The Science

The Role of Palliative Surgery in the Management of Acute Intestinal Obstruction Secondary to Peritoneal Carcinomatosis

Current data and future perspectives on DNA methylation in ovarian cancer (Review)

Ovarian cancer (OC) represents the most prevalent malignancy of the female reproductive system. Its distinguishing features include a high aggressiveness, substantial morbidity and mortality, and a lack of apparent symptoms, which collectively pose significant challenges for early detection. Given that aberrant DNA methylation events leading to altered gene expression are characteristic of numerous tumor types, there has been extensive research into epigenetic mechanisms, particularly DNA methylation, in human cancers. In the context of OC, DNA methylation is often associated with the regulation of critical genes, such as BRCA1/2 and Ras‑association domain family 1A. Methylation modifications within the promoter regions of these genes not only contribute to the pathogenesis of OC, but also induce medication resistance and influence the prognosis of patients with OC. As such, a more in‑depth understanding of DNA methylation underpinning carcinogenesis could potentially facilitate the development of more effective therapeutic approaches for this intricate disease. The present review focuses on classical tumor suppressor genes, oncogenes, signaling pathways and associated microRNAs in an aim to elucidate the influence of DNA methylation on the development and progression of OC. The advantages and limitations of employing DNA methylation in the diagnosis, treatment and prevention of OC are also discussed. On the whole, the present literature review indicates that the DNA methylation of specific genes could potentially serve as a prognostic biomarker for OC and a therapeutic target for personalized treatment strategies. Further investigations in this field may yield more efficacious diagnostic and therapeutic alternatives for patients with OC.

A retrospective study on incidence, diagnosis, and clinical outcome of gastric-type endocervical adenocarcinoma in a single institution

Abstract Background Gastric-type endocervical adenocarcinoma is rare but the most common subtype of cervical adenocarcinoma not associated with human papillomavirus. It is more aggressive with a shorter five-year survival rate compared to human papillomavirus-associated usual type endocervical adenocarcinoma. The objectives of our study were to determine the incidence and clinical-pathological characteristics of Gastric-type endocervical adenocarcinoma in a single institution. Methods Twenty four cases of invasive cervical adenocarcinoma were identified between January 2000 and December 2015, from the Saskatoon Health Region pathology database using International Endocervical Adenocarcinoma Criteria and Classification to retrospectively classify endocervical adenocarcinoma. Immunohistochemistry was performed with antibodies for Gastric mucin-6 (MUC-6), p16 INK4a , cyclin-dependent kinase inhibitor 2A (p16), p53 protein (p53), estrogen and progesterone receptors. Clinical and pathological data was retrieved from pathology reports and charts. Statistical analysis was performed using Mann-Whitney U test and Chi-Square test. Results Using the International Endocervical Adenocarcinoma Criteria and Classification criteria, 19 cases (79.2%) were classified as human papillomavirus-associated usual type endocervical adenocarcinoma, and five cases (20.8%) as Gastric-type endocervical adenocarcinoma. In our study 40% of Gastric-type endocervical adenocarcinoma cases presented at stage III compared to none of the usual type endocervical carcinoma cases. All the Gastric-type endocervical adenocarcinoma cases were positive for MUC-6, and negative for p16. 60% Gastric-type endocervical adenocarcinoma cases demonstrated mutant type p53 staining. In contrast, 84.2% of human papillomavirus-associated usual type endocervical adenocarcinoma cases showed block like nuclear and cytoplasmic positivity with p16 antibodies. The Gastric-type endocervical adenocarcinoma group had significantly shorter median survival time than human papillomavirus-associated usual type endocervical adenocarcinoma group, Gastric-type endocervical adenocarcinoma is 22 months compared to human papillomavirus-associated usual type endocervical adenocarcinoma at 118 months ( p  = 0.043). Conclusions In this study, Gastric-type endocervical adenocarcinoma accounted for 20.8% of all cervical adenocarcinoma with higher stage at presentation and shorter overall survival. Criteria proposed by International Endocervical Adenocarcinoma Criteria and Classification (IECC) are simple and reproducible in differentiating between, HPV- associated (HPVA) and non HPV associated (NHPVA) endocervical adenocarcinoma. Although none of the IHC assays is specific for GAS, but p16, MUC-6, ER, PR and p53 may further aid in confirming GAS and to differentiate it from benign and malignant mimics.

Disparities in the change of cervical cancer mortality rate between urban and rural Chiang Mai in the era of universal health care and the Thai national screening program

Abstract Background The Ministry of Public Health of Thailand established universal health coverage (UHC) in 2002, which also included national-level screening for cervical cancer in 2005. This study examined the changes in mortality of cervical cancer in rural and urban areas in Chiang Mai Province of northern Thailand during the era of UHC and the immediately preceding period. Methods Data of cervical cancer patients in Chiang Mai in northern Thailand, who died from 1998 through 2012, were used to calculate the change in age-standardized rates of mortality (ASMR) using a joinpoint regression model and to calculate estimated annual percent changes (APC). The change in mortality rate by age groups along with changes by geographic area of residence were determined. Results Among the 1177 patients who died from cervical cancer, 13(1%), 713 (61%) and 451 (38%) were in the young age group (aged < 30), the screening target group (aged 30–59) and the elderly group (aged ≥60), respectively. The mortality rate among women aged 30–59 significantly declined by 3% per year from 2003 through 2012 (p < 0.001). By area of residence, the mortality rate in women targeted by the screening program significantly decreased in urban areas but remained stable in more rural areas, APC of − 7.6 (95% CI: − 12.1 to − 2.8) and APC of 3.7 (95% CI: − 2.1 to 9.9), respectively. Conclusion The UHC and national cervical cancer screening program in Thai women may have contributed to the reduction of the mortality rate of cervical cancer in the screening target age group. However, this reduction was primarily in urban areas of Chiang Mai, and there was no significant impact on mortality in more rural areas. These results suggest that the reasons for this disparity need to be further explored to equitably increase access to cervical cancer services of the UHC.

Asymmetric Power Relations in Gynaecological Consultations for Cervical Cancer Prevention: Biomedical and Gender Issues

A generic qualitative research, using a poststructuralist feminist perspective, was conducted in a Spanish gynaecology unit with the following aims: (a) to analyse how asymmetric power relations in relation to biomedical knowledge and gender shape the medical encounters between gynaecologists and women diagnosed with cervical intraepithelial neoplasia and (b) to explore the cognitive, moral, and emotional responses expressed by patients. A total of 21 women diagnosed with cervical intraepithelial neoplasia were recruited through purposive sampling. Semi-structured interviews were recorded and transcribed, and a thematic analysis was carried out. Two major themes were identified: (a) gendered relations in cervical intraepithelial neoplasia medical encounters are based on hidden, judgmental moral assumptions, making women feel irresponsible and blamed for contracting the human papillomavirus infection; (b) biomedical power is based on the positivist assumption of a single truth (scientific knowledge), creating asymmetric relations rendering women ignorant and infantilised. Women reacted vehemently during the interviews, revealing a nexus of cognitive, moral, and emotional reactions. In medical encounters for management of cervical intraepithelial neoplasia, patients feel they are being morally judged and given limited information, generating emotional distress. Healthcare professionals should question whether their practices are based on stereotypical gender assumptions which lead to power asymmetries during encounters.

IL-6 regulates epithelial ovarian cancer EMT, invasion, and metastasis by modulating Let-7c and miR-200c through the STAT3/HIF-1α pathway

Interleukin-6 (IL-6) and hypoxia-inducible factor-1α (HIF-1α) play important roles in epithelial-mesenchymal transformation (EMT) and tumor development. Previous studies have demonstrated that IL-6 promotes EMT, invasion, and metastasis in epithelial ovarian cancer (EOC) cells by activating the STAT3/HIF-1α pathway. MicroRNA (miRNA) is non-coding small RNAs that also play an important role in tumor development. Notably, Let-7 and miR-200 families are prominently altered in EOC. However, whether IL-6 regulates the expression of Let-7 and miR-200 families through the STAT3/HIF-1α signaling to induce EMT in EOC remains poorly understood. In this study, we conducted in vitro and in vivo investigations using two EOC cell lines, SKOV3, and OVCAR3 cells. Our findings demonstrate that IL-6 down-regulates the mRNA levels of Let-7c and miR-200c while up-regulating their target genes HMGA2 and ZEB1 through the STAT3/HIF-1α signaling in EOC cells and in vivo. Additionally, to explore the regulatory role of HIF-1α on miRNAs, both exogenous HIF blockers YC-1 and endogenous high expression or inhibition of HIF-1α can be utilized. Both approaches can confirm that the downstream molecule HIF-1α inhibits the expression and function of Let-7c and miR-200c. Further mechanistic research revealed that the overexpression of Let-7c or miR-200c can reverse the malignant evolution of EOC cells induced by IL-6, including EMT, invasion, and metastasis. Consequently, our results suggest that IL-6 regulates the expression of Let-7c and miR-200c through the STAT3/HIF-1α pathway, thereby promoting EMT, invasion, and metastasis in EOC cells.

Genomic and Molecular Characteristics of Ovarian Carcinosarcoma

Ovarian carcinosarcoma (OCS) is a rare malignancy with a poor prognosis. It is a biphasic tumor with malignant epithelial and mesenchymal components. A few mutations commonly seen in cancer have been identified in OCS, including TP53, PIK3CA, c-myc, ZNF217, ARID1A, and CTNNB1. Some OCS tumors have shown vascular endothelial growth factor positivity and limited HER2 expression. There is evidence of homologous recombination deficiency in OCS. This malignancy can be categorized as copy number high but has not been shown to have a high tumor mutational burden. There are mixed findings regarding the presence of biomarkers targeted by immune checkpoint inhibitors in OCS. For treatments other than systemic chemotherapy, the data available are largely based on in vitro and in vivo studies. In addition, there are case reports citing the use of poly-ADP ribose polymerase inhibitors, vascular endothelial growth factor inhibitors, and immunotherapy with varying degrees of success. This review paper will discuss the molecular and genomic characteristics of OCS, which can guide future treatment strategies.

Underreported Breast and Cervical Cancer Deaths Among Brought-In-Dead Cases in Zambia

Testing the content for a targeted age‐relevant intervention to promote cervical screening uptake in women aged 50–64 years

Objectives Low uptake of cervical screening in women in their 50s and 60s leaves them at elevated risk of cancer in older age. An age‐targeted intervention could be an effective way to motivate older women to attend cervical screening. Our primary objective was to test the impact of different candidate messages on cervical screening intention strength. Design A cross‐sectional online survey with randomized exposure to different candidate messages. Methods Women aged 50–64 years who were not intending to be screened when next invited were recruited through an online panel. Those meeting the inclusion criteria ( n  = 825) were randomized to one of three groups: (1) control group, (2) intervention group 1, (3) intervention group 2. Each intervention group saw three candidate messages. These included a descriptive social norms message, a diagram illustrating the likelihood of each possible screening outcome, a response efficacy message, a risk reduction message and an acknowledgement of the potential for screening discomfort. We tested age‐targeted versions (vs. generic) of some messages. The primary outcome was screening intention strength. Results After adjusting for baseline intention, social norms ( p  = .425), outcome expectancy ( p  = .367), risk reduction ( p  = .090), response efficacy ( p  = .136) and discomfort acknowledgement messages ( p  = .181) had no effect on intention strength. Age‐targeted messages did not result in greater intention than generic ones. Conclusions There was no evidence that a single message used to convey social norms, outcome expectancy, risk reduction or response efficacy had an impact on intention strength for older women who did not plan to be screened in future.

The Impact of Polycystic Ovary Syndrome (PCOS) on the Risk of Developing Ovarian Cancer and Thyroid Disorders: A Comprehensive Review

Abstract: Polycystic ovary syndrome (PCOS) is a common hormonal disorder that affects women. It is characterized by hyperandrogenism, polycystic ovarian morphology, and other related disorders. It is associated with various health conditions, such as infertility and increased risk of heart problems. Ovarian cancer is also a significant concern, as it is the fifth leading cause of death in women. While there is evidence suggesting a potential association between PCOS and ovarian cancer, the exact nature of this relationship remains unclear. Thyroid disorders, particularly hypothyroidism and Hashimoto's thyroiditis, have also been linked to PCOS. The presence of hypothyroidism can contribute to the development of polycystic ovarian morphology, affecting ovulation and hormone balance. Many works have shown a higher ubiquity of autoimmune thyroid disease in PCOS patients, indicating a potential association between the two conditions. The occurrence of PCOS, hirsutism, and acne underscores the frequency of endocrine disorders in women. This review paper examines the present relevant work on the association between PCOS and ovarian cancer as well as PCOS and thyroid disorders. A systematic literature search was conducted on the internet, such as PubMed, Scopus, and Google Scholar database, to identify peer-reviewed publications pertaining to PCOS, ovarian cancer, and thyroid disorders. While some studies have delineated a significant link between PCOS and ovarian cancer or thyroid disorders, others have yielded inconclusive results. Further research is necessary to establish a definitive causal relationship between these conditions. Understanding the relationship between PCOS, ovarian cancer, and thyroid disorders is crucial for early detection, accurate diagnosis, and effective management of these conditions. Identifying potential risk factors and developing appropriate screening strategies can improve women's health outcomes and reduce the burden associated with these disorders.

Time-synchronized 2-deoxy-2-[18F]fluoro-D-glucose PET/MRI with MR-active trigger and Bayesian penalized likelihood reconstruction: Diagnostic utility for locoregional extension of endometrial cancer

Minimal misregistration of fused PET and MRI images can be achieved with simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI). However, the acquisition of multiple MRI sequences during a single PET emission scan may impair fusion precision of each sequence. This study evaluated the diagnostic utility of time-synchronized PET/MRI using an MR active trigger and a Bayesian penalized likelihood reconstruction algorithm (BPL) to assess the locoregional extension of endometrial cancer. Fifty-five patients with endometrial cancer who underwent pelvic 2-deoxy-2-[ The T classification by time-synchronized PET/MRI was the most concordant with the pathological T classification for the two readers. Time-synchronized PET/MRI had a significantly higher diagnostic performance for deep MI and higher confidence level scores than overlapping PET/MRI for the novice reader (p = 0.033 and p = 0.038, respectively). The differences in bladder dimension on sequential PET/MRI were significantly larger than those on overlapping and time-synchronized PET/MRI (p <0.001). Time-synchronized PET/MRI is superior to conventional PET/MRI for assessing the locoregional extension of endometrial cancer.

Circular RNA circ_0011385 promotes cervical cancer progression through competitively binding to miR‐149‐5p and up‐regulating SOX4 expression

AbstractCircular RNAs (circRNAs), emerging as a new type of non‐coding RNAs, play important roles in cancers. Instead, the functions and mechanisms of circ_0011385 in cervical cancer (CC) are still inconclusive. Microarray data GSE102686 was downloaded from Gene Expression Omnibus (GEO) database, and were utilized to screen out circRNAs differently expressed in CC tissues. Circ_0011385, miR‐149‐5p, SRY‐box transcription factor 4 (SOX4) mRNA expressions in CC tissues and cells were probed by quantitative real‐time PCR (qRT‐PCR). CC cell lines with circ_0011385 knockdown were constructed, and he multiplication, migration, invasion, and apoptosis of CC cells were evaluated by cell counting kit‐8 (CCK‐8) method, transwell assay, and flow cytometry. In addition, the targeting relationships between miR‐149‐5p and circ_0011385 or SOX4 mRNA 3′UTR were probed by dual‐luciferase reporter gene assay and RNA pull‐down assay. The regulatory function of circ_0011385 and miR‐149‐5p on SOX4 expression was studied with western blot. Expressions of circ_0011385 and SOX4 mRNA were raised in CC tissues and cells, while miR‐149‐5p expression was decreased. Knocking down circ_0011385 restrained the multiplication, migration, and invasion of CC cells and induced the apoptosis. Circ_0011385 directly targeted miR‐149‐5p, and SOX4 was the target of miR‐149‐5p, which could be positively regulated by circ_0011385. Circ_0011385 elevates SOX4 expression by targeting miR‐149‐5p, thus participating in promoting the malignant biological behaviors of CC cells.

Ovarian cancer: identifying and managing familial and genetic risk—summary of new NICE guidance

Prognostic factors of 87 ovarian yolk sac tumor (OYST) patients and molecular characteristics of persistent and recurrent OYST

We aimed to explore the characteristics of OYST, particularly for persistent and recurrent OYST, in order to explore potential treatment options and thereby improve patient outcomes. We retrospectively reviewed the clinical records of all patients with OYST at Fudan university Shanghai Cancer Center from December 3, 2005 to November 27, 2020. Furthermore, and performed whole-exome sequencing on 17 paired OYST (including 8 paired persistent and recurrent OYST) tumor and blood samples to elucidate the aberrant molecular features. Totally, 87 OYST patients were included between 2007/03/13 and 2020/11/17. With a median follow-up of 73 [3-189] months, 22 patients relapsed or disease persisted. Overall, 17 patients died with a median overall survival of 21 [3-54] months. Univariate and multivariate analysis revealed tumor histology and residual lesions were independently associated with event free survival and overall survival, cycles to AFP normalization were another independent risk factor for overall survival. For the 8 persistent and recurrent OYST: cancer driver genes including ANKRD36, ANKRD62, DNAH8, MUC5B, NUP205, RYR2, STARD9, MUC16, TTN, ARID1A and PIK3CA were frequently mutated; cell cycle, ABC transporters, HR, NHEJ and AMPK signal pathway demonstrated as the most significantly enriched pathways; TMB, DNA MMR gene mutation and MSI were significantly higher. Mutation signature 11, 19 and 30 were the dominant contributors in persistent and recurrent OYST mutation. Persistent and recurrent OYST associated with poor prognosis, and probably susceptible to immune checkpoint blockade therapy. Molecular characteristics contributed to predict the persistence and recurrence of OYST.

Cell Cycle-Related Centromere Protein F Deficiency Suppresses Ovarian Cancer Cell Growth by Inducing Ferroptosis

Objectives: This study aimed to investigate the involvement of the cell cycle-related protein centromere protein F (CENPF) in the development of ovarian cancer (OC) and explored its relationship with ferroptosis. Design: The databases were analysed to identify differential expression of cell cycle-related proteins between individuals with OC and normal individuals. Immunohistochemistry and statistical analysis were conducted on ovarian tissues obtained from 40 patients with epithelial OC and 20 normal individuals. In vitro experiments were performed using SKOV3 and HEY epithelial OC cell lines. Participants/Materials, Setting, Methods: The mRNA microarray dataset, consisting of GSE14001, GSE54388, GSE40595, and GSE14407, was downloaded from the Gene Expression Omnibus (GEO) database to investigate the genes associated with cell cycle regulation in OC cells. CENPF was selected as the subject of study through differential analysis.Assessed the expression of CENPF in both OC patients and normal ovarian tissues using immunohistochemistry. Lentivirus infection was employed to downregulate CENPF expression, and subsequent experiments including Cell Counting Kit-8 assay, cell cycle analysis, transwell assay, and wound-healing assay were conducted to investigate the effects of CENPF on proliferation, invasion, migration, and cell cycle regulation in OC cells. The reactive oxygen species (ROS) and the malondialdehyde (MDA) assays were performed to assess the involvement of CENPF in cellular redox reactions. Western blot analysis was conducted to examine the expression levels of ferroptosis-related proteins (GPX4, SLC7A11, DMT1, and protein 53 [p53]). Results: By querying and integrating cell cycle-related genes from the GEO database, in silico analyses using The Cancer Genome Atlas database combined with immunohistochemical studies, we discovered that CENPF is upregulated in OC tissues and is related to survival. Downregulation of CENPF inhibited biological function of OC cells, increased intracellular ROS and MDA levels, and downregulated the GPX4 protein and the SLC7A11/xCT protein, but upregulated the DMT1 protein and the tumour p53 expression to induce ferroptosis. Limitations: This study did not investigate ferroptosis-related studies following CENPF overexpression, and the findings have not been validated in animal studies. Conclusions: Our findings demonstrated that the deficiency of CENPF played a crucial anti-oncogenic role in the progression of OC through the mechanism of ferroptosis.

The long non-coding RNA NEAT1 promotes the progression of human ovarian cancer through targeting miR-214-3p and regulating angiogenesis

Abstract Background Angiogenesis and metastasis contributes substantially to the poor outcome of patients with ovarian cancer. We aimed to explore the role and mechanisms of the long non-coding RNA NEAT1 (nuclear enriched abundant transcript 1) in regulating angiogenesis and metastasis of human ovarian cancer. NEAT1 expression in human ovarian cancer tissues and cell lines including SKOV-3 and A2780 was investigated through in situ hybridization. Gene knockdown and overexpressing were achieved through lentivirus infection, transfection of plasmids or microRNA mimics. Cell viability was measured with the cell counting kit-8 assay, while apoptosis was determined by flow cytometry. Cell migration and invasion were evaluated by transwell experiments, and protein expression was determined by western blot assays or immunohistochemistry. Duo-luciferase reporter assay was employed to confirm the interaction between NEAT1 and target microRNA. In vivo tumor growth was evaluated in nude mice with xenografted SKOV-3/A2780 cells, and blood vessel formation in tumor was examined by histological staining. Results NEAT1 was highly expressed in ovarian cancer tissues of patients and cell lines. MiR-214-3p was identified as a sponging target of NEAT1, and they antagonizedeach other in a reciprocal manner. NEAT1-overexpressing SKOV-3 and A2780 cells had significantly increased proliferation, reduced apoptosis, and augmented abilities of migration and invasion, while cells with NEAT1-knockdown displayed markedly attenuated traits of malignancies. Additionally, the levels of NEAT1 appeared to be positively correlated with the expression levels of angiogenesis-related molecules, including Semaphorin 4D (Sema4D), Sema4D receptor Plexin B1, T-lymphoma invasion and metastasis-inducing protein-1 (Tiam1), and Rho-like GTPases Rac1/2/3. In the xenograft mouse model, more NEAT1 expression resulted in faster in vivo tumor growth, more blood vessel formation in tumor tissues, as well as higher expression levels of angiogenesis-related molecules and CD31. Conclusions NEAT1 promotes angiogenesis and metastasis in human ovarian cancer. NEAT1 and miR-214-3p are promising targets for developing therapeutics to treat human ovarian cancer.

Risk stratification and molecular heterogeneity of endometrial cancer and expression profile of TIM-3: A retrospective cohort study

The present study aimed to implement ProMisE classification and risk grouping on a retrospective cohort of 628 patients with endometrial cancer (EC) and determine the molecular heterogeneity across subtypes and subgroups, as well as to investigate the potential beneficiary for TIM-3 checkpoint inhibition in ECs. Protein expressions of p53, MMR, TIM-3 and CD8 were measured by immunohistochemistry, and massively parallel sequencing was conducted for 128 cancer-related genes. Patients were categorized into four ProMisE subtypes: MMR-deficient (MMRd), POLE-ultramutated (POLEmut), p53-wild type (p53wt), and p53-abnormal (p53abn), and were subjected to risk classification. 43 (6.9%) patients belonged to POLEmut, 118 (18.8%) to MMRd, 69 (11%) to p53abn, and 398 (63.3%) to p53wt. Compared to the 2016 stratification system, the 2021 ESGO/ESTRO/ESP risk stratification integrated with molecular classification revealed that 11 patients (11/628, 1.8%) were upgraded due to the p53abn signature, whereas 23 patients (23/628, 3.7%) were downgraded due to the POLEmut signature. JAK1 and RAD50 mutations showed higher frequencies in patients with aggressive phenotypes. RAD51B mutation was significantly related to poor RFS of the p53wt subtype but not of the other three molecular subgroups. TIM-3 expression was detected in 30.9% immune cells (ICs) and 29.0% tumor cells (TCs) in ECs, respectively. It was frequently expressed in POLEmut and MMRd ECs as compared to that in the other two molecular subtypes in TCs and ICs. Our study revealed the molecular heterogeneity across subtypes and subgroups. The new risk stratification system changed the risk grouping of some patients due to the integration of molecular features. RAD51B mutation can further stratify the recurrence risk in the p53wt subtype. Patients with MMRd or POLEmut may benefit most from immunotherapy against TIM-3.

Effect of comorbid mood and anxiety disorders on breast and cervical cancer screening in immune-mediated inflammatory disease

We aimed to examine rates of breast and cervical cancer screening in women with immune-mediated inflammatory diseases (IMID), including inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA) versus a matched cohort with IMID; and examine the association of psychiatric comorbidity with screening in these populations. We conducted a retrospective cohort study in Manitoba, Canada using administrative data. We identified women with IBD, MS and RA, and controls without these IMID matched on age and region. Annually, we identified individuals with any active mood/anxiety disorder. Using physician claims, we determined the proportion of each cohort who had cervical cancer screening within three-year intervals, and mammography screening within two-year intervals. We modeled the difference in the proportion of the IMID and matched cohorts who underwent mammography; and pap tests using log-binomial regression with generalized estimating equations, adjusting for sociodemographics, comorbidity and immune therapy use. We tested for additive interactions between cohort and mood/anxiety disorder status. During 2006–2016, we identified 17,230 women with IMID (4,623 with IBD, 3,399 with MS, and 9,458 with RA) and 85,349 matched controls. Having an IMID was associated with lower (-1%) use of mammography; however, this reflected a mixture of more mammography in the IBD cohort (+2.9%) and less mammography in the MS (-4.8 to -5.2%) and RA (-1.5%) cohorts. Within the IBD, MS and RA cohorts, having an active mood/anxiety disorder was associated with more mammography use than having an inactive mood/anxiety disorder. The MS and RA cohorts were less likely to undergo Pap testing than their matched cohorts. In the absence of an active mood/anxiety disorder, the IBD cohort was more likely to undergo Pap testing than its matched cohort; the opposite was true when an active mood/anxiety disorder was present. Among women with an IMID, mood/anxiety disorder influence participation in cancer screening.

WT1 Positive Ovarian Endometrioid Tumors: Observations From Consult Cases and Strategies for Distinguishing From Serous Neoplasms

Ovarian endometrioid carcinoma, more than any other type of ovarian epithelial malignancy, demonstrates a varied morphology which can cause problems in diagnosis. In tubo-ovarian tumor pathology, WT1 is a commonly used marker as it is consistently expressed in low-grade and high-grade serous carcinomas and is often considered a specific marker of a serous phenotype. However, ovarian endometrioid neoplasms may also express WT1 which may contribute to misdiagnosis. We report our experience with 23 ovarian endometrioid neoplasms (4 borderline tumors, 19 carcinomas), mainly received in consultation, which were WT1 positive (diffuse in 11 cases) which often contributed to misdiagnosis. Endometriosis was identified in the same ovary in 6 cases and squamous elements in 7. We describe strategies for distinguishing such neoplasms, which may exhibit morphologic overlap with serous tumors, from low-grade and high-grade serous carcinomas and stress that a diagnosis of HGSC is unlikely with two grossly and histologically normal fallopian tubes. We also stress that a panel of markers should always be used rather than relying on a single marker and that when the morphology is classical of an endometrioid carcinoma, diagnostic immunohistochemistry is not needed given the potential for confusion in cases showing “aberrant” staining. We also discuss the phenomenon of “aberrant” immunohistochemical staining in endometrioid carcinomas which appears more common than in other ovarian carcinomas.

Artificial intelligence and allied subsets in early detection and preclusion of gynecological cancers

Monomeric myeloperoxidase is a specific biomarker for early-stage ovarian cancer

Menopausal hormone therapy for BRCA mutation carriers: A case for precision medicine

Histone Deacetylation Regulated by KDM1A to Suppress DACT1 in Proliferation and Migration of Cervical Cancer

Objective. Increased expression of KDM1A and decreased expression of DACT1 in cervical cancer cells were noticed in a previous study. This study is aimed at exploring the mechanism behind the KDM1A regulation on DACT1 in cervical cancer cells. Methods. The expression profile of KDM1A and DACT1 in cervical cancer tissues was searched in TCGA database. In vitro experiments verified the effect of KDM1A and DACT1 on proliferation and migration ability of cervical cancer cell lines after cell transfection. The interaction of KDM1A with HDAC1 was identified by coimmunoprecipitation (Co-IP). The expression levels of KDM1A and DACT1 in cervical cancer cell lines were determined by qRT-PCR and western blot. Results. TCGA database showed that cervical cancer tissues had elevated expression of KDM1A and decreased expression of DACT1, which was consistent with the observation in cervical cancer cell lines. KDM1A was found to negatively regulate DACT1 through histone deacetylation. Meanwhile, the downregulation of KDM1A or overexpression of DACT1 could suppress the cell proliferation and migration ability in HeLa and SiHa cells. Cotransfection of KDM1A and DACT1 overexpression could reverse the increased cell proliferation and migration ability induced by KDM1A overexpression. Conclusion. KDM1A can downregulate DACT1 expression through histone deacetylation and therefore suppress the proliferation and migration of cervical cancer cells.

HER2 puzzle pieces: Non-Coding RNAs as keys to mechanisms, chemoresistance, and clinical outcomes in Ovarian cancer

Ovarian cancer (OC) presents significant challenges, characterized by limited treatment options and therapy resistance often attributed to dysregulation of the HER2 signaling pathway. Non-coding RNAs (ncRNAs) have emerged as key players in regulating gene expression in OC. This comprehensive review underscores the pivotal role of ncRNAs in modulating HER2 signaling, with a specific focus on their mechanisms, impact on chemoresistance, and prognostic/diagnostic implications. MicroRNAs, long non-coding RNAs, and circular RNAs have been identified as essential regulators in the modulation of the HER2 pathway. By directly targeting key components of the HER2 axis, these ncRNAs influence its activation and downstream signaling cascades. Dysregulated ncRNAs have been closely associated with chemoresistance, leading to treatment failures and disease progression in OC. Furthermore, distinct expression profiles of ncRNAs hold promise as reliable prognostic and diagnostic markers, facilitating personalized treatment strategies and enhancing disease outcome assessments. A comprehensive understanding of how ncRNAs intricately modulate HER2 signaling is imperative for the development of targeted therapies and the improvement of patient outcomes. The integration of ncRNA profiles into clinical practice has the potential to enhance prognostic and diagnostic accuracy in the management of ovarian cancer. Further research efforts are essential to validate the clinical utility of ncRNAs and elucidate their precise roles in the regulation of HER2 signaling. In conclusion, ncRNAs play a crucial role in governing HER2 signaling in ovarian cancer, impacting chemoresistance and providing valuable prognostic and diagnostic insights. The exploration of ncRNA-mediated HER2 modulation offers promising avenues for the development of personalized treatment approaches, ultimately advancing patient care and outcomes in OC.

Study protocol: Yarning about HPV Vaccination : a qualitative study of factors influencing HPV vaccination among Aboriginal and Torres Strait Islander adolescents in Australia

Introduction Aboriginal and Torres Strait Islander women experience a higher burden of cervical cancer than non-Indigenous women in Australia. Cervical cancer is preventable partly through human papillomavirus (HPV) vaccination; in Australia, this is delivered through the national school-based immunisation programme. While HPV vaccination uptake is high among Australian adolescents, there remain gaps in uptake and completion among Aboriginal and Torres Strait Islander adolescents. This study aims to gain a comprehensive understanding of the barriers and facilitators to HPV vaccination uptake and completion among Aboriginal and Torres Strait Islander adolescents in Queensland, Australia. Methods and analysis The study will be guided by an Indigenist research approach and an ecological model for health promotion. Yarning, a qualitative Indigenous research method, will be conducted in up to 10 schools. Participants will include Year 7 (12/13 years old) Aboriginal and Torres Strait Islander adolescents; parents/caregivers; and local key informants and immunisation programme partners involved in the delivery of school-based HPV immunisation programme. Participants will be recruited through school representatives and investigator networks using purposive and snowball sampling and samples of convenience. Field notes, HPV vaccination clinic observations and sequential diagramming of the HPV vaccination process will be conducted. Thematic analysis of data will be led by Aboriginal and Torres Strait Islander researchers. Synthesised sequential diagrams of the process of HPV vaccination and qualitative themes summarising key findings will be produced. Ethics and dissemination The Aboriginal Health and Medical Research Council of New South Wales Ethics Committee (1646/20), the Australian National University Human Research Ethics Committee (HREC, 2020/478), the HREC of the Northern Territory Department of Health and Menzies School of Health Research (19-3484) and the Townsville Hospital and Health Service HREC (HREC/QTHS/73789) have approved the study. Dissemination will occur via conferences and peer-reviewed publications. Further dissemination will be determined in partnership with the Aboriginal and Torres Strait Islander Steering Committee, including Youth Representatives and Consultation Network.

“Whilst you are here…” Acceptability of providing advice about screening and early detection of other cancers as part of the breast cancer screening programme

AbstractObjectivesThis research aimed to assess women's willingness to receive advice about cervical and bowel cancer screening participation and advice on cancer symptom awareness when attending breast cancer screening.MethodsWomen (n = 322) aged 60–64 years, living in the United Kingdom, who had previously taken part in breast cancer screening were recruited via a market research panel. They completed an online survey assessing willingness to receive advice, the potential impact of advice on breast screening participation, prospective acceptability and preferences for mode and timing of advice.ResultsMost women would be willing to receive information about cervical (86%) and bowel cancer screening (90%) and early symptoms of other cancers (92%) at a breast cancer screening appointment. Those who were not up to date with cervical cancer screening were less willing. Prospective acceptability was high for all three forms of advice and was associated with willingness to receive advice. Women would prefer to receive advice through a leaflet (41%) or discussion with the mammographer (30%) either before the appointment (27%), at the appointment (44%) or with their results (22%).ConclusionsWhile there is high willingness and high acceptability towards using breast cancer screening as a teachable moment for advice about prevention and early detection of other cancers, some women find it unacceptable and this may reduce their likelihood of attending a breast screening appointment.Patient or Public ContributionThis study focused on gaining women's insights into potential future initiatives to encourage screening and early diagnosis of cancer. Members of the public were also involved in piloting the questionnaire.

Rational Combinations of PARP Inhibitors with HRD-Inducing Molecularly Targeted Agents

Cancers with wild-type BRCA, homologous recombination proficiency, or de novo or acquired resistance to PARP inhibition represent a growing population of patients who may benefit from combinatorial PARP inhibitor strategies. We review targeted inhibitors of angiogenesis, epigenetic regulators, and PI3K, MAPK, and other cellular signaling pathways as inducers of homologous recombination deficiency, providing support for the use of PARP inhibitors in contexts not previously considered susceptible to PARP inhibition.

Mapping sentinel lymph nodes in early-stage ovarian cancer (MELISA) trial - a further step towards lymphadenectomy replacement

Sistematic pelvic and para-aortic lymphadenectomy is part of the staging surgery for early-stage epithelial ovarian cancer, with no therapeutic value. The Mapping Sentinel Lymph Nodes In Early-Stage Ovarian Cancer (MELISA) trial prospectively assessed the SLN detection rate and the diagnostic accuracy of the SLN mapping technique in patients with early-stage epithelial ovarian cancer. This prospective, single-arm study included patients diagnosed with early-stage epithelial ovarian cancer (FIGO stages I and II), via either primary surgery or re-staging surgery. SLN mapping was performed by injecting 0.2 mL of 37-mBq Thirty patients were included. SLNs were identified in 27 patients (90%). Detection rates in primary and re-staging surgery were 89% and 92%, respectively. Para-aortic drainage was the predominant lymphatic spread, observed in 26 of 27 patients. Ultrastaging pathologic reports listed 1 SLN with macrometastasis, 1 with micrometastasis, and 5 with isolated tumor cells; the sensitivity of SLN mapping was 100%, with a false-negative rate of 0%. Univariate analysis showed a nonsignificant higher proportion of patients with uterine fibroids, adenomyosis, and endometriosis (100%, 67%, 67%, respectively) in patients in whom SLNs were not detected. SLN mapping has a high detection rate (90%) and is an accurate technique for detecting lymph node involvement in early-stage epithelial ovarian cancer. SLN mapping is a potential alternative to systematic lymphadenectomy to reduce associated morbidity, but further research is needed to evaluate the impact of SLN mapping on oncologic outcomes and its cost-effectiveness.

Should the management of high grade cervical squamous intraepithelial lesion (HSIL) be different in HIV-positive women?

Abstract Background This study compares the management and outcome of high grade squamous intraepithelial lesions (HSIL) in HIV-positive and -negative women and identifies risk factors for treatment failure. Methods This retrospective, controlled study includes 146 HIV-positive women, matched for HSIL, age and year of diagnosis, with 146 HIV-negative women. Differences were analysed using parametric and non-parametric tests and Kaplan–Meier survival curves. A binary logistic regression was used to assess risk factors for treatment failure. Results Persistence of cervical disease was observed most frequently in HIV-positive women (42 versus 17%) (p  &lt;  0.001) and the cone biopsy margins were more often invaded in HIV-positive-women than in HIV-negative ones. (37 versus 16%; p  &lt;  0.05). HIV-positive women, with successful cervical treatment had better HIV disease control: with significantly longer periods of undetectable HIV viral loads (VL) (19 versus 5 months; p  &lt;  0.001) and higher CD4 counts (491 versus 320 cells/mm3; p  &lt;  0.001). HIV-positive women with detectable VL at the time of dysplasia had 3.5 times (95% IC: 1.5–8.3) increased risk of treatment failure. Being treated through ablative therapy was associated with a 7.4, four-fold (95% IC: 3.2–17.3) increased risk of treatment failure compared to conization Conclusion HIV-positive women have a higher risk of treatment failure of HSIL than do HIV-negative women, especially when ablative therapy is used and in women with poor control of their HIV infection. The management and the follow- up of HSIL’s guidelines in this high-risk population should be adapted consequently: for HIV-positive women with uncontrolled viral load, excisional treatment should be the preferred therapy, whereas for women with undetectable viral load, CD4  +  lymphocytes higher than 500 cells/mm3 and with a desire of pregnancy, ablative therapy may be considered.

Factors Influence on Pap Test Screening among Lahu Hill Tribe Women in Remote Area Thailand

Papanicolaou test is widely used to screening cervical cancer but low attend rate. There is one mountainous area found high participation rate. This study aimed to determine the factors associated with successful Pap test among Lahu hill tribe women. The quantitative cross-sectional study was used in this study. Data were collected from 650 Lahu hill tribe women by simple random sampling. The interview forms with reliability coefficient and validity of 0.78 and 0.91 were administered to participants. The data were analyzed by using descriptive statistics and Chi-square test. The 96.15% of the Lahu hill tribe women had taken Pap test and 74.31% obtained the screening more than once. The contraceptive use and frequency of Pap test obtaining significantly associated with cervical cancer screening (p <0.001). The participants showed good level of knowledge in cervical cancer and the screening test (64.31% and 76.46% respectively). Most of participants received the cervical cancer disease information (87.17%) and screening information (66.92%) from health care professionals, which may influence on well cervical screening co-operation.  Conclusions: The suitable health promotion model should provide to promote knowledge, attitude and motivate continuous cooperation in cervical cancer screening among hill tribe women.