries, the accuracy of these tests is a debated issue. In the present study we compare the diagnostic accuracy of the triple test with that of colposcopy for the diagnosis of premalignant and malignant cervical lesions. A cross-sectional study was performed in 328 women referred to the gynecology clinic at Shahid Sadoughi Hospital, affiliated to Yazd University of Medical Sciences (SSUMS), Yazd, Iran, from March 2016 to June 2018. As the first step, a Pap smear was obtained from all participants. Visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) was performed in accordance with the known protocol. A colposcopy was then conducted in all participants, biopsy samples were obtained, and histological features studied. Finally, the results were compared by statistical analysis. The age range of the participants was 30 - 50 years. Of 328 women, 60 (18.3 %) were postmenopausal. Two-hundred and five patients (62.5 %) had an abnormal Pap smear, 165 (50.3 %) had abnormal results on colposcopy, and 141 (43 %) had abnormal histopathology reports. The VIA was positive in 129 patients (39.3 %) and the VILI in 177 (54 %). The results of the triple test were reported to be positive in 205 cases (51.52 %). The sensitivity of the triple test in the detection of premalignant and malignant cervical lesions was 78.7 % and 69 %, respectively. The sensitivity and specificity of colposcopy in the detection of premalignant and malignant cervical lesions was 80.1 % and 72.2 %, respectively. The diagnostic accuracy of the triple test and colposcopy in the detection of premalignant and malignant cervical lesions was 73 % versus 75 %. Since the results of the study showed that the diagnostic accuracy of the triple test is equivalent that of colposcopy, the former may be used in low-income countries and areas lacking access to colposcopy.

Effectiveness of a Health Education Program to Improve Knowledge and Attitude Towards Cervical Cancer and Pap Smear: A Controlled Community Trial in Malaysia

We examined the effectiveness of a health education program to improve; knowledge and attitude towards cervical cancer and Pap smear, and uptake of Pap smear test among female entrepreneurs in Kedah, a northern state of Malaysia. This controlled community trial involved 210 women from the districts of Alor Setar and Sungai Petani. Simple random sampling was applied to select 105 women from each district. Self-administered questionnaires were used to obtain information about the variables of interest. Health education intervention program included educational talk, demo video, experience sharing, pamphlet distribution, and text message reminders. Evaluation of outcomes was performed twice. The text message reminders acted as the cues to action that were sent between the two evaluation times at one-month interval. Women in the control group received educational talk alone. In the control group, evaluation of outcomes was done only once, which was one month after the educational talk. Knowledge on cervical cancer and Pap smear, and attitude towards Pap smear among women in both intervention and control group improved significantly at Evaluation stage 1. However, no further improvements were observed in the intervention group at Evaluation stage 2. The uptake of Pap smear in the intervention group increased significantly from 48.0% at Baseline to 68.0% at Evaluation stage 1 (P.

Diagnostic Performance of F-18 FDG PET/CT Compared with CA125, HE4, and ROMA for Epithelial Ovarian Cancer

This study aimed to examine the diagnostic performance of F-18 fluorodeoxyglucose positron emission tomography with computed tomography (F-18 FDG PET/CT) compared with cancer antigen 125 (CA125), human epididymis protein 4 (HE4), and risk of ovarian malignancy algorithm (ROMA) score to distinguish epithelial ovarian cancer from benign tumors. A total of 46 patients with pelvic masses, who underwent F-18 FDG PET/CT, CA125, and HE4 before surgery between January 2015 and December 2018, were included in this retrospective study. The diagnostic performance of CA125, HE4, ROMA score, and maximum standardized uptake value (SUVmax) to differentiate epithelial ovarian cancer from benign pelvic tumors was examined by receiver operating characteristic curve analysis. Among the 46 patients, 28 were cases of ovarian cancers and 18 were of benign. The mean values of CA125, HE4, ROMA score, and SUVmax were significantly higher in the ovarian cancer group than the benign group. In early cancer stages (stages I and II), Area under the curve for SUVmax was significantly higher than CA125 and ROMA score (0.778 for CA125, 0.753 for HE4, 0.682 for ROMA score, and 0.922 for SUVmax). SUVmax using F-18 FDG PET/CT showed a high diagnostic accuracy for differentiating epithelial ovarian cancer from benign pelvic tumors, including early stage ovarian cancer. F-18 FDG PET/CT can be a useful modality for the assessment of pelvic mass..

Next Generation Sequencing-Based Germline Panel Testing for Breast and Ovarian Cancers in Pakistan

Pathogenic germline mutations in BRCA1/2 constitute the majority of hereditary breast and/or ovarian cancers worldwide. Incidence and mortality rate of breast and ovarian cancers in Pakistani women is high. Thus, to establish the diagnosis for targeted therapy in Pakistan, we conducted Next-generation sequencing-based germline testing for the detection of BRCA1/2 oncogenic variants associated with breast and ovarian cancer subtype. Peripheral blood of 24 women, diagnosed with breast and epithelial ovarian cancers, was taken from the recruited cases with the consent of performing germline genetic testing. DNA was isolated from the peripheral blood and subjected to indexed BRCA Panel libraries. Targeted NGS was performed for all coding regions and splicing sites of BRCA1 and BRCA2 genes using AmpliSeq for Illumina BRCA Panel and Illumina MiSeq sequencer (placed at AFIP). Analysis of the sequencing results has been done by using Illumina bioinformatics tools. We detected 421 variants having a quality score of 100 in all cases under study. The list of identified variants in BRCA1 and BRCA2 genes was narrowed down after filtering out those which did not pass q30 and those with a minor allele frequency (MAF) > 0.05 based on gnomAD browser. To classify these variants, clinical significance was predicted using external curated databases. As a result, we interpreted (n = 4) 16.7% pathogenic variants in BRCA1 and (n = 6) 25% variants of uncertain significance (VUS) in both genes. Descriptive statistics depicted that the age and BMI of BRCA positive cases are less than BRCA negative cases. Our findings exhibit an initial report for the NGS based cancer genetic testing in Pakistan.  This will enable us to pursue screening and diagnosis of hereditary BRCA mutation utilizing the latest state-of-the-art technique locally available in Pakistan ultimately resulting in targeted cancer therapy.

Prognostic Factors for Advanced Epithelial Ovarian Cancer Following Primary Cytoreductive Surgery or Neoadjuvant Chemotherapy

To examine the association between clinicopathological factors and survival in advanced epithelial ovarian, tubal, and primary peritoneal cancers patients who had primary cytoreductive surgery (CRS) and those that received neoadjuvant chemotherapy (NAC). Women who had CRS or NAC between 2008-2017 were included. Association between clinical characteristics, pretreatment imaging, serum markers, surgical and pathological factors, and disease recurrence/progression/death was examined in multivariable analysis. Two hundred and three women were recruited in this study (CRS 128 women and NAC 75 women). Median overall survival was 33.7 months for the CRS group and 27.9 months for the NAC group (p=0.04). Median progression-free survival was 14.9 months in the CRS group and 12.1 months in the NAC group (p=0.04). For the CRS group, factors independently associated with increased risk of death included primary peritoneal carcinoma (adjusted hazard ratio [aHR] 6.94), stable disease/progression at treatment completion (aHR 5.97), and initial tumor size of more than 12 cm (aHR 1.87). For the NAC group, stable disease/progression after complete treatment (aHR 6.45) and pre-treatment platelet to lymphocyte ratio of more than 310 (aHR 2.20) were significantly associated with an increased risk of death. NAC appeared to be a good alternative treatment for stage III/IV tubo-ovarian carcinoma. The worse survival outcome associated with primary peritoneal carcinoma and large initial tumor size in the patients who received CRS suggested that NAC could be an attractive option for those with these characteristics.

Knowledge, Attitudes, and Practices Regarding Cervical Cancer Screening among Omani Women Attending Primary Healthcare Centers in Oman: A Cross-Sectional

This study aimed to assess knowledge, attitudes, and practices regarding cervical cancer, cervical cancer screening, and Papanicolaou (Pap) smear testing among Omani women attending primary healthcare centers in Oman, and to establish a correlation with various sociodemographic characteristics. A multi-center cross-sectional survey was carried out from August 2019 to January 2020 and included 805 women attending 18 primary healthcare centers. A pre-tested questionnaire was utilized to assess the participants' sociodemographic characteristics, cervical cancer risk factors, knowledge, attitudes, and practices related to cervical cancer, cervical cancer screening, and Pap smear testing. All 805 women participated in the study (response rate: 100%). Overall, 67.5% and 50.9% had heard of cervical cancer and Pap smear testing, respectively; however, only 13.4% and 10.9% demonstrated high levels of knowledge concerning these topics. Knowledge was significantly associated with educational level, type of educational qualification (i.e. if their degree was related to healthcare), monthly income, and employment status (p ≤ 0.05 each). Only 15.7% of the participants had previously undergone Pap smear testing, although 42.7% were willing to undertake such screening in future. No associations were noted between Pap smear practice or willingness and sociodemographic characteristics, family history of cervical cancer or personal history of cervical cancer or related risk factors. Knowledge regarding cervical cancer and Pap smear testing was suboptimal among a cohort of Omani women attending primary healthcare centers in Oman. This may be a factor behind the increased number of cervical cancer cases in Oman; as such, a well-structured awareness and educational program is needed to address this issue.

Evaluating the Performance of Hybrid Capture 2 Test as a Primary Screening Test from Studies Conducted in Low and Middle-Income Country Settings- Special Focus India

Among the screening tests for cervical cancer, advantages of screening with second generation molecular Hybrid Capture 2 (HC2) test is the high sensitivity and negative predictive value that makes it easy to implement as a cervical cancer screening policy necessitating less screening rounds. High income countries are now implementing HC2 test in their national cervical cancer screening program. Since the acceptance of any screening test depends on the sensitivity of the test, the current study was carried out to evaluate the sensitivity of HC2 test reported from Low- and Middle-income countries (LMIC) which share major burden of cervical cancer globally and to establish if HC2 test could be used as a primary screening test in India. The population based cross sectional studies from LMICs which evaluated HC2 test as a primary screening modality to diagnose Cervical intraepithelial neoplasm grade 2 and above (CIN2+) lesions were included. A total of 18 studies from LMIC involving 1,13,086 women were reviewed for sensitivity of HC2 as a primary screening test. The overall average sensitivity and specificity to diagnose CIN2+ lesions were 79.84% (95% CI-71.01,86.73) and 85.63% (95% CI- 84.37,86.92) respectively. India demonstrated an average sensitivity and specificity of 65% (95% CI 57,77) and 93% (95% CI- 92,94) respectively. Results from LMIC demonstrate a comparably low sensitivity of HC2 test to diagnose CIN2+ lesions as compared to that reported from High income countries. Sensitivity of HC2 was substantially low for India. The current study discusses issues of HC2 assay and the role of untreated Reproductive tract infections as probable causes for low sensitivity of the test. This needs further research in an attempt to improve the sensitivity of the test in an era of self-sampling and low-cost HPV test on horizon to improve the coverage for cervical cancer..

Predictive Value of Marker of Proliferation Ki-67 and Cell Cycle Dependent Protein kinase Inhibitor P16INK4a in Cervical Biopsy to Determine Its Biological Behaviour

The aim of the study is to analyse the Immuno-histochemical expression of   Ki-67  and P16INK4a in CIN and cervical cancer cases  and  their utility to determine the accuracy of histological diagnosis and prediction of biological behavior of cervical lesion. A retrospective cross-sectional study was carried in 110 numbers of cervical biopsy that included 25 CIN1, 21 CIN2, 12 CIN3, 26 SCC and 01 adenocarcinoma and 25 non neoplastic lesion. The tissue sections were stained with Ki-67 and P16INK4a. Ki-67 expression was seen in 55.5% (61/110) cases of cervical lesion., out of which 3.6% (4/110; cervicitis -2/110 and metaplasia-2/110) cases were non dysplaia, 51.8% (57/110) cases were dysplasia /CIN of varying grade including invasive cancer. P16INK4a expression was noted 51.8% (57/110). There was an increasing trend of the intensity of Ki-67 and P16INK4a from focal positivity in low grade lesion to diffuse intensity in higher grade lesion and is statistically significant. There was strong association between the two variables Ki-67 and P16INK4a positive cases with their histologic grade. Though histopathology remains the ''gold standard'' for the diagnosis of CIN, both low and high-grade, biomarkers like Ki-67 and P16INK4a have emerged as helpful adjuncts. Their combined use may assist in the histopathologic classification of preinvasive lesions and facilitate the distinction from nondysplasia.

Knowledge and Attitude towards Cervical Cancer and Human Papillomavirus among Pharmacists in Japan

The objective of this study was to assess the knowledge and attitude towards cervical cancer and human papillomavirus (HPV) among pharmacists in Japan. Questionnaires were disseminated to 788 pharmacists employed by the Tsuruha Holdings Inc. A total of 617 pharmacists responded, generating a response rate of 78.3%. Of the 362 females and 255 males, vaccination rates were 14.4% and 0.8%, respectively. In terms of cervical cytology, 35.1% of females received it once every two years, and 26.2% received it irregularly. As for HPV testing, 12.2% of females received it once every two years, and 16.6% received it irregularly. The rate of "school curriculum" as an information source was significantly higher among younger pharmacists; while "internet", "media", "training seminar for pharmacist", "advertisement in medical institution", "internal manual", and "others" were significantly higher among older pharmacists. The proportion of pharmacists with knowledge on general questions, except for those about HPV testing, was significantly higher among females than males. The vaccination rates of younger pharmacists were significantly higher than those of older pharmacists. The screening rates of cervical cytology were significantly higher among older than younger pharmacists, and also among those with at least 10 years of experience than those with less. There were no differences in the screening rates of HPV testing according to age or pharmacist experience. The proportion of pharmacists with knowledge about cervical cancer and HPV significantly varied depending on sex, age, and experience as a pharmacist. This study suggested that spreading the knowledge about cervical cancer and HPV might be effective for increasing the rates of cervical cancer screening.

Repeated Positive Cervical HPV Testing and Absent or Minor Cytology Abnormality at Pap Smear. What is the Next Step?

Human papillomavirus (HPV) screening has significantly reduced cervical cancer (CC) mortality. Women who consecutively test positive for high-risk HPV without and minor changes on reflex cytology (atypical squamous cells of undetermined significance [ASC-US] or low-grade squamous intraepithelial lesion [LSIL]) or dysplasia on cervical colposcopy-oriented biopsy are always referred to colposcopy. The aim of the present study was to assess whether this guidance is appropriate for COBAS HPV testing with reflex cytology. A cross-sectional, retrospective study was carried out in 5,227 women who underwent routine CC screening over a period of five years (2012-2017). All HPV tests were performed using Cobas®4800 HPV. The study included women attending gynecology appointments whose first HPV test was positive and who had any type of follow-up. Patients' HPV test results as well as cytology and biopsy findings obtained during the abovementioned period were analyzed. A descriptive and comparative statistical study was conducted using this data. A total of 765 out of 6003 HPV tests performed in 5,227 women were positive, and 141 women who had a positive HPV test (with negative for intraepithelial lesion or malignancy [NILM] or inflammation, or ASC-US and LSIL cytology, but no lesions on colposcopy, or absence of dysplasia on histology) repeated the HPV test at least once. Of these 141 women, 6 were diagnosed with high-grade squamous intraepithelial lesion (HSIL) during the follow-up period. All cases of HSIL were diagnosed after the second HPV test. This study shows that, at cervical cancer screening, all women testing positive for HPV regardless of Pap smear result should be referred to colposcopy.

Alterations in miRNA Expression and Their Role in the Pathogenesis of Cervical Cancer

Cervical cancer has a high incidence and mortality rate, affecting more than half a million women in 2018. Its development is strongly related to high-risk HPV infection. After infection, several cellular molecules are affected, including microRNAs (miRNAs), which are the focus of our study. We aimed to investigate changes in microRNA expression associated with cervical cancer and analyze the biological significance of these changes induced by HPV proteins. We analyzed transcriptome data retrieved from the NCBI website to investigate miRNA and gene expression in cervical cancer. We evaluated the alteration in expression of miRNAs and genes (between normal tissues and cervical cancer) using the GEO2R tool and selected those with significantly altered expression (p-value < 0.05). The target genes of miRNAs were predicted using the miRNA Pathway Dictionary Database. Subsequently, we created a network of biological pathways affected by miRNA deregulation using Cytoscape software and associated the altered miRNAs with the Hallmarks of Cancer using COSMIC v84. We identified 10 miRNAs and 82 target genes with significantly altered expression levels in cervical cancer that matched the predicted results. In addition, the deregulation of these genes causes changes in 52 biological pathways. These miRNAs affected pathways such as interferon signaling (miR-106b-5p and miR-1183), signaling by interleukins (miR-557, miR-106b-5p, miR-15a-5p, and miR-21-5p), oxidative stress-induced senescence (miR-557 and miR-15a-5p), cell cycle checkpoints (miR-557), transcriptional regulation by P53 (miR-557 and miR-15a-5p), and the exchange of oxygen and carbon dioxide in erythrocytes (miR-15a-5p). Alterations in miRNA expression play an important role in the pathogenesis of cervical cancer, affecting several biological pathways and Hallmarks of Cancer, such as immune system regulation, cell cycle regulation, and energy metabolism. Thus, their analysis can contribute to the development of diagnostic and prognostic biomarkers and more effective treatments for cervical cancer.

National Cervical Cancer Screening in Thailand

Cervical cancer is an important public health problem in Thailand. It was the most common cancer in Thai women with the incidence rate of 23.4 per 100,000 women in 1990. The aim of this study was to share the experiences and summary the outcome of cervical cancer screening program in Thailand. The Ministry of Public Health in cooperation with the National Health Security Office, launched the National Cervical Cancer Screening Program, covering 76 provinces nationwide under Universal Coverage Scheme in 2005. The screening method are Pap smear and Visual Inspection with Acetic acid (VIA) for women aged 30-60 and 35-45 respectively with a 5-year screening interval. Detecting cervical pre-cancerous lesions will follow by day care treatment such as cryotherapy, Loop Electrosurgical Excision Procedure, etc. Results: The first phase (2005-2009), was carried out on 3,124,855 women, the coverage reached 77.5%. For the second phase (2010-2014), 7,637,226 women were screened, reaching 53.9% coverage of target women. However, we have few data of follow up examination after abnormal screening. Therefore, we conducted new system to get more follow up data in 2019. Under the coordination of many related partners, 10,762,081 women have been screened during 2005-2014. The incidence rate declined to 11.7 per 100,000 women which is ranked as the third most common in women in 2014. This article briefly reviews the challenge of implementing an efficient cervical cancer screening in Thailand. In 2020, HPV testing has been introduced as a primary screening test for all Thai women attending public health sector instead of conventional Pap test.

Development and Validation of Questionnaire to Assess Knowledge about Cervical Cancer among Women Aged 20 to 65 years in Oman

This study aimed to develop and validate a questionnaire to assess awareness of cervical cancer, its risk factors, and methods of prevention among Arabic-speaking women aged 20 years and over. The study took place at primary healthcare institutions, Al Buraimi Governorate, Oman, between November 2018 to February 2019. In phase I, seventy items concerning cervical cancer and its prevention were generated through a literature review. In phase 2, the questionnaire was validated through calculating the content validity index (CVI) for both item level (I-CVI) and the scale level (S-CVI), in this phase a shortened English questionnaire of 55 items was formed, then rigorously translated to the Arabic language in phase III. The questionnaire was tested for reliability in two stages: A pilot and a large field test in phase IV. A total of 55 out of 70 items formed the final version of the questionnaire. The final instrument had an S-CVI/Ave of 0.92. The questionnaire called the Knowledge in Cervical Cancer and Prevention Methods 55-items (KCCPM-55). The Cronbach alpha coefficient was 0.940 for the whole questionnaire, and ranged between 0.57 to 0.93 for each of the domains. Test-retest reliability was examined in a subsample of the total participants sample (r = 0.769, p < 0.001). The KCCPM-55 has been successfully developed in the Arabic language and found to be a valid and reliable instrument for assessing the level of knowledge about cervical cancer and prevention methods among women aged 20 to 65 years in Oman.

In Vitro Anticancer Activities of Senna singueana Leaf Extracts against HeLa Cell Lines

The present demonstrated that SSL-CH extract selectively inhibits the growth of HeLa cell lines though activation of p53 and Bax genes medaied proapoptotic pathway signifying it is a potential alternative anticancer agent for cervical cancer. The selective cytotoxicity of diethyl ether, chloroform, ethyl acetate, and ethanolic leaf extracts of S. singueana were evaluated against cervical HeLa and normal mouse fibroblast L929 cell lines using MTT assay. At (IC50) concentration 20 µg/ml) of effective chloroform leaf extract of S. singueana (SSL-CH) was chosen to evaluate its nuclear apoptotic changes by using Acridine Orange/Etidium Bromide dual staining.  Subsequently, apoptotic induction potential of SSL-CH extract was assessed by RT-qPCR analysis of apoptotic genes p53 and Bax. Treatment SSL-CH extract selectively inhibited the dose depended proflretion of HeLa cell lines with IC50 of 20 µg/ml. AO/EB dual staining showed SSL-CH extract induced late apoptosis of 49.42% in compared to the control. RT-PCR analyses demonstrated that SSL-CH extract profoundly upregulated the proapoptotic genes p53 to12.85 (***p≤0.01), Bax to 11.61 (**p≤0.01), caspase-9 to 40.62 (***p≤0.01), and caspase-3 to 11.61 folds (**p≤0.01) respectively and down regulated antiapoptotic genes Bcl-2 to 0.9 (**p≤0.001) and survivin gene to 1 (***p≤0.001) at 2×IC50 (40 µg/mL) in comparison to control, confirming activation of the intrinsic apoptotic pathway. These findings demonstrated that SSL-CH extract could serve as a potential alternative therapeutic agent for cervical cancer treatment with affordable and fewer side effects comparison with cisplatin.

Analysis of the Prevalence and Quantification of viral load of different human papillomavirus types in Turkish women population

Persistent infection with high-risk (HR) Human Papilloma Virus (HPV) genotypes has been shown to play a significant role in the development of cervical intraepithelial neoplasia (CIN) and CC (cervical cancer). The present study aimed to determine the distribution and quantification of viral load of HPV genotypes in numerous genital samples obtained from women undergoing routine gynaecological care in different regions of Turkey. HPV typing was done by HPV QUANT-21 Quantitative RT-PCR Kit®, which is intended for the specific identification and quantification of low-risk (HPV 6, 11, 44) and high-risk (HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) from female subjects in Turkey. From the total of 5975 samples, 2777 were positive for at least one HPV genotype, with an overall frequency of 46.4%. 1695 patients were positive for only one or more LR-HPV genotypes (61%) and 812 patients were positive for one or more HR-HPV genotypes (29%). The frequency of LR-HPV genotypes was 31.4%, while the frequency of HR-HPV genotypes was 118.8%. Our tecnology had a positive advantage to calculate the concentration of each genotypes. Although genotype 52 ranked fifth in frequency, it showed the highest mean concentration, with a value of 5.38 log (copies/sample). The presence and genotype of viruses before HPV vaccination have also gained importance. The data obtained would provide guidance for prevention strategies, mainly of vaccination. We decided to add a new estimate to the effectiveness of currently available HPV vaccines and the development of screening programs to prevent and decrease the incidence of CC in Turkey. Further studies would be planned to measure and define the high infection level that can lead to the development of cervical neoplasia. Using this tecnology could give us a clinical desicion to degree the cytological changes.

The Immune-related ceRNA Network in Prognosis of Cervical Cancer

Immunotherapy is gaining attention and it is being included as one of the treatment strategies for cancer patients. However, the molecular mechanisms of immune-related genes and their affinity for cervical cancer progression remain unclear. In this study, we have developed an immune-related competing endogenous RNA [ceRNA] network and assessed the tumour infiltrating immune cells towards the prognosis of cervical cancer. Differential RNA expression pattern between stages I and II-IV of cervical cancer patients from The Cancer Genome Atlas [TCGA] was analyzed. Immune-related ceRNA network based on the immune gene signatures were retrieved and their targets were predicted using miRwalk 3.0. CIBERSORT was employed to identify the immune cell types based on their respective transcripts. The prognostic significance of RNAs in the ceRNA network and immune cell subsets was analyzed. Significant differences in 22 long non-coding RNAs [lncRNAs], 15 microRNAs [miRNAs], and 252 messenger RNAs [mRNAs] between stages I and II-IV of cervical cancer were observed. Further, we shortlisted the 49 immune-related mRNAs based on immune gene signature and predicted their target miRNAs and lncRNAs. A potential ceRNA network of 4 lncRNAs, 10 miRNAs, and 11 mRNAs had a strong correlation for prognosis. Out of 11 protein-coding immune mRNAs, IRF4 and AZGP1 had high degrees of interaction. In addition, the evaluation of immune cell subsets showed increased infiltration of M1 macrophages had better survival outcome. We have identified an immune-related ceRNA network based on differentially expressed transcripts between stages I and II-IV which may help predict the prognosis of cervical cancer.

Expression of CD44v6 and RCAS1 in Uterine Cervical Carcinoma Infected with Human Papillomavirus and Its Effect on Cell Proliferation and Differentiation

To investigate the expression of CD44v6 and RCAS1 and the presence of HPV in cervical cancer tissues, to determine serum RCAS1 levels, and to evaluate these components in correlation with clinicopathologic features and survival. A total of 52 patients consisting of 28 squamous cell carcinoma (SCC) and 24 adenocarcinoma cases, were studied. RCAS1 and CD44v6 expression was evaluated using immunohistochemical staining. HPV 16 and 18 E6 genes were detected using PCR, and serum RCAS1 concentrations were measured using ELISA. Associations between these factors and clinicopathologic features and survival were analyzed. CD44v6 expression was significantly higher in SCC compared with that in adenocarcinoma (P<0.001). It also showed a significant relation to histologic grade (P<0.001) and tumor size (P=0.03). RCAS1 expression was higher in adenocarcinoma than in SCC (P=0.001), and it showed a borderline relation with histological grade (P=0.057). Overall survival was not significantly different in both CD44v6 and RCAS1 expression; however, FIGO stage (P=0.025) and tumor size (P=0.042) resulted statistically different. The pre-surgical treatment serum RCAS1 levels were not associated with any clinicopathological variables. The presence of HPV 16 E6 was higher in SCC, while the presence of HPV 18 E6 was higher in adenocarcinoma (P<0.001). Detection of HPV 16 E6 was significantly associated with expression of CD44v6. The presence of HPV both HPV 16 E6 and HPV 18 E6 was found in cancer tissues with RCAS1 expression, but without any statistical significance. CD44v6 and RCAS1 expression seems to be involved in tumor proliferation and differentiation, but it is not implicated in the progression and invasion of cervical cancer infected by HPV. Pre-treatment levels of serum RCAS1 in cervical cancer are not a diagnostic and predictive biomarker.

Analysis of Rapid arc-based Radiation Therapy on Dosimetric Parameters in Cervical Cancer Patients with and without Bone Marrow Sparing

The standard treatment for cervical cancer is chemoradiation therapy. Pelvic radiation is associated with higher dose to bone marrow (BM) causing interrupted treatment due to haematologic toxicity with inferior outcomes. This study aims to evaluate rapid arc technique in sparing pelvic BM and dosimetric parameters for pelvis V5GY, V10GY, V20GY, V30GY, and V40GY dose. Twenty one cervical cancer patients were selected for the analysis. Planning target volume (PTV) contours, total pelvic BM and surrounding structures contours were standardised. Two rapid arc based procedures were designed for individual patient. One was done using bone marrow sparing (BMS) constraints while other was performed without BMS constraints. Data for both plans was calculated with regard to PTV, normal structures and pelvic BM. Difference in dose distribution in both groups was analysed using Wilcoxon and Friedman ANOVA test. In the presence of BM constraint a significant changes in pelvic BM dose for values of V10GY (p=0.002), V20GY (p=0.002) and V40GY (p=0.025) was observed. The coverage of PTV was found to be unaffected by adding BM constraint. The BM is radiosensitive structure so dosage is linked with haemtological toxicity. Increased dose is associated with higher grade of haematological toxicity in pelvic radiotherapy. The study suggests that adding BM constraint in plans reduced the pelvic BM dose while not affecting PTV coverage and dose to bowel, bladder and rectum. Bone marrow constraint in pelvic radiotherapy can be considered for better treatment toleration and to determine its role in decreasing haematological toxicity.

Knowledge Attitude and Practice of Postpartum Parturients Towards Cervical Cancer and Cervical Cancer Screening; Is Lack of Knowledge the Misleading Scapegoat?

The aim of this study was to assess knowledge, attitude, and practices towards cervical cancer screening among postpartum subjects. This cross-sectional study was conducted at inpatient obstetrics ward at Thammasat University Hospital (TUH), Thailand. The period of study was between July 2020 and July 2021. Subjects were term Thai pregnant women who had age between 20 and 45 years old and delivered at TUH. Demographic characters, knowledge, attitude and practices regarding cervical cancer screening were collected. A total of 388 parturient was recruited into the study. Average age was 31 years old. Around 90 percent of subjects knew that every woman age between 21and 65 years old with or without children should be screened for cervical cancer despite having only 46.6 percent (181/388) of subjects that underwent postpartum cervical cancer screening. Almost half of the participant agreed that risky sexual behavior of both genders was not the cause of cervical cancer. Despite the availability of the HPV vaccine throughout the country, only 74.2 percent acknowledged that HPV was the cause and only 70.4% heard about the HPV vaccine. The mean attitude about the cervical cancer was relatively high with the mean of 3.19±0.46. Although the higher the score the better the attitude toward the statement, there were several correlations of having such attitude. Attention to postpartum cervical cancer screening was quite low even though high knowledge of cervical cancer and screening. Scant knowledge was not all of the troubles that we believed long time ago.

Health-Related Quality of Life of Patients with Cervical Cancer According to the Duration of Treatment and Cancer Progression

The purpose of this study was to assess health-related quality of life (HRQoL) in Korean patients with cervical cancer according to the duration of treatment and cancer progression of cervical cancer. This study included 452 outpatients with cervical intraepithelial neoplasia (CIN) or invasive cervical cancer from six tertiary hospitals in South Korea. The questionnaire included the EQ-5D-3L instrument, patients' age, cancer progression (CIN or invasive cervical cancer), treatment duration (<1 year, ≥1 year but <2 years, and ≥2 years), treatment method (surgery, chemotherapy, radiation therapy), and presence of recurrence. HRQoL indices were calculated for these independent factors, and the mean was compared using ANOVA. Multiple regression analysis was performed to analyze factors affecting HRQoL in patients with cervical cancer. The EQ-5D index was 0.93 for patients with CIN, 0.87 for patients with invasive cervical cancer, and 0.78 for patients with recurrent invasive cervical cancer. HRQoL was significantly lower as the CIN progresses to cervical cancer. HRQoL of patients with invasive cervical cancer was lowest within 1 year of treatment in all stages. In addition, the HRQoL of patients with CIN or invasive cervical cancer who received chemotherapy and radiotherapy was lower than that of patients who underwent surgery. Multiple regression analysis showed that the HRQoL decreased significantly as increasing age, the first year of treatment after diagnosis, cancer recurrence, or chemotherapy. The HRQoL of patients with cervical cancer is affected not only by the stage of cancer progression but also by the duration of treatment and the type of treatment. As a result, when trying to apply the quality of life of patients with cervical cancer to cost-utility analysis, it is necessary to consider the duration and the type of treatment they receive.

Twelve Years Implementation of Cervical and Breast Cancer Screening Program in Indonesia

The study aimed to measure achievement of the national program of cervical and breast cancer screening in Indonesia after 12 years implementation and factors associated with the number of the screening. This was a cross-sectional study with descriptive and analytic analysis. Secondary data was collected from Directorate of Non Communicable Disease Control, Ministry of Health. From 2007 to 2018, the program was implemented in all 34 provinces, at 51% primary health centers (PHC) with 3 providers each. Total women aged 30-50 years screened was 3,664,625 (9.8% of the target). The number rose gradually from 2007 to 2014, with significant increase from 2015 to 2018. Bali province had the highest coverage (31%) and Papua had the lowest (1%). We found a wide disparity of coverage among provinces. There was 3.4% of VIA-positive, 16.1% was treated with cryotherapy, 1.3 per 1,000 of suspected cervical cancer, 5,4% lump in the breast, and 0.7 per 1,000 suspected breast cancer. Factors associated with number of the screening were number of PHC providing screening, number of GP, total provider, number of NCD post, number of Village with NCD Post, and income of the province. The cervical and breast cancer screening program was running in all provinces in more than half of primary health centers in Indonesia. National coverage (9.8%) was far below the target and varied widely among provinces. Number of PHC with screening services, number of GP, number of total provider, number of NCD post, number of Village with NCD Post, and income of the province have association with cervical and breast cancer screening.

A Study of Cytokeratin-7 Expression and Clinicopathological Correlation in Dysplasia and Squamous Cell Carcinoma of the Cervix

Cytokeratin (CK) proteins play a vital role in cancer diagnosis, of which,CK-7 is a prominent marker of squamocolumnar junction cells corresponding to the the initiating site of cervical cancer.The current study is aimed to evaluate the expression pattern of CK-7 and to corelate with the clinicopathological features in patients with cervical dysplasia and invasive squamous cell carcinoma. The hysterectomy and biopsy specimens from women with cervical dysplasia (n=60) and carcinoma (n=60) were evaluated histopathologically and processed for immunohistochemistry (IHC) staining to assess for CK-7 expression. The relationship between CK-7 expression and tumor characteristics like histological type of cervical intraepithelial neoplasia (CIN), tumor type and grade was evaluated. Data was analyzed using the Chi-square test ,wherein the  p value ≤ 0.05 were taken for statistical significance. Positive CK-7 expression was observed in 25 (41.67%) dysplasia and in 34 (56.67%) carcinoma cases. Majority of the cases were CIN III (n=31, 51.67%), large cell non-keratinizing tumor type (n=54, 90%) and moderately differentiated grade of tumor (n=52, 86.67%), out of which 18 (58.1%), 34 (62.96%) and 30 (57.69%) cases were CK-7 positive, respectively. The difference in clinical diagnosis and tumor characteristics over CK-7 expression was significant (p<0.05). The pattern of CK-7 expression in dysplasia and carcinoma cases were diffuse in 23 (38.33%) and 31 (51.67%) respectively and patchy in 2 (3.33%) and 3 (5%) of them, respectively. Significant positive CK-7 expression in cervical dysplasia and carcinoma indicates a good clinical course and its role as a useful predictable marker for cancer progression.

Prevalence of BRCA1/2 Mutation in High-Grade Non-Mucinous Ovarian Carcinoma

Ovarian cancer is the third most common cancer among women with the most common subtype being high-grade ovarian carcinoma (90%), characterized by high genomic instability and somatic loss-of-function variants in BRCA1/2 genes. BRCA testing in patients with Epithelial Ovarian Cancer (EOC) is recommended because of its role in genome counseling, as well as enabling therapeutics. This study aimed to determine the prevalence of somatic BRCA1/2 mutations in high-grade (non-mucinous) ovarian carcinoma cases. This research was a descriptive observational study with a retrospective approach. The sample used data from somatic BRCA1/2 mutation results with a diagnosis of high-grade non-mucinous ovarian carcinoma from surgery specimens at the Anatomic Pathology Laboratory of Dr. Soetomo General Academic Hospital, Surabaya, during 2019-2022. The total number of samples was 49 cases. The collected data includes the distribution of somatic BRCA1/2 mutation cases, histopathological diagnoses, age groups, and T stage. Among 49 cases, 9 cases had positive BRCA mutations, with 6 cases positive for BRCA1 mutations and 3 cases positive for BRCA2 mutations, all in HGSOC. No somatic BRCA1/2 mutations were detected in EnOC and OCCC. The highest somatic BRCA1/2 mutation rate occurred in the 50-59 age group. The distribution of cases based on T stage showed that most high-grade (non-mucinous) ovarian carcinomas were at T3 stage (61.22%), particularly in HGSOC (17.86% of BRCA1 and 10.71% of BRCA2 mutation cases). The occurrence of somatic BRCA1/2 mutations in high-grade non-mucinous ovarian carcinoma at our hospital from 2019-2022 was 18.37%, all in HGSOC.

Expression of Programmed Death-1 Ligands (PD-L1 and PD-L2) in Endometrial Carcinoma: Immunohistochemical Study

On basis of knowledge about the relationship between the immunity and cancer; cancer immunotherapies were introduced. Immune checkpoint regulators rank among the most crucial of those tactics. Programmed Death Ligand-1 (PD-L1) and Programmed Death Ligand-2 (PD-L2) are 2 ligands of Programmed Death-1 (PD-1); an immune checkpoint regulator. PD-L1 and PD-L2 antibodies have been effective in treating a variety of malignancies in clinical trials. Few of these antibodies have been approved for clinical use by the Food and Drug Administration (FDA). The purpose of this study was to assess the immunohistochemical expression of PD-L1 and PD-L2 by tumor cells (TC) and tumoral stroma immune cells (IC) in endometrial carcinoma (EC) and their association with the tumor's clinico-pathologic characteristics. For 62 EC cases, PD-L1 and PD-L2 immunohistochemical expression was examined in the TC and IC. Positive TC PD-L1 (25.8% of cases) was linked to high stromal tumor infiltrating lymphocytes (TILs) and high tumor grade. High TC PD-L2 (33.9% cases) was associated with non-endometrioid types, high tumor grade, and high FIGO stage. Positive IC PD-L1 (51.6% of cases) was correlated to non-endometrioid types, high tumor grade, high FIGO stage and high stromal TILs. High IC PD-L2 expression (14.5% of cases) was associated with lympho-vascular space invasion. Both PD-L1 and PD-L2 expression in both TC and IC were found to be directly correlated. Crucially, some of the PD-L1 negative cases had significant expression of PD-L2. Our results supported PD-L1 & PD-L2 expression in EC, particularly in high grade, high FIGO stage, non-endometrioid and TILs rich tumors, highlighting such cases as candidates for anti- PD-1 therapy. Furthermore, the identification of PD-L2 positive PD-L1 negative cases may indicate the combination of PD-L1 and PD-L2 testing to nominate cases that may benefit from the PD-1 pathway targeting therapies.

Barriers to Cervical Cancer Screening through Pap Smear Examination among Women Attending the Gynecology Polyclinic at Dr. Zainoel Abidin General Hospital in 2024: A Cross-Sectional Study

Cervical cancer remains the fourth most common cancer among women globally and a leading cause of cancer-related mortality in low- and middle-income countries (LMICs). Despite the availability of effective screening methods such as the Pap smear, screening uptake remains suboptimal. Barriers such as limited awareness, socioeconomic challenges, cultural beliefs, and inadequate access to healthcare services contribute to this gap. Identifying these factors is essential to inform effective interventions and reduce cervical cancer mortality. This study aimed to identify the barriers and facilitators associated with Pap smear screening uptake among women attending the Gynecology Clinic at Dr. Zainoel Abidin General Hospital, Banda Aceh. A cross-sectional study was conducted in 2024 involving 200 female outpatients. Data were collected using structured questionnaires based on the Health Belief Model to evaluate personal, cultural, and social factors influencing screening behavior. Descriptive statistics, chi-square tests, and binary logistic regression analyses were performed to determine significant predictors of Pap smear uptake. Although 49.5% of participants were aware of Pap smear screening, only 11.5% had undergone the procedure. Barriers identified included low educational attainment, limited monthly income, cultural misconceptions, and lack of spousal support. Logistic regression analysis revealed that perceived benefits (OR = 1.937; 95% CI: 1.011-3.711), self-efficacy (OR = 2.143; 95% CI: 1.088-4.222), positive attitudes toward screening (OR = 2.637; 95% CI: 1.386-5.017), and spousal support (OR = 2.084; 95% CI: 1.074-4.043) were significant predictors of Pap smear utilization. Socioeconomic barriers, negative attitudes, low self-efficacy, and insufficient spousal support substantially hinder Pap smear screening among women in this setting. Comprehensive interventions that incorporate community education, culturally sensitive approaches, and family engagement strategies are urgently needed to improve screening uptake and support cervical cancer prevention efforts in resource-limited areas.

Enhancing Personalized Chemotherapy for Ovarian Cancer: Integrating Gene Expression Data with Machine Learning

Ovarian cancer's complexity and heterogeneity pose significant challenges in treatment, often resulting in suboptimal chemotherapy outcomes. This study aimed to leverage machine learning algorithms, gene selection, and gene expression data to improve chemotherapy results. The mutual_info_classif approach was employed to identify the most informative genes for predicting treatment responses. Ten machine learning techniques were used to assess and optimize the predictive potential of these genes. By examining the reciprocal relationships between gene expression and chemotherapy outcomes, the study identified a subset of 20 critical genes essential for treatment efficacy. Among the selected genes, the Random Forest classifier demonstrated the highest accuracy, achieving 97% accuracy, 98% precision, 97% recall, and a 97.5% F1-score in predicting treatment responses. With statistical significance (p = 0.019), the carboplatin predictor successfully distinguished between platinum-sensitive and platinum-resistant patients. Additionally, the combined predictor for the platinum-taxane regimen revealed a significant difference in survival between predicted responders and non-responders, with median survival times of 12.9 months and 8.1 months, respectively (p < 0.045). The exceptional performance of this model highlights its ability to integrate complex gene expression data, facilitating the development of personalized chemotherapy regimens.

Designing and Implementing a Cancer Screening Program for Underserved Tribal Women in Jharkhand

The status of cancer screening in India is concerning, especially in tribal states like Jharkhand, where the percentage of women who have ever undergone screening for cervical, breast, and oral cancer is 0.5, 0.1, and 0.2 percent, respectively. Adopting the community-led approach, Karkinos Healthcare, a purpose driven oncology platform, conducted a cancer screening program in collaboration with a livelihood-focused NGO in selected districts of Jharkhand. This study aims to describe the program's implementation and assess the program's performance vis a vis provision of care continuum from screening to treatment. The program was designed to provide comprehensive services including cancer awareness, enrolment for specialized cancer insurance for one year to cover the cost of treatment, risk assessment, screening for oral, breast, and cervical cancers, diagnostics to screen positive cases, and treatment to the confirmed cancer cases. A total of 16875 women underwent risk assessments, all of whom were invited for screening at community clinics. A total of 5993 women (34.9%) reported at community clinics and 5873 (34.9%), 5843 (34.7%), and 5029 (29.9%) underwent screening for oral, breast, and cervical cancer. 70% of the total HPV-positive cases had high-risk types other than HPV 16 and 18. 22.4% of the total screened women were navigated for advanced diagnostics and treatment among which 6 confirmed cases of cancer were reported. While the program design tried to address the implementation challenges like fragmented care, accessibility, and affordability of cancer care services, conversion from screening to treatment was limited.

Exploring Indonesian Primary Schoolgirls’ Experiences of School-based HPV Vaccination, Knowledge of HPV Risks and Prevention, and Preferences for Cervical Cancer Education

In 2016, Indonesia introduced its Human Papillomavirus (HPV) vaccination demonstration program for girls in grades 5 and 6 of primary school, to reduce cervical cancer (CC) burden in selected provinces and test the viability of nationwide vaccination. This study explored schoolgirls' experience of school-based HPV vaccination, their knowledge of HPV and HPV vaccination, and their preferences for cervical cancer (CC) education. An online survey was conducted with schoolgirls who experienced HPV vaccination between 2019 and 2021 through the demonstration program. Using purposive sampling, respondents were recruited through partnerships with primary public health centres and primary schools in Jakarta and Yogyakarta. Data analysis was conducted using Chi-square test, Independent-samples t-test, and one-way ANOVA. One hundred and forty primary schoolgirls with a mean age of 12.2 years (SD = 0.70) completed the survey. Schools and mothers were identified as key actors in socialising children about important health information and as girls' preferred sources of information. The average summed score for girls' knowledge of HPV, the HPV vaccine, and CC after being vaccinated was 5.07 out of 10 (SD 0.23). Significant differences in the mean knowledge scores among participants with different preferences regarding CC education in school were observed. While schoolgirls' experiences of HPV vaccination were largely positive, their knowledge of critical health information regarding HPV vaccination and CC prevention needs improving. Thus, it is necessary to provide parents, and school-based educators with culturally appropriate strategies and comprehensive evidence-based information about HPV vaccination and CC prevention more effectively to children.

In Vitro Antiviral and Anticancer Effects of Tanacetum sinaicum Essential Oil on Human Cervical and Breast Cancer

Cervical cancer has been linked to human papillomavirus (HPV) types 16 and 18. Essential oils (EOs) are vital natural products of plants with various therapeutic and biological properties. The purpose of this study is to investigate and assess Tanacetum sinaicum essential oil's possible antiviral and anticancer properties, with a focus on its in vitro effects on human cervical cancer and human breast adenocarcinoma cell lines. Tanacetum sinaicum EO was extracted via hydrodistillation (HD) and characterized using gas chromatography-mass spectrometry (GC-MS). MTT assay was used to determine the cell viability of Hela (a human epithelial cervical cancer) and MCF-7 (human breast adenocarcinoma) cell lines. Quantitative real-time polymerase chain reaction (PCR) was utilized to assess the antiviral efficacy of EO against HPV-16 and 18, and anti-metastatic characteristics. The biological activity of EO was assessed using Autophage and Cell genotoxicity via the comet assay. EO is mostly composed of chrysanthenyl acetate, thujone, and verbenol. The cell viability was reduced after 24 hours of incubation at doses from 100 to 400 µg/ml. Concentrations of 800 to 3,200 µg/ml significantly inhibit cell growth. After a 24-hour incubation period, doses ranging from 100 to 400 µg/ml reduced cell viability from 62 to 72%. Concentrations of 800 to 3,200 µg/ml significantly suppress cell growth by over 95%. In MCF7 and HeLa cell lines, EO lowered virus copy numbers in a dose-dependent manner, with higher concentrations of the oil inhibiting virus replication more effectively. EO treatment increased the number of autophagosomes/autolysosomes and acidic vesicular organelles in both cell lines. On the HeLa and MCF7 cell lines, EO demonstrated antiproliferative and antimetastatic effects. The results demonstrated that EO had dose-dependent genotoxic effects on both cancer cell lines, as evidenced by DNA damage. Tanacetum sinaicum EO is a prospective source of natural bioactive compounds that can be employed in pharmaceutical and medicinal applications due to its antiviral, antiproliferative, anti-metastatic and genotoxic properties.

Prevalence of High-Risk HPV Detection and HPV Vaccination in Cervical Cancer Screening During the HPV Vaccination Era at Siriraj Hospital – Thailand’s Largest National Tertiary Referral Center

To investigate the prevalence of high-risk (HR) human papillomavirus (HPV) detection and HPV vaccination among women undergoing cervical cancer screening during the HPV vaccination era at Siriraj Hospital - Thailand's largest national tertiary referral center. This prospective cross-sectional study was conducted at our center's outpatient gynecology clinic during September-December 2021. Women aged ≥18 years with no previous hysterectomy, no history of preinvasive or invasive cervical cancer, and no current pregnancy who visited for cervical cancer screening were eligible for enrollment. Women with abnormal vaginal discharge/bleeding, and specimens with inadequate cellularity were excluded. We collected sociodemographic data, history of HPV vaccination, cervical cytology results, and high-risk HPV testing results. Reverse transcription polymerase chain reaction was used to determine HPV genotype. A total of 216 women (mean age: 41.7 years (range: 25-65), 75.9% premenopausal) were enrolled. Twenty of 216 (9.3%) women tested positive for HR-HPV, and 15 of 216 (6.9%) women had been previously vaccinated for HPV. The most common HPV genotypes detected were Group B infection (HPV 35/39/51/56/59/66/68) (38.9%), followed by HPV16 (27.78%), Group A infection (HPV 31/33/52/58) (27.8%), and HPV18 (5.56%). No HPV45 infection was detected. The detection rate of cytologic abnormalities was 4.16%. Three-quarters (77.8%) of patients with cytologic abnormalities were HR-HPV positive. Among the 216 women who underwent cervical cancer screening in this study, there was a 9.3% prevalence of HR-HPV infection, and a 6.9% prevalence of HPV vaccination. Among the 15 vaccinated women, 2 tested positive for HPV16 (1 normal cytology, 1 abnormal cytology).

Evidence of Knowledge, Attitude, and Practice Regarding Human Papilloma Virus Vaccination at the Community Level in India: A Systematic Review and Meta-analysis

Effective vaccines for the prevention of cervical cancers are available in India. The existing knowledge and attitude regarding the Human Papillomavirus (HPV) vaccine varies widely among available studies. Our study aimed to estimate pooled prevalence related to knowledge, attitude, and practice of HPV vaccination in India. We conducted systematic searches in PUBMED, EMBASE, CINHAL, PROQUEST, and Cochrane Library databases using database-specific search strategies. The random effects model was used for estimating the pooled proportion of knowledge, attitude, and practice. The outlier studies were identified using the Baujat test. Egger's regression test and funnel plots were used to identify publication bias. Database-specific search strategies yielded 2,377 records from five databases. We identified 48 studies for full-text retrieval after screening titles and abstracts. Finally, 27 studies were included in the meta-analysis. The pooled prevalence of knowledge regarding HPV vaccines in India was 0.22 (CI;0.14-0.31, I2 =99.5%). The pooled prevalence of positive attitudes towards the uptake of HPV vaccines in India was 0.45 (CI;0.33-0.57, I2 =100%). The pooled prevalence of coverage of HPV vaccines in India was 0.04 (CI;0.02-0.07, I2 =96%). Significant publication bias was present for the studies' reported knowledge and coverage. The knowledge, attitude, and coverage of the HPV vaccine were low in India. It suggests effective strategies to improve knowledge and attitudes towards HPV vaccination in India.

Community Screening for High-Risk Human Papilloma Virus Infection using Self-Sampling and ‘Point-Of-Care’ Test

HR-HPV types 16 and 18 are responsible for pre-invasive and invasive lesions of the cervix, accounting for 70-80% of the total subtypes. The aim of this study was to investigate the prevalence of high-risk HPV subtypes 16 and 18 in self-collected vaginal samples using real-time micro-PCR and to study the acceptability of self-sampling. Eligible women (30-65 years) were screened from a semi-urban area of Uttarakhand (India) using self-sampling. High-risk HPV genotypes (16/31 and 18/45) were tested using real-time micro-PCR technique with results available in one hour. The positive results were validated by standard RT-PCR for high-risk HPV 16, 18, separately and for 12 other high-risk genotypes, combined. Ease of the procedure, level of comfort, and recommendation to other women were studied and the acceptability of self-sampling was analyzed using the Likert scale. Of 975 eligible women screened, 45 participants tested positive for HR-HPV (16/31,18/45) using real-time micro-PCR with a prevalence of 4.6%. Positive samples were further tested through routine RT-PCR and 60% were found to be HR-HPV 16 and 18 positive. For self-sampling, 96.72% (n=943) participants were 'very satisfied' and 94.15% (n=918) found self-sampling to be 'very comfortable' and 88.51% (n=863) stated that they will strongly recommend this test to other eligible women in the community. We conclude that HR-HPV testing with limited genotyping showed a prevalence of 4.6%, 60% of these were HPV 16/18 positive. Point of care testing was feasible in the community and self-sampling was acceptable.

Mutation Spectrum Analysis of BRCA1/2 Genes for Hereditary Breast and Ovarian Cancer in the Indian Population

The objective of this study was to determine the prevalence and spectrum of genetic mutations linked to inherited breast and ovary cancer (HBOC) in the Indian population, and to evaluate the correlation of BRCA mutation types, frequency, and incidence with age, gender, and personal and family history. A retrospective cohort of 500 Indian HBOC patients, meeting NCCN criteria who underwent BRCA1/2 testing from 2017 to 2023 were shortlisted for this study. The anonymized data was retrieved from medical records. Genetic analysis was conducted using Next Generation Sequencing (NGS) on the Thermo Ion GeneStudio™ S5 System, with positive mutations confirmed via Sanger sequencing. Peripheral blood samples were processed for DNA extraction, library preparation, and variant classification following ACMG guidelines. Out of the 500 patients, 119 (23.8%) were positive for BRCA mutations, and 381 (76.2%) were negative. The prevalence of BRCA pathogenesis, likely pathogenicity, and variants of uncertain significance (VUSs) were 14.8%, 1.6%, and 7.4%, respectively. A total of 128 mutations were detected in the positive BRCA1/2 patients. A statistically significant correlation was found between BRCA mutations with the patient and family history. A total of 38.8% of the patients with mutations had a family history of BC, OC or BC/OC, while 7.6% had other cancers. BRCA mutations were predominant (26.2%) in the age group of 46-65 Y. Among the 128 mutations, 59.3% (76/128) and 40.6% (52/12) of the patients had mutations in BRCA1 and BRCA2, respectively. Missense mutations were the most common in both the BRCA1 (30.26%) and BRCA2 (55.77%) genes, followed by frameshift (22.3%) and nonsense (17.3%) mutations in BRCA1 and BRCA2, respectively. BRCA positivity was detected in 23.8% of the patients. A statistically significant association was shown between BRCA mutations and patient and family history.

Evaluation of Dynamic Multi-Leaf Collimator (MLC) versus Fixed MLC for Intensity Modulated Radiotherapy (IMRT) Using the Agility 160-Leaf Collimator

This study aimed to evaluate the efficacy of static or step-and-shoot intensity-modulated radiotherapy (ssIMRT) and dynamic intensity-modulated radiotherapy (dIMRT) delivery techniques for various treatment sites. The treatment planning system (TPS) was utilized to develop optimal treatment plans for twenty-seven patients selected for this comparative study, including nine with head and neck cancer, nine with prostate cancer, and nine with cervical cancer. The prescribed doses were 7000cGy/33fr, 7425cGy/33fr, and 5000cGy/25fr for the nasopharynx, prostate, and cervix cases, respectively, in both ssIMRT and dIMRT delivery techniques. Plans were generated using the Monaco treatment planning system with a 6MV photon beam and nine equidistant fields. Plan evaluation criteria included dose-volume histogram analysis, dose homogeneity index, conformity index, radiation delivery time, and monitor unit requirements. All plans were optimized to ensure that 98% of the planning target volume (PTV) received at least 95% of the prescribed dose, while meeting the planning objectives for organs at risk. dIMRT plans exhibited superior conformity (CI = 0.85 ± 0.05) compared to ssIMRT plans (CI = 0.79 ± 0.08), with statistically significant differences (P < 0.01). Inhomogeneity within the PTV was significantly higher in ssIMRT plans (HI = 0.10 ± 0.02) compared to dIMRT plans (HI = 0.09 ± 0.01), with a significant difference (P < 0.01). Delivery time per fraction was significantly lower in dIMRT compared to ssIMRT (P < 0.01). Furthermore, dIMRT plans required a higher mean monitor unit value (1335.4 ± 172.2) compared to ssIMRT plans (974.4 ± 133.6) with a significant difference (P < 0.001). The findings of this study indicate that dIMRT provides improved target coverage, homogeneity, and conformity while reducing treatment delivery time compared to ssIMRT.

Acceptance of Self-Sampling and Knowledge about Human Papillomavirus among Women in Mongolia

Mongolia faces a significant burden of cervical cancer, with the highest prevalence of Human Papillomavirus (HPV) in the region. Cervical cancer ranks as the third most common cancer among women in the country. This study aimed to assess the acceptance of self-sampling among young women in Mongolia and evaluate their knowledge regarding HPV and cervical cancer. In this study, participants provided a self-administered vaginal swabs to detect high-risk HPV genotypes. Both acceptability of self-sampling using swabs and participants knowledge regarding HPV and cervical cancer through a scored questionnaire were assessed.  The knowledge scale was categorized into three groups: low (0-2), moderate (3-4) and high (5-6). A total of 203 women aged 24-28 years completed the questionnaire and provided self-administered vaginal swabs. The majority (95.1%) found self-sampling technique using Copan Self Vaginal FLOQSwabs® easy to perform. Additionally, 98.5% indicated that the self-swab instructions were clear and comprehensive, while 94.1% reported no pain during the process. Furthermore, 67.8% of participants expressed a preference for performing the swab in a clinic rather than at home. All respondents chose self-sampling due to greater personal privacy, tranquility, reduced anxiety and time optimization. The questionnaire results revealed an overall low level of knowledge about HPV among participants, with a mean score at 1.9 out of 6 [95%CI 1.67-2.21] and a moderate level of knowledge regarding cervical cancer risks, with a mean score at 3.7 out of 6 [95%CI 3.19-4.21]. This pattern was consistent across both vaccinated and unvaccinated cohorts, indicating a strong demand for enhanced awareness of HPV and cervical cancer. This study demonstrates the high acceptance of self-sampling among young women aged 24-28 years in Mongolia. However, it also  underscores a significant need for improved awareness initiatives concerning HPV and cervical cancer in Mongolia.

Epidemiology of Uterine Cancer in Sarawak, Borneo, A 20-Year Review

This study aimed to determine the epidemiology of uterine cancer in Sarawak, Malaysia, using data from a population-based cancer registry. The study population included all women diagnosed with uterine cancer in Sarawak, Malaysia between January 1996 and December 2015. Data on demographic and clinical characteristics were obtained from the Sarawak Cancer Registry. The crude incidence rate, age-standardized incidence rate (ASR), and incidence risk ratios (IRR) were calculated. Joinpoint regression analyses were performed to assess trends in incidence rates. A total of 811 women were diagnosed with primary uterine cancer during the study period. The overall crude incidence rate for uterine cancer in Sarawak for the period 1996-2015 was 3.7 per 100,000. The ASR was 4.4 per 100,000 with a 95% CI (4.1-4.8). The ASR in 2011-2015 is 1.6 times higher than the ASR of uterine cancer in 1996-2000. Higher incidence rates were observed in women aged 40-59 years and those aged 60 years and above. Chinese women had the highest ASR, followed by Malay and Iban women. Joinpoint regression analyses showed a significant increase in cases of uterine cancer among all ethnic groups and age groups. The incidence of primary uterine cancer in Sarawak, Malaysia, has increased over the past 20 years, with higher incidence rates observed in older age groups and among Chinese women. The findings suggest the need for continued efforts to improve the prevention, early detection, and treatment of uterine cancer in Sarawak.

Human Epididymis Protein 4 (HE4) and Cancer Antigen 125 (CA125) for Prediction of Optimal Primary Surgery in Non-Mucinous Epithelial Ovarian Cancer

To determine the relationship between pre-operative HE4 and CA125 levels in non-mucinous epithelial ovarian cancer cases (EOC) and outcomes of primary surgery for prediction of optimal surgery. A retrospective study was performed on non-mucinous EOC who underwent primary surgery at King Chulalongkorn Memorial Hospital from 2016 to 2020. Demographic and clinical characters were collected. Histopathology and pre-operative tumor markers namely HE4 and CA125 were also recruited. Primary surgical outcomes were classified as optimal (OS) and suboptimal surgery (SS). One hundred and seventy patients were enrolled in the study. There were 130 and 40 cases in OS and SS, respectively. Average age and body mass index (BMI) of EOC were 54.2 years old and 23.1 Kg/m2, respectively. Both groups had comparable demographic characteristics. Two-thirds (103/170) and one-third (63/170) had early stage and clear cell histopathology, respectively. The median level of HE4 were 118.60 and 603.45 pmol/L in OS and SS, respectively. OS and SS had average CA125 at 146.95 and 814.70 U/L, respectively. The best cut-off point of HE4 and CA125 less than 170.95 pmol/L and 316.4 U/mL gave predicting OS with area under curve (AUC) at 0.78 and 0.75, respectively. HE4 and CA125 cut-off point had sensitivity, specificity, positive predict value (PPV) and negative predictive value (NPV) at percentage of 60.8/60.8, 87.5/82.5, 94.1/91.9 and 40.7/39.3, respectively. HE4 and CA125 of non-mucinous EOC among OS had significantly less than SS and could be the predicting of optimal surgery.

Ten-Year Follow-Up of Women at High Risk for Familial Breast and Ovarian Cancer in Otago and Southland, New Zealand

Care for families affected by Familial Breast and Ovarian Cancer (FBOC) is challenging as a broad range of professions and specialties are involved. The aim was to review management and outcomes for a cohort of women at high risk for familial breast and ovarian cancer. Ten-year retrospective follow-up study of individuals in Southern New Zealand  assessed by Genetic Health Service New Zealand to be high risk for FBOC and without a personal cancer diagnosis at time of consultation. Twenty women were identified; twelve underwent genetic testing, and a pathogenic BRCA variant was identified in eleven. Eight women had no testing, as no index case was available. Guidelines had been fully adhered to in 55% of women, regardless of BRCA status. Six did not undergo appropriate breast surveillance. To date, seven of the 11 patients who tested positive for a pathogenic BRCA variant (64%) had risk-reducing surgeries. Two women were diagnosed with breast cancer on surveillance imaging; none were diagnosed with ovarian cancer. Four women were lost to follow-up, one of whom subsequently presented with a symptomatic breast cancer. To our knowledge, this is the first study providing long-term data for FBOC in New Zealand. Overall, guidelines were followed satisfactorily, but some women did not receive appropriate surveillance or referrals. An integrated interdisciplinary long-term care provision model in New Zealand might help to address gaps in FBOC surveillance and management.

Update on HPV Vaccination Policies and Practices in 17 Eastern European and Central Asian Countries and Territories

In 2021, a survey was conducted as part of the regional program of the United Nations Population Fund (UNFPA) Regional Office for Eastern Europe and Central Asia (EECA) to assess the policies and practices relating to HPV vaccination and cervical cancer screening in the 17 countries and territories included in this region. Since then, very substantial progress has been made with HPV vaccination across the region so another survey was conducted establish the current situation. A 10 question survey covering the policies, plans and practices for HPV vaccination was prepared. As cervical cancer prevention is a priority for the UNFPA, its offices in the 17 countries and territories included in this study are well placed to identify the people who can provide authoritative data for this survey. Working with the UNFPA offices, the questionnaires were sent to these national experts in May 2023, with data collected until 30 June 2023. All countries and territories returned completed questionnaires. In the period from 30 June 2021 to 30 June 2023, the number of countries and territories that have implemented or are implementing HPV vaccination programs has doubled. As of 30 June 2021, only 6 of 17 countries and territories had implemented national HPV vaccination programmes, and by 30 June 2023, another 6 could be added to this list. Of the 4 countries with sub-optimal vaccination coverage rates in 2021, none showed substantial improvement over the 2-year period. The implementation of HPV vaccination programs across the region is progressing very rapidly with ≈70% of the countries and territories implementing or having implemented national programs. However, greater attention needs to be given to ensuring that both the old and the new programs will achieve high coverage rates.

External Beam Radiotherapy Interdigitated with High Dose Rate(HDR) Intracavitary Brachytherapy versus External Beam Radiotherapy followed by Sequential HDR Intracavitary Brachytherapy for Locally Advanced Carcinoma Cervix–Randomized Control Study

In cervical cancer treatment, overall treatment time (OTT) is an important prognostic factor. This study compares the clinical outcomes when High-Dose-Rate Intracavitary-Brachytherapy(HDR-ICRT) is interdigitated with external beam radiotherapy(EBRT) versus sequential HDR-ICRT after EBRT in the treatment of locally advanced carcinoma cervix. Histologically confirmed carcinoma cervix patients [FIGO Stage IIB-IVA (except IIIC-2)] were included and randomized into two groups. The study group received EBRT 50Gy in 25 fractions with interdigitated HDR-ICRT 7Gy per fraction weekly for three fractions starting after completion of 3 weeks of EBRT or as soon as cervical os became negotiable thereafter. Patients in the control group received EBRT 50Gy in 25 fractions with sequential HDR-ICRT 7Gy per fraction weekly for three fractions starting one week after completion of EBRT. All patients were regularly followed up during and after radiotherapy for local toxicity and disease control. This study enrolled 102 patients; 51 in each arm. Median OTT in study and control arm were 46 and 60 days, respectively. Median follow-up duration was 24 months (two years). Loco-regional control after two years of follow-up was 84.31 % and 72.54% of patients in study arm control arm respectively (p-value 0.148). Two (3.92%) patients from study arm and eight (15.68%) from control arm had residual disease. Two patients in study arm and one from control arm had local recurrence. Two patients from study arm three patients from control arm developed distant metastases. RTOG mucosal grade III acute mucosal toxicity in either arm. Cervical-os negotiability was limiting factor for interdigitated HDR-ICRT. Interdigitated HDR-ICRT with EBRT may give local control with manageable toxicities as compared to sequential HDR-ICRT, with the advantage of significant reduction in OTT..

Histopathology and ARID1A Expression in Endometriosis- Associated Ovarian Carcinoma (EAOC) Carcinogenesis Model with Endometrial Autoimplantation and DMBA Induction

Ovarian carcinoma is one of the most deadly malignancies in the gynecologic field. The cause is not yet known, and the clinical symptoms are not specific. Endometrioid carcinoma and ovarian clear cell carcinoma can originate from endometriosis and are known as endometriosis-related ovarian carcinoma (EAOC). Development of EAOC experimental animal models is needed for basic research and clinical preparation of human tissue tests. This study aimed to determine the role of the ARID1A gene mutation in the carcinogenetic process of EAOC in experimental animal models induced with DMBA. In this study, the EAOC experimental model was developed using the autoimplantation technique and DMBA induction. This study involved placebo surgery mice (sham), endometrial autoimplantation, and a combination of endometrial autoimplantation and DMBA induction, which were sacrificed at weeks 5, 10, and 20, respectively. Histopathological assessment and immunohistochemical ARID1A staining with an assessment of positive percentages were carried out on 200 cells. This study produced 1 (20%) atypical endometriosis and 1 (20%) clear cell carcinoma at implantation and after 10 weeks of DMBA induction, and 100% endometrioid carcinoma in the DMBA-induced group. ARID1A staining did not show any significant difference (p = 0.313) in all groups. The combination of endometrial autoimplantation techniques and DMBA induction in the ovary produced atypical endometriosis, clear cell carcinoma, and endometrioid carcinoma, where time is an important factor. There was no significant difference in ARID1A expression between the treatment and control groups.

The Platelet to Lymphocyte and Neutrophil to Lymphocyte Ratios in Predicting Response to Platinum-based Chemotherapy for Epithelial Ovarian Cancer

The patients with advanced-stage ovarian cancer have higher factors complicating surgery; thus, the best choice for them is surgery with chemotherapy with six cycles of adjuvant chemotherapy. Generally, chemotherapy can be evaluated in various ways, phsychal examination, radiology examination, and laboratory examination. This study aims is to examine if the measurement of the platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) can be used to predict a patient's response to chemotherapy. Analytic observational study with a case-control design conducted in the Dr. Hasan Sadikin Hospital in Bandung from 2017 to 2018. This study used the medical record of ovarian cancer patients with post-surgery complete blood counts and histopathological reports. The sample size was determined based on the categorical test's statistical calculation to obtain a total number of at minimal 90 samples. All the study subjects who had undergone complete chemotherapy were followed up for 6 months. Their response to chemotherapy was assessed with a clinical examination, ultrasonography, and a CA-125 blood test every 3 months. In 2017-2018, 504 patients were diagnosed with ovarian cancer at the Dr. Hasan Sadikin Hospital in Bandung, Indonesia. After reassessment, 116 patients had stage I to III ovarian cancer and underwent cytoreduction followed by platinum chemotherapy. The age, cancer stage, and types of epithelial cells in the platinum-sensitive and platinum-resistant patients were characterized. There were significant differences between the two groups in age and cancer stage characteristics (p < 0.05). The increase in platelet/lymphocyte (p = 0.003) and neutrophil/lymphocyte ratios (p = 0.026) are associated with the increase in the response to platinum chemotherapy against epithelium-based cancers. A patient's NLR and PLR are strongly associated with his response to chemotherapy.

Cytokines as Prognostic Biomarkers of Epithelial Ovarian Cancer (EOC): A Systematic Review and Meta-Analysis

The value of cytokines as epithelial ovarian cancer (EOC) prognostic factors has been widely investigated. This study aimed to determine the role of single cytokine as a biomarker prognosis in EOC. We conducted a systematic review and meta-analysis of studies reporting cytokine as the prognostic predictor in EOC based on PRISMA guideline. We included English articles investigating associations of preoperative cytokines level in tissue, blood or ascites with overall survival (OS) or disease-free survival (DFS) from PUBMED and EBSCO. Summary hazard ratios (HRs) and confidence intervals (CIs) were calculated. Fifty studies investigating twenty types of cytokines in tumor tissue, serum, and ascites from 5,376 patients were included. Pre-operative high VEGF level was associated with poor OS (HR 2.28, 95%CI [1.28, 3.28]) and DFS (HR 2.13, 95%CI [1.63, 2.78]) in serum and OS (HR 1.80, 95%CI [1.45, 2.23]) in tissue. IL-6 level in blood was associated with DFS (HR 1.60, 95%CI [1.21, 2.11]). There was no single cytokine which investigated by at least 2 studies reporting hazard ratio in ascites, so we did not conduct the meta-analysis. Other cytokines (serum IL-8; ascites fluid IL-8, IL-10, IFN-γ, TNF-α; and ovarian tissue TGF-α, CSF-1, IL-10 ,TGF-β1, IL-17) associated with the poorer prognosis, could not be pooled due to lack of studies. Pre-operative VEGF level in serum and tissue specimen seem to be the potential candidate of an unfavorable prognostic biomarker for EOC. The evidence was lacking to support the other cytokines investigated in blood, tissue and ascites as prognostic biomarkers for EOC.

Human Papillomavirus and Cervical Cancer Knowledge, Perceptions, and Screening Behavior: A Cross-Sectional Community-Based Survey in Rural Philippines

Cervical cancer is the second most common cancer among women in the Philippines. Cervical cancer screening is an effective method to reduce incidence. However, screening utilization is limited. This study aims to assess human papillomavirus (HPV) and cervical cancer knowledge, perceptions, and screening utilization, and to investigate factors influencing screening utilization among rural women in the Philippines. This cross-sectional community-based study was conducted among 338 rural women aged 20-50 years, with a child under 5 years old registered in one of four public rural health centers in Tacao Island, Masbate Province in October 2017. A questionnaire administered via face-to-face interviews elicited information about demographic characteristics, knowledge, perceived susceptibility and perceived severity of HPV and cervical cancer, and cervical cancer screening utilization. Mean age of participants was 32.5 years. Only 13.9% of participants had ever had cervical cancer screening. Although most women had heard of cervical cancer screening, their knowledge about the cause, risk factors, and preventive measures of HPV and cervical cancer was limited. Older age and higher education status were significantly associated with screening utilization. However, knowledge and perceived susceptibility and severity showed no association. The main reason for having screening was due to a health professional's request or recommendation, and the reasons for not having screening were cost, not having symptoms, and fear of pain or discomfort and/or embarrassment during the procedure.  Conclusions: Health education must increase knowledge about HPV and cervical cancer and screening among women, including the nature and progression of cervical cancer, benefits of screening, screening cost, and screening procedure. Health care providers have an important role in educating and motivating women to undergo screening.

The Optimal Cut-Off Point of the Andex Model for the Prediction of the Ovarian Cancer Risk

Objective: This study aimed to assess the effectiveness and determine the optimal cut-off point of the ADNEX model in women presenting with a pelvic or adnexal tumor. Method: All women presented with adnexal mass and were scheduled for operation at Hue University of Medicine and Pharmacy Hospital and Hue Central Hospital, Vietnam during June 2019 – May 2021 were included and categorized according to their histopathologic reports into ovarian cancer groups and benign ovarian tumor groups. Multivariable logistic regression was used to explore for potential predictors. The ADNEX model with and without CA125 was used to assess the risk of ovarian cancer preoperative. The goldden standard to evaluate the accuracy of ultrasonography using the ADNEX model was the pathological report. In addition, the accuracy as well as optimum cut-off point of the ADNEX model was estimated with and without CA125. Results: A total of 461 participants were included in analysis and predictive model development, 65 patients in ovarian cancer group and 361 in benign tumor group. The ADNEX model combined with CA125 proved to be a useful predictor with an area under ROC of 0.961 (0.940 – 0.977) with Youden’s index of 0.8395, p < 0.001. The ADNEX model without CA125 also had high predictive value between benign and malignant tumors, with an area under ROC of 0.956 (0.933 – 0.973) with Youden’s index of 0.8551, p < 0.001. Cut-off of the ADNEX with CA125 was 13.5 and without CA125 was 13.1 for sensitivities were 90.8 (81.0 – 96.5) and 93.9 (85.0 – 97.5), specificities 93.2 (90.2 – 95.5) and 91.67 (88.5 – 94.2). The difference in the predictive value of malignancy-risk between the ADNEX model with CA125, without CA125 was not statistically significant, p=0.4883. Conclusion: The ADNEX model, with or without the combining marker CA 125, provides a valuable predictive value for ovarian tumor malignancy preoperative.

Ovarian Cancer-Self Assessment: An Innovation for Early Detection and Risk Assessment of Ovarian Cancer

The modality to detect ovarian cancer at an early stage is very limited. Early diagnosis determines the prognosis. This study aimed to develop a risk assessment tool for early detection of ovarian cancer using artificial intelligence. To accomplish this, the presence of ten signs and symptoms reported by patients with ovarian cancer was assessed. This study was carried out as a cohort study of patients diagnosed with suspected ovarian tumors undergoing cytoreduction operation at Hasan Sadikin Hospital, Bandung, from December 2019 to September 2020. Compared to ovarian cancer self-assessment through questionnaire, postoperative histopathology in patients with suspected ovarian tumors. The questionnaire proceeded by artificial intelligence is grouped into risk and no risk. Statistical analyses were done using Chi-Square and Exact Fisher Test. In total, 115 patients included in this study. The differences were statistically significant in terms of the six variables (abdominal bloating, nausea/vomiting, decreased of appetite, fullness, menstrual disturbance, and weight loss) ovarian cancer self-assessment compared to postoperative histopathology with a tendency towards benign ovarian tumors (p0.05).  According to the artificial intelligence grouping, fifty-five patients were at risk, and sixty patients were not at risk. The Fifty-five risk patients were related  with postoperative histopathology diagnosis (with RR 0.682 and CI 95% 0.519-0.895). Risk assessments based on ovarian cancer self-assessment unfortunately were not comparable to postoperative histopathology as a single predictor. Ten variables in ovarian cancer artificial intelligence self-assessment for early detection needs improvement in adding another variable like tumor marker and ultrasonography assessment.

The Association of Molecular Biomarkers in the Diagnosis of Cervical Pre-Cancer and Cancer and Risk Factors in Senegalese

Cervical intraepithelial neoplasia (CIN) grading is subjective and affected by substantial rates of discordance among pathologists. Although recent studies have suggested that p16INK4a may be a useful surrogate biomarker of cervical neoplasia, Ki-67 and human papillomavirus testing have also been shown to be useful in detecting neoplasia. The purpose of this study was to determine the expression of p16INK4a and Ki-67 in cervical neoplasia and its correlations with cofactors. The study involved 69 patients with and without cervical neoplasia who underwent colposcopic directed biopsy. On each patient, two samples were taken; the first was used for immunohistochemistry and the second for molecular testing, using HPV16and18 genotyping Real-Time PCR Kit. The study revealed the expression level of p16INK4a and Ki-67 in a descending order, from invasive squamous cell carcinoma (SCC), CIN2/3, CIN1 and non-dysplastic lesions. Correlations showed an association between the staining of p16NK4a and Ki-67 with the increase of age (OR: 1.79 (95%IC: 0.49 - 6.55), p = 0.037) and marital status (OR: 0.17 (95%IC: 0.04 - 0.68), p = 0.003). We found that the expressions of p16INK4a and Ki-67 were significantly different between invasive SCC vs non-dysplasia (OR: 44.57 (95%IC: 4.91 - 403.91), p <0.0001). The study showed significant correlation between HPV 16and18 infection with p16 INK4a and Ki-67 expression (OR: 0.13 (95%IC: 0.03 - 0.52), p <0.0001). Strong expression of p16INK4a and Ki-67 were observed in invasive squamous cell carcinoma, moderate staining was found in CIN2/3, weak staining in CIN1 and normal histology. Our findings indicate that p16INK4a and Ki-67 expressions associated strongly with cervical pathology. Therefore, p16/Ki-67 could be considered as a suitable biomarker for cervical cancer screening, particularly in HPV-based screening programs.

Metabolic Reprogramming and Lipophagy Mediates Survival of Ascites Derived Metastatic Ovarian Cancer Cells

The study was aimed at understanding the survival of metastatic ovarian cancer spheroids in the malignant ascites microenvironment. All the assays were performed using aseptically collected patient samples. The cells were characterized for the expression of ovarian and cancer stem cell markers using immunocytochemistry. The presence of lipid in the primary metastatic cancer spheroids were confirmed by neutral fat staining using Oil Red-O and transmission electron microscopy. The mRNA expression of autophagy and lipid metabolism genes was analyzed using RT-PCR. The lipid content was analyzed using lipidomics analysis. Etomoxir and chloroquine were used to study the effect of inhibition of autophagy in the metastatic cells. The data were analyzed using appropriate statistical tools and a p-value <0.05 was considered to be statistically significant. Metastatic ovarian cancer spheroids exhibit cancer stem like properties and undergo a metabolic reprogramming when they disseminate from the primary tumor. We report here the accumulation of numerous cytoplasmic lipid droplets and lipophagic vesicles in the metastatic cells in contrast to their primary tumors. In addition we also report that these cells depend on lipophagy for the utilization of lipids rather than the conventional lipolytic pathway. The lipidomics analysis data reveals that the metastatic cells possess high levels of unsaturated fatty acids. We have also reported the occurrence of distinct accumulation of multiple nuclei in the patient derived metastatic cells. Inhibition of beta-oxidation and autophagic machinery using etomoxir and chloroquine resulted in cell death suggesting a potential mode to suppress metastatic cancer cells. Metabolic reprogramming is a characteristic feature of the metastatic ovarian cancer cells that are persisting in the malignant ascites. Targeting of the metastatic by gaining an insight into the various metabolic and molecular changes that occur in the metastatic niche provides a promising therapeutic approach in management of the disease.

Incidence, Mortality and Survival Analysis of Epithelial Ovarian Cancer in Brunei Darussalam

This study provides population-based study of cancer incidence, mortality and survival rates for women diagnosed with epithelial ovarian cancer (EOC), and evaluate the prognostic factors of EOC patients survival in Brunei Darussalam. This is a retrospective  study of patients diagnosed with EOC between 1st January 2007 and 31st December 2017 in Brunei Darussalam. Crude, age-specific, age-standardized incidence and mortality rates per 100,000 women were calculated. Kaplan-Meier method was used to determine the overall 5-years survival rate. Log-rank test was used to examine the differences in survival between groups. The multivariable Cox Proportional Hazard regression models were used to estimate the hazard ratio for overall survival and to identify the prognostic factors. A total of 207 patients were included in the study. The crude incidence and mortality rates were 9.7 and 3.6 per 100,000 respectively while the age-standardized incidence and mortality rates were 11.3 (95% CI: 9.7,12.9) and 4.5 (95% CI: 3.4,5.6) per 100,000 respectively in the period 2007-2017. The overall mean age at diagnosis was 48.4 (standard deviation=15.3) years. The overall survival rates at 1, 3, and 5 years for EOC patients were 79.7%, 69.7%, and 61.4% respectively. Age at diagnosis, cancer stage, and histology were significant prognostic factors for patients' survival. Older age at diagnosis (≥70 years vs <40 years), regional or advanced stage (vs localized stage) and having undifferentiated or other epithelial ovarian (vs serous carcinoma) were associated with having higher hazard of death. Early detection of disease should be emphasized through public education and  raising awareness to improve survival rates of patients with EOC.

Endocan-microvascular Density in Primary Ovarian Carcinoma

Epithelial ovarian cancer is among the leading causes of death in women and is driven by angiogenesis. Microvascular density (MVD) can be used to evaluate angiogenesis in carcinomas and thus it can be used as a potential biomarker for ovarian cancer. This study is aimed to establish the association between endocan-MVD with clinicopathological factors in primary epithelial ovarian cancer. The clinicopathological characteristics were acquired from the medical records filed between January 2008 and December 2018 of 89 epithelial ovarian cancer cases in Hospital Universiti Sains Malaysia, Kelantan, Malaysia. Sectioned samples were analyzed for endocan through immunohistochemistry followed by the quantification of MVD. The association between clinicopathological characteristics and endocan-MVD was analyzed using the Pearson chi-square test and Fischer's exact test. All cases of epithelial ovarian carcinomas were positive for endocan. The mean ± standard deviation value of endocan-MVD level was 21.6±14.60 microvessels per 200x field. A total of 53 (59.6%) cases had low and 36 (40.04%) had high endocan-MVD values. High endocan-MVD level had a significant association with the older age group (p-value = 0.009), smaller tumor size (p-value<0.001), type II tumor (p-value<0.001), high-grade tumor (p-value<0.001), advanced FIGO stage (p-value=0.002), and presence of tumor recurrence (p-value=0.017). No significant association was found between endocan-MVD and the other clinicopathological characteristics such as race, pre-operative serum CA-125 level, presence of diabetes mellitus, endometriosis, lymph node involvement, distant metastasis, and family history of malignancy. Endocan-MVD showed a significant association with age, tumor size, tumor type, tumor grade, FIGO stage, and recurrence in primary epithelial ovarian cancer. Thus, endocan-MVD could be implemented as a reliable marker to predict prognosis in epithelial ovarian cancer in the future.

The Correlation between YAP and RhoA Expression in Prostate and Ovarian Tumor Stroma

Cancer associated fibroblasts (CAFs) are a mesenchymal cell type found in most solid tumors modulating cancer metastasis by building up and remodeling the extracellular matrix (ECM) structure. We aimed to evaluate the correlation between RhoA and YAP expression  in the stroma cells obtained from prostate and ovarian cancer tissues. We analyzed two microarray datasets obtained from NCBI Gene Expression Omnibus(GEO). The sample type of two datasets was RNA, which is displaying the transcriptome profiling. The tumor stroma of patients with invasive prostate cancer and high-grade serous ovarian cancer were obtained from datasets Independent t-test was used to analyze the differentially expressed YAP between normal stroma and cancer stroma. In addition, Pearson's correlation was run to analyze the correlation between YAP and RhoA expressions. In comparison with normal stroma tissues, YAP1 was overexpressed in prostate and ovarian cancer stroma tissues (prostate cancer stroma, p <0.05; ovarian cancer stroma, p < 0.001). Furthermore, a positive correlation was detected between YAP and RhoA expressions in stroma of both tumor types. This correlation was positively strong in prostate cancer stroma (R=0.607) and positively weak in ovarian cancer stroma (R=0.248). We found that YAP was overexpressed in prostate and ovarian cancer stroma. Furthermore, the correlation between RhoA and YAP expression suggested that RhoA-YAP signals could physiologically be involved in tumor stroma. Thus, targeting RhoA-YAP may be an intriguing avenue for cancer therapeutics in neoplastic epithelial cells as well as tumor stroma.

Knowledge and Attitude Toward Human Papillomavirus Infection and Vaccination among Thai Women: A Nationwide Social Media Survey

This study was performed first to assess Thai women's knowledge and attitude toward Human papillomavirus (HPV) infection and vaccination and second to find out factors associated with knowledge in this regard. The survey announcement was advertised via Facebook from 17 May 2019 to 14 June 2019 to recruit women aged 18-26 years living in Thailand. A score below 5 out of total score of 10 on the survey was considered as a poor level of knowledge. Multivariate analysis was applied to identify factors associated with HPV infection and vaccination knowledge. A total of 1,175 participants were recruited. The participants' median age was 22 years. Approximately, 46% of the participants had poor level of knowledge regarding HPV infection and vaccination. Factors associated with poor knowledge included low educational level (adjusted OR, 1.35; 95% CI 1.04-1.77), low family income (adjusted OR, 2.14; 95% CI 1.65-2.78), being Christian (adjusted OR, 4.04; 95% CI 1.22-13.40), being engaged in sexual intercourse (adjusted OR, 0.75; 95%CI 0.58-0.97), and being unvaccinated against HPV infection (adjusted OR, 5.74; 95% CI 3.07-10.74). Nearly half of the Thai women who participated in the survey had poor level of knowledge regarding HPV infection and vaccination, indicating a need for more effective health education intervention. Factors associated with knowledge included socioeconomic status and sexual behavior..

Prevalence and Type Distribution of Human Papillomavirus Recovered from the Uterine Cervix of Nigerian Women: A Systematic Review and Meta-Analysis

Background: Infection with an oncogenic type of human papillomavirus is a prerequisite for the development of precancerous cervical lesions and its subsequent progression to cervical cancer. With an alarming increase in the detection of other suspicious papillomavirus genotypes in both healthy and women with cervical lesions, there is a need for comprehensive data on cervical papillomavirus infection to address cervical cancer and other associated disease burden, especially in Sub-Sarahan Africa, where the bulk of the problem exists. The present study was conducted to develop comprehensive data on the prevalence and circulating genotypes of human papillomavirus in various risk categories in Nigeria. Methods: A systematic review and meta-analysis of peer-reviewed publications on cervical papillomavirus infection were performed. Relevant data were extracted from eligible studies published in PubMed, Web of Science, Embase, Scopus, and Google Scholar, from inception to July 31, 2019. The random-effect model was used to estimate the pooled prevalence. We identified 327 potential studies and pooled data from 18 studies, involving 5697 women aged 15-86 years. Results: The overall pooled prevalence of cervical papillomavirus infection was 42% (95%CI: 30-54%) in the general population and 37% (95%CI: 25-50%) among women living with HIV/AIDS, with the predominance of genotypes 16, 18, 31, 35, 52, 58 and 45. The highest prevalence was observed in teenagers and young adults and the second peak in women 50 years and above. Conclusion: The prevalence of cervical human papillomavirus infection is cumulatively high in Nigeria and HIV is a strong co-factor. We, therefore, strongly recommend the co-screening of human papillomavirus and cervical cancer and integration of the intervention strategy into the existing HIV-care guideline in Nigeria.

Knowledge, Attitudes, and Practices Regarding Cervical Cancer Screening among HIV-infected Women at Srinagarind Hospital: A Cross-Sectional Study

In recent years, the lives of HIV-infected patients in Thailand have improved significantly due to continuous advances in treatment. However, the rate of cancer related to HIV infection (especially cervical cancer) is likely to increase. Although the World Health Organization (WHO) recommends Papanicolaou testing in all HIV-infected women, few of these patients receive this kind of screening in Thailand. Therefore, we conducted this study to evaluate the knowledge, attitudes, and practices of these patients with regard to cervical cancer screening. This cross-sectional study was conducted in HIV-infected women aged 18-65 years from April to November 2019 via a self-administered cervical cancer screening questionnaire, which consisted of four parts: demographic data, knowledge, attitudes, and practices. Three hundred HIV-infected women were recruited. Most of the participants had good attitudes toward screening and practiced adequate screening (75.3% and 71.3%, respectively). However, only 62 participants (20.7%) demonstrated adequate knowledge. The crucial factors that were associated with adequate screening practice were age 40-49 years-old (AOR =3.26, 95%CI=1.02-10.37), CD4 cell count (AOR = 3.41, 95%CI = 1.29-8.99), having been advised about cervical cancer screening (AOR= 6.23, 95%CI 1.84-21.07), and attitude toward screening (AOR= 5.7, 95%CI = 2.23-14.55). The major reasons for not undergoing screening were embarrassment (41.86%), lack of symptoms (41.86%), fear of the results (36.04%), and fear of pain (36.04%). The reasons for inadequate testing were disregard and misconceptions about the procedure. To prevent invasive cervical lesions in HIV-infected women, health care providers should inform these patients about the importance of regular cervical cancer screening..

CyclinA1 Promoter Methylation in Self-Sampling Test

Self sampled HPV testing is a cervical cancer screening method . However, cytology in self-sampled specimen cannot be used as a triage test.  Therefore, other methods for triage should be considered. CyclinA1 (CCNA1) promoter methylation has strong association with cervical precancerous and cancerous lesion. The objective of this study was to compare the diagnostic value of CCNA1 and self-sampled specimen for detecting high-grade cervical intraepithelial lesions or worse (CIN2+). A cross sectional study was conducted. Women with abnormal cytology or positive for high risk HPV (hrHPV) indicated for colposcopic examination were enrolled.  Self-collected sampling for hrHPV DNA (SS-HPV) and CCNA1 were performed. hrHPV DNA testing was done by Cobas 4800 method. CCNA1 promoter methylation was detected by CCNA1 duplex methylation specific PCR. Histopathologic result as CIN2+ obtaining from colposcopic directed biopsy or excisional procedure  was considered as positive a gold standard. The results of hrHPV and CCNA1 were reported as positive or negative. Sensitivity specificity, positive predictive value, and negative predictive value of SS-HPV and CCNA1 were calculated by comparing the results with the gold standard. Two hundreds and eighty women were recruited. High-grade cervical lesions and cervical cancer (CIN2+) were diagnosed in 21.8% (61 cases) of the patients. The most common type of hrHPV was non 16, 18 subtype, followed by HPV16 and 18. CCNA1 was positive in 13 patients out of whom, twelve were CIN2+. Sensitivity of CCNA1 was 19.7 % and its  specificity and accuracy were 99.5% and 82.14%, respectively.  The sensitivity of SS-HPV was 70.5%, and its  specificity and accuracy were 39.2% and 43.3%, respectively. Due to high specificity and positive predictive value of CCNA1, it can be used as alarming sign of having high-grade cervical intraepithelial lesions, especially in patient who has positive hrHPV DNA test based on self-collected sampling..

Cost of Treatment for Cervical Cancer in India

Cervical cancer is a major public health problem in India leading to high economic burden, which is disproportionately borne by the patients as out-of-pocket expenditure (OOPE). Several publicly financed health insurance schemes (PFHIs) in India cover the treatment for cervical cancer. However, the provider payment rates for health benefit packages (HBP) under these PFHIs are not based on scientific evidence. We undertook this study to estimate the cost of services provided for treatment of cervical cancer and  cost of the package of care for cervical cancer in India. The study was undertaken at a large public tertiary hospital in North India. The health system cost was assessed using a mixed micro-costing approach. The data were collected for all the resources utilized during service delivery for cervical cancer patients. To evaluate the OOPE, randomly selected 248 patients were interviewed following the cost of illness approach. Logistic regression was used to assess the factors associated with catastrophic health expenditure (CHE). Health system cost for different cervical cancer treatment modalities i.e. radiotherapy, brachytherapy, chemotherapy and surgery, ranges from INR 19,494 to 41,388 (USD 291 - 617). Furthermore, patients spent INR 4,042 to 23,453 ( USD 60 - 350) as OOPE. Nearly 62% patients incurred CHE, and 30% reported distress financing. The odds of CHE (OR: 25.39, p-value: <0.001) and distress financing (OR: 15.37, p-value: 0.001) were significantly higher in poorest-income quintile. The HBP cost varies from INR 45,364 to 64,422 (USD 676 - 960) for brachytherapy and radiotherapy respectively. Cervical cancer treatment leads to high OOPE in India, which imposes financial hardship, especially for the poorest. The coverage of risk pooling mechanisms like PHFIs should be enhanced. The findings of our study should be used to set the reimbursement rates of providing cervical cancer treatment under PFHI schemes.

Exploring the Barriers to Cervical Cancer Screening through the Lens of Implementers and Beneficiaries of the National Screening Program: A Multi-Contextual Study

Cervical cancer is a major reason for morbidity and mortality in Low and Middle income countries. The National Programme for Prevention and Control of Cancers, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS) sets out broad national guideline to implement Cervical cancer screening. However, an implementation strategy for cervical cancer screening is not in place for districts. Although opportunistic screening takes place, implementation is hindered by psychological and physical barriers for women, as well as insufficient capacity on the part of implementers. This qualitative study aims to identify the specific barriers that prevent the uptake of cervical cancer screening. Women who could benefit from cervical cancer program were interviewed to explore the factors that influenced their uptake of the cervical screening offered. Key informant interviews were conducted with implementers of the NPCDCS and with public health staff of three States (Himachal Pradesh, Meghalaya and Karnataka), to understand their perception of determinants of the utilization of screening services. The general health concern among the participants was low, and routine check-ups were considered unimportant. Poor knowledge about cervical cancer, benefits of screening service availability, as well as a general sense of well-being, embarrassment or anxiety related to the screening procedure, fear of being judged for lack of modesty, and stigma were common barriers to screening uptake. In addition to a general unawareness of cervical cancer geographical inaccessibility of screening as a barrier to participate in cervical cancer screening, in certain regions. It is essential to increase the knowledge on cervical cancer and on the benefits of screening among Indian women. Providing information and cues to action by health workers and professionals can facilitate the decision to participate. Implementers need to be involved to ensure context specific implementation of the National programme to overcome these barriers.

Validation of the Functional Assessment of Cancer Therapy with Cervical Cancer Subscale (FACT-CX) for Quality of Life in Thai Patients Prior to Chemoradiotherapy

Cervical cancer is the second most common cancer in Thailand. For cervical cancer, there is no cancer specific quality of life questionnaire. This study aims to develop and validate Thai FACT-CX. The cross-sectional study included all women aged ≥18 years with stage IB2-IIIB who planned to undergo chemoradiotherapy. Those who did not understand Thai language, had other cancers (except for skin cancer), were diagnosed with impaired cognition and/or overt psychosis, and major depression were excluded. The FACT-CX comprises 42 items with 5 domains and a score range of 0-168. The WHOQOL-BREF comprises 26 items with 4 domains and a score range of 26-130. The participants were interviewed about demographic and clinical data. Both questionnaires were self-completed.  Factor analysis was used to compare our data with the previous structure. The reliability used Cronbach's alpha. Spearman's correlation determined relationship between the domains of the modified FACT-CX and WHOQOL-BREF. Both questionnaires were compared with socioeconomic and clinical variables using the Ranksum test and Kruskal-Wallis test. P-value > 0.05 considered significant. The 245 participants included. Expletory factor analysis revealed an accumulative variance of 0.42 with 4 factors. The internal consistency was 0.84, 0.81, 0.78, 0.77 and 0.90 for perception of self, suffering symptoms, family support, life resilience and total questions. There was correlation between the domains of the modified FACT-CX and WHOQOL-BREF.  Both the modified FACT-CX and WHOQOL-BREF could identify differences between the groups of patients. Finally, the Thai modified FACT-CX was found to be reliable and valid for measuring quality of life among untreated cervical cancer patients..

Human Papillomavirus Detection and Abnormal Anal Cytology in HIV-infected Patients Using p16/Ki-67 Dual-Staining

We investigated human papillomavirus (HPV) infection and detected anal squamous intraepithelial lesions by modified liquid-based cytology (LBC) and p16/Ki67 dual-staining. Anal swabs (n=393) were collected from patients with HIV infection. Anal cells were kept in 95% ethyl alcohol for modified LBC. DNA was extracted from cells for HPV detection and genotyping using real-time PCR and reverse line blot hybridization. Nine samples (2.3%) were unsatisfactory specimens, 74.8% (294/393) were negative for intraepithelial malignancies (NILM) and 22.9% (90/393) exhibited squamous intraepithelial lesions (SIL). In the latter category, 13.7% of samples (54/393) contained atypical squamous cells of undetermined significance (ASCUS), 6.9% (27/393) were classified as low-grade SIL (LSIL) and 2.3% (9/393) as high-grade SIL (HSIL). A total of 331 from 393 swab samples were suitable for detection of HPV infection. Among these, 34.1% (113/331) were positive. HPV 58 (15.9%) was the most common genotype, followed by HPV 18 (14.2%) and HPV 16 (11.5%). The severity of abnormal cells was significantly associated with HPV infection. Dual staining with p16/Ki-67 was performed on 130 samples: in 30.8% (40/130) of samples positive staining was significantly associated with severity of abnormal cells. Agreement between cytology, p16/Ki67 dual-staining and high-risk HPV detection was 100% in HSIL samples. Interestingly, eight apparently NIML cases might have contained abnormal cells, since they were positive by both p16/Ki67 dual-staining and high-risk HPV detection. Anal specimens screened using modified LBC with 95% ethyl alcohol solution as the fixative are suitable for screening anal precancerous lesions by cytology, HPV testing and p16/Ki-67 dual staining.

Community-based Mobile Cervical Cancer Screening Program in Rural India: Successes and Challenges for Implementation

The aim of this study is to demonstrate the feasibility; mention the challenges encountered and highlight the success of implementing a community-based mobile cervical cancer-screening program in rural India. Communities were mobilized through extensive peer education and by screening in existing community spaces using a mobile clinic model. An initial "screen and treat" protocol was transitioned to "screen, test, and treat" using Pap smears for confirmatory testing, and cryotherapy or Loop Electrosurgical Excision Procedure (LEEP) for treatment. We trained 50 Peer Educators and conducted 190 screening camps in 58 locations. Of 3,821 registered women, 3,544 (92.8%) accepted screening. Overall, 440/3544 (12.4%, 95% CI 11.3-13.5%) women had VIA-positive lesions. Under "screen and treat", 56/156 (35.9%) women accepted same-day treatment. Under "screen, test, and treat", 555/762 (72.8%) women received a Pap smear. Overall, 83 women underwent cryotherapy (n=56) and LEEP (n=27). Of those, 49 (59.0%) participants were followed up, with normal VIA results up to two years after treatment. In summary, the peer educators promoted awareness of cervical cancer and helped in gaining buy-in from communities. Acceptance of same-day treatment was low and accompanied by loss to follow-up, limiting the utility of VIA in these studies. Mobile infrastructure utilized in community spaces brought screening directly to rural women. Culturally appropriate methods to increase linkage to treatment and additional screening options such as HPV DNA testing should be explored.

Inhibitory Effect of Eco-Friendly Naturally Synthesized Silver Nanoparticles from the Leaf Extract of Medicinal Detarium microcarpum Plant on Pancreatic and Cervical Cancer Cells

Recently, nanoparticle synthesis by eco-friendly methods has received tremendous attention due to the method advantages and also because of the application of the nanoparticles in cancer research. Therefore, in this study, we synthesized silver nanoparticles from Detarium microcarpum leaf phytochemicals and evaluated its inhibitory effect on pancreatic and cervical cancer cells. Silver nanoparticles (dAgNps) were synthesized by reacting phytochemicals of D. microcarpum leaves with silver nitrate for 12 hours. Cell viability assay was carried out to investigate the cytotoxic effect of dAgNps on HeLa and PANC-1 cells. Scanning electron microscopy (SEM) and transmission electron microscopy(TEM) results revealed the average sizes of dAgNps are 81 nm and 84 nm respectively. The x-ray diffraction (XRD) pattern of dAgNps was similar to that of face centered cubic(fcc) structure of silver as reported by joint committee on powder diffraction standards (JCPDS) and fourier-transform infrared spectroscopy (FTIR) analysis showed that some phytochemicals of D. microcarpum such as polyphenols and flavonoids were likely involved in the reduction of Ag+ to form nanoparticles. Finally, cell viability assay revealed dAgNps inhibited PANC-1 and HeLa cell proliferations with IC50 values of 84 and 31.5 µg/ml respectively. In conclusion, the synthesized nanoparticles from D. microcarpum leaves (dAgNps) have inhibitory effect on pancreatic and cervical cancer cells.

Factors that Affected Women Undergoing Cryotherapy Following Cancer Screening with Visual Inspection of the Cervix Using Acetic Acid Method

The Indonesian government has applied the cancer "see and treat" method which involves a visual inspection using acetic acid (VIA), followed by a cryotherapy procedure, to reduce the incidence of cervical cancer. However, compliance with the program is still low in the targeted population. This study aims to see what factors influence women to receive cryotherapy treatment if they have positive VIA result. This cross-sectional study was conducted among 356 VIA positive women, aged 30-50 years old, registered at Temanggung District Health Office, Central Java, Indonesia between March 29 and April 31, 2018. Data on whether subjects underwent cryotherapy, their demographic profile, education, knowledge about cryotherapy, and family support were collected in a direct interview using a structured questionnaire. A statistical analysis was carried out to observe the influence of all the variables on subjects' decisions on cryotherapy. In our study, 217 women (60.69%) received cryotherapy, while 139 women (39.04%) did not. Among all the variables analyzed, the factors affecting the subjects' likelihood to undergo cryotherapy are their knowledge about cervical cancer and screening (PR=0.776;95%CI=0.660-0.913;p=0.003), their residences distance from health centre (PR=0.795;95%CI=0.650-0.971;p=0.016), permission from their family (PR=0.675;95%CI=0.556-0.820;p=0.018), and being accompanied by their family (PR=0.824;95%CI=0.700-0.970;p=0.026). Age, marital status, occupation, and education background did not show a significant correlation with the women's decisions to receive cryotherapy. Interestingly, the result of our study indicates that women are less willing to undergo the cryotherapy procedure if they have good knowledge about the cryotherapy procedure and its importance in cervical cancer's prevention. Providing higher quality and more accessible health facilities with cryotherapy services are important in influencing women's willingness to receive cryotherapy. Family support, in the form of permission given by spouses, and if they accompanied the patient to seek cryotherapy care are observed as factors influencing women's willingness to have the procedure..

Value of CCNA1 promoter methylation in triaging ASC-US cytology

Using HPV testing to triage ASC-US still has some problems of unnecessary colposcopy in many cases. A previous study reported that methylation of CCNA1, a tumor suppressor gene, can differentiate between low and high grade lesions. This study was designed to evaluate the diagnostic values and application of CCNA1 methylation in the patients with ASC-US group.Materials and methods:Cross sectional analytic study was conducted in the patients with ASC-US cytology. HPV DNA testing and CCNA1 promoter methylation testing were performed. The patients were sent for colposcopic examination and biopsy. Biopsy results were considered as gold standard. Diagnostic test of HPV test and CCNA1 methylation test were calculated for sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), likelihood ratio for test positive and negative and 95% confidence interval.Results:One hundred and seventy patients were enrolled. Mean age was 39.7 years old. HR-HPV was positive in 70% of the patients. HPV type 16, type 18 and non-16,18 were 12.4%, 4.7% and 42.4%, respectively. CIN2+ were found in 12.4% (21 cases). CCNA1 promoter methylation was positive in 5 cases. CCNA1 had high specificity 99.3%, NPV 89.2% and PPV 80% in detection of CIN2+ but sensitivity was 19%. Likelihood ratio for positive test was 28.4 and likelihood ratio for negative test was 0.8. HPV test had sensitivity of 90.5% and NPV of 95.9% but low specificity and PPV as 31.5% and 15.7%, respectively.Conclusion: CCNA1 promoter methylation testing had very high specificity, likelihood ratio for the positive test and PPV (99.3%, 28.4 and 80.0, respectively). Therefore, CCNA1 promoter methylation test may be used in the HPV DNA positive cases to classify the urgency of colposcopy and the colposcopist should pay more attention to CCNA1 positive patients because of their higher chance to identify the significant lesions.

Factors Affecting Survival Outcome After Percutaneous Nephrostomy as Palliative Urinary Diversion in Obstructive Uropathy due to Advance Cervical Cancer Patients

Cervical cancer is the 3rd most common cancer in women. In late stages, obstructive uropathy due to mass infiltration is common and the mainstay of treatment for this condition is palliative urinary diversion through percutaneous nephrostomy. Nevertheless, complications due to nephrostomy may have adverse effects on some patients. Further study is necessary to determine whether nephrostomy is suitable for all cervical cancer patients with obstructive uropathy. This study aims to identify the determinants of survival rate of cervical cancer patients undergoing nephrostomy for obstructive uropathy and determine the group of cervical cancer patients that would benefit the most from nephrostomy. Data were obtained from medical records of cervical cancer patients in Hasan Sadikin Central Public Hospital from January 2018 to December 2019. Log-rank analysis was performed to assess the survival rate of patients based on clinical conditions (age, metastasis, and ECOG performance status) and initial laboratory results (hemoglobin, leukocyte, thrombocyte and blood acidity). A total of 163 cases were identified from the medical records, with a median survival of 5(1-17) months. The results of the analysis showed that the survival rates of cervical cancer patients undergoing nephrostomy were significantly affected by age (p = 0.0001), metastasis (p = 0.0001), and ECOG performance status (p = 0.0001), while laboratory findings were not significant factors affecting survival (pHb=0.501; pLeu=0.634; pTr=0.077; pBGA=0.687). The survival after nephrostomy in advanced cervical cancer patients is largely affected by age, metastasis, and performance status. The choices of doing nephrostomy in those patients should be considering those factors to maximize the benefit over the risk of complications..

Role of microRNAs in Predicting the Prognosis of Cervical Cancer Cases: A Systematic Review and Meta-Analysis

There is growing evidence for the possible use of microRNAs (miRNAs) in cancers as diagnostic as well as prognostic biomarkers in the present era of Personalized Medicine. The objective of the present systematic review and meta-analysis was to assess the prognostic role of microRNAs in uterine cervical cancers. A systematic review and meta-analysis was carried out searching electronic databases for published articles between January 2009 and August 2020 based on standard systematic review guidelines. Meta-analysis was performed by pooling the hazard ratio (HR) with 95% confidence interval (CI) to assess the prognostic value of deregulated miRNAs by the random-effects model. In the present meta-analysis, the aberrant expression of 14 microRNAs in 1,526 uterine cervical cancer cases before definitive therapy from 14 case-control studies were assessed. The pooled HR of two miRNAs, miRNA-155 and miRNA-224 which were upregulated in cervical cancer tissues was 1.76 (95% CI 1.27-2.45) revealing significant association with overall poor survival. Meanwhile, the pooled HR was 1.53 (95% CI 0.94-2.94) when all the deregulated miRNAs in cervical cancer tissues were evaluated. The pooled HR of downregulated miRNAs was 1.46 (95% CI 0.81, 2.64). Meanwhile, the pooled HR of three upregulated miRNAs-425-5p, 196a, 205 in the serum sample was 1.37 (95% CI 0.45 -4.20). The downregulation of aberrant miRNAs was not associated with poor overall survival rates.

The Prognostic Value of Cancer Stem Cell Markers in Cervical Cancer: A Systematic Review and Meta-Analysis

Prognostic biomarkers in cervical cancer are widely investigated, including cancer stem cell (CSC) markers. However, their significance remains uncertain. This study aimed to determine the role of cervical cancer stem cell (CCSC) markers for survival. We conducted a systematic review and meta-analysis (PROSPERO CRD42021237072) of studies reporting CCSC markers as the prognostic predictor based on PRISMA guidelines. We included English articles investigating associations of CCSCs expression in tissue tumor with overall survival (OS) or disease-free survival (DFS) from PubMed, EBSCO, and The Cochrane Library databases. The quality of studies was analyzed based on Newcastle-Ottawa Quality Assessment Scale. From 413 publications, after study selection with inclusion and exclusion criteria, 22 studies were included. High expressions of CCSC markers were associated with poor OS and DFS (HR= 1.05, 95% CI: 1.03 - 1.07, P <0.0001; HR= 1.31, 95% CI: 1.09 - 1.17, P <0.00001; respectively). Sub-analysis of individual CCSC markers indicated significant correlations between CD44 (HR= 1.14, 95% CI: 1.07 - 1.22, P 0.0001), SOX2 (HR= 1.58, 95% CI: 1.17 - 2.14, P 0.003), OCT4 (HR= 1.03, 95% CI: 1.01 - 1.06, P 0.008), ALDH1 (HR= 1.36, 95% CI: 1.13 - 1.64, P 0.001), and CD49f (HR= 3.02, 95% CI: 1.37 - 6.64, P 0.006) with worse OS; OCT4 (HR= 1.14, 95% CI 1.06 - 1.22, P 0.0003), SOX2 (HR= 1.11, 95% CI: 1.06 - 1.16, P <0.0001), and ALDH1 (HR= 1.22, 95% CI: 1.10 - 1.35, P 0.0002) with poor DFS. We did not conduct a meta-analysis for MSI-1 and CK17 because only one study investigated those markers. Expressions of OCT4, SOX2, and ALDH1 were associated with poor OS and DFS in cervical cancer tissue. These markers might have potential roles as prognostic biomarkers to predict unfavorable survival.

Clinicopathological Prognostic Factors Influencing Survival Outcomes of Vulvar Cancer

The prognostic factors for survival in squamous cell carcinoma (SCCA) of vulva cancer such as groin node involvement, postmenopausal status, tumor size, margin status, tumor grade, lymph vascular space invasion (LVSI) were reported in the past. However, with limited data from Southeast - Asian population, the present study was conducted to evaluate the clinicopathological prognostic factors for survival outcomes of this disease after treatment with surgery. All SCCA vulva cancer patients who underwent surgery between January 2006 and December 2017 were reviewed. The clinicopathological factors were analyzed to identify the prognostic factors for the progression-free survival (PFS) and overall survival (OS) using the Kaplan- Meier method and Cox-Proportional Hazard model. One hundred twenty-five patients were recruited. The independent poor prognostic factors for PFS were groin node-positive and  pathologic tumor diameter of more than 25 mm. Whereas postmenopausal status and groin node positive were independent poor prognostic factors for OS. Groin node-positive was the only one independent poor prognostic factor for both PFS and OS. In addition, the tumor diameter longer than 25 mm. was independent poor prognostic factors for PFS while postmenopausal status was independent poor prognostic factors for OS. Special adjuvant treatment for patients with these factors should be further investigated. .

An Evaluation of Phosphate Buffer Saline as an Alternative Liquid-Based Medium for HPV DNA Detection

HPV detection has been proposed as part of the co-testing which improves the sensitivity of cervical screening. However, the commercially liquid-based medium adds cost in low-resource areas. This study aimed to evaluate the performance of ice-cold phosphate buffer saline (PBS) for HPV detection. HPV DNA from SiHa cells (with 1-2 copies of HPV16 per cell) preserved in ice-cold PBS or PreserveCyt solution at different time points (24, 36, 48, 72, 120 and 168 h) was tested in triplicate using Cobas 4800. The threshold cycle (Ct) values of both solutions were compared. An estimated false negative rate of PBS was also assessed by using the difference in Ct values between both solutions (∆Ct) and Ct values of HPV16-positive PreserveCyt clinical samples (Ctsample) at corresponding time points. Samples with a (Ctsample+∆Ct) value > 40.5 (the cutoff of HPV16 DNA by Cobas 4800) were considered as false negativity. The Ct values of HPV16 DNA of SiHa cells collected in PBS were higher than PreserveCyt ranging from 0.43 to 2.36 cycles depending on incubation times. There was no significant difference at 24, 72, 120, and 168 h.  However, the Ct values were statistically significantly higher for PBS than PreserveCyt at 36 h (31.00 vs 29.26), and 48 h (31.06 vs 28.70). A retrospective analysis in 47 clinical PreserveCyt collected samples that were positive for HPV16 DNA found that 1 case (2%) would become negative if collected in ice-cold PBS. The PBS might be an alternative collecting medium for HPV detection in the low-resource areas. Further evaluations are warranted.

The Cost of Locally Advanced Cervical Cancer in Thailand: an Empirical Study for Economic Analysis

To evaluate cost of illness of locally advanced cervical cancer patients from societal perspective in three scenarios including completely cured without severe late side effects (S1), completely cured with late grade 3-4 gastrointestinal side effects (S2.1) or genitourinary side effects (S2.2), and disease recurrence and death (S3). The incidence-based approach was conducted. The cost was calculated for 5-year time horizon starting for the treatment initiation. Direct medical costs were extracted from hospital database. Cost of using two-dimensional technique and three-dimensional conformal radiation therapy were calculated separately. Direct non-medical costs and indirect costs in terms of productivity loss were based on actual expenses from the interview of 194 locally advanced cervical cancer patients from two tertiary hospitals in Bangkok, during June to December 2019. All costs were converted to US dollar in 2019 values. For 5 years, cost of illness per patient for using two-dimensional technique and three-dimensional conformal radiation therapy were US $8,391 and US $10,418 for S1, US $18,018 and US $20,045 for S2.1, US $17,908 and US $19,936 for S2.2, and US $61,076 and US $63,103 for S3, respectively. The economic burden for newly diagnosed locally advanced cervical cancer patients in Thailand in 2018 was approximately US $129 million and US $131 million for using two-dimensional technique and three-dimensional conformal radiation therapy, respectively. Cost from S3 accounted for 70% of all total cost. Premature death was the most important cost driver of cost of illness accounted for 64 % of the total cost estimates. Cost of illness of locally advanced cervical cancer patients produced significant economic burden from societal perspective. Disease recurrence and early death from cancer was the most influential cause of this burden.

Racial Disparities Associated with the Prevalence of Vaccine and Non-Vaccine HPV Types and Multiple HPV Infections between Asia and Africa: A Systematic Review and Meta-Analysis

Cervical Cancer is the 6th most common and 3rd most deadly cancer among women. Despite the fact that the majority of the countries in Asia and Africa have a similar economy and low life expectancy, the mean age-standardized incidence rate (ASIR) of cervical cancer is substantially higher in Africa than in Asia. This study identified the correlates of the higher ASIR rates in Africa relative to Asia against two timelines; 2004-2009 and 2010-2017. Peer-reviewed articles published between 2004 and 2017 were selected using the PRISMA standard. Sources of articles included Google Scholar, Scopus, PubMed Central, and EMBASE. Search keywords included: HPV genotypes, cervical cancer, HPV vaccine, and multiple infections in Africa and Asia. Twenty-nine and seventeen full-length articles were selected from Africa and Asia, respectively. The pooled prevalence of HPV infection up to 2017 was higher in Africa (41.8%; 95% CI: 35.9, 47.7) than in Asia (24.2%; 95% CI: 16.22, 32.2) at p< 0.001. Between 2004-2009 and 2010-2017 timelines, the pooled prevalence of HPV infection decreased from 49.1% to 36.7% (OR': 1.66, 95% CI: 1.51-1.80) in Africa and increased from 16.9% to 20.5% (OR': 0.79, 95% CI: 0.71-0.86) in Asia. However, the pooled prevalence of multiple HPV infections and non-vaccine high-risk HPV infections were higher among African women diagnosed with cancer (30.9% and 5.2%) than their Asian counterparts (21.0% and 2.0%, respectively) at p< 0.001. Additionally, the pooled prevalence of the five most prevalent high-risk HPV types in Africa were HPV16 (35.3%), HPV52 (14.2%), HPV35 (12.4%), HPV18 (10.4%), and HPV58 (10.0%), while that of Asia were HPV16 (37.3%), HPV52 (16.2%), HPV58 (14.7%), HPV33 (7.4%) and HPV18 (7.2%). This study suggests that the higher prevalence of HPV, multiple HPV and non-vaccine HPV infections could be responsible for the higher ASIR in Africa than in Asia.

Survival Analysis of Cervical Cancer Patients: A Case Study of Bhutan

The purpose of the study is to identify the risk factors such as age, the stage of patients based on the International Federation of Gynecology and Obstetrics system (FIGO stage) and treatment type, and their effect on the survival of cervical cancer patients receiving treatments at Jigme Dorji Wangchuck National Referral Hospital (JDWNRH) in Bhutan between January 2014 and December 2019. In this retrospective study, all 357 women diagnosed with cervical cancer were included. Kaplan-Meier model was applied to estimate survival, and the log-rank test was performed to compare survival distributions between subgroups stratified by each of the risk factors. Baseline demographics, cervical cancer stages, and treatment options were analyzed as factors and predictors of survival by Cox proportional hazards model. The overall estimated 1- to 5-year survival rates are 82.1% (95% CI: 77.8-86.7), 75.6% (70.4-81.1), 65.2% (58.2-73.0), 62.3% (54.7-70.9) and 55.4% (44.9-68.3). The results reveal that age group, FIGO stage, treatment, and frequency of hospital visits are significant factors affecting the survival of cervical cancer patients in Bhutan. Patients aged >45 years increases the risk of dying (HR: 2.1, 95% CI: 1.2-3.9) compared to the young age group (≤45 years). Treatment types other than surgery only are significantly associated with an increased risk of mortality in patients with cervical cancers. The more frequency of hospital visits also reduces the risk of dying (HR: 0.1, 95% CI: 0-0.3). FIGO stage IV is the most significant risk factor for mortality with a hazard ratio of 6 (95% CI: 2.1-17.6). The five-year survival rate of cervical cancer patients in this study was low. Late diagnosis of cervical cancer appears to be mainly associated with a higher risk of dying. The results provide valuable information for further research and policymaking in the prevention and management of cervical cancer. .

Synergistic Effect of Barbadensis miller and Marsdenia Condurango Extracts Induces Apoptosis Promotes Oxidative Stress by Limiting Proliferation of Cervical Cancer and Liver Cancer Cells

Drug synergy is the combine effect of drug efficacy. Synergistic combinations of active ingredients have proven to be highly effective and more useful in therapeutics. In contrast, the individual effect of drug is usually undesirable and mostly used for selecting drug-resistant mutations. Purpose of this study was to check synergistic effects of both plants (Barbadensis miller and Marsdenia condurango) against liver and cervical cancer. Culturing of HeLa (cervical cancer cell line) and HepG2 (liver cancer cell line) cells, IC50 evaluation, viability assays (trypan blue, crystal violet), p53 ELISA and immunocytochemistry, MUSE analysis (count and viability), antioxidants (GSH, SOD, CAT), at the end RT-PCR was performed. IC50 evaluation was done of each plant individually and with combination for synergistic effects, IC50 with plants combination (synergism) was applied on further viability assays (trypan blue, crystal violet, MUSE analysis via count and viability kit) p53 ELISA and immunocytochemistry for evaluation of cellular apoptosis, antioxidants assays (GSH, SOD, CAT), and RT-PCR with proliferative and apoptotic markers along with internal control. According to current study it was observed that synergistic effect of these plants has more anticancer properties with minimum effective dose. It was also observed that extracts possess the ability to induce apoptosis, restrict proliferation and enhanced oxidative stress.

The Effect of Indian Fig Fruit Extract on Human Papilloma Virus containing Cervical Cancer Cells (HeLa) by Decreasing the HPV18 L1 Gene Load

Global trend is moving towards the use of natural phytochemicals to fight against pathogens. Human cervical cancer is directly associated with onco-potent type of Human Papilloma Virus (HPV). There is no known medicine for clearance of HPV type whose persistence is the cause of occurrence and re-occurrence of cervical cancer. The different species of fig fruit and their latex are reported to have HPV associated genital warts clearance capability. In the current investigation, the effect of the methanol extract of Ficus benghalensis L. fruits on HPV type18 viral load in HeLa cell line was tested by doing PCR using HPV L1 primers (MY09/My011) and the cytotoxicity was also analysed by MTT assay. The induction of apoptotic activity in terms of DNA fragmentation and hyper-chromic effects of DNA was analysed. The PCR results showed a reduction in the HPV18 DNA and also the treatment exhibited a promising cytotoxicity with IC50 value at 211.86 μg/ml. The DNA samples from treated HeLa cells showed DNA shearing and laddering as a mark of apoptotic DNA fragmentation (Fig. 2) and the UV absorbance value at 260 nm was found to be significantly (p <0.01) higher in the DNA sample treated with fruit extract compared to the untreated DNA sample. The Ficus benghalensis L. fruit extract reduced the HPV viral load in HPV18 containing HeLa cells and showed an effective cytotoxicity on HeLa cell line. It also could induce the apoptotic activity in HeLa cell line and this study results suggest that the Ficus benghalensis L. fruits can be used to fight against cervical carcinoma, acting on HPV load.

Cancer Screening Literacy among Vietnamese Population: Does Annual Checkup Improve Cancer Screening Literacy?

Colorectal, breast, and cervical cancers disproportionately impact the Vietnamese population. However, research on cancer prevention among this population was very limited. The purpose of this study is to examine the cancer screening literacy levels for these three types of cancers among rural Vietnamese and investigate correlates of cancer screening literacy. A sample of 226 Vietnamese men and women aged 25-70 years old was recruited from rural Vietnam and finished a self-administered questionnaire. Andersen's Behavioral Model was used to guide this cross-sectional study to identify modifiable variables. Bivariate analysis was used to explore the relationship between demographic factors and cancer screening literacy levels. Multiple linear regressions were also used to identify significant factors for cancer literacy levels. Cancer screening literacy levels of Vietnamese men and women were low regarding all three types of cancers, especially HPV symptom questions. Only about 24% of women answered correctly on "most people with genital HPV have no visible signs/symptoms" and less than 18% answered correctly on "I can transmit HPV to my partner(s) even if I have no HPV symptoms." Findings suggested that having an annual checkup was associated with higher colorectal (β=.15, p <.05), breast (β=.25, p <.001), and cervical (β=.18, p <.01) cancer screening literacy. Public health efforts should focus on encouraging annual checkups in the Vietnamese population. During the annual checkup, health care professionals should educate patients about importance of cancer screening and provide recommendations for regular cancer screenings to reduce cancer health disparities.

Acceptability and Concordance of Self- Versus Clinician- Sampling for HPV Testing among Rural South Indian Women

Despite being largely preventable, HPV-related cervical cancers continues to be the second highest cause of cancer deaths among Indian women. HPV testing using self-sampled samples may offer an opportunity to expand cervical cancer screening in India where there is currently a shortage of providers and facilities for cervical cancer screening. The study examines acceptability and concordance of self vs. clinician collected samples for HPV-relted cervical cancer screening among rural South Indian women. Between May and August 2017, eight mobile screening clinics were conducted among 120 eligible women in rural villages in Mysore District, India. Women over the age of 30 underwent informed consent process and then self-sampled a sample for cervicovaginal HPV DNA testing. Next, the women underwent clinical exam where the clinician collected a cervicovaginal HPV DNA sample. Following the clinical exam, all participants answered an interviewer-administered questionnaire to assess their history of cervical cancer screening and acceptability of self- and clinician-sampling methods. To assess diagnostic accuracy, concordance of self- and clinician-sampled HPV DNA specimens was calculated in addition to five measures of acceptability (feeling of caring, privacy, embarrassment, genital discomfort, and genital pain). Study participants had a median age 39 years, about four-in-ten (41.7%) had a secondary education or above, the vast majority (87.5%) were married and only 3.4% reported having screened for cervical cancer. For all measures of participant acceptability, self-sampling was rated significantly higher than clinician-sampling. Cohen's kappa was 0.73 (95% CI: 0.34, 1.00), indicating substantial agreement between self- and clinician-sampling. This study demonstrates that HPV self-sampling for cervical cancer screening is feasible and acceptable in a community setting among South Indian rural women. Concordance between self-sampling and clinician-sampling was adequate for screening in community settings.  .

Experience of Human Papillomavirus Vaccination Project in a Community Set Up-An Indian Study

Initial introduction of HPV vaccination from 2006 to 2008 was largely confined to high-income countries (HIC), such as Australia, the United States, and Europe, where cervical cancer incidence is lowest. Much of the post-introduction literature has come from HICs, with a focus on coverage levels achieved, provider acceptability and early impact of vaccination on disease endpoints. However, there are a few literature evaluating the mechanics of delivery, feasibility of the health system and acceptability from low and middle income countries (LMICs). The primary objective was to evaluate the feasibility, acceptability and safety of two dose HPV vaccination in adolescent girls between 9-14 years. After an orientation camp followed by filling up of prevaccine questionnaires by parents on HPV related diseases and its vaccines and informed consent, girls between9-14years were vaccinated. They were asked to report any side effects in the next 24 hours after each dose. Parents were contacted on Day 7 and Day 30 to enquire about any side effects . Total 3 visits were required i.e two for the vaccination and one visit at 7th month post completion of second dose. To estimate the acceptability, successful completion of two doses by at least 80% of the girls were measured. For measurement of acceptability, either of the parents were recalled along with their daughter at 7th month and were asked to fill up a pre-set questionnaire. After institutional ethical clearance, 555 girls were recruited in the study from rural parts of West Bengal, India between July, 2017 to November, 2017. Out of which, 544 girls (98%) received their 2nd dose between January, 2018 and May, 2018 without any serious adverse effects. No serious adverse effect was reported on follow up till December, 2019. The introduction of HPV vaccination is feasible in large scale and the vaccine is well accepted and safe..

Quality of Actions to Control Cervical Cancer in Bahia, Brazil

To assess the quality of the actions to control cervical cancer (CC) and its correlates. This is a cross-sectional study conducted from January to March 2019 in 19 municipalities in Bahia, Brazil, with a sample of 241 doctors and nurses from primary health care (PHC). Three dependent variables were chosen- "Performance of educational, promotion, prevention, and monitoring actions" (D1); "Access to diagnostic tests" (D2); "Non-occurrence of high grade cervical squamous intraepithelial lesions (HSIL)" (D3). Poisson regression with robust variance was used, adopting hierarchical input variables to estimate the prevalence ratios and confidence intervals of 95%. The following prevalence rates were found: D1  39.8% (95% CI: 33.8-46.2); D2  73.9% (95% CI: 67.9-79.1); and D3  46.4% (95% CI: 39.9-53.0). These dimensions remained associated with the dependent variables: D1- having professional training courses on the topic; consideration to ensure that collection takes place appropriately by a professional; and women having access to medical transport; D2- nurses treating low-grade lesions; D3- recording the Papanicolaou in electronic medical records; D1 and D2- professionals joining the service through public tender; D1 and D3- working in the PHC (≥ 2 years); D2 and D3- recording Papanicolaou in physical records; and performance of Papanicolaou by residents. Better trained professionals and professionals working in stable work arrangements are associated with comprehensive actions to control CC. Such strategies indicate that investments in work management result in a more organized PHC and more solution-centered work processes. Therefore, working in the PHC for a longer time and nurses performing more clinical actions (collection and treatment) are favored by such organizational actions. Investments in diagnostic support contribute to perceptions of more comprehensive actions to control CC. .

Is Pap Test Awareness Critical to Pap Test Uptake in Women Living in Rural Vietnam?

Cervical cancer is the second leading cause of cancer death among Vietnamese females. By detecting precancerous cells, Pap test screening plays a critical role in the fight against cervical cancer. The present study aims to investigate health-related factors associated with receipt of Pap test among Vietnamese females living in rural Vietnam, particularly examining the correlation between awareness level of the Pap test and the receiving of Pap test. Anderson's Behavioral Model of Health Services Use was utilized as the present study's theoretical framework. A self-administrated questionnaire was completed among 193 females residing in Quantri City, Vietnam. Only 15.5% (N=30) of participants in our sample have had a Pap test. Pap test awareness (OR = 18.38, p <.001) was a strong predictor of Pap test receipt. Participants who had heard about Pap test were 18.38 times more likely to take a Pap test compared to those who had no prior knowledge. Besides the awareness, variables including employment (OR = .18, p <.05), and health insurance coverage (OR = 10.75, p <.05) were significantly associated with Pap test uptake. Findings from the present study suggests interventions should be provided through public health efforts to enhance awareness of Pap test by aiming at increasing primary prevention of cervical cancer, especially among Vietnamese women living in rural areas, in order to reduce cancer health disparities.

Prevalence of Abnormal Anal Cytology in Women with Abnormal Cervical Cytology

The aim of this study was to evaluate the prevalence of abnormal anal cytology in women presenting with abnormal cervical cytology (intraepithelial lesion or cervical cancer) at the largest tertiary university hospital in Thailand. A cross-sectional prospective study design was used. Anal cytology was performed on 145 women with abnormal cervical cytology between June 2014-Octoble 2014. If abnormal anal cytology was detected, anoscopy was performed with biopsy in any suspicious area of precancerous change. Prevalence of abnormal anal cytology was 5.5% (8 patients). Of 8 patients, six patients presented with low-grade squamous intraepithelial lesion, one patient with high-grade squamous intraepithelial lesion, and one with atypical squamous cell cannot exclude high-grade squamous intraepithelial lesion. Abnormal anoscopic impression was found in 3 cases, as follow: The first case showed faint acetowhite lesion and anoscopic impression was low grade squamous intraepithelial lesion; the second case was reported as human papillomavirus (HPV) change by anoscopic impression; and the third case showed dense acetowhite lesion with multiple punctation and pathologic examination showed anal intraepithelial neoplasm III (AIN3). The last patient underwent wide local excision of AIN3 with split-thickness skin graft reconstruction. Final pathology confirmed AIN3 with free resection margin. Prevalence of abnormal anal cytology was 5.5%  in patients with abnormal cervical cytology. The prevalence might be support anal cytology screening in this group of patients.

Diagnostic Accuracy of Fluorescein Sodium for Targeted Cervical Biopsies

Visual inspection methods for cervical cancer screening are widely used in low resource settings. Fluorescent sodium could improve accuracy of cancer screening. This study aimed to assess diagnostic accuracy of fluorescein sodium (FNa) to detect cervical neoplasia. Seventy consecutive patients referred for colposcopy were enrolled prospectively. Acetic acid, Lugol's iodine, and FNa were used sequentially. Biopsies were taken from all abnormal areas. If there was no obvious abnormality, two random biopsies and endocervical curettage were done. Reference standard was the highest grade lesion on cervical biopsy with a threshold of CIN2+. The patterns of each staining agent were recorded as absent, faint, or distinct. Diagnostic accuracy estimates with 95% confidence intervals were calculated. Correlation between the various tests were also determined using the kappa statistic. There were 27 cases of CIN2+ (38.6%). The sensitivity of any fluorescence for CIN2+ was 82% (62, 94) and for distinct fluorescence was 59% (39, 78). The specificity was 65% (49, 79) for any fluorescence and 95% (84, 99) for distinct fluorescence, the same as for Swede score > 7. For any fluorescence, the positive likelihood ratio was 2.34 (1.5, 3.65) and the negative likelihood ratio was 0.28 (0.13, 0.65). For distinct fluorescence, the positive likelihood ratio was 12.74 (3.18, 51.1) and the negative likelihood ratio was 0.43 (0.27, 0.68). There was moderate correlation between FNa and the other tests. Distinct fluorescence with FNa was very specific, low cost, and easy to perform and may contribute to confirm CIN2+ disease.

Analysis of Nuclear Encoded Mitochondrial Gene Networks in Cervical Cancer

Cervical cancer (CC) is one of the most common female cancers in many developing and underdeveloped countries. High incidence, late presentation, and mortality suggested the need for molecular markers. Mitochondrial defects due to abnormal expression of nuclear-encoded mitochondrial genes (NEMG) have been reported during cancer progression. Nevertheless, the application of NEMG for the prognosis of CC is still elusive. Herein, we aimed to investigate the associations between NEMG and CC prognosis. The differentially expressed genes (DEG) in the TCGA-CESC dataset and NEMGs were retrieved from TACCO and Mitocarta2.0 databases, respectively. The impact of methylation on NEMG expression were predicted using DNMIVD and UALCAN tools. HCMDB tool was used to predict genes having metastatic potential. The prognostic models were constructed using DNMIVD, TACCO, GEPIA2, and SurvExpress. The functional enrichment analysis (FEA) was performed using clusterProfiler. The protein-protein interaction network (PPIN) was constructed to identify the hub genes (HG) using String and CytoHubba tools. Independent validation of the HG was performed using Oncomine and Human Protein Atlas databases. The druggable genes were predicted using DGIdb. Among the 52 differentially expressed NEMG, 15 were regulated by DNA methylation. The expression level of 16, 10, and 7 has the potential for CC staging, prediction of metastasis, and prognosis. Moreover, 1 driver gene and 16 druggable genes were also identified. The FEA identified the enrichment of cancer-related pathways, including AMPK and carbon metabolism in cancer. The combined expression of 10 HG has been shown to affect patient survival. Our findings suggest that the abnormal expression of NEMGs may play a critical role in CC development and progression. The genes identified in our study may serve as a prognostic indicator and therapeutic target in CC..

“I Just Went for the Screening, But I Did Not Go for the Results”. Utilization of Cervical Cancer Screening and Vaccination among Females at Oyibi Community

Cervical cancer screening and vaccination practices is reported to have  low coverage in most developing countries. It has been reported that most women are aware of cervical cancer screening and vaccination worldwide.  Nevertheless, the rate at which women participate in  cervical cancer screening and vaccination was found to be low both locally and internationally. Consequently, in sub-Saharan Africa, cervical cancer screening programs have poor coverage. The aim of this study was to explore the practices of cervical cancer screening and vaccination among females at Oyibi community. The researchers employed a qualitative exploratory design to recruit 35 participants put into five Focus Group Discussions (FGDs).  Five FGDs were formed with seven (7) members in each group. The members were purposely recruited. The sample size was based on data saturation. Data was retrieved using a semi-structured interview guide. The researchers served as moderators in the group. Two (2) main themes with Eight (8) subthemes were generated from the data analysis. The themes were; (cervical cancer screening and vaccination practices), and (perceived benefits of cervical cancer screening and vaccination). The subthemes that emerged were as follows: types of cervical screening and vaccination done by participants, experiences during cervical cancer screening, experiences during cervical cancer vaccination, decision to go for cervical cancer screening and vaccination, willingness to recommend cervical cancer screening and vaccination to other women,  early detection of cervical cancer through early screening, benefits of cervical cancer vaccination, and willingness to receive cervical cancer vaccine. The study also revealed that most of the women who had done the screening and vaccination were young (19-29 years). The results from the study indicated that the participants' utilization of cervical cancer screening and vaccination were poor although they were conscious of the benefits of cervical cancer screening and vaccination and were willing to recommend it to their relatives and their loved ones. .

The Life Quality and Sexual Function of Women Underwent Radical Hysterectomy

Up to date, there no studies were conducted on the quality of life (QL) and sexual function (SF) of women from Kazakhstan treated for cervical cancer. The study was aimed at the assessment of the QL and SF of women of the Kazakh population who underwent radical hysterectomy compared with chemo-radiotherapy group. The study was conducted prospectively on 157 women of the Kazakh population. 92 women underwent radical hysterectomy (RH) and 65 underwent chemo-radiotherapy (CRT). The information was collected before treatment (T1), 6 months (T2) and 12 months (T3) after treatment. The women's average age was 41.12 ± 5.4 in the RH group and 47.24 ± 6.1 in the CRT group (p = 0.2). We did not detect significant differences between both groups according to the QLQ C-30 questionnaire (T1). The differences between the RH and CRT groups (p≤0,05) were observed in terms of physical functioning, fatigue, nausea and vomiting, pain during the T2 period. High rates of emotional functioning (p = 0.03), global health and QL (p = 0.02), and symptoms of fatigue (p = 0.04) were detected in the RH group compared to the CRT group during T3. However, pain symptoms (p = 0.001), nausea and vomiting and loss of appetite (p = 0.03) were dominated the CRT group. According to the results of FSFI-6 in the RH group, indicators for the domains "desire" (p = 0.02), "excitement" (p = 0.03), and "orgasm" (p = 0.05) were high, unlike in the CRT group during the T3 period. Nevertheless, the number of complains on the 'pain during intercourse' in the CRT group was higher than in the RH group (p = 0.001). Women who underwent RH had better health scores, global health status, and SF compared with patients treated with CRT.

Risk of High-Grade Cervical Lesions in Atypical Squamous Cells of Undetermined Significance (ASC-US) Cytology: Comparison between HIV-Infected and HIV-Negative Women

Women with human immunodeficiency virus (HIV) infection have an increased risk of HPV infection, cervical neoplasia. This study was undertaken to compare the risk of having high-grade cervical lesions defined as cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in HIV-infected versus HIV-uninfected women who had atypical squamous cells of undetermined significance (ASC-US) on cervical cytology. Fifty-seven HIV-positive women aged 25-65 years with ASC-US cytology undergoing colposcopic examination between January 2008 and December 2020 at Chiang Mai University Hospital were reviewed. By matching 1:5 ratio, 285 HIV-negative women with ASC-US cytology in the same period were recruited as controlled subjects for comparison. The patient characteristics, HIV status, CD4 cell count within 6 months of colposcopy, antiretroviral therapy, parity, contraception, smoking history, number of sexual partners, and histopathology on cervical biopsy were analyzed. Mean age ± SD of the HIV-positive and HIV-negative groups was 44.28 ± 8.53 years and 44.28 ± 9.68 years, respectively. HIV-positive women were significantly less likely to use contraceptive methods (36.8 % versus 48.8 % in HIV-negative women; P = 0.002). HIV-infected women significantly had more sexual partners than HIV-uninfected women. Both groups had similar risk for CIN 2+ (5.3 % in HIV-positive women compared with 4.9 % in HIV-negative women; odds ratio [OR] = 1.08, 95% confidence interval [CI] = 0.30 -3.87). After adjustment for no contraception use and number of sexual partners, the risk of CIN2+ in HIV-infected women remained unchanged; adjusted OR= 1.15, 95% CI = 0.27-4.92, P= 0.846). The risk of underlying high-grade cervical lesions in women with ASC-US on cervical cytology was approximately 5 %, regardless of HIV status.

Influence of Static Magnetic Field on HeLa and Huo2 Cells in the Presence of Aloe vera Extract

This research aimed to assess the impact of static magnetic field (SMF) on apoptosis rate and cell cycle progression in the presence of Aloe vera Crude Extract (ACE) in normal (Huo2) and cancer cells (HeLa). The specimens were split into one untreated group (control) and two experimental groups, including treatment with ACE (Alo) and compound treatment with SMF and ACE (Alo+SMF). MTT assay determined the IC50 value, and flow cytometry was employed to evaluate cell cycle distribution and apoptosis rates. Statistical analysis was carried out through a two-way ANOVA followed by Tukey's post hoc test. Our results showed that combination treatment with SMF (10 mT) and ACE (Alo+SMF) significantly inhibited the cell proliferation. This increased the cell number in G2/M stage and early apoptosis in cancer cells compared to ACE treated cells after 24 and 48h but reduced the number of Huo2 cells in G2/M phase and early apoptosis after 24h. The effect of AEC on HeLa cells was intensified with increasing the SMF exposure time, such that the early apoptosis rate in Alo+SMF group had an approximate 4-fold increase compared to Alo group. This research proposes that the combination treatment accelerates the apoptosis induction of HeLa cell. During the interphase, there were significant differences between the cancer and healthy cells concerning the cell cycle. Moreover, exposure time may play an important role in the impact SMF on both healthy and cancer cells in the presence of AEC.

Awareness about Human Papillomavirus Vaccine and Its Uptake among Women from North India: Evidence from a Cross-Sectional Study

This study aims to estimate the prevalence of human papillomavirus (HPV) vaccine usage and determine the factors for awareness about HPV vaccine among women in reproductive age group. This is a cross-sectional survey under a cervical cancer prevention study. The sample size was 1020 women, aged 15-49 years [550 in Delhi and 470 in Rohtak]. Bivariate analysis and Fisher exact test along with binary logistic regression analysis were used to determine the factors for awareness. About 18.0 % [Delhi: 24.2 % and Rohtak: 10.9 %] of the respondents had heard about the vaccine against cervical cancer. The women aged more than 30 years [AOR: 1.35; CI: 0.94, 1.94] were more likely to be aware of cervical cancer vaccine as compare to women of 30 years and less. However, the women from Rohtak [AOR: 0.90; CI: 0.48, 1.66] were less likely to be aware of vaccine against cervical cancer in reference to women aged 30 years and more [AOR: 1.61; CI: 1.01, 2.56] from Delhi. About 0.6 % [Delhi: 1.1 % and Rohtak: 0.0 %] of the respondents had received HPV vaccine. Women tend to have limited knowledge about cervical cancer vaccine and immunisation practices. The women's demographic makeup varied significantly between the two sites, i.e , Rohtak and Delhi, which had an impact on how well they understood and utilised the cervical cancer vaccination. It is worth mentioning that none of the women from Rohtak had received the immunisation. The awareness of the cervical cancer vaccine among women from the Rohtak was lower than the Delhi women.

Can portable Colposcopes Replace Standard-of-care Colposcopes? A Crossover Trial of Two Portable Colposcopes with a Standard-of-Care Video Colposcope

Screen positive women need to be triaged by colposcopy which is a major challenge in low-middle income countries. Portable colposcopes may overcome many challenges, reduce referrals and enable a single visit approach. This study assessed the performance of portable colposcopes and potential to reduce referral. This crossover randomised study enrolled women aged 25 to 65 years with abnormal screening result or cervical symptoms. All women underwent visual inspection with acetic acid (VIA), HPV test, colposcopy with two portable colposcopes (Gynocular®, Gynius, Sweden, and Pocket® transvaginal colposcope, Duke University, NC, USA) and a standard video colposcope, and biopsy. Colposcopic Swede score agreement between portable and video colposcopes, as well as agreement of Swede score with histology were calculated for each device. The potential impact of portable colposcopes in a single visit approach was assessed based on the final diagnosis. Among 250 subjects, 27(10.80%) had high-grade cervical intraepithelial neoplasia (CIN2+) lesions. Swede scores for Pocket and Gynocular colposcopes were similar to video colposcope in 248 (99.20%) and 247 (98.80%) subjects, respectively (agreement scores 0.9969 and 0.9954, respectively). At a Swede score cut-off of ≥5, all three devices had identical sensitivity, specificity, positive and negative predictive value of 96.30%, 92.30%, 60.50% and 99.50,. Ablative treatment offered at field setting would result in optimal treatment in 52.0% and 85.1% cases when screened with VIA and HPV test respectively; using Pocket colposcope could improve this to 94.0% and 95.9%, respectively. Overtreatment and referral rates reduced from 46.8% and 12.4% to 4.8% and 6.0%, respectively, when VIA test is followed by triage with pocket colposcope. These outcomes were comparable to screening with HPV followed by colposcopy triage. Pocket colposcope performed comparably to the video colposcope. Used by healthcare providers in the field setting, they can augment the results of VIA significantly.

Knowledge, Attitude and Practice of Commercial Sex Workers Regarding Cervical Cancer and Its Screening, Daulatdia Brothel, Rajbari District, Bangladesh, 2020-2021

Background: Cervical cancer is the second most common cancer in females in Bangladesh. This is caused by Human Papilloma Virus (HPV). Multiple sex partners, HIV infection, smoking, using birth control pills, and having more than three children are risk factors of cervical cancer. Hence, female sex workers have a high prevalence of infection with high risk HPV genotypes which eventually may causes cervical cancer. Unfortunately, the status of knowledge, attitude and practice among female sex workers regarding cervical cancer is mostly unknown. The aim of the study was to assess the knowledge, attitude and practice of women living in Daulatdia brothel regarding cervical cancer and its screening.  Methods: A cross-sectional knowledge-practice survey was conducted among 400 female sex workers in Daulatdia Brothel, Rajbari District, Bangladesh. The women’s total score on knowledge, and practice were categorized as sufficient or insufficient. We calculated frequencies and used binary logistic regression to describe and assess the association between scores and socio-demographic characteristics of respondents. Results: Most sex workers (61%) were between 29 to 35 years, married at 13 to 15 years of age, and divorced (91%). Middle aged sex workers were more likely have a VIA test  than women in the 29 to 35 years group (18%, OR:5.2; CI: 2.0, 13.5). Less than half of the studied women (40%) had sufficient knowledge regarding cervical cancer and 12% knew that infection by HPV is a risk factor. Respondents with primary and secondary education were more likely to have sufficient knowledge than the illiterate (42%, OR: 1.32; CI: 0.82, 2.12). Practices to prevent cervical cancer were very poor. Nearly all women (99%) would recommend other women to have a VIA test. There were only 7% who had a VIA test and 2% were vaccinated against HPV. Unmarried sex workers were more likely to take action to prevent cervical cancer. Sex workers educated up to the primary level were more likely to have a VIA or other tests than the illiterate sex workers (10%, OR: 1.3; CI: 0.6, 3.2). Conclusion: Sex workers in Daulatdia brothel were less knowledgeable about cervical cancer and less likely to have a VIA test and poor practices towards preventing cervical cancer. The sex workers underutilized the VIA test and HPV vaccine.

Results of Self-Sampling Methodology Impression for Cervical Cancer Screening in Mongolia

Mongolia is a sparsely populated country; however, almost fifty percent of the population lives in the capital city. Medical care services and exceptionally well-organized cervical cancer screening tests are limited in remote areas. To improve cervical cancer screening test coverage, we compared the interest between physicians taking samples and self-sampling among the attendees in this study. A total of 175 women participated in this study. The hundred twelve women visited the Gynecology ward, and the sixty-three women were provided with the cervical self-sampling test kit and filled out a questionnaire. Subsequently, the acceptability of physician taking and self-sampling were evaluated using a questionnaire. All specimens were processed using the TACAS LBC system, and the quality of samples was tested by cytology. Regarding the acceptability of self-sampling, the selections for subsequent screening were 36% self-sampling and 64% gynecologist-sampling methods. The acceptability rates were higher in the remote areas than the urban areas. However, 64% of the participants lacked knowledge that the causative agent of cervical cancer is the human papillomavirus, and 66.9% mainly were sexually transmitted. In addition, 82.3% of the women surveyed were unaware that there was a vaccine to prevent cervical cancer, but 88.6% wanted to be vaccinated. Of most women, 44.4% chose self-sampling due to no embarrassment in the gynecological examination. The self-sampling preferences were dominant in the old age group (61.6%). The cytology satisfaction rate in physician-sampling (99.1%) was higher than in the self-sampling group (69.8%). The Implementation of the self-sampling tool may be considered a primary screening. The self-sampling test can adopt into the early screening program and may increase the coverage of the screening program and improve the quality.

Perspectives of Medical Experts’ on Health Culture for Human Papillomavirus (HPV) Vaccination Compared to Auxiliary Health Workers

The viewpoints of Shahid Beheshti University of Medical Sciences medical experts'' were compared with those of auxiliary health workers regarding health culture related to human papillomavirus vaccination in 2020. In this cross-sectional study, 220 medical experts' (gynecologists, cultural, psychological, infectious, dermatological, and educational) and auxiliary health workers were randomly selected and investigated. The required data were collected using a researcher-made questionnaire modeled on international questionnaires. These questionnaire contained demographic information on the subjects' age and sex as well as health culture was also assessed by measuring the knowledge, attitude, and practice of the subjects. The mean age of the included medical experts' and auxiliary health workers was 38.0 3±8.3 and 35.2±7.5 years old, respectively. There was a significant difference in the knowledge of auxiliary health workers as 55.3 ± 3.8 in comparison with the medical experts' as 51.6 3± 6.3 (p <0.002). There was a significant difference on whether changing cultural attitudes about the need for vaccination could be effective on reducing sexually transmitted diseases between the auxiliary health workers  and medical experts'  (p <0.001). There was a significant difference in the knowledge of auxiliary health workers 55.3 ± 3.8 in comparison with the psychology and cultural experts' as 48.5± 6.3, 48.3± 6.8 (p<0.001) respectively. Knowledge among the auxiliary health workers was significantly different from that of psychology and cultural experts' in relation to health culture for human papillomavirus vaccination. It was indicated that these experts need to upgrade their health culture knowledge to increase the rate of community participation in human papillomavirus vaccination.

P16/Ki-67 Dual Staining in Positive Human Papillomavirus DNA Testing for Predictive Diagnosis of Abnormal Cervical Lesions in Northeastern Thai Women

Cervical cancer screening can effectively reduce new cervical cancer cases, including in Thailand. The abnormal results are subsequently referred for colposcopy. To avoid unnecessary colposcopy, an efficient triage is still needed for validation. This study aimed to investigate the overall positivity of cytology-based screening, HPV detection, and p16/Ki-67 dual staining and evaluate different triage strategies for predictive diagnosis of abnormal cervical lesions in northeastern Thailand. Cervical cells were collected from 191 women who came for cervical screening in the gynecological outpatient department during March 2019-February 2020. Pap smear samples were classified into 6 groups including 17 atypical glandular cells (AGC), 21 atypical squamous cells of undetermined significance (ASC-US), 7 atypical squamous cells - cannot exclude HSIL (ASC-H), 26 low-grade squamous intraepithelial lesions (LSILs), 19 high-grade SILs (HSILs) and 101 no squamous intraepithelial lesion (noSIL). Polymerase chain reaction (PCR) was performed for HPV DNA detection. HPV genotyping was determined by reverse line blot hybridization. P16/Ki-67 dual staining was performed by using CINtec PLUS Cytology kit. Biopsies from abnormal screening were collected for surgical pathology classification. High-risk HPV (HR-HPV) infection was 2.97%, 29.41%, 38.10%, 57.14%, 46.15% and 84.21% in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL cytology respectively. P16/ Ki-67 in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL was 0.99%, 5.88%, 9.52%, 42.86%, 26.92% and 63.16%, respectively (P-value < 0.001). Among p16/Ki-67 positive cases, 96.15% (25/26) were infected with HPV and 84.62% (22/26) were HR-HPV. The overall positivity of each and co-testing between cytology or HPV DNA testing or p16/Ki-67 dual staining was evaluated. In each cervical lesion, primary HPV DNA testing showed the highest sensitivity, but low specificity. The combined all HPV/HR-HPV with p16/Ki-67 detection increased the specificity of abnormal cervical lesions. P16/Ki-67 dual stain cytology in HPV-positive women performs well for diagnosis of abnormal cervical lesions and should be considered for management of HPV-positive women to avoid unnecessary colposcopy referrals.

Identification of Malignancy in PAP Smear Samples Using the CGB3 and NOP56 Genes as Methylation Markers

Although various improvements have been made in the reporting of the Papanicolaou (PAP) test in recent years, there remain several challenges that have yet to be addressed in terms of determining a standardized methodology for categorizing atypical squamous cells of undetermined significance (ASC US). The present study focuses on evaluating the performance of the methylation status of two genes (CGB3 and NOP56) using a total of 200 PAP samples, which were divided into the "determined" group, with 78 samples based on cytology, and the "undetermined" group (ASC US), with 122 samples. The promoter methylation status of the CGB3 and NOP56 genes was detected for the 200 PAP samples using methylation specific PCR (MSP). The diagnostic abilities of the CGB3 and NOP56 genes in PAP samples were measured, and receiver operating characteristic (ROC) curves were generated using Python programming language. Based on the validation of CGB3 and NOP56 methylation in the 200 PAP samples, both genes exhibited higher methylation percentages in abnormal samples compared with normal samples. In addition, on the basis of diagnostic performance analysis, the CGB3 gene exhibited the highest sensitivity and specificity in both histology based ASC US and cytology based 'determined' PAP samples, with significant diagnostic abilities [area under the curve (AUC) values of 0.83 and 0.74, respectively, where AUC ≥0.5 was determined to be significant] to distinguish between the "normal" and "abnormal" samples. The findings of the present study will contribute toward identifying a DNA methylation marker for the early detection of abnormal samples before they reach the initial stages of cervical cancer, and should prove to be helpful for clinicians in terms of diagnosing patients whose cells are ASC US..

Association between Prestored Smartphone Monitored Physical Activity and the Risk of HPV Infection and Cervical Cancer

This study was to determine the prevalence of HPV in non-vaccinated women from East China, and the association between prestored smartphone monitored physical activity and the risk of human papillomaviruses (HPV) infection and cervical cancer. We retrospectively reviewed medical records of unvaccinated women received first-time cervical HPV screening in the Affiliated Cancer Hospital of University of Chinese Academy of Sciences between March 2018 and December 2019. HPV genotyping was examined by the GenoArray. Physical activity defined by any movements at speeds of 0.5-2 m/s was obtained from smartphones. We collected prestored physical activity data for 6 months prior to the HPV screening. Logistic regression models were applied to determine the association between physical activity and the risk of HPV infection and cervical cancer. A total of 11,730 women were initially included. Women with cervical cancer had significantly higher prevalence of infection with any high-risk (HR) HPV, or with individual HPV16, 18, 31, 33, 45, 52 and 58. Among them, 896 controls and 289 cervical cancer women had information of smartphone monitored physical activity. Multivariate logistic regression analysis showed that more daily physical activity time (or distance) was a protective factor for infection with any HR HPV, or infection with HPV16, but not other individual HPVs. Increased age, less physical activity time (or distance), and infection with any HR HPV (16, 18, 31, 52 and 58) were associated with a significantly increased risk of cervical cancer. In contrast, obesity was not associated with risk of HPV infection and cervical cancer. The high prevalence of HPV infection in unvaccinated women highlights the importance of prevention. More daily physical activity time (or distance) may help to reduce the risk of HPV infection and cervical cancer. Smartphone monitoring is an effective tool for recording physical activity..

The Trend and Prediction of Cervical Cancer Incidence in Delhi, India: An Age-Period-Cohort Analysis

The objective of the study is to assess the trend of age-standardised incidence rate (ASIRs) of cervical cancer, standardised median age at diagnosis, and projection of cervical cancer incidence rate and the number of new cases up to 2030. The projections help in making strategies for resource allocation to circumvent the future burden. The data were extracted from the Delhi population-based cancer registry from 1990 to 2014. Joinpoint regression analysis was applied to ASIRs to assess the trend. The natural cubic splines age-period-cohort (APC) model was fitted to project the incidence rate and incidence cases. The trend of standardised median age at diagnosis and percentage of cervical cancer to total women cancer was also assessed using regression analysis. Projections of new cases are decomposed into three components aging, the structure of the population, and age-specific incidence rate. The age-standardised incidence rate of cervical cancer decreased with an annual decline at a rate of 2.98% (95% CI -3.48 to -2.47) from 1990 to 2014. The standardised median age at diagnosis showed an upward trend with an average annual increase of 0.167 per year and the median age increased by 4.18 years during 25-years period, this change was due to the shifting of the peak from 40-44 in 1990 to 60-64 in 2014. The APC model revealed ASIRs would decline by 43.8% in 2030 compared to average ASIRs 2010-2014, albeit a net 12% increase in the incidence cases. An increase in incidence cases is primarily attributed to the aging of the population and population  growth by 38.87% and 33.84% respectively.  The trend analysis of  cervical cancer ASIRs in pre (< 50 years) and post menopause (≥ 50 years) showed a decreasing trend. However, the ratio of cervical to total women increased over time from 1:1 in 1990 to 2:3 in 2014. The declining trend in ASIRs was observed in Delhi and will continue to decrease up to 2030.  The burden of the number of new cases of cervical cancer showed an upward trend primarily due to the aging of the population and shifting of population structure. To counter this big challenge a cost-effective vaccination for vulnerable populations, community-based screening programs, and awareness about cervical cancer prevention might help in eliminating this preventable cancer.

Prevalence and Predictors of Cervical Cancer Screening among Reproductive Age Group Women: Evidence from Cross-Sectional Study in Rohtak and Delhi

The present study aims to estimate the prevalence and determine the factors for cervical cancer screening among women in the reproductive age group in Delhi and Rohtak, India. The data were utilized from a survey conducted as part of a larger study to increase the access to cervical cancer screening and care by MAMTA-Health Institute for Mother and Child in collaboration with the Health Departments of Palam, New Delhi, and Rohtak, Haryana between 2015 and 2017. Data pertaining to the socio-economic and demographic information along with the information related to cervical cancer screening were utilized for the present study. The sample size was 1020 women in reproductive age group. Descriptive statistics (percentage and frequency distribution), bivariate analysis along with multivariable analysis were done to represent the results.  The Fisher exact test was used to test the level of significance during bivariate analysis. About 35.2% [Delhi: 44.9% and Rohtak: 23.8%] of the respondents had heard about cervical cancer screening. Further about 3.9% [Delhi-2.9% and Haryana-5.1%] had screened for cervical cancer. Women who had heard about cervical cancer were five times more likely to go for screening [aOR: 5.27; CI: 2.53,10.96]. It was found that women over 30 years of age had 12.04 significantly higher  odds of going for cervical cancer screening in reference to women aged 30 years and less [aOR: 12.04; CI: 3.01,53.20]. Women from households with a monthly income of more than 15000 had 2.98  significantly higher odds of going for cervical cancer screening in reference to women from households with an income of 5000 and less [aOR : 2.98; CI: 1.12,9.09]. Findings suggest that awareness about cervical cancer screening test along with its thorough knowledge about its benefits would be an effective intervention to increase the uptake of cervical cancer screening.

Prevalence of Tissue BRCA Gene Mutation in Ovarian, Fallopian Tube, and Primary Peritoneal Cancers: A Multi-Institutional Study

Ovarian, fallopian tube, or primary peritoneal cancer patients with BRCA gene mutation have enhanced sensitivity to platinum-based regimens and PARP inhibitors. However, the knowledge regarding BRCA mutation in Thai patients is limited. This study aimed at identifying the prevalence and characteristics of somatic and germline BRCA 1 and 2 mutations in Thai patients with these cancers. The paraffin blocks of tumors with histology of high grade serous, high grade endometrioid, or clear cell carcinoma obtained between June 2016 and December 2017 were analyzedto evaluate BRCA mutation using next-generation sequencing system. Blood or normal tissue paraffin blocks of positive patients were further tested for germline BRCA mutation. Tissue paraffin blocks of 178 patients were collected but only 139 were analyzed. Positive BRCA mutation was identified in 24 patients (17.3%): BRCA1 in 13 cases, BRCA2 in 10 cases, and BRCA1 and 2 in the rest one. Germline mutation study in blood or normal tissue in 23 positive patients revealed BRCA mutation in 14 cases, BRCA1 in 8 cases and BRCA 2  in 6 cases. Overall, the prevalence of somatic and germline mutation was 6.5% (9 out of 138 patients) and 8.7% (14 out of 138 patients), respectively. The most common histology associated with BRCA mutation was high grade serous cancer (27.3%). No significant difference was found between patients with or without BRCA mutation in terms of stage, outcome, platinum status, and survival outcome. BRCA mutation was demonstrated in less than 10% of Thai ovarian cancer patients. Higher rate of mutation was found in high grade serous cancer..

Quality of life and Its Determinants among Cervical Cancer Patients in South India

Cervical Cancer is the leading cause of morbidity and mortality in India. It affects the patient's, physical and psychological state which results in lower quality of life (QoL). Women with cervical cancer may require counselling and time to enable them to deal with the disease and its treatment. The present study aimed to determine the quality of life and its determinants among cervical cancer patients. A cross-sectional study was undertaken from April 2017 to September 2017 in a regional cancer centre in South India. Cervical cancer patients (N= 210) with histological confirmation were interviewed at the hospital. European Organization of Research and Treatment of Cancer (EORTC) questionnaire core module, QLQ-C30 Version 3.0, and recommended scoring algorithm were used to measure and analyse QoL. The Association of socio-economic determinants on quality of life was evaluated using multiple logistic regression. Among 210 cervical cancer patients enrolled, the majority 106 (50.5%) of women were between the age group 46 to 59 years and most, i.e.  167(63.0%) were not literate. The median score in the global health status was 50.0[IQR 33.3 - 66.7], 66.7[IQR 60.0 - 80.0] in physical functioning, and 83.3[IQR 66.7 - 83.3] in pain symptoms respectively which were poor compared to reference score of EORTC for all normal females and those with any cancer. The factors which were significantly associated with the GHS QoL score were the advanced stage of disease (OR:2.1, 95%CI: 1.1 - 3.9) and the age of the patients ≥60 years compared with ≤ 45 years (OR:18.4, 95%CI: 6.8 - 50.1). Cervical cancer patients had poor global health status compared to the reference score for all females with any cancer and the normal females. Advanced stage of cancer and older age have a significant association with QoL.

Genotype Distribution and Prevalence of High-Risk Human Papillomavirus Infection among Women in Samsun Province of Turkey

The human papillomavirus (HPV) is an important public health problem that can cause cervical cancer. HPVs were classified into high-risk (HR-HPV) and low-risk (LR-HPV) types. In this study, we aimed to determine the prevalence and genotype distribution of HR-HPV infection in Samsun province in Turkey. Cervical smear samples taken from 5406 women over a 23-month period were evaluated for the presence of HPV infection. The detection of HPV genotypes was performed using RT-PCR technology. HPV detection and genotyping were performed using RT-PCR method. HR- HPV types are divided into 3 groups as type 16,  type 18 and other types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, with or without type 16 and 18).  The results were evaluated statistically. The mean age of HR-HPV positive patients was 39.56 years (20-68 years). The prevalance of HR-HPV types did not differ between different age groups (p˃0.05). Overall, 9.17% of women (496/5406 samples) were found to be positive at least one type of HR-HPV. HPV type 16 was detected in 28.62%, type 18 in 9.67%, and other types in 78.83%. The most common HR-HPV type was other types (p˂0.001). Type 16 was most common than type 18 (p˂0.001). The patients were evaluated by dividing them into 6 age groups. Type 16 positivity was higher in 30-39 ages while type18 and other types positivity were higher in the 40-49 age group. When the 23-month period of HPV test was evaluated according to months and seasons, the highest prevalance was seen in June 2021 and Summer 2021. To our knowledge, this is the first large-scale study of HR-HPV prevalence and genotype distribution among women in Samsun Province of Turkey.  The other types containing one or more types made up the majority of the studied population.

Human Papillomavirus Type 16 L2 Gene Sequence Variation Analysis in Indonesian Cervical Cancer Specimens

Human papillomavirus type 16 (HPV16) is the most prevalent etiology of cervical cancer in Indonesian women. The L2 minor capsid protein has considerable potential as a broad-protective antigen target of the cervical cancer vaccine strategies, yet the data on L2 gene variation is still minimal. In this research, we determined the variations of the HPV16 L2 gene sequences in Indonesian cervical cancer specimens. We cross-sectionally observed 23 DNA isolates of HPV16 positive cervical cancer specimens stored in the laboratory of the Center for Diagnostic and Research on Infectious Diseases (PDRPI Lab), Faculty of Medicine, Universitas Andalas, Padang, Indonesia. We detected and amplified the HPV16 L2 gene sequences in the samples, followed by sequencing, DNA alignment, single nucleotide polymorphisms (SNPs) analysis, and phylogenetic tree reconstruction. As many as 35 SNPs were found, consist of 18 synonymous SNPs (sSNPs) and 17 non-synonymous SNPs (nsSNPs). Amino acid variations were mostly detected at S269P (100%) and L330F (43.48%) with no variation in the immuno-protective region near L2 N-terminus. A total of 5 HPV16 phylogenetic sub-lineages were found closely related to A1 (n=5), A2 (n=12), A3 (n=2), A4 (n=3), and C (n=1). The variations of HPV16 L2 gene sequences are mainly located in the central region of the L2 sequences, and the cross-protective region near the L2 N-terminus is remarkably conserved. This study should enhance the information about HPV16 L2 gene variation in Indonesia.

The Short-Term Impact Of COVID-19 Pandemic on Cervical Cancer Screening: A Systematic Review and Meta-Analysis

A systematic review and meta-analysis were carried out to assess the pooled proportion of women screened for cervical cancer before and during the COVID-19 pandemic. After ruling out registered or ongoing systematic reviews in the PROSPERO database regarding the impact of the COVID-19 pandemic in cervical cancer screening, the protocol of our systematic review and meta-analysis was registered in PROSPERO (CRD42021279305). The electronic databases were searched for articles published in English between January 2020 and October 2021and the study was designed based on PRISMA guidelines updated in 2020. Meta-analysis was accomplished in STATA version 13.0 (College Station, Texas 77,845 USA). The pooled proportion of women who had undergone cervical cancer screening was reported with 95% CI. In order to quantify the heterogeneity, Chi2 statistic (Q statistic) and I2 index were used. The meta-analysis included seven studies from Slovenia, Italy, Ontario (Canada), Scotland, Belgium, and the USA, comprising 403,986 women and 199,165 women who were screened for cervical cancer before the COVID-19 pandemic in 2019 and during the pandemic in 2020, respectively. The pooled proportion of women screened for cervical cancer in 2019 was 9.79% (95% CI 6.00%-13.59%, 95% prediction interval 0.42%-23.81%). During the pandemic, the pooled proportion of screened women declined to 4.24% (95% CI 2.77%-5.71%, 95% prediction interval 0.9%-17.49%). There was a substantial drop in the cervical cancer screening rate due to lockdowns and travel restrictions to curb the COVID-19 pandemic. Scaling up cervical cancer screening strategies is essential to prevent the long-term impact of cervical cancer burden.

Efficacy of Oral Zinc Sulfate Supplementation on Clearance of Cervical Human Papillomavirus (HPV); A Randomized Controlled Clinical Trial

Human Papillomavirus is one of the most crucial infectious disease in gynecology disease. To assess the efficacy of supplemental zinc treatment in clearance of HPV infection. Eighty zinc-sufficient women between 21-55 years, with positive HPV DNA testing, and abnormal cervical cytology in Pap test (ASCUS or LISL) were randomly divided to case (n=40) and control group (n=40). Case group received oral tablets of zinc sulfate twice a day for 3 months while control group received no placebo. During follow-up patients underwent repeat HPV DNA test and PAP test and were evaluated for clearance/persistence of HPV infection and regression/progression in the lesion grading. As far as demographics, serum zinc levels and the relevant risk factors for persistence of HPV were concerned, there was no significant difference between two groups, except for the frequency distribution of HR-HPV which was significantly higher in case  group. Zinc treatment for 3 months reduced the risk of persistence of HPV infection and progression from baseline cytology (OR = 0.130) (CI 95% 0.04-0.381; p <0.001) and 0.301 (95% CI 0.777-0.116; p = 0.012), respectively. Age, initial cytology, HPV type, and contraceptive method were not related to persistence of HPV. Serum zinc levels increased in the casr group as a result of oral zinc consumption for 3-month period, though without any statistical significance (p = 0.407). The results of the following study suggested that oral intake of zinc sulfate supplement for 3 months increases the rates of HPV clearance and resolution of pre-existing cervical lesion.

Geographic Characteristics of Various Cancers in Yogyakarta Province, Indonesia: A Spatial Analysis at the Community Level

Cancer remains a significant public health problem in Indonesia and worldwide. Yogyakarta Province has the largest number of cancer cases in Indonesia. Maps of the distribution of cancer cases are useful tools for stratification of cancer risk and for selective prevention strategies. The aim of this study was to determine the spatial distribution of cancer cases in Yogyakarta Province. Cancer patient data registered by the Yogyakarta Provincial Health Office during 2019-2020 were analysed in this study (n=9,933). To evaluate cancer pattern distributions, ArcGIS 10.2 and Excel 2016 software were used. The mean participant age (± standard deviation) was 55.08 ± 15.46 years, and 79.40% were female. Breast and cervical cancer were the most frequently diagnosed, and the majority of patients were located in Sleman district. The incidence of all cancer types varied by county-level. The majority of cancer patients lived below the poverty line. Cancer screening rates were low, and screening was limited to breast and cervical cancer. Various types of cancers were identified in Yogyakarta, Indonesia; of them, breast and cervical cancer predominated. Most of the cancer patients were from Sleman district and economically poor areas. Geospatial techniques are useful for identifying environmental factors related to cancer and improving cancer control strategies and resource allocation.

Impact of Polymorphism in Base Excision Repair and Nucleotide Excision Repair Genes and Risk of Cervical Cancer: A Case-Control Study

Last few years, several studies all over the world revealed the association of DNA repair genes with risk of developing different type of cancers, but were ambiguous to support the evidences in case of cervical cancer risk. These differences in earlier studies directed us to study the association of polymorphisms of BER genes (XRCC1, hOGG1, XPC) and NER genes (XPC, XPD) with cervical cancer susceptibility in the women of rural population of Maharashtra. The genetic polymorphism in BER and NER pathway genes was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using DNA isolated from intravenous blood samples of patients and normal controls. The study included 400 clinically confirmed cervical cancer patients and 400 healthy women from a tertiary care hospital (Krishna Hospital and Medical Research Centre) of south-western Maharashtra. The association of polymorphisms was confirmed by Odds ratio (OR) with 95% confidence interval. The single nucleotide polymorphism (SNP) of BER genes including XRCC1, hOGG1 and APE1 were analyzed and the results were noted that 27466AA (OR=4.88; 95% CI: 3.61- 6.60; p<0.0001) and 28152AA (OR=2.89; 95% CI: 1.57- 5.31; p=0.0005) genotypes of XRCC1 (rs25489, rs25487) were significantly associated with cervical cancer risk. The 1245GG genotype of hOGG1 (rs1052133) (OR=45.30; 95% CI: 3.76- 7.46; p=0.001) also showed significant correlation, whereas 2197GG genotype of APE1 (rs1130409) gene showed negative association with cervical carcinogenesis (OR=0.59; 95% CI: 0.35- 0.97; p=0.005). Similarly when we studied SNPs of NER genes including XPC and XPD genes, 21151TT genotype of XPC (rs 2228000) was positively associated with cervical cancer development and 23591AA genotype of XPD (rs1799793) showed negative association (OR=0.34; 95% CI: 0.17- 0.64; p=0.001). The findings from this study supported that rs25489, rs25487SNPs of XRCC1, rs1052133 of hOGG1 and rs2228000 of XPC may increase cervical cancer risk, whereas rs1130409 SNP of APE1 and rs1799793 SNP of XPD gene lower the risk of cervical cancer in the studied population.

Women’s Knowledge on Cervical Cancer Risk Factors and Symptoms: A Cross Sectional Study from Urban India

Early-stage cervical cancer diagnoses may be the consequence of timely medical care in the presence of symptoms which can be linked to awareness of the symptoms and risk factors. This study aims to determine the knowledge about risk factors and symptoms of cervical cancer and associated factors among women aged 20-49 years. Data were utilized from the survey under the intervention "Increasing access to cervical cancer screening and care through the community-centric continuum of care initiative in India" (2015). The sample size was 1,020 women in the age group of 20-49 years. Descriptive statistics, along with bivariate analysis, was done to represent the preliminary results. Multivariable regression analysis was used to represent the estimates. About 40.1% [Delhi: 56.9% and Rohtak: 20.4%] and 45.5% [Delhi: 52.2% and Rohtak: 37.7%] of respondents had good knowledge about risk factors and symptoms of cervical cancer, respectively. Respondents with primary educational status had an 86% significantly higher likelihood for good knowledge about identified risk factors of cervical cancer [ adjusted odds ratio (aOR): 1.86; CI: 1.12-3.10]. Respondents who were married or widowed/divorced/separated had significantly higher odds for good knowledge about identified risk factors and symptoms of cervical cancer in reference to respondents who were never married. Respondents from Rohtak had 72% and 35% significantly higher odds for good knowledge about identified risk factors [aOR:0.28; CI: 0.21,0.39] and symptoms [aOR:0.65; CI: 0.48,0.88] of cervical cancer, respectively, in reference to respondents from Delhi. Overall awareness about cervical cancer and Human papillomavirus (HPV) as the causative agent was low, more so in Rohtak. This is extremely worrisome as blocking HPV infection is one of the most effective ways to prevent cervical cancer. Moreover, the knowledge about the risk factors and symptoms of cervical cancer is also inadequate, particularly in women from Rohtak.

Comparison between Single Versus Twice Application of Topical 85% Trichloroacetic Acid in the Treatment of Cervical Intraepithelial Neoplasia; A Randomized Clinical Trial on Efficacy and Tolerability

To compare the efficacy and safety of up to two-time administration of 85% TCA, as a promising alternative therapy to conservative and surgical management of grade one to three CINs. In this two-armed randomized clinical trial, a total of 53 patients with biopsy-proven CIN lesions were allocated to two groups of TCA treatment. The first group (n=26) received a single dose of local therapy with 85% TCA while the second group (n=27) was treated on two separate occasions with a two-week interval. Two participants (one in each group) were lost to follow-up. At the two-month follow-up after TCA application, a colposcopy-guided biopsy was performed for all patients and the pathological specimens were studied by a single experienced pathologist to determine the post-intervention grading of CIN. Two groups were comparable in terms of age and base-line lesion grading, as CIN 1 lesions comprised the majority of cases (54%), followed by CIN 2(37%). While our sample was a poor representative of CIN3 lesions (7%), no significant difference was noticed between the single and twice TCA treated groups with a response rate of 52% and 54% respectively (either complete remission to normal histology or regression to any low-grade lesion). Either separate analysis (with respect to the base-line grading within each treatment group) or combined analysis (regardless of CIN sub-group) could not generate any statistical significance. The second dose of TCA did not increase the frequency of reported adverse events. The second dose of topical 85% TCA does not seem to increase the CIN response rate more so than its single dose. However, further controlled clinical trials with larger samples are warranted to verify current findings. The use of TCA was not limited by any major side effect, therefore, the potential to achieve an increased efficacy with more frequent TCA applications is appealing.

The Acceptance of Human Papillomavirus Self-Sampling Test among Muslim Women:A Systematic Review

Human Papillomavirus (HPV) self-sampling test has the potential to increase cervical cancer screening rate. Although every screening test has its own advantages and disadvantages, culture and religion can be significant predictors for the acceptability of screening tests among patients, including the HPV self-sampling test. This systematic review intends to identify and review published literature on the acceptance of HPV self-sampling test among Muslim women globally. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) review protocol was utilised to guide this systematic review. We also used the Mixed Method Appraisal Tool (MMAT) for the evaluation of articles, and data from selected papers were retrieved and analysed using thematic analysis. This systematic review includes seven publications that discussed on Muslim women's perceptions of HPV self-sampling test. This comprises articles that revealed Muslim women's acceptance of the HPV self-sampling test, including considerable positive factors that influenced their approval. On the other hand, the test's disadvantages were mentioned, which served as barriers for these women's participation. Convenience, cultural sensitivity, and availability were positive features, whereas religious taboo, low self-confidence, and perceived cost were some of the negative factors that were discussed. This review emphasises the positive and negative aspects that have an impact on the acceptance of HPV self-sampling test among Muslim women. Identifying the elements that influence HPV self-sampling test acceptance will help policymakers to better understand cervical cancer screening programmes and further guide future plans in reducing the incidence of cervical cancer.

The Appropriate of Cone Depth in Loop Electrical Excision Procedure (LEEP) for Negative Pathological Margin from High Grade Precancerous Lesion of Cervix, Retrospective Study

To determine the appropriate cone depth for treating high grade precancerous lesions to achieve negative pathological margins of cones from LEEPs. Other factors associated with positive pathological margin were also investigated. A Retrospective study recruited 170 patients who received indications for LEEP during January 2015 to July 2020 were enrolled. The participants were operated by a single cut of LEEP and not had previously conization before. All patient data were collected into two groups, including negative and positive cone margin groups. Then, we used the cone depth by calculating from cone tissue after formalin fixation to eliminate shrinkage effect. The appropriate cut-off points for cone depth were calculated by ROC and analyzed factors that influence positive cone margin. The depth of cone (mm ±SD) of negative margin group was 8.70 (±3.36) and 6.13 (±2.28) mm in positive margin group. The appropriate cut-off points for cone depth were calculated by ROC presented at resection depth of 7.21 mm, which displayed proper cone depth with a sensitivity of 63.53% and specificity of 71.76%. Elderly age (adjusted OR 1.061, 95%CI 1.008-1.117, p=0.002), number of quadrants of lesion involvement (adjusted OR 1.182, 95%CI 1.312-2.513, p=<0.001) and glandular involvement (adjusted OR 3.648, 95%CI 1.605-8.292, p=0.002) were the significant risk factors for positive margin. The appropriate cone depth for treating high grade precancerous lesions was at least 7.21 mm to achieve a negative cone margin from LEEP. The significant factors associated with positive cone margin include elderly age, more quadrants of lesion involvement and glandular involvement.

A Phytochemicals Approach Towards the Treatment of Cervical Cancer Using Polyphenols and Flavonoids

Despite enormous progress in cancer biology, oncologists are still struggling to retrieve the methods and drugs to cure cancer which remains a global threat to humans. Plant-derived natural compounds, also known as phytochemicals, carry therapeutic potential and could be taken as dietary supplements, which are a radical way to resist as well as cure cancer. The present study reveals the anti-cancerous potential of a few phytochemical constituents under in vitro conditions and their mode of action on cervical cancer. SiHa was treated with phytochemicals viz. Quercetin dihydrate, Gallic Acid, and Naringin with varying concentrations to assess their cytotoxicity potential by various methods and also to elucidate their IC50 values. All three compounds reduced the cell number and viability, along with alterations in cancer cell morphology. The diagnosed IC50 values of the compounds were 160µM, 200µM, and 1500µM for Quercetin dihydrate, Gallic Acid, and Naringin, respectively. DNA fragmentation assay and gene expression analysis were also used to assess apoptosis and anti-proliferative activity of compounds. We found fragmented DNA in treated cells as assessed by gel electrophoresis assay. These phytochemicals elicit an apoptotic response in SiHa cells by significantly up-regulating the gene expression level of p53 and p21 (p-value <0.005). Considering the anti-cancer and anti-proliferative potential of Quercetin dihydrate, Gallic Acid, and Naringin on the cervical cancer cell line, these phytochemicals could be used as an alternative or concurrent cancer therapeutic approach. However, further in-depth elucidation of their mode of action, safety, and efficacy should be explored.

Anti Proliferative and Apoptotic Effect of Soluble Ethyl Acetate Partition from Ethanol Extract of Chromolaena Odorata Linn Leaves Against Hela Cervical Cancer Cell line

Cervical cancer is the leading cause of cancer death in women. Chemotherapy is one of the treatment modalities with many side effects. This study aimed to evaluate the anticancer activity of soluble ethyl acetate partition of Chromolaena odorata (C. odorata) leaves on HeLa cells of cervical cancer. The cytotoxicity activity of the soluble ethyl acetate extract of the C. odorata leaves was analyzed by MTT colorimetry assay. The apoptosis activity was determined by double staining and flow cytometry techniques. Doubling time assay was used to observed HeLa cells proliferation. The IC50 of soluble ethyl acetate partition of this plant was 82.41± 6.73 µg/ml against HeLa cells. The apoptosis activity showed that HeLa cells underwent morphological changes in dose-dependent manner while the highest number of dead cells was observed after treatment with 500 µg/ml of the partition. Flow cytometry analysis showed that treatment with IC50 and 2x IC50 resulted in death of more than 97% cells (p-value <0.05 in both comparisons). Proliferation of HeLa cells was also inhibited following treatment with ½ IC50, IC50, and 2xIC50 in the first 24 hours (p-value <0.05 in all comparison). The findings of this study suggested that the soluble ethyl acetate partition from ethanol extract of C. odorata leaves had cytotoxic and antiproliferative properties against HeLa cells.

Detection of Global DNA Methylation in Cervical Intraepithelial Neoplasia and Cancerous Lesions by Pyrosequencing and Enzyme-Linked Immunosorbent Assays

Cervical cancer is one of the most significant cancer found in women worldwide especially in developing countries. Previous reports showed that global DNA hypomethylation was correlated with various types of cancer including cervical cancer. Long interspersed nuclear element-1 (LINE1) pyrosequencing and Enzyme linked-immunosorbent assay (ELISA) assays were used for detection of global DNA methylation. The ELISA results were compared to bisulfite LINE1 pyrosequencing assay. Different cervical cancer cell lines (CaSki, SiHa, HeLa, ME180, MS751, C33A) showed low global methylation percentage when compared to normal white blood cells by ELISA assay (1.47%-5.09% vs 8.20%, respectively) and by LINE1 pyrosequencing (20%-45% vs 62%, respectively). Global DNA methylation levels in cervical cancer samples were lower than precancerous lesions (Normal-CIN3) by LINE1 pyrosequencing (mean, 48.8% vs 56.9%, respectively, p<0.05) and ELISA assay (mean, 3.03% vs 3.85%, respectively, p<0.05). Global DNA hypomethylation was predominantly found in cervical cancer samples detected by ELISA and LINE1 pyrosequencing assays and could be used as triage tests in cervical cancer screening. ELISA assay is a suitable method for detection of global  DNA methylation in large population; however, it should be further evaluated in a large clinical samples in order to be used as screening method.

Detecting Human Papillomavirus Type 16 in Cervical Cancer Patients with Molecular Variation of Gene L1 in Riau Province Indonesia

Cervical cancer is the second most deadly cancer in the world after breast cancer. The cancer is caused by infection of high risk Human Papillomavirus (HPV) type 16. It is often found in cervical cancer of which the genome structure is composed of L1 proteins. The L1 protein makes up the viral capsid that has an important role in causing the cervical epithelium. Several studies have found the differences in HPV nucleotides variants that lead to changes in amino acids that disrupt the structure, the natural function of the virus itself, and ultimately lead to changes in biological functions including host immunological recognition. Variation of the L1 gene also affects the effectiveness of existing vaccines. This research was a descriptive study conducted at the laboratory of microbiology, the Faculty of Medicine, Universitas Riau, Pekanbaru from February to August 2018. The study was aimed at looking at the molecular variations of the L1 HPV type 16 gene and examining phylogenic kinship. The SNPs (Single Nucleotide Polymorphism) which occurred in 26 sample isolates are the substitution of C/G (6240), A/G (6432), T/G (6686), C/T (6824). These variations also cause changes in amino acids, insertion of ATC nucleotide bases (6902), and deletions of GAT bases (6954). There are  molecular variations of the L1 HPV type 16 gene which can cause different host immune responses. Phylogenic kinship of HPV type 16 isolate in Riau is similar to  Asian-American isolate.

Evaluation of Mismatch Repair (MMR) and Breast Cancer-1 (BRCA-1) Statuses in Epithelial Ovarian Cancer

This study aims to evaluate the expression of BRCA1 and MMR proteins using immunohistochemistry (IHC) in epithelial ovarian cancers and to explore their clinicopathological correlations. IHC was performed and interpreted for BRCA1, MLH1, MSH2, MSH6, and PMS2. The results were then compared with clinical and pathological variables. Over a period of 19 months, 508 specimens containing ovarian tissue were received, either as part of a hysterectomy or as isolated samples for various indications. Among these, 24.01% (122/508) showed invasive epithelial ovarian cancer. Of these, 49 resection specimens had sufficient tumor tissue for detailed immunohistochemistry (IHC) analysis and were included in the study. Among the evaluated cases, 51% (25/49) of invasive epithelial ovarian cancers exhibited deficient mismatch repair (dMMR). No significant correlation was observed between dMMR and pMMR with respect to grade, cellularity, and high-grade features. Patients with dMMR showed better survival, which may be due to improved response to chemotherapy in these cases. Total loss of BRCA1 was seen in 36.7% (18/49) of cases. BRCA1 loss was associated with poor predictive factors but had better prognosis. Loss of BRCA1 was associated with aggressive tumors but had better response to chemotherapy. Both MMR and BRCA1 were independent variables. The overall survival of our patient population with epithelial ovarian cancer was 86.8%. A significant number of patients displayed dMMR and BRCA1 loss by IHC. These patients may benefit from targeted therapy, and IHC may serve as an acceptable technique for each evaluation.

Multimodal Prehabilitation in Indian Women with Advanced Ovarian Cancer: Enhancing Nutritional, Psychological, and Surgical Recovery

Malnutrition is common among women with gynecologic cancers, particularly advanced ovarian cancer, and adversely impacts treatment tolerance, surgical recovery, and quality of life. The neoadjuvant chemotherapy (NACT) phase provides a unique opportunity to introduce prehabilitation interventions to improve perioperative outcomes. To evaluate the feasibility and impact of a culturally tailored, home-based multimodal prehabilitation program on perioperative outcomes in Indian women with advanced ovarian cancer undergoing NACT.  Methods: Sixty women planned for NACT were enrolled and allocated to either a prehabilitation group (n = 30) or control group (n = 30). The intervention include yoga-based physiotherapy, individualized nutritional counseling, and psychological support. Outcomes assessed pre- and post-NACT included body mass index (BMI), hemoglobin, serum albumin, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), skeletal muscle index (SMI), Hospital Anxiety and Depression Scale (HADS) scores, in each group and between group comparisons of perioperative outcomes. Both groups showed significant within-group improvements in nutritional and inflammatory markers. Between-group comparisons revealed a smaller decline in BMI (-1.29 vs. -4.51; p < 0.001) and a greater reduction in HADS scores (-4.5 vs. -1.5; p =0.013) in the prehabilitation group. Hospital stay was significantly shorter in the prehabilitation group (median: 4 vs. 5.5 days;  p = 0.005), while reductions in intraoperative blood loss and postoperative complications did not reach statistical significance. Greater physiotherapy session attendance correlated with reduced BMI loss (ρ = -0.4187, p = 0.022). Multivariable analysis showed that prehabilitation and physiotherapy adherence were associated with smaller BMI declines, and prehabilitation reduced the odds of prolonged hospitalization. Implementing a culturally adapted multimodal prehabilitation program is feasible and improves short-term nutritional, psychological, and perioperative outcomes in women undergoing NACT for advanced ovarian cancer.

Publisher

EpiSmart Science Vector Ltd

ISSN

2476-762X