Journal

Cancer Reports

Papers (82)

Routine Tumor Testing for Homologous Recombination Deficiency in Patients With High Grade Epithelial Ovarian Cancer at a Statewide Gynecological Cancer Service in Western Australia: An Observational Study

ABSTRACTBackgroundPoly‐ADP ribose polymerase inhibitors have been shown to improve progression‐free survival in patients with advanced high‐grade epithelial non‐mucinous ovarian cancers characterized by a deficiency in homologous recombination (HRD). Guidelines recommend all patients with advanced high‐grade epithelial ovarian cancer undergo genomic tumor testing for HRD. Our aim was to evaluate the first year of HRD testing at the statewide Western Australia Gynecologic Cancer Service to assess factors associated with obtaining a diagnostic HRD testing result.MethodsRetrospective chart review.ResultsHRD testing was indicated in 84 patients, and ordered in 79, of which three had non‐diagnostic/inconclusive results, all due to insufficient tumor quantity. One patient had the sample collected using a 20‐gauge core biopsy needle under image guidance, one patient following interval debulking surgery, and one following primary debulking surgery. Of 76 patients with an HRD result, HRD was positive in 29 (38.2%). A somatic BRCA mutation was detected in six of these 29 patients (20.6%) and HRD positive, BRCAwt was detected in 23 of 29 patients (79.4%). All core biopsies with 16‐ and 18‐gauge needles had a diagnostic HRD result. Ten of 11 patients who were treated by neoadjuvant chemotherapy and whose biopsies were obtained at interval cytoreductive surgery had sufficient tumor tissue for testing and had a diagnostic HRD result. All ascitic/pleural fluid samples sent for HRD testing yielded diagnostic results.ConclusionsCompliance with HRD testing was high, and only three of 79 (3.8%) patients had non‐diagnostic results.

Long‐Term Survival Obtained by Repeated Cytoreductive Surgery and S‐1 Plus Cisplatin Chemotherapy at Each Instance of Disease Progression in a Patient With Metastatic Urachal Carcinoma: A Case Report

ABSTRACTBackgroundUrachal carcinoma (URC) is a rare tumor of the urinary bladder, of which the histology usually resembles that of colorectal adenocarcinoma. Achievement of cure in patients with metastatic URC is difficult, and the survival rate of these patients has remained unsatisfactory despite various efforts.CaseA 74‐year‐old female patient presented to us complaining of gross hematuria. Abdominal and thoracic computed tomography revealed a mass in the dome of the bladder with a single lung nodule. The two tumors, which were resected by partial cystectomy and video‐assisted thoracic surgery, respectively, were diagnosed by postoperative histopathology as adenocarcinomas. Subsequent to the surgeries, bilateral ovarian metastases and another lung metastasis, which appeared metachronously, were also resected. The repeated cytoreductive surgery combined with administration of S‐1 plus cisplatin chemotherapy at each instance of disease progression eventually yielded a durable progression‐free survival; even at 5 years after the initial therapy, the patient remained asymptomatic with no limitation of activities despite the failure to achieve “cure”.ConclusionNot only some degree of sensitivity of the tumor to chemotherapy, but also the repeated cytoreductive surgeries might allow prolonged survival with a good quality of life in elderly patients with metastatic URC, even in the absence of cure and failure of genetic testing to suggest any potentially effective second‐line drugs. To improve the survival of patients with metastatic URC, complementary therapy suggested by the results of genomic profiling may be necessary along with other multimodality therapy, including sequential metastasectomy and chemotherapy.

Applying Parse's Theory in Caring for a Depressed Patient Following Hysterectomy With Oophorectomy: A Case Study

ABSTRACTBackgroundDepression is a common complication in women undergoing hysterectomy. By utilizing nursing theories in patient care, improved care standards, more affordable care costs, and greater quality of life can be achieved. Parse's theory of human becoming is among the nursing theories prioritizing each individual's conception of quality of life as a crucial nursing goal. This study aimed to apply Parse's theory of human becoming to the care of a depressed patient following a hysterectomy with oophorectomy.CaseThe participant was a 44‐year‐old woman who underwent hysterectomy with bilateral oophorectomy on January 1, 2023, following a diagnosis of grade 1 right ovarian cancer. After three days of hospitalization, she returned home to live with her husband and four children. Postoperative care was provided by a home care nurse—also the researcher—who observed signs of emotional distress and depressive symptoms, including social withdrawal, irritability, and loss of interest in daily activities. The nurse implemented nursing interventions grounded in Parse's Human Becoming Theory, including therapeutic communication, mindfulness practices, journaling, and involving the family in emotional support. Data were analyzed using Parse's qualitative research methodology (2011).ConclusionBased on the first principle of Parse's theory (meaning), the findings showed that patients' meaning and values of life changed from “disappointment” to “hope.” In the second principle (rhythmic patterns), contradictory patterns of “dependency‐nondependency” and “hope‐disappointment” were identified. Based on the third principle (transcendence), with the actual presence of a nurse and the implementation of care and treatment, the patient's mental state switched from “depression and despair” to “hope and happiness.” This research found that Parse's theory of nursing was effective in alleviating depression in patients following hysterectomy with oophorectomy surgery. This study also highlights the importance of utilizing nursing theories in patient care.

Integrative Analysis of Novel Ferroptosis‐Related Genes Signatures as Prognostic Biomarkers in Ovarian Cancer

ABSTRACTBackgroundFerroptosis, an iron‐dependent form of cell death, has been implicated in the pathogenesis of several types of cancer. Nevertheless, the exact correlation between ferroptosis‐related gene mutations and their influence on ovarian cancer (OV) diagnosis and treatment strategies remains to be fully elucidated. It is crucial to identify the ferroptosis‐related gene signature in OV and elucidate the impact of these mutations and their expression on the diagnosis and treatment of OV.MethodsIn this study, we collected data from the TCGA and GEO databases. We utilized various tools and packages for data analysis, including the cBio Cancer Genomics Portal, Tumor Immune Estimation Resource (TIMER), GSVA package, and WGCNA R packages.ResultsOur results showed that ferroptosis subtypes 1 (FS1) and 2 (FS2) exhibited different levels of expression and tumor mutation burden (TMB). FS2 had a higher TMB level and survival rate compared to FS1. Furthermore, our analysis identified three ferroptosis‐related genes, including IFNG, KEAP1, and PHKG2, as key biomarkers in prognosis prediction and potential targets for OV cancer therapy. The elevated expression levels of IFNG, KEAP1, and PHKG2 were found to be correlated with a good prognosis. These three genes showed a positive correlation with TMB in OV. We also observed that high TMB was more robustly associated with immune response‐related gene expression, including CD28, CD40L, and type I IFN family members. Moreover, high TMB was associated with increased T cell infiltration and exhibited a distinct gene signature, which highlights the potential of IFNG, KEAP1, and PHKG2 as predictive markers for T cell infiltration and the tumor microenvironment status in OV. A significant correlation exists between the expression levels of KEAP1 and PHKG2 and TMB in OV cell lines.ConclusionIn conclusion, our study identified KEAP1, IFNG, and PHKG2 as potential prognostic biomarkers and therapeutic targets in OV. Their expression and mutation burden were correlated with a good prognosis. The association between ferroptosis subtypes, TMB, and survival rates further supports the relevance of these biomarkers. Additionally, the positive correlation between KEAP1, IFNG, and PHKG2 with TMB and immune response‐related gene expression highlights their potential as predictive markers for immunotherapy efficacy in OV. The observed association of high TMB with increased T cell infiltration and distinct gene signature further emphasizes its role as a potential biomarker for immune response. Further research is warranted to validate these findings and explore their clinical implications in OV treatment.

Progesterone Enhances Sensitivity of Ovarian Cancer Cells to SN38 Through Inhibition of Topoisomerase I and Inducing Ferroptosis

ABSTRACTBackgroundProgesterone rapidly induces ovarian cancer cell death through non‐genomic actions mediated by the membrane progesterone receptor (mPR).AimsWe investigated the combined effects of progesterone and SN38, an active metabolite of irinotecan, on ovarian cancer cells.Methods and ResultsmPR‐positive and PR‐negative ovarian cancer cell lines were utilized in experiments. Tumor cells were exposed to SN38 or cisplatin for 48 h following exposure to progesterone for 30 min. The viable cell counts were measured using a colorimetric assay and the expression of topoisomerase I (TOPO‐I), the direct target of SN38, was observed with or without exposure to progesterone. Moreover, we investigated the relationship between several types of programmed cell death and the SN38 sensitivity enhancement effect of progesterone using specific cell death inhibitors. The chemosensitivity to SN38 was 8.7‐ to 26.0‐fold higher with the administration of progesterone than that without (p < 0.01), but not to cisplatin in ovarian cancer cells. Progesterone suppressed the expression of TOPO‐I mRNA by less than 50% (p < 0.01). Furthermore, among various programmed cell death inhibitors, only the ferroptosis inhibitor attenuated the progesterone‐induced SN38 chemosensitivity enhancement effect.ConclusionsProgesterone increased sensitivity to SN38 by suppressing TOPO‐I expression and inducing ferroptosis. The combination of progesterone and irinotecan could be a novel treatment modality for ovarian cancer.

A Single Arm Pilot Observational Study to Evaluate the Safety and Feasibility of a Pre‐Operative Very Low Calorie Diet in Severely Obese Patients With Endometrial Cancer

ABSTRACTBackgroundPre‐operative very low calorie diets (VLCDs) can achieve rapid and safe weight loss, yet no studies have evaluated VLCDs in the severely obese endometrial cancer population prior to surgery. Our aim was to evaluate the safety and feasibility of a 4–6 week pre‐operative nutritional intervention with the Optifast VLCD prior to surgery in patients with clinical stage 1, Grade 1 endometrioid endometrial adenocarcinoma and a body mass index ≥ 35 kg/m2.MethodsThis was an investigator‐initiated single‐arm prospective observational study. Co‐primary endpoints were safety and feasibility. Secondary endpoints were changes in anthropometric measures, blood pressure, biochemistry, perioperative complications, length of stay and final tumour stage. Tolerability and compliance of the VLCD were assessed by fortnightly questionnaires and urinary ketones.ResultsTwenty‐eight patients were enrolled, of which 25 underwent the intervention. 22/25 patients (88%) completed at least 4 weeks of Optifast. Mean (SD) age was 56.4 (6.3) years, and mean body mass index (BMI) was 45.2 (7.1) kg/m2. Significant decreases in weight (mean 8.2 kg [3.6]), BMI (mean 3.1 kg/m2 [1.3]), waist and hip circumference (mean 5.7 [6.5] and 4.5 cm [4.1], respectively), and diastolic blood pressure (10 mmHg [14.1]) were observed (p < 0.001 for all). One patient had a flare of gout. All patients had laparoscopic surgery without adverse events. Optifast was considered acceptable, and compliance was 40% to 61.9%. Eighty‐eight percent (22/25) of patients had FIGO 2009 Stage 1A Grade 1 endometrioid endometrial adenocarcinoma on final staging.ConclusionsA 4–6 week pre‐operative VLCD in severely obese clinically low‐risk endometrial cancer patients appears safe, feasible and well tolerated.

Comparing the Effectiveness of Artificial Intelligence Models in Predicting Ovarian Cancer Survival: A Systematic Review

ABSTRACTBackgroundThis systematic review investigates the use of machine learning (ML) algorithms in predicting survival outcomes for ovarian cancer (OC) patients. Key prognostic endpoints, including overall survival (OS), recurrence‐free survival (RFS), progression‐free survival (PFS), and treatment response prediction (TRP), are examined to evaluate the effectiveness of these algorithms and identify significant features that influence predictive accuracy.Recent FindingsA thorough search of four major databases—PubMed, Scopus, Web of Science, and Cochrane—resulted in 2400 articles published within the last decade, with 32 studies meeting the inclusion criteria. Notably, most publications emerged after 2021. Commonly used algorithms for survival prediction included random forest, support vector machines, logistic regression, XGBoost, and various deep learning models. Evaluation metrics such as area under the curve (AUC) (18 studies), concordance index (C‐index) (11 studies), and accuracy (11 studies) were frequently employed. Age at diagnosis, tumor stage, CA‐125 levels, and treatment‐related factors were consistently highlighted as significant predictors, emphasizing their relevance in OC prognosis.ConclusionML models demonstrate considerable potential for predicting OC survival outcomes; however, challenges persist regarding model accuracy and interpretability. Incorporating diverse data types—such as clinical, imaging, and molecular datasets—holds promise for enhancing predictive capabilities. Future advancements will depend on integrating heterogeneous data sources with multimodal ML approaches, which are crucial for improving prognostic precision in OC.

The Role of CA‐125 in the Management of Ovarian Cancer: A Systematic Review

ABSTRACTBackgroundOvarian cancer is frequently occurring and fatal for women. CA‐125 is important in the screening, diagnosis, and treatment of ovarian cancer. This review study was conducted to explore the influence of CA‐125 in addressing ovarian cancer.MethodsTo investigate the role of CA‐125 in ovarian cancer, we conducted a comprehensive search for high‐quality articles in the Medline, Web of Science Core Collection and Scopus databases using the keywords “ovarian cancer,” “ovarian carcinoma,” “ovarian neoplasms,” and “CA‐125” from the 2000 to 2024. We included full‐text, peer‐reviewed articles in English with relevant keywords published since 2000. We excluded case reports, commentaries, letters to the editor, books, case series, systematic reviews, animal studies, and articles that were not accessible in full text.ResultsAfter screening the 7947 records, 88 studies were included in this review. In the literature review, it was found that researchers utilized CA‐125 for diagnosing ovarian cancer, its predicting, evaluating treatment response, assessing ovarian cancer survival, and early detection of recurrence. In some cases, researchers employed additional tumor markers alongside CA‐125 to enhance the test's sensitivity.ConclusionCA‐125 has become a pivotal marker for ovarian cancer. Its role in the diagnosis, treatment, and ongoing assessment of ovarian cancer cannot be overstated. Continuous monitoring of CA‐125 levels can provide comprehensive insights, and categorizing patients as low‐risk or high‐risk based on CA‐125 levels could lead to better outcomes. Integrating CA‐125 with other biomarkers may enhance the accuracy of the test and elevate its relevance in patient care.

Risk Factors and Clinical Outcomes of Recurrence in Adult Ovarian Granulosa Cell Tumors

ABSTRACTPurposeGranulosa cell tumors (GCTs) of the ovary are rare but clinically significant malignancies. Despite advances in treatment, recurrence has remained a substantial challenge. This study aimed to identify clinical outcomes and potential prognostic risk factors for recurrence in patients diagnosed with GCTs.MethodsIn a retrospective cohort study, the ovarian cancer database of the gynecological tertiary referral cancer center, Mashhad University of Medical Sciences, Mashhad, Iran, was searched from August 2012 to August 2023 to find GCT cases. Demographic, clinical, pathological, intervention‐related factors, follow‐up, and survival findings were meticulously collected. Data were analyzed using SPSS v 23.ResultsNinety‐two patients with GCTs, including 86 AGCT and 6 JGCT subjects, were identified. Based on further analysis of AGCT patients, most patients were ages under 50 (58.1%), clinically presented pain (32.6%), and abnormal uterine bleeding (27.9%) as the most frequent symptoms. Stages IA (64.0%) and IC (20.9%) were common. Five‐year overall and progression‐free survival were 98.2% and 90.8%, respectively. With a median follow‐up time of 72 (0.0–180) months, disease recurrence was observed in 19 patients (23.9%), and five patients (5.4%) died of the disease. Stage IV was a hazard factor of recurrence (HR = 7.62, 95%CI (1.89–30.63); p = 0.004).ConclusionsThe present study provides valuable insights into the outcomes and potential risk factors for recurrence in ovarian AGCTs. It duplicates the importance of stage in the prognosis of AGCT patients and highlights the safety of fertility‐sparing surgery in stage I and the lack of need to administer chemotherapy in stage IC.

Radiomics Signatures Based on Computed Tomography for Noninvasive Prediction of CXCL10 Expression and Prognosis in Ovarian Cancer

ABSTRACTBackgroundOvarian cancer (OC) is an aggressive gynecological tumor usually diagnosed with malignant ascites and even observed widespread metastasis or distant spread.AimsWe aimed to develop and identify radiomics models according to computed tomography (CT) for preoperative prediction of CXCL10 expression and prognosis in patients with OC.MethodsGenomic data with CT images and corresponding clinicopathological parameters were extracted from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). To analyze the prognosis, we carried out the univariate Cox regression analysis (UCRA), multivariate Cox regression analysis (MCRA), and Kaplan–Meier (KM) analysis. For the data reduction, logistic regression, operator regression, least absolute shrinkage selection, radiomic feature construction, and feature selection were utilized. The predictive performance of the radiomic signatures was assessed using the analyses of the receiver operating characteristic (ROC) curve, decision curve (DCA), and precision‐recall (PR) curve. To evaluate the correlation between the radiomic score (Rad‐score) and CXCL10 expression, the Wilcoxon rank‐sum test was applied.ResultsThree radiomics models effectively predicted CXCL10 expression levels (AUC = 0.791, 0.748, and 0.718 for the set of training; AUC = 0.761, 0.746, and 0.701 for the set of validation). A higher Rad‐score significantly correlated with upregulated CXCL10 expression.ConclusionCXCL10 expression can be predicted noninvasively and preoperatively via radiomic signatures based on contrast‐enhanced CT images.

Germline BRCA1‐Mutated Synchronous and Metachronous Pancreatic Acinar Cell Carcinoma With Long‐Term Survival

ABSTRACTBackgroundPancreatic acinar cell carcinoma (PACC) is a rare pancreatic neoplasm. Recently, molecular analysis revealed that PACC shows a high frequency of the BRCA1/2 mutation and is likely to be considered a cancer associated with hereditary breast and ovarian cancer (HBOC). Hereditary cancers, including HBOC, are characterized by multifocal and/or metachronous tumors. However, no case reports exist of germline BRCA1‐mutated synchronous and metachronous PACC.CaseA 58‐year‐old man was diagnosed with synchronous and metachronous PACC at the age of 56 and underwent two surgeries. Ten months after the second surgery, the patient developed multiple liver metastases. Gemcitabine plus nab‐paclitaxel therapy was administered as first‐line chemotherapy. After seven cycles, computed tomography examination revealed progressive disease (PD). Therefore, modified FOLFIRINOX (mFFX) was administered as second‐ line chemotherapy. After 19 cycles of mFFX, comprehensive cancer genomic profiling (CGP) identified a BRCA1 pathogenic variant that was confirmed to be germline origin. Accordingly, we treated the patient with olaparib; however, he was diagnosed with PD after 4 months. He subsequently died 5 years and 9 months after the initial surgery, and 3 years and 10 months after chemotherapy. Based on the genetic data of the patients, his family members received genetic counseling followed by cascade testing. Consequently, the same gBRCA1 pathogenic variant was detected in the son and his surveillance for HBOC‐related cancers was initiated.ConclusionWe diagnosed a 58‐year‐old man with a synchronous and metachronous PACC with germline BRCA1 pathogenic variant. Considering that PACC is likely to have BRCA1/2 mutations responsible for HBOC, we need to be aware of the possible presence of multifocal and/or metachronous tumors in patients with PACC. Additionally, patients with PACC should undergo genetic examinations, which would be beneficial in determining treatment strategies and health care for blood relatives.

Assessing Sarcopenia in Advanced‐Stage Ovarian Cancer Patients Undergoing Neoadjuvant Chemotherapy: A Case Series

ABSTRACTObjectivesIn ovarian and other cancers, low muscle mass and density are associated with poorer clinical outcomes. However, screening for cancer‐related sarcopenia (typically defined as low muscle mass) is not routinely conducted. The European Working Group on Sarcopenia in Older People (EWGSOP) recommends an algorithm for sarcopenia screening and diagnosis in clinical settings, with sarcopenia based on muscle strength and mass, and severity on physical performance. We explored the application of the EWGSOP2 algorithm to assess sarcopenia in six ovarian cancer patients receiving neoadjuvant chemotherapy.MethodsWe assessed sarcopenia risk with the SARC‐F screening questionnaire (at risk ≥4 points), muscle strength with a handgrip strength test (cut point <16 kg) and five times sit‐to‐stand test (cut point >15 s), muscle mass by skeletal muscle index (SMI in cm2/m2 from a single computed tomography [CT] image; cut point <38.5 cm2/m2), and physical performance with a 4‐m gait speed test (cut point ≤0.8 m/s).ResultsOf six participants, none were identified as “at risk” for sarcopenia based on SARC‐F scores. Two participants were severely sarcopenic based on EWGSOP2 criteria (had low muscle strength, mass, and physical performance), and five participants were sarcopenic based on muscle mass only.DiscussionOvarian cancer patients with low muscle mass during neoadjuvant chemotherapy may not be identified as sarcopenic based on the EWGSOP2 diagnostic algorithm. While lacking a universally accepted definition for cancer‐related sarcopenia and cancer‐specific recommendations for the screening, diagnosis, and treatment of sarcopenia, ovarian cancer clinicians should focus on the diagnosis and treatment of low muscle mass and density.

Common and novel haplotype structures between different types of cancer

AbstractBackgroundBackground: Genome‐wide association studies (GWAS) have identified hundreds of genetic variants associated with cancer risk. GWAS data are important for cancer prevention and understanding the underlying mechanisms of cancer.AimsThis study aimed to investigate the genetic association between different types of cancer using GWAS data and a bioinformatics approach.Methods and resultsThe significant GWAS variants associated with more than one cancer type were identified. Common linkage disequilibrium (LD) variants between different types of cancer were identified by 1000 genomes phase 3 LD data. Haplotype blocks were identified by analyzing 1000 Genomes phase 3 genotyping data in the GWAS populations. Subsequent analyses included functional SNP analyses and TCGA gene expression. The results associated with significant GWAS variants (P<5E‐8) showed the following haplotype associations in European population: GT rs4808075‐rs8170 haplotype on BABAM1 with breast and ovarian cancers, GC rs16857609‐rs11693806 haplotype on DIRC3 with breast and thyroid cancers, GCG rs380286‐rs401681‐rs31487 haplotype on CLPTM1L with skin and lung cancers, GGG rs4430796‐rs11651052‐rs11263763 haplotype on HNF1B with prostate and endometrial cancers, and GT rs10505477‐rs6983267 haplotype on CASC8 associated with colorectal and prostate cancers. All these genes had significantly different expressions in tumor tissues (P<1E‐3). In addition, the rs11693806 variant is located in the hsa‐miR‐873‐5p binding site and has an enhancing effect on the hsa‐miR‐873‐5p:DIRC3 interaction.ConclusionThese novel haplotype structures and miRNA:lncRNA interactions are important for understanding the common genetic link between cancers. These results can potentially be used in genetic panels.

The protective effect of vitamin D on ovarian reserve and anti‐mullerian hormone in patients undergoing chemotherapy for breast cancer, a randomized phase ΙΙ clinical trial

AbstractBackgroundReduced ovarian reserve is among the crucial long‐term side effects of using chemotherapy agents in breast cancer, yielding early ovarian failure. On the other hand, vitamin D is an essential factor in protecting the follicles and an important predictive factor for successful IVF therapy.AimThe aim of this study is evaluation of vitamin D as a agent that can reduce fertility complications of chemotherapy specially in young women.MethodsBreast cancer patients undergoing chemotherapy at two cancer institutes were enrolled in this study. The case group received 1000 IU of calcitriol, and the AMH level was measured at the baseline, after chemotherapy, and six months after chemotherapy. The primary end point was improvement in the AMH level after six months of chemotherapy. the secondary endpoint was to evaluate the predictive factors of AMH level decline during chemotherapy.ResultsBetween 2018 and 2019, 18 and 15 patients were enrolled in the case and control groups, respectively. The mean AMH level (ngr/ml) of the patients in the case and control group were 3.16 and 2.37 ng/mL, respectively (p‐value = .16). These levels were 0.387 and 0.19 after six months (p‐value = .38). The AMH rise immediately after chemotherapy cycles to six months after chemotherapy, in the case and control groups were 0.86 and 0.44 ng/mL, respectively, which was slightly higher in the case group but not statistically significant between two groups (p‐value = .054).ConclusionDespite a minimal rise in the AMH level after six months of chemotherapy, the study could not demonstrate any protective effect of vitamin D on patients' ovarian reserve undergoing chemotherapy for breast cancer. Further larger studies are needed to evaluate the effect of vitamin D supplements on ovarian reserve beside optimal dose and duration.

An assessment of survival outcomes among ovarian cancer patients at the National and Referral Hospital in Kenya

AbstractBackgroundOvarian cancer has been shown to have poor survival outcomes attributed to late presentation. In Kenya, information on the survival outcomes of ovarian cancer patients is scarce. Therefore, the objective of this study was to examine the survival outcomes among patients with ovarian cancer treated at Kenyatta National Hospital (KNH).AimsA hospital‐based retrospective cohort study was performed at KNH to examine the survival outcomes of 112 ovarian cancer patients. The study employed a structured data abstraction tool to acquire patients' relevant socio‐demographic and clinical characteristics from the patient's medical records. The data obtained were analyzed using SPSS version 29.0 statistical software. Kaplan–Meier and Cox regression analyses were used to determine the survival outcome and predictors of mortality among ovarian cancer patients, respectively.Methods and resultsThe mean age of the patients in this study was 51.28 ± 14.24 years. Most patients (59.8%) had evidence of distant metastasis during the follow‐up period. One‐third (33%) of patients were deceased. The mean‐cancer‐specific survival time among the study participants was 40.0 ± 3.0 months. The 5‐year survival rate was 44%, with most patients experiencing disease progression during the last follow‐up. Combination therapy (p < .001) was the only statistically significant predictor of mortality in ovarian cancer patients.ConclusionThe study found that the 5‐year survival rate among ovarian cancer patients was poor, with most patients experiencing disease progression during the last follow‐up period.

The role of non‐genomic actions of progesterone and its membrane receptor agonist in ovarian cancer cell death

AbstractBackgroundProgesterone therapy is a relatively inexpensive treatment option for endometrial and breast cancers, with few side effects. Two signaling pathways usually mediate the physiological effects of progesterone, namely genomic and non‐genomic actions. Genomic action occurs slowly via the nuclear progesterone receptor (PR), whereas the membrane progesterone receptor (mPR) induces rapid non‐genomic action.AimsWe investigated the effects of progesterone and various PR agonists on ovarian cancer cells.Methods and ResultsPR expression of six serous ovarian cancer cell lines was examined by western blotting, and mPR expression was examined by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). PR‐negative and mPR‐positive ovarian cancer cells were exposed to progesterone and seven types of PR agonists (medroxyprogesterone acetate [MPA], dehydroepiandrosterone, dienogest, levonorgestrel, drospirenone, pregnenolone, and allopregnanolone) at 10–400 μM, and viable cell counts after exposure for 30 min were measured using the water‐soluble tetrazolium (WST‐1) assay. Ovarian cancer cell lines were exposed to 100 μM progesterone, and the expression of BAX, a pro‐apoptotic protein, after 1–5 min was examined by western blotting.Western blotting detected no PR expression in the six serous ovarian cancer cell lines. In contrast, RT‐qPCR detected mPR expression in all six serous ovarian cancer cell lines. Progesterone and MPA‐induced cell death in all tested ovarian cancer cell lines in a concentration‐dependent manner, whereas no effect was observed for other PR agonists. Western blotting revealed that pro‐apoptotic protein BAX expression occurred 1 min after exposure to progesterone, suggesting that the cytocidal effects are mediated by rapid non‐genomic action.ConclusionProgesterone and MPA exhibited a rapid cytocidal effect on PR‐negative ovarian cancer cells through non‐genomic action. Progesterone and MPA could be novel adjuvant therapies for ovarian cancer.

Bioinformatics Analysis Identifies Lipid Droplet‐Associated Gene Signatures as Promising Prognostic and Diagnostic Models for Endometrial Cancer

ABSTRACTBackgroundEffective diagnostic and prognostic tools are critical for early detection and improved outcomes in endometrial cancer (EC). Although metabolic dysregulation plays a key role in EC pathogenesis, the clinical relevance of lipid droplet–associated genes (LDAGs) remains largely unexplored. This study aims to establish LDAG‐based gene signatures with strong diagnostic and prognostic potential in EC.AimsTo identify LDAG signatures with prognostic and diagnostic utility in EC.Methods and ResultsA curated set of LDAGs was systematically analyzed across publicly available EC datasets to identify differentially expressed LDAGs (DE‐LDAGs). Survival‐associated DE‐LDAGs were then identified using univariate Cox regression. A four‐gene prognostic model was developed through LASSO‐based feature selection followed by multivariate Cox regression and validated using Kaplan–Meier survival and time‐dependent receiver operating characteristic (ROC) analyses. From the same pool of survival‐associated DE‐LDAGs, a six‐gene diagnostic model was constructed using LASSO, ROC analysis, and logistic regression. Model performance was evaluated using ROC curves and support vector machine (SVM) classification. Functional enrichment and protein–protein interaction (PPI) network analyses were conducted to assess the biological relevance of the identified genes.Our results demonstrate that the four‐gene prognostic model (LMLN, LMO3, PRKAA2, and RAB10) stratified EC patients into high‐ and low‐risk groups with significantly different survival outcomes (p < 0.05; time‐dependent AUC > 0.70). The six‐gene diagnostic model (AIFM2, ABCG1, LIPG, DGAT2, LPCAT1, and VCP) demonstrated near‐perfect classification of tumor versus normal tissues (AUC ≈0.99 in ROC analysis; 99.8% accuracy in SVM analysis). Functional enrichment linked DE‐LDAGs to lipid metabolism, ER stress response, cholesterol homeostasis, and autophagy, underscoring their biological relevance in EC pathobiology.ConclusionThis study provides the first comprehensive analysis of LDAGs in EC, establishing robust prognostic and diagnostic gene signatures with strong biological relevance. These signatures support a metabolism‐driven framework for EC classification and may offer potential clinical utility in early detection, risk stratification, and personalized treatment.

The Prognosis Prediction Model for Endometrial Cancer Based on DNA Methylation Signature

ABSTRACT Background DNA methylation alteration is a common event during the carcinogenesis and progression of endometrial cancer (EC). Our study aimed to investigate the value of DNA methylation‐related genes in predicting the prognosis and immunotherapy response for EC patients. Methods The clinical information and the expression of DNA methylation‐related genes of 544 endometrial cancers were obtained from the Cancer Genome Atlas (TCGA) database. The univariate Cox regression analysis and the LASSO regression analysis were subsequently used to identify prognosis‐related methylation regulators and construct a risk model. Gene functional enrichment analysis, immune infiltration analysis, drug sensitivity analysis, and molecular feature analysis were performed in different subgroups. Results 25 methylation‐Related gene signatures were found in EC patients and are correlated to tumor differentiation and tumor metastasis. By LASSO‐Cox regression analyses, a recurrence prediction model and a prognostic‐related model were constructed based on methylation‐related genes in the TCGA training cohort. The Area Under the Curve (AUC) values of the recurrence prediction model were 0.671, 0.708, and 0.689 for 1‐, 3‐, and 5‐year time points, respectively, while those of the prognostic model were 0.731, 0.717, and 0.725. The relationship of risk score (RS) with ER/PR‐related genes, immune checkpoint expressions, and IC50s of paclitaxel, cisplatin, tamoxifen, and cetuximab was investigated. The results showed That patients in the low‐risk group are more effective in cetuximab and immune checkpoint blockade (ICB) treatment. Conclusions The model based on the methylation‐related genes showed promising outcomes in predicting the recurrence and treatment response of EC. The patients with high‐risk scores showed a poorer prognosis and may benefit more from the treatment of cetuximab or immune checkpoint inhibitors.

Assessment of Health‐Related Quality of Life in Thai Endometrial Cancer Patients: A Comparative Analysis Using EQ5D Utility Scores Across States

ABSTRACTBackgroundRates of endometrial cancer, the sixth most common in women, are rising. HRQoL, reflecting health beyond clinical contexts, includes disabilities and daily functioning impacts. Measured by various tools such as EuroQoL‐5 Dimensions (EQ‐5D‐5L), it aids in economic evaluation of interventions.AimsThe purpose of this study was to analyze Health‐Related Quality of Life (HRQoL), measured by the EQ‐5D‐5L instrument, in different states of endometrial cancer (EC) patients.Methods and ResultsWe conducted a cross‐sectional study on EC patients who underwent follow‐up at Siriraj Hospital, Thailand, between January and June 2023. Patients were classified into five groups: early state, advanced state, curative state, locoregional recurrent state, and distant recurrent/progression state. Demographic and socioeconomic data were collected. EQ‐5D‐5L and visual analog scale instruments (EQ‐VAS) were used to compared between disease states. Descriptive statistics were used to summarize patient characteristics, and the Mann–Whitney U test (p ≤ 0.05) compared EQ‐5D‐5L scores across groups.The study included 56 EC patients, with a mean age of 60.1 ± 10.9 years and a mean BMI of 26.8 ± 5.3 kg/m2. The EQ‐5D scores were as follows: 0.9055 (IQR 0.8193–0.9436) for the early state, 0.8308 (IQR 0.7997–0.8611) for the advanced state, 0.9235 (IQR 0.8521–0.9855) for the curative state, 0.9096 (IQR 0.6249–0.9577) for the locoregional recurrent state and 0.5778 (IQR 0.2884–0.8521) for the distant recurrent/progressive state. The median EQ‐VAS for each state was 70, 75, 82.5, 75, and 65, respectively. The EQ‐5D values had significantly deteriorated after distant metastasis/progression compared to curative states (p‐value = 0.003). Mobility and pain/discomfort appeared to be the two main concerns.ConclusionThe findings show the substantial negative impact of distant metastasis or disease progression on HRQoL. These findings will be used to guide future economic research in the field of endometrial cancer treatment.

Tumor‐infiltrating immune cell score as an independent prognostic predictor for endometrial carcinoma: Insights from a comprehensive analysis of the immune landscape

AbstractBackgroundImmune cells are crucial components in the tumor microenvironment and have a significant impact on the outcomes of patients.AimsHere, we aimed to establish a prognostic score based on different types of tumor‐infiltrating immune cells for Endometrial Carcinoma (EC).Methods and ResultsWe enrolled and analyzed 516 EC patients from The Cancer Genome Atlas. The relative abundance of 22 immune cells were estimated by using the CIBERSORTx algorithm. Cox regression was performed to identify potential prognostic immune cells, which were used to develop a Tumor‐infiltrating Immune Cell Score (TICS). The prognostic and incremental value of TICS for overall survival were compared with traditional prognostic factors using the C‐index and decision curves. Clustering analysis using all immune cells identified three immune landscape subtypes, which had weak correlation with survival. A TICS was constructed using CD8T cells, resting memory CD4 T cells, activated NK and activated DCs, and classified patients as low‐, moderate‐ and high‐risk subgroups. The low‐risk subgroup had higher tumor mutation burden and activation of IL2/STAT5, IL2/STAT3 and IFN‐gamma response pathways. Conversely, the high‐risk subgroup was associated with DNA copy number variation, hypoxia and EMT process. The TICS subgroups significantly predicted overall survival, which was independent of patient age, tumor stage, grade and molecular classification. Moreover, we developed a nomogram incorporating TICS and clinicopathologic factors, which significantly improved the predictive accuracy compared to the clinicopathologic model alone.ConclusionThe TICS is an effective and independent prognostic predictor for EC patients and may serve as a useful supplement to clinicopathological factors and molecular subtyping.

One‐Step Nucleic Acid Amplification Analysis of Sentinel Nodes in Endometrial Cancer Versus Ultrastaging: First Long‐Term Follow‐Up Data of Discordant Cases

ABSTRACTAimsEndometrial cancer (EC) is the most common gynecological cancer worldwide and its incidence is rising. The cornerstone of its management is surgical treatment with nodal staging. A monocentric study investigating the potential of the molecular biology method of one‐step nucleic acid amplification (OSNA) in sentinel lymph node (SLN) analysis was conducted at our institution between April 2016 and January 2018. Histopathological ultrastaging was used as the reference standard for SLN examination and OSNA as the index test. The aim of this study was to assess the long‐term outcome of patients with discordant SLN and OSNA results. To our knowledge, this is the first study exploring this issue.Methods and ResultsPatients were followed in line with the current ESMO/ESGO/ESTRO recommendations. The institutional electronic database was retrospectively searched for patients' follow‐up data from April 2016 till March 2023. Only patients who provided a written valid consent and had a positive OSNA and negative ultrastaging of their SLN analysis were included in the study. The primary endpoint was the retrospective analysis of their clinical outcome. Data from 58 patients enrolled into our previous study were reviewed and 12 discordant patients who met the inclusion criteria for this study were identified. The median follow‐up was 83 months. Disease recurrence was detected in 3 (25%) patients, two of these were nodal and both patients died. One patient had a solitary lung metastasis which was surgically treated, and the patient was disease‐free during the whole study period.ConclusionThe recurrence rate of patients included in the study was in the intermediate‐high and high‐risk group range, and hence, higher than expected based on ultrastaging results. Furthermore, benign epithelial inclusions do not seem to adversely affect OSNA SLN analysis in EC patients.

Integrated Identification and Immunotherapy Response Analysis of the Prognostic Signature Associated With m6A, Cuproptosis‐Related, Ferroptosis‐Related lncRNA in Endometrial Cancer

ABSTRACTBackgroundEndometrial cancer (EC) stands as the predominant gynecological malignancy impacting the female reproductive system on a global scale. N6‐methyladenosine, cuproptosis‐ and ferroptosis‐related biomarker is beneficial to the prognostic of tumor patients. Nevertheless, the correlation between m6A‐modified lncRNAs and ferroptosis, copper‐induced apoptosis in the initiation and progression of EC remains unexplored in existing literature.AimsIn this study, based on bioinformatics approach, we identified lncRNAs co‐expressing with cuproptosis‐, ferroptosis‐, m6A‐ related lncRNAs from expression data of EC. By constructing the prognosis model in EC, we screened hub lncRNA signatures affecting prognosis of EC patients. Furthermore, the guiding value of m6A‐modified ferroptosis‐related lncRNA (mfrlncRNA) features was assessed in terms of prognosis, immune microenvironment, and drug sensitivity.MethodOur research harnessed gene expression data coupled with clinical insights derived from The Cancer Genome Atlas (TCGA) collection. To forge prognostic models, we adopted five machine learning approaches, assessing their efficacy through C‐index and time‐independent ROC analysis. We pinpointed prognostic indicators using the LASSO Cox regression approach. Moreover, we delved into the biological and immunological implications of the discovered lncRNA prognostic signatures.ResultsThe survival rate for the low‐risk group was markedly higher than that for the high‐risk group, as evidenced by a significant log‐rank test (p < 0.001). The LASSO Cox regression model yielded concordance indices of 0.76 for the training set and 0.77 for the validation set, indicating reliable prognostic accuracy. Enrichment analysis of gene functions linked the identified signature predominantly to endopeptidase inhibitor activity, highlighting the signature's potential implications. Additionally, immune function and drug density emphasized the importance of early diagnosis in EC.ConclusionFive hub lncRNAs in EC were identified through constructing the prognosis model. Those genes might be potential biomarkers to provide valuable reference for targeted therapy and prognostic assessment of EC.

Tamoxifen use and risk of endometrial cancer in breast cancer patients: A systematic review and dose–response meta‐analysis

AbstractBackgroundWorse prognosis of endometrial cancers (EC) in tamoxifen‐treated women compared to non‐tamoxifen‐treated women been proposed. The relationship between tamoxifen treatment of breast cancer (BC) and the risk of EC is controversial and there is no agreement between publication results on this issue (the answer to all comments provided in the page 2 of manuscript). The aim of this study is investigation the association between tamoxifen treatment and the risk of EC in patients with BC.Methods and ResultsWe conducted a comprehensive search with related keywords in MEDLINE/PubMed, SCOPUS, and Web of Science databases until April 16, 2022. Random‐effects model (DerSimonian and Laird) was used to pool risk ratios (RRs) with 95% confidence intervals (CIs) of EC. Dose, cumulative dose, and duration‐response analysis were performed in linear and non‐linear states. Twenty‐six studies reported a relation between tamoxifen treatment and risk of EC in patients with BC. Results showed a direct relationship between tamoxifen use and EC (RR: 2.03, 95% CI: 1.68–2.45; I2:76%). By increase the age of participants, the risk of EC was decrease (coef = −.0206), although this was not statistically significant (p = .37). Linear dose–response model indicated a direct significant association between dose and duration use of tamoxifen and EC (dose: exe(b) = 1.019, p = .001; duration: exe(b) = 1.014, p = .001). Non‐linear dose–response analysis confirmed linear analysis.ConclusionThis study highlights that tamoxifen use is a significant risk factor related to the incidence of EC in patients with BC.

Conditional disease‐free survival rates and their associated determinants in patients with epithelial ovarian cancer: A 15‐year retrospective cohort study

AbstractBackgroundThe most common type of ovarian cancer (OC) is epithelial ovarian cancer (EOC) which is the most lethal gynecologic malignancy in adult women.AimThis study aimed to determine the conditional disease‐free survival (CDFS) rates and their associated determinants in patients with EOC.Methods and resultsThe clinical and demographic data of 335 patients with confirmed EOC at Motahari Clinic (Shiraz, Iran) were retrospectively reviewed and analyzed. Traditional DFS (TDFS) and CDFS were calculated using the Kaplan–Meier method and cumulative DFS estimates, respectively. To evaluate the effects of the prognostic determinants on the DFS of the patients, a multiple covariate Cox analysis using the landmarking method was applied.The 1‐ and 3‐year TDFSs were 81.1% and 47.0%, respectively, and decreased over time. At baseline, a higher stage tumor and endometrioid histology were associated with a higher risk of recurrence when compared to stage I and other histological subtypes, respectively. The hazard of recurrence for older women (age ≥55 years) was approximately twice and three times more than that of women aged <45 years at 1‐ and 3‐year landmark time points, respectively.ConclusionThe age at diagnosis, defined by a cut‐off of 55 years, was a prognostic factor for the CDFS of EOC women. Moreover, patients with advanced‐stage EOC (ASEOC) (stages III and IV) and endometrioid histology had poorer CDFSs compared to those with early‐stage EOC (ESEOC) (stages I and II) and other histological types. In ESEOC patients with age at diagnosis of >55 years, CDFS gradually decreased in 3 years after remission which should be considered for follow‐up care decision‐making.

Study of the Role of the Tumor Microenvironment in Ovarian Cancer ( MICO ): A Prospective Monocentric Trial

ABSTRACT Background Ovarian cancer (OC) is one of the most aggressive tumors requiring new therapeutic approaches. Immunotherapy represents an opportunity, but to date, OC patients do not appear to benefit from current protocols. A better understanding of the composition of the tumor microenvironment (TME), especially in its immune components, could unveil mechanisms of immune suppression in a useful way to predict response to therapies and develop new therapeutic approaches. Method The MICO (tumor MICroenvironment of Ovarian cancer) study is a single‐center observational study. Starting from peritoneal biopsy of high‐grade serous ovarian carcinoma (HGSOC), the purpose of the MICO study is to generate tumor patient‐derived organoid (PDOs) cultures and evaluate the concordance between in vitro platinum‐based chemotherapy sensitivity and in vivo sensitivity. Simultaneously, we will characterize through multiparameter cytofluorimetric analysis the composition of the OC TME, focusing on B lymphocytes and mast cells whose roles in ovarian cancer remain controversial and underinvestigated. Furthermore, patients experiencing recurrence will be longitudinally followed to monitor changes in the TME composition and the responsiveness of PDOs to in vitro stimulation with drugs. Discussion The association between the composition of the TME, the reactivity of the PDOs, and patients' disease progression will be analyzed to identify whether specific subpopulations of tumor‐infiltrating immune cells could be predictive factors of the disease outcomes. The comparison of molecular profiles, in vitro response to drugs, and clinical‐pathological data will allow the definition of a pattern capable of predicting the response of the primary tumor for the identification of those patients who may benefit from specific treatment. Strengths and Limitations The results of our study could help to better understand the OC behavior, may have implications for the development of effective immunotherapy and targeted pharmacological therapies for epithelial OC in a personalized medicine perspective. This will be a monocentric trial with an involvement of only 43 patients, so further studies will need to confirm our results. Trial Registration The clinical trial has been registered at Clinical‐Trials.gov with the identifier NCT06272240 on 02/14/2024

Cervical Cancer Screening and Associated Factors Among Women of Reproductive Age in Sidama Regional State of Ethiopia: A Cross‐Sectional Survey

ABSTRACT Background Africa and sub‐Saharan Africa reported higher cervical cancer cases globally. Cervical cancer is the second most leading cause of cancer in Ethiopia. Yet, the evidence was low for cervical cancer screening practices in Ethiopia. Aim In this study, we assessed the cervical cancer screening and associated factors among reproductive‐age women in Sidama Region, Bensa, Ethiopia. Methods A facility‐based cross‐sectional study design was conducted from January 1, 2023 to March 30, 2023 in Bensa district. Data were collected using a pre‐tested and structured questionnaire. Multivariable logistic regression was used to identify the associated factors with knowledge, attitude, and practice of cervical cancer screening. Results One hundred forty‐seven 147 (36.7%) had good knowledge, 218 (54.4%) had a favorable attitude towards cervical cancer screening and only 60 (15%) respondents were screened for cervical cancer. Women having better educational status was 1.6 (AOR: 95% CI: 1.0, 2.5) times more likely to have knowledge of cervical cancer screening. Women being the protestant religion followers (AOR: 1.9; 95% CI; 1.0–3.4), Sidama ethnic group (AOR: 4.5; 95% CI: 2.1–9.7), having no formal education (AOR: 1.7; 95% CI: 1.1–2.7), and having good knowledge of cervical cancer (AOR: 2.2; 95% CI: 1.4–3.4) were associated with a positive attitude towards screening for cervical cancer. The odds of cervical cancer screening were low among Amhara's ethnic categories (AOR: 0.2; 95% CI: 0.1–0.5), while higher in women with single marital statuses (AOR: 2.4; 95% CI: 1.2–4.8), and those who have information about cancer screening (AOR: 2.0; 95% CI: 1.1–3.8). Conclusion The results of this study showed that cervical cancer screening practice was low. The respondents' knowledge and education status were positively associated with screening for cervical cancer.

Necroptosis‐related regulatory pattern and scoring system for predicting therapeutic efficacy and prognosis in ovarian cancer

AbstractBackgroundOvarian cancer is difficult to treat and is, therefore, associated with a high fatality rate. Although targeted therapy and immunotherapy have been successfully used clinically to improve the diagnosis and treatment of ovarian cancer, most tumors become drug resistant, and patients experience relapse, meaning that the overall survival rate remains low.AimsThere is currently a lack of effective biomarkers for predicting the prognosis and/or outcomes of patients with ovarian cancer. Therefore, we used published transcriptomic data derived from a large ovarian cancer sample set to establish a molecular subtyping model of the core genes involved in necroptosis in ovarian cancer.Methods and ResultsClustering analysis and differential gene expression analyses were performed to establish the genomic subtypes related to necroptosis and to explore the patterns of regulatory gene expression related to necroptosis in ovarian cancer. A necroptosis scoring system (NSS) was established using principal component analysis according to different regulatory patterns of necroptosis. In addition, this study revealed important biological processes with essential roles in the regulation of ovarian tumorigenesis, including external encapsulating structure organization, leukocyte migration, oxidative phosphorylation, and focal adhesion. Patients with high NSS scores had unique immunophenotypes, such as more abundant M2 macrophages, monocytes, CD4+ memory T cells, and regulatory T cells. Immune checkpoint CD274 had a greater expression in patients with high NSS values.ConclusionThis NSS could be used as an independent predictor of prognosis to determine the sensitivity of ovarian cancer to various small‐molecule inhibitors, immune checkpoint inhibitors, and platinum‐based chemotherapy drugs.

Exploitation of Biocomputational Approaches for siRNA ‐Mediated Gene Silencing of HPV : A Novel Therapeutic Strategy for Cervical Cancer

ABSTRACT Background With recurrent high‐risk human papillomavirus (HPV) infections, especially HPV16 and HPV18, cervical cancer is the fourth most common disease among women. The functional alterations of the E6 and E7 proteins are essential to the oncogenic process of high‐risk HPVs and cervical cancer development. Aims The objective of this research is to design highly targeted and efficient small interfering RNAs (siRNAs) that target both HPV16 and HPV18, employing cutting‐edge computational approaches to enhance therapeutic potential through a systematic bioinformatics‐driven approach. Methods and Results This study utilized the i‐Score Designer to identify and evaluate four potential small interfering RNAs (siRNAs) (E6_69, E6_451, E7_66, and E7_193) based on various algorithm criteria, including Ui‐Tei, Amarzguioui, i‐Score, and Reynolds scores. Consequently, a docking analysis was conducted to elucidate the intermolecular interactions between the RNA‐induced silencing complex (RISC) proteins and the designed siRNAs. All siRNAs passed the recommended cutoff values, indicating a strong potential for gene silencing. Thermodynamic and structural analyses revealed that the designed siRNAs had favrable melting temperatures and free energies, suggesting adequate stability for effective gene silencing. Further, docking analysis demonstrated significant binding affinities and interaction profiles with the major RISC proteins (Dicer, Ago2, TRBP). The E6_69 and E7_193 significantly showed strong binding and intermolecular interactions, especially with Ago2, highlighting the potential for HPV gene silencing. Conclusion The study revealed the potential of the designed siRNAs in silencing the E6 and E7 genes and their therapeutic applications against HPV. Future research should focus on validating these findings across various experiments, both in vivo and in vitro, and exploring alternative delivery approaches to enhance therapeutic efficacy.

Successful Diagnosis and Treatment of Early Postpartum Choriocarcinoma

ABSTRACTBackgroundPostpartum placental choriocarcinoma is a rare gestational trophoblastic tumor, with an incidence of approximately one in 50 000. Patients often present with persistent postpartum hemorrhage, which can lead to delayed diagnosis, hematogenous metastasis, and ultimately, a poor prognosis.CaseA 35‐year‐old woman was admitted to the Emergency Department 39 days after a cesarean section due to persistent heavy vaginal bleeding. Initial evaluation revealed a serum β‐human chorionic gonadotropin (β‐hCG) level of 7868 mIU/mL, transvaginal ultrasound identified a vascularized uterine mass with myometrial invasion, and MRI suggested residual tissue implantation. Following exclusion of retained products of conception, postpartum choriocarcinoma was suspected. The patient underwent five cycles of FAV chemotherapy (fluorouracil + actinomycin D + vincristine), resulting in undetectable β‐hCG levels and resolution of imaging findings after two cycles. Three additional consolidation cycles were administered, with complete remission confirmed at the final follow‐up.ConclusionPregnancy‐related causes must always be ruled out in women of childbearing age who present with irregular vaginal bleeding, even during the postpartum and lactation periods. In patients with postpartum bleeding, vigilance should be heightened to rule out the possibility of a pregnancy‐related Sertoli cell tumor.

Integrative Genomic and Functional Approaches Identify FUOM as a Key Driver and Therapeutic Target in Cervical Cancer

ABSTRACTBackgroundCervical cancer remains a global public health challenge, particularly in regions with limited access to screening and vaccination. While high‐risk HPV infection is the primary cause, the genetic and molecular mechanisms driving cervical cancer progression are not fully understood.ObjectiveThis study integrates Mendelian randomization (MR) and single‐cell RNA sequencing (scRNA‐seq) to identify causal eQTL‐related genes and explore their roles in tumorigenesis. Functional experiments were conducted to validate key findings.MethodsMR analysis identified eQTL‐related genes with significant causal associations with cervical cancer. Functional enrichment and Gene Set Variation Analysis (GSVA) revealed their involvement in key pathways. scRNA‐seq explored cell‐specific expression patterns and immune cell infiltration in the tumor microenvironment (TME). In vitro experiments, including qRT‐PCR, siRNA knockdown, migration, proliferation, and colony formation assays, validated the biological roles of pivotal genes.ResultsA total of 307 eQTL‐related genes were identified, enriched in pathways such as Th17 cell differentiation, TNF, and IL‐17 signaling. scRNA‐seq revealed cell‐specific expression of key genes, including FUOM, which was elevated in cervical cancer cells. FUOM knockdown significantly reduced cell proliferation (by 37%, p < 0.001), migration (by 43%, p < 0.001), and colony formation (by 62%, p < 0.001). Regulatory analysis identified miRNAs as upstream modulators of these genes.ConclusionThis study identifies FUOM as a novel driver gene in cervical cancer progression and highlights its role in tumorigenesis and immune modulation. These findings provide insights into potential biomarkers and therapeutic targets, offering a foundation for personalized treatment strategies.

CareHPV, Papanicolaou Positivity Status, and Their Association With Behavioral Risk Factors in Rural Women of Kamrup District, Assam, India

ABSTRACTBackground and ObjectivesScreening of rural women of Assam by careHPV test for high‐risk HPV (hr‐HPV) DNA and Papanicolaou (PAP) test for abnormal cytology.MethodThis prospective cross‐sectional study included 480 non‐pregnant women participants aged 20–70 years from Kamrup District, Assam. Two cervical scrap samples were obtained from eligible enrolled women. The Hr‐HPV DNA test by CareHPV was performed with one cervical scrap, and a second cervical scrap sample was used for the Papanicolaou (PAP) test. The statistical analysis was done using RStudio for variables. A p‐value < 0.05 was considered to be statistically significant.ResultsWomen having positive hr‐HPV DNA outcomes were 3.33% (16/480) and 7.7% (37/480) women had positive PAP. Tobacco chewing was significantly associated with positive hr‐HPV DNA (p = 0.04) and positive PAP (p = 0.03) status. Alcohol‐consuming women have a significantly higher risk of positive hr‐HPV DNA (p < 0.00001) and positive PAP (p‐0.04) outcomes. Irregular menstruation (p = 0.004) and urogenital tract infection (p = 0.008) also have significant risk for a positive hr‐HPV DNA status. The positive hr‐HPV DNA status was also significant in women having > 3 numbers of children birth (p = 0.003).ConclusionWe found that the positive hr‐HPV DNA status among rural women in Kamrup, Assam, was significantly associated with alcohol consumption, tobacco chewing, irregular menstruation, urogenital tract infection, and more than three children birth. The abnormal cytology outcome was also substantially associated with tobacco chewing and alcohol consumption.

CircFAM188A Regulates Autophagy via miR‐670‐3p and ULK1 in Epithelial Ovarian Carcinoma

ABSTRACTBackground and AimsCircRNAs and autophagy are closely involved in the physiological and pathological processes of ovarian cancer; however, their exact mechanisms are still undetermined. This investigation aimed to elucidate the function and associated pathways of circFAM188A, which modulates proliferation, autophagy, and invasion in ovarian cancer (EOC).MethodsThe expression of circFAM188A in the tissues of EOC patients was assessed via RT‐PCR. To elucidate proliferation, invasion, and autophagy in the tumor cells, Transwell, 5‐ethynyl‐2′‐deoxyuridine (EdU), and mRFP‐GFP‐LC3 reporter assays were conducted. The binding sites between circ‐FAM188A and the miR‐670‐3p, miR‐670‐3p and YY1 were predicted using bioinformatics and verified by dual‐luciferase reporter assays. Pulldown assays demonstrated binding between ULK1 and circ‐FAM188A. ULK1 was found to be crucial in the initial stage of autophagy. Moreover, an in vivo xenograft model was established by subcutaneous injection of nude mice with EOC cells.ResultExpression of circ‐FAM188A was increased in EOC tissues relative to normal ovarian tissues and circ‐FAM188A overexpression promoted proliferation, invasion, and autophagy; these effects were reversed by circ‐FAM188A silencing. miR‐670‐3p and circ‐FAM188A co‐localized in the cytoplasm. circ‐FAM188A enhanced YY1 expression by sponging miR‐670‐3p and was also shown to interact with ULK1.ConclusionIt is thus suggested that circ‐FAM188A modulates autophagy by sponging miR‐670‐3p as well as interacting with ULK1.

Identification of prognostic factors and construction of nomogram to predict cancer‐specific survival for patients with ovarian granulosa cell tumors

AbstractBackgroundOvarian granulosa cell tumors (OGCTs) feature low incidence, indolent growth and late recurrence. Treatment for recurrent OGCTs is challenging.MethodsThe present study was designed to explore the prognostic factors and establish a nomogram to predict cancer‐specific survival (CSS) for OGCTs patients. Enrolled in the study were 1459 eligible patients in the Surveillance, Epidemiology, and End Results (SEER) database, who were randomized to the training (n = 1021) or testing set (n = 438) at a ratio of 7:3. Univariate and multivariate Cox regression analyses were employed to screen the prognostic factors. The predictors were determined by using the Least absolute shrinkage and selection operator (LASSO) regression analysis. The model was constructed via the Cox proportional hazards risk regression analysis. The performance and clinical value of the nomograms was assessed with C‐index, calibration plots, and decision curve analysis.ResultsAge, pTNM stage, tumor size, surgery of the primary tumor, surgery of regional lymph nodes (LNs), residual disease after surgery, and chemotherapy were considered as significant predictive factors for CSS in OGCTs patients. After screening, the prognostic factors except surgery of regional LNs and chemotherapy were employed to build the nomogram. With desirable discrimination and calibration, the nomogram was more powerful in predicting CSS than the American Joint Committee on Cancer staging system in clinical use.ConclusionThis novel prognostic nomogram, which comprises a stationary nomogram and a web‐based calculator, offers convenience for clinicians in personalized decision‐making including optimal treatment plans and prognosis assessments for OGCTs patients.

Urologic Fistulas in Czech Women With Gynaecologic Malignancies

ABSTRACTIntroductionIn developed countries, urologic fistulas arise mainly from malignancies, radiotherapy, or surgical trauma. Hysterectomy and radiation therapy are both critical components of the treatment of women with cancers. Urologic fistulas significantly reduce the quality of life of cancer patients, and may result in delays or even refusal of adjuvant treatment by these patients, thereby negatively impacting both short‐ and long‐term cancer survival.Materials and MethodsA 10‐year retrospective study of urologic fistulas associated with gynaecologic malignancies at the University hospital Hradec Kralove, Czech Republic was conducted. Descriptive statistics of the fistula and treatment characteristics of women with malignant fistulas were conducted using the NCSS 22 statistical software program (NCSS, Keysville, Utah).ResultsCervical cancer was mostly commonly associated with urologic fistulas (36, 76.8%). Most of the malignant fistulas were complex (41, 87.2%) vesicovaginal (23, 48.9%) fistulas (VVFs). More than two‐thirds (33, 70.2%) of the fistulas were diagnosed following radiotherapy, with a time interval from radiotherapy to fistula diagnosis of between 3.00 and 14.50 years. Primary fistuloraphy was performed for all the six cases with simple VVFs and seven (41.2%) of the 17 patients with complex VVFs. Treatment success rate was 83.33% and 14.3% for simple and complex fistulas, respectively. All the failed complex fistula repairs recurred.ConclusionMalignant fistulas predominantly follow radiotherapy for cervical cancers, and are usually detected up to 15 years post‐radiotherapy. Most are complex VVFs, which are difficult to treat, with a high rate of recurrence.

Omentum provides a special cell microenvironment for ovarian cancer

AbstractBackgroundOvarian cancer seriously threatens women's health because of its poor prognosis and high mortality. Due to the lack of efficient early detection and screening methods, when patients seek doctors' help with complaints of abdominal distension, back pain and other nonspecific signs, the clinical results always hint at the widespread metastasis of disease. When referring to the metastasis of this disease, the omentum always takes precedence.Recent findingsThe distinguishing feature of the omentum is adipose tissue, which satisfies the energy demand of cancer cells and supplies a more aggressive environment for ovarian cancer cells. In this review, we mainly focus on three important cell types: adipocytes, macrophages, and mesenchymal stem cells. Besides, several mechanisms underlying cancer‐associated adipocytes (CAA)‐facilitated ovarian cancer cell development have been revealed, including their capacities for storing lipids and endocrine function, and the release of hormones, growth factors, and adipokines. Blocking the reciprocity among cancer cells and various cells located on the omentum might contribute to ovarian cancer therapy. The inhibition of hormones, growth factors and adipokines produced by adipocytes will be a novel therapeutic strategy. However, a sufficient number of trials has not been performed. In spite of this, the therapeutic potential of metformin and the roles of exercise in ovarian cancer will be worth mentioning.ConclusionIt is almost impossible to overcome completely ovarian cancer at the moment. What we can do is trying our best to improve these patients' prognoses. In this process, adipocytes may bring promising future for the therapy of ovarian cancer.

Risk Factors for Cervical Cancer inGhana

ABSTRACTBackgroundThe major burden of cervical cancer occurs in low‐ and middle‐income countries. In Ghana, it is the second most common cancer among women. Infection with high‐risk human papilloma virus (HPV) has been established as the cause of cervical cancer. As such, it is important to identify risk factors that may affect progression from HPV infection to cancer.AimsWe assessed the risk factors assocaited with cervical cancer in Ghana.MethodsTo identify the risk factors for cervical cancer, we conducted an unmatched case–control study in two hospitals in Ghana where most cervical cancer cases are diagnosed. Women with histologically confirmed cervical cancer were the cases, whereas women without cancer seeking care at the two hospitals were controls. A structured questionnaire was administered to the women, after which cervical samples were sent for HPV deoxyribonucleic acid (DNA) testing.ResultsOverall, 206 cases and 230 controls were recruited. After adjusting for possible confounders, women with the highest educational level had a significantly lower risk of cervical cancer than those with no or little formal education. Parity was a major risk factor (odd ratio [OR] for five or more children = 7.9; 95% CI: 2.3–27.6), with risk increasing with increasing parity (pfor trend <0.001). Women reporting the use of a homemade sanitary towel during menstruation also had an increased risk of cervical cancer compared with women who used a pad (OR: 7.3; 95% CI: 2.5–22.0).ConclusionIn this Ghanaian population, high parity and poor personal hygienic conditions were the main contributing factors to the risk of cervical cancer after adjustment for the presence of high‐risk HPV genotypes.

Brain Metastases in Cervical Cancer: A Global Systematic Review and Meta‐Analysis of Incidence and Clinicopathological Features

ABSTRACT Background Cervical cancer (CC) remains the fourth most prevalent malignancy among women globally, with a disproportionate burden in low‐ and middle‐income countries, where it is often diagnosed at advanced or metastatic stages. Aims Despite an increasing number of case reports and institutional studies on brain metastases (BMs) arising from CC, current understanding of their epidemiology, clinical presentation, and prognostic implications remains fragmented and lacks comprehensive synthesis. Methods We executed a systematic and unrestricted search of five major databases, PubMed/Medline, Scopus, Embase, Web of Science, and Google Scholar, covering all records up to April 19, 2025. Studies were eligible for inclusion if they provided a clear report on the incidence of BMs among CC patients. The quality and risk of bias of the selected studies were independently appraised using the Joanna Briggs Institute (JBI) assessment criteria. For statistical analysis, we utilized STATA version 17, implementing random‐effects meta‐analytical models to estimate the aggregated incidence along with corresponding 95% confidence intervals (CIs). Results A total of 17 studies encompassing 33 datasets were included in the final analysis. The global pooled incidence of BMs among cervical cancer patients was estimated at 0.65% (95% CI: 0.46–0.85). Incidence was highest in Turkey (1.83%, 95% CI: 0.91–2.75) and lowest in South Africa (0.22%, 95% CI: 0.0–0.47). Among histologic subtypes, neuroendocrine carcinoma exhibited the highest pooled incidence of BMs at 10.60% (95% CI: 0.0–21.63), followed by adenocarcinoma at 0.89% (95% CI: 0.14–1.64). The pooled mean survival time following the diagnosis of BMs was 6.80 months (95% CI: 5.08–8.52), while the mean interval from the initial cervical cancer diagnosis to the development of BMs was 28.15 months (95% CI: 24.27–32.03). Conclusion Although BMs in cervical cancer are rare, they are associated with dismal survival outcomes and poor prognosis. These findings underscore the importance of vigilant surveillance in high‐risk patients and may inform the development of more targeted and effective therapeutic and preventive strategies.

Impact of virtual education based on health belief model on cervical cancer screening behavior in middle‐aged women: A quasi‐experimental study

AbstractBackgroundCervical cancer is one of the most common cancers in women worldwide and a cause of high mortality among people. Pap smear screening is an appropriate method to prevent cervical cancer and reduce its mortality.AimThis study aimed to determine the effect of web‐based education based on the Health Belief Model (HBM) on cervical cancer screening behavior in middle‐aged women.Methods and ResultsThis study is a quasi‐experimental interventional research that was conducted on 240 middle‐aged women aged 40–59 years in Isfahan, Iran, in 2022. An online educational intervention based on the constructs of the Health Belief Model was conducted for the intervention group using the Triple‐B platform. The information on the intervention and control groups was collected before, immediately after the intervention, and 2 months later using a valid questionnaire. The gathered Data was analyzed using ANOVA and LSD post‐hoc, independent samples t test, chi‐square, and MANCOVA statistical tests in SPSS 26 software. After the intervention, the mean scores of knowledge, perceived susceptibility, perceived severity, perceived benefits, self‐efficacy, and internal cues to action in the intervention group increased and the mean score of perceived barriers decreased (p < .001). The mean score of the external cues to action did not show a significant difference between the intervention and control groups before, immediately, and 2 months after the intervention. Two months after the intervention, 32 women (26.2%) in the intervention group and two women (1.7%) in the control group performed the Pap smear test.ConclusionWeb‐based educational intervention based on HBM using different strategies such as question and answer, presentation of infographics, lectures, brainstorming, showing videos and numerous educational images can be an effective way for increasing knowledge and cognitive variables of women and doing Pap smear test.

Clinical advantage and outcomes of computed tomography‐based transvaginal hybrid brachytherapy performed only by sedation without general or saddle block anesthesia

AbstractBackgroundThree‐dimensional image‐guided brachytherapy is the standard of care in cervical cancer radiotherapy. In addition, the usefulness of the so‐called “hybrid brachytherapy (HBT)” has been reported, which involves the addition of needle applicators to conventional intracavitary brachytherapy for interstitial irradiation.AimTo evaluate the clinical outcomes of CT‐based HBT consisting of transvaginal insertion of needle applicators (CT‐based transvaginal HBT) and only intravenous sedation without general or saddle block anesthesia.Methods and resultsThis is a retrospective chart review of patients who received definitive radiotherapy, including CT‐based transvaginal HBT, between February 2012 and July 2019. The inclusion criteria were as follows: (i) histologically diagnosed disease, (ii) untreated cervical cancer, (iii) International Federation of Gynecology and Obstetrics (FIGO) stage IB1–IVA disease in the 2008 FIGO staging system, and (iv) patients who underwent CT‐based transvaginal HBT at least once in a series of intracavitary brachytherapy. Overall, 54 patients fulfilled the eligibility criteria in the present study. The median follow‐up period was 32 (IQR, 19–44) months. No patient complained of symptoms such as persistent bleeding or abdominal pain after the treatment. The 3‐year local control (LC), disease‐free survival, and overall survival rates for all 54 patients were 86.6%, 60.3%, and 90.7% (95% CI [81.3%–100.0%]), respectively. The 3‐year LC rate was 87.7% in patients with FIGO III–IVA and 90.4% in tumor size >6.0 cm. The incidence rate of late adverse events, grade ≥3, in the rectum and bladder was 0% and 1.8%, respectively. In the dose‐volume histogram analyses, transvaginal HBT increased the dose of HR‐CTVD90 by ~7.5% without significantly increasing the dose of organs at risk.ConclusionConsidering the favorable clinical outcomes, CT‐based transvaginal HBT may be a good option for treating cervical cancer.

Influence of Pre‐Vaccination HPV Status on Vaccine Effectiveness Among Chinese Women: A Multicenter Cross‐Sectional Study

ABSTRACTBackground and AimsHuman papillomavirus (HPV) vaccines have been available in China for only 8 years, and routine HPV testing is not recommended prior to vaccination. Therefore, evaluation of HPV vaccine effectiveness and the impact of pre‐vaccination HPV infection status on vaccine protective effect in Chinese women is warranted.MethodsFrom June 2022 to June 2023, women aged 18 to 50 years without a history of cervical or uterine excision were recruited from three medical institutions. Baseline characteristics were compared between vaccinated and unvaccinated participants, with inverse probability treatment weighting (IPTW) applied to adjust for confounding factors. HPV infection rates and vaccine effectiveness (VE) were calculated. Additionally, a sub‐group analysis was conducted among vaccinated women to explore the impact of pre‐vaccination HPV infection status.ResultsAfter adjusting for group differences, the vaccine effectiveness against new HPV16/18 infections was 76.1% (95% CI: 58.7%–86.2%) among 2285 participants. Older age and possession of a master's degree or higher were identified as protective factors, whereas increased parity and exclusive use of oral contraceptives were determined to be risk factors for HPV16/18 infection. Women with unknown pre‐vaccination HPV status exhibited significantly higher post‐vaccination rates of high‐risk HPV infections (RR 4.278, 95% CI: 2.537–7.215) compared to those who were HPV‐negative prior to vaccination. However, no significant difference in new high‐risk HPV infection rates was observed between pre‐vaccination HPV‐negative and HPV‐positive women.ConclusionIn addition to HPV vaccination, factors such as age, parity, exclusive use of oral contraceptives, and higher education attainment were independently associated with HPV16/18 infection rates. Pre‐vaccination HPV infection status did not significantly influence the protective efficacy of the HPV vaccine against previously unencountered HPV types.

Evaluating Sequencing Strategies for Endometrial Microbiome Profiling in Endometrial Cancer: A Comparative Study of Short‐ and Long‐Read 16S rRNA Approaches

ABSTRACT Background Endometrial cancer (EC) is the most common gynaecological malignancy globally, with rising incidence and notable disparities in outcomes. In New Zealand, EC rates have increased significantly, particularly among Māori and Pacific women, who face higher risks of advanced disease and poorer outcomes. Microbial dysbiosis has been implicated in EC pathogenesis, but characterising the uterine microbiome is challenging due to low microbial biomass and high contamination risk. Aims This study aimed to pilot a protocol that could inform the preparation of a larger cohort trial. Short‐read Illumina MiSeq and long‐read Oxford Nanopore Technologies (ONT) 16S rRNA gene sequencing were investigated to profile the uterine microbiome in people with EC. Methods and Results Uterine and vaginal swabs were analysed to assess platform performance in terms of DNA recovery, sequencing success, diversity metrics, and taxonomic resolution. The impact of sample freezing or immediate lysis prior to DNA extraction was also evaluated. ONT sequencing provided enhanced species‐level resolution and improved detection of low‐abundance taxa but showed variable performance in low‐yield samples. Freezing prior to cell DNA extraction modestly increased bacterial 16S copy numbers and improved community consistency. Contamination was a problem across both platforms, particularly in low‐biomass samples, but can be minimised during data analysis. Conclusion This study provides practical guidance for sequencing platform selection and sample handling in uterine microbiome research. Our findings support future efforts to elucidate microbial contributions to EC pathogenesis and highlight the importance of rigorous contamination control. Importantly, this is the first presentation of a New Zealand cohort and contributes valuable data from an underrepresented population and informs future research in diverse clinical settings.

Establishment of a Model to Predict the Prognosis of Endometrial Carcinoma Using Tumor‐Infiltrating Lymphocytes Evaluated With Artificial Intelligence: A Retrospective Analysis

ABSTRACT Background The objective of this study was to establish a new model for predicting the prognosis of endometrial carcinoma (EC) using tumor‐infiltrating lymphocytes (TILs) based on artificial intelligence (AI). Methods Patients with EC who were treated between 1989 and 2022 were included in this study. For each patient, one hematoxylin and eosin‐stained slide containing the most invasive frontline of the tumor was selected and digitized. The area within a 500 μm width span, extending 250 μm toward the stroma and tumor from the manually annotated invasive frontline, was automatically annotated. The average number of lymphocytes per area (μm 2 ) in the annotated area was calculated using AI. Patients were classified into the High‐TIL and Low‐TIL groups, and survival analysis was conducted. Four mismatch repair (MMR)‐related proteins were evaluated using immunohistochemical staining. Results A total of 659 patients were included: 346 (52.5%) in the High‐TIL group and 313 (47.5%) in the Low‐TIL group. MMR deficiency was observed more frequently in the High‐TIL group than in the Low‐TIL group ( p  < 0.01). Progression‐free survival (PFS) and overall survival (OS) were better in the High‐TIL group than in the Low‐TIL group (both p  < 0.01). Multivariate analysis revealed that TIL status was a prognostic factor for PFS (hazard ratio [HR] (95% confidence interval [CI]) 0.61 (0.43–0.87); p  < 0.01) and OS (HR (95% CI) 0.54 (0.33–0.86); p  = 0.01). Conclusion TILs evaluated using AI could accurately and significantly predict the prognosis of EC. Further studies are needed to establish new methods for evaluating TILs in ECs.

Bacterial Infections Role in Gynecological Cancers Development: Narrative Review

ABSTRACT Background Gynecological cancers are among the most common cancers in women that affect female reproductive organs. The most common gynecological cancers are ovarian, cervical, uterine/endometrial, vaginal, and vulvar cancer. Women's reproductive organs have a dynamic and relative microbial balance. The disruption in the balance of the microbiome could result in numerous gynecological diseases, as well as, gynecological cancers. In this study, we aimed to review new findings on the role of different bacterial infections in various types of gynecological cancers. Recent Findings The role of bacterial infection, as an external factor, has been established in several cancers. However, the ways in which bacteria can promote the development of cancer are not fully understood. It seems that inflammation induced by bacterial infections could promote carcinogenesis. In addition, bacterial toxins and effector proteins play important roles in the progression of cancer. In this review, we attempt to present the different bacterial infections, which have been linked to gynecological cancers development. According to different researches, Chlamydia , Mycoplasma , and Bacteroides spp. are the most common bacterial infections associated with gynecological cancers. Conclusion Evaluation of microbiome in reproductive organs of the patients with gynecological cancer and studies on prevention and control of the infections in the patients could be useful in verification of pathogenesis of the diseases and also founding suitable therapeutic interventions.

Ovarian Cancer Mortality Predictors in Public Oncology Centers, Addis Ababa, Ethiopia: A Case–Control Study

ABSTRACT Background Ovarian cancer remains the most lethal gynecologic cancer and has the worst prognosis among all female reproductive malignancies worldwide. In Ethiopia, ovarian cancer is the third most prevalent malignancy among women, following breast and cervical cancers. Despite extensive research on the topic, evidence regarding the determinants of mortality among ovarian cancer patients remains limited. Therefore, the primary aim of this study was to identify predictors of ovarian cancer mortality among patients receiving care at oncology centers in Addis Ababa, Ethiopia. Methods A facility‐based case–control study was conducted among women with ovarian cancer enrolled at oncology centers in Addis Ababa. A total of 137 cases and 274 controls were selected using the stratified sampling method. Data were extracted from patient records with a structured data extraction tool. The effect of each predictor variable on ovarian cancer mortality was estimated using binary logistic regression at the 5% level of significance and the final model's goodness of fit was tested with the likelihood ratio test. Results This study included 411 ovarian cancer patients. Advanced FIGO stage (III&IV) (AOR: 2.85, 95% CI: [1.27–6.39]), advanced age (≥ 60) (AOR: 8.71; 95% CI: [3.89–19.48]), and comorbidity (AOR: 3.24, 95% CI: [1.69–6.19]) were found to be independent predictors of mortality, whereas urban residency (AOR: 0.36; 95% CI: [0.19–0.66]) and nonepithelial histological type (AOR: 0.12, 95% CI: [0.03–0.53]) were found to be protective factors. Moreover, patients not receiving pain medication had lower odds of mortality (AOR: 0.39; 95% CI: [0.22–0.69]). Conclusions Multivariable logistic regression analysis identified the following factors as significant predictors of mortality among ovarian cancer patients: advanced FIGO stage, comorbidities, advanced age, nonepithelial histology, pain medication, and urban residency. Therefore, early detection through timely clinical evaluation and diagnosis and treatment should be emphasized. Moreover, patients identified with significant predictors of mortality should receive targeted clinical attention and closer follow‐up to improve survival outcomes.

Conservative Resolution of a Vesicovaginal Fistula Including Laser Therapy in a Patient Who Underwent Recurrent Surgery After Prior Radiotherapy for Endometrial Cancer

ABSTRACTBackgroundIsolated vaginal vault recurrence of endometrial cancer can be treated with rescue radiotherapy. However, in previously irradiated patients, surgical resection can be considered the treatment of choice. Vesicovaginal fistulas (VVFs) sometimes complicate the surgical intervention because of the presence of massive ischemia and fibrosis of pelvic tissue from previous irradiation. Traditional strategies for the treatment of VVFs include endoscopic treatment (when feasible) or a laparoscopic, robotic, or open abdominal approach in some experiences through a transvesical route. The last approach can be associated with long inpatient hospital stays, postoperative complications, and failure, especially in obese patients. Our report proposes a conservative approach with prolonged catheterization and placement of nephrostomy tubes to treat a VVF with laser therapy of the fistula.CaseWe present the case of a woman with a second relapse of endometrial cancer at the level of the vaginal vault, after a hysterectomy and then radiotherapy for a first relapse, who underwent robotic partial colpectomy, with an intraoperative bladder lesion, which was repaired with interrupted stitches. However, the patient developed a vesicovaginal fistula. A conservative approach was initially undertaken as an alternative to the surgical repair of the fistula. After the clinical and radiological confirmation of the fistula andconsidering the patient's clinical condition, the multidisciplinary team proposed a conservative management of the fistula as an alternative to fistula surgical repair. Bladder catheter Ch 20 and bilateral nephrostomy did not completely resolve the fistula, with a minor residual linkage between the bladder and the vaginal vault after 8 months from the robotic surgery. A single/month diode laser application for 3 months was added to the conservative treatment. Cystography was negative at the end of laser sessions, and both nephrostomies were removed 1 week later. After 6 months, clinical and radiological follow‐up was negative, and no further vaginal urine loss was recorded.ConclusionWe believe that conservative management of a complex vesicovaginal fistula after multiple treatments for endometrial cancer is possible. In this scenario, laser therapy can be a valuable clinical tool to improve the outcome, with reduced invasiveness for the patient.

Epidemiology of cervical cancer in Iran in 2016: A nationwide study of incidence and regional variation

AbstractBackgroundCervical cancer is a common, and fatal cancer in women worldwide. This cancer is the fourth most common cancer in women after breast, colorectal, and lung cancer.AimsThis study aims to investigate the age‐standardized incidence rate (ASR) and the geographical distribution of Cervical Cancer in Iran.MethodsThis study was designed as a descriptive cross‐sectional investigation. The study sample comprised all individuals registered as cervical cancer patients in the National Cancer Registry system in 2016. The crude rate and ASR for each province were computed independently. Furthermore, we employed ArcMap10.5 software and geographic information system to conduct an analysis of the gathered data. In order to ascertain the spatial distribution and clustering of cervical cancer incidence, we utilized Moran's I, which measures spatial autocorrelation.ResultsWe studied a total of 808 cases of cervical cancer with a median age to be 52.19 years (IQR≈1.35). Among these cases, 685 (84.7%) were diagnosed based on the pathological reports with morphological verification, while 81 patients (10.1%) were clinically identified, and 42 cases (5.2%) were diagnosed using the death certificate‐only method. Squamous cell carcinoma accounted for 61% of all cases (n = 497). The ASR of cervical cancer in Iran was 1.90 per 100 000 populations. The provincial ASR ranged from 0.29 to 5.03 per 100 000, with the highest rates observed in Golestan (5.03), East Azerbaijan (4.07), and Ilam (3.72). We found no clustering patterns in the distribution of provincial crude, age‐specific, and age‐standardized incidence rates (p > .05).ConclusionThe incidence of cervical cancer in Iran was lower than the global average, and we did not identify any significant disparities in the incidence rates among the provinces. Although there were differences in incidence rates among the areas, these were not clustered. It is crucial to remember that cervical cancer is still a major public health issue in Iran, and in order to lessen the disease's burden, national initiatives to enhance screening, early identification, and access to efficient treatment should continue to be top priorities.

Surgical Management of Ovarian Masses in Children: A Comparative Analysis by Pediatric Surgeons and Gynecologists at Two Academic Hospitals in Johannesburg

ABSTRACT Background and Objectives Existing literature on ovarian masses necessitating intervention in children by pediatric surgeons and gynecologists in Low‐ and Middle‐Income Countries is sparse and lacks collaborative standardization in management between the two subspecialties. Therefore, this study seeks to assess the range of ovarian masses presenting to these two specialties and to explore variations in management. Methods A 15‐year retrospective review of surgically biopsied or excised ovarian masses between subspecialties at two academic hospitals in Johannesburg. Results We identified 288 patients, six with bilateral disease and 294 ovarian masses. The mean age was 13.34 years (SD ±5.12). The most common presentation was abdominal pain in 149/288 (51.74%); 117 patients (40.62%) were from pediatric surgery and 171 (59.38%) from gynecology departments. There were 127/288 (44.09%) non‐neoplastic and 161/288 (55.90%) neoplastic lesions, of which 110/161 (68.33%) were benign and 51/161 (31.67%) malignant. The neoplastic lesions consisted of 107/161 (66.45%) germ cells, 28/161 (17.39%) surface epithelial tumors, and 26/161 (16.14%) sex cord‐stromal tumors. Ovarian‐sparing surgery was done in 56/288 (19.44%) patients, 22/117 (18.80%) in pediatric surgery, and 34/171 (19.88%) in gynecology. Laparoscopy was done in 57/288 (19.79%) patients, 24/117 (20.51%) in pediatric surgery, and 19/171 (19.29%) in gynecology. The survival rate in benign masses was 100%, and 86.28% in malignancies. Conclusion This study highlights the diverse spectrum of ovarian masses managed by pediatric surgeons and gynecologists. A laparoscopic approach combined with ovarian preservation, which was comparable between specialties, should be the preferred method for managing benign lesions whenever feasible. These findings underscore the need for standardized, collaborative guidelines between pediatric surgeons and gynecologists to ensure consistent and optimal management of ovarian masses in children.

Global, regional and national burden, incidence, and mortality of cervical cancer

AbstractAimAmong gynecological cancers, cervical cancer is the most common cause of cancer‐related death in developing countries. This study analyzes the incidence, mortality, and burden of cervical cancer using the Global Burden of Disease (GBD) 2019 study.Materials and MethodsThe GBD (2019) data on cervical cancer was extracted from the Global Health Data Exchange (GHDx) query tool. Age‐standardized rate (ASR) incidence, deaths, lost years of life (YLLs), years of life with disabilities (YLDs), and adjusted years of life with disabilities (DALYs) of cervical cancer in women were extracted. Data were extracted globally for 204 countries and groups based on a socio‐demographic index (SDI), World Health Organization (WHO) regions, continents, World Bank regions, and 22 GBD regions.ResultsThe higher standardized age incidence of cervical cancer is in lower SDI countries, Africa, the African region (According to the WHO), and Sub‐Saharan Africa (According to GBD regions). The highest deaths of ASR is in countries with low SDI, low‐income group, Africa, the African region (According to the World Health Organization), and Sub‐Saharan Africa (According to GBD regions). According to SDI classification, the highest DALYs ASR is in low SDI countries, World Bank Low‐income countries, African and then American continents, African region, Sub‐Saharan Africa, and then Latin America & Caribbean‐WB (Based on GBD regions).ConclusionIn 2019, incidence, mortality, and DALYs of cervical cancer mostly affected countries with lower socioeconomic status. Given that cervical cancer is highly preventable, access to screening services and the presence of trained and knowledgeable health care staff can reduce illness, suffering, and death caused by this malignancy. It is recommended to use the national and international potentials to reduce the incidence of this malignancy.

Anthropometric factors and the risk of ovarian cancer: A systematic review and meta‐analysis

AbstractBackgroundExcess weight is convincingly associated with several cancers, but the association with ovarian cancer is insufficiently clarified, in particular regarding subgroups defined by menopausal status and ovarian cancer histologic type.AimsWe carried out a comprehensive systematic review and meta‐analysis of overweight and obesity in relation to ovarian cancer with focus on different subgroups.Methods and ResultsWe searched PubMed and Web of Science for relevant cohort and case–control studies published from inception to June 2021 in English language and using a clear definition of overweight and obesity. We combined maximally adjusted risk estimates using a random effects model. We analyzed data from 15 cohort and 26 case–control studies, including 28 471 ovarian cancer cases. The relative risk of ovarian cancer for overweight and obesity was 1.06 (95% confidence interval [CI] = 1.00–1.12) and 1.19 (95% CI = 1.11–1.28), respectively. Among premenopausal women, increased ovarian cancer risk was noted for overweight (RR 1.34; 95% CI = 1.03–1.75) and obesity (RR 1.51; 95% CI = 1.21–1.88). By comparison, among postmenopausal women no statistically significant association was found for overweight (RR 1.00; 95% CI 0.87–1.14) and obesity (RR1.03; 95% CI = 0.82–1.31). Increased risk was found for mucinous (RR 1.44; 95% CI = 1.03–2.01) and clear cell (RR 1.82; 95% CI = 1.11–2.99) ovarian cancer subtypes, but not for serous (RR1.12; 95% CI = 0.84–1.50;) and endometroid subtypes (RR1.24; 95% CI =0.96–1.60).ConclusionsObesity is associated with increased ovarian cancer risk. That relation is largely due to a positive association between adiposity and ovarian cancer among premenopausal but not postmenopausal women and among cases with mucinous and clear cell but not serous or endometrioid histology.

Identification of dysregulated miRNAs‐genes network in ovarian cancer: An integrative approach to uncover the molecular interactions and oncomechanisms

AbstractBackgroundOvarian (OV) cancer is considered as one of the most deadly malignancies in women, since it is unfortunately diagnosed in advanced stages. Nowadays, the importance of bioinformatics tools and their frequent usage in tracking dysregulated cancer‐related genes and pathways have been highlighted in researches.AimThe aim of this study is to investigate dysregulated miRNAs‐genes network and its function in OV tumors based on the integration of microarray data through a system biology approach.MethodsTwo microarray data (GSE119056 and GSE4122) were analyzed to explore the differentially expressed miRNAs (DEmiRs) and genes among OV tumors and normal tissues. Then, through the help of TargetScan, miRmap, and miRTarBase databases, the dysregulated miRNA‐gene network in OV tumors was constructed by Cytoscape. In the next step, co‐expression and protein‐protein interaction networks were made using GEPIA and STRING databases. Moreover, the functional analysis of the hub genes was done by DAVID, KEGG, and Enrichr databases. Eventually, the regulatory network of TF‐miRNA‐gene was constructed.ResultsThe potential dysregulated miRNAs‐genes network in OV tumors has been constructed, including 109 differentially expressed genes (DEGs), 25 DEmiRs, and 213 interactions. Two down‐regulated microRNAs, miR‐660‐3p and hsa‐miR‐4510, have the most interactions with up‐expressed oncogenic DEGs. CDK1, PLK1, CCNB1, CCNA2, and EZH2 are involved in protein module, which show significant overexpression in OV tumors according to The Cancer Genome Atlas (TCGA) data. EZH2 shows amplification in OV tumors with remarkable percentage. The transcription factors TFAP2C and GATA4 have the pivotal regulatory functions in oncotranscriptomic profile of OV tumors.ConclusionIn current study, we have collected and integrated different data to uncover the complex molecular interactions and oncomechanisms in OV tumors. The DEmiRs‐DEGs and TF‐miRNA‐gene networks reveal the potential interactions that could be a significant piece of the OV onco‐puzzle.

Changes of Microbiome in Human Papillomavirus Infection and Cervical Cancer: A Systematic Review and Meta‐Analysis

ABSTRACT Background and Objectives We aimed to conduct a systematic review and meta‐analysis of high‐throughput sequencing studies to assess changes in microbiome alpha, beta diversity, and composition differences in patients with human papillomavirus (HPV) infection and cervical cancer. Methods The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to include original studies. The effect size estimates with a 95% confidence interval were combined using a random effects model. The meta‐analysis was performed using the Stata MP16 software. Results A total of 64 studies were included, with a meta‐analysis of the diversity index performed on a subset of seven studies. Microbial diversity of patients infected with HPV was observed to be significantly different from that of healthy controls (CHAO index: 95% CI 0.42, 5.03, I 2  = 99.18%, p  < 0.05). Subgroup analysis based on the sample collection region showed a significant difference between vaginal microbiota of the treatment group and control group, as measured by the Shannon index (95% CI 0.12, 0.97, I 2  = 67.09%, p  < 0.05). Further, subgroup analysis of samples sequenced with the primer pair for the V3–V4 region showed a statistically significant difference in alpha diversity (Shannon index: 95% CI 0.28, 0.72, I 2  = 0.00%, p  < 0.05) between treatment and control groups. The microbial diversity varied between patients with inferior cervical lesions (low‐grade squamous intraepithelial lesion) and healthy controls (Shannon index: 95% CI 0.02, 0.58, I 2  = 0.00%, p  < 0.05). The bacterial marker genera differed at each cervical lesion stage. Gardnerella was prevalent during the HPV infection stage, but its proportion decreased after the occurrence of cervical lesions. In contrast, the proportions of Prevotella , Porphyromonas , and Dialister increased during the cervical cancer stages. Conclusions Patients with simple HPV infections frequently exhibit unstable microbial diversity and are influenced by various factors. The microbial environment continues to change after the occurrence of cervical lesions and is correlated with the severity of cervical lesions.

Effect of bariatric surgery on endometrial cancer regression as part of fertility sparing treatment

AbstractIntroductionObesity is a major risk factor in the development of endometrial cancer (EC) in young patients of reproductive age. Fertility sparing treatment is a viable option for a select group of patients with early EC, and involves systemic and intra‐uterine hormonal therapy. Weight loss has been associated with improved outcomes in this group. Bariatric surgery (BS) has been shown to be the most efficient and durable method of weight loss in obese patients. However, there is a paucity of data studying the benefit of BS as part of fertility sparing treatment.MethodsWe present a retrospective case series of five patients who are undergoing fertility sparing treatment for early EC, who also underwent BS for treatment of obesity and related comorbidities. We aim to show early regression of EC for all the patients and also report on the other health benefits of BS.ResultsAll five patients in the series achieved regression of EC within 6 months of undergoing BS. They also achieved significant weight loss consistent with previous studies, and three patients who had comorbidities related to obesity had remission of these conditions. One of the patients with EC regression also managed to conceive with IVF (In‐vitro Fertilisation).ConclusionPatients on fertility sparing treatment for early EC who underwent BS was associated with early regression within 6 months, significant weight loss and resolution of comorbidities. BS could be a promising component of fertility sparing treatment. Long term, prospective studies are required to confirm the benefits reported in this case series.

Forty‐eight‐year‐old female MUTYH carrier presenting with five concurrent primary cancers

AbstractBackgroundMUTYH‐associated polyposis is a rare disorder resulting from mutations involved in DNA mismatch repair. This results in an increased susceptibility to colonic adenomatosis and other cancers. Studies have examined the resulting frequency of extracolonic manifestations; however, these typically occur alone, concurrently, or temporally separate from an already diagnosed colorectal cancer in individuals with a biallelic mutation.CaseReported here is a case of five distinct primary neoplasms presenting simultaneously in a patient monoallelic for an MYH mutation. These neoplasms included squamous cell carcinoma of the vulva, rectal adenocarcinoma, synchronous anal adenocarcinoma, papillary thyroid carcinoma, and ovarian serous psammocarcinoma. Throughout her course, she underwent multiple surgical procedures, neoadjuvant chemoradiation, with further adjuvant therapy, and treatment ongoing. Due to her unique presentation, she underwent genetic testing that demonstrated she was monoallelic for an MYH mutation.ConclusionThe patient had a positive response to her treatment and surgical procedures with ongoing adjuvant therapy. She will continue to undergo further genetic testing, and testing for her children is being considered. This case demonstrates a unique presentation associated with a monoallelic MYH mutation that is not described in the current literature and warrants further investigation.

Development and validation of an immune prognostic signature for ovarian carcinoma

AbstractBackgroundOvarian cancer (OC) causes a significant proportion of cancer‐related deaths in women. Recently, immunotherapy has emerged as a substantial player in cancer treatment. Lymphocyte infiltration, an important indicator of immune activity and disease aggressiveness, can be identified by gene expression profiling of immune‐related genes of tumours which may prove useful in prognosis of patients.AimsThe aim of this study is to identify and validate a novel immune gene‐based prognostic signature for OC.Methods and resultsHere, we extracted the expression of immune‐related genes and performed the Cox regression analysis and identified five genes with significant correlation with survival in training cohort of patients (n = 286). We utilised regression coefficient and expression level of five genes to calculate immune prognostic signature (IPS) score for OC patients. In univariate and multivariate Cox regression analysis with other clinicopathological factors, we showed that IPS is an independent predictor of survival (P value <0.01). More importantly, we utilised 404 patients from TCGA dataset as the validation cohort and validated the survival capability of IPS in the univariate and multivariate analysis (P value <0.001). Interestingly, KM analysis showed a significant difference in survival of patients with high and low IPS score in both datasets (training dataset P value <0.01, validation dataset P value <0.01). Further, we showed that all the five genes are differentially expressed and involved in immune modulation among other pathways. Interestingly, GSEA analysis showed that high IPS patients had low immune activity and activated EMT and other oncogenic pathways.ConclusionIn summary, we have developed and validated robust immune‐related gene‐based prognostic signature to identify the OC patients with high immune activity who can be taken for immunotherapy.

Compliance to treatment guidelines and survival in women undergoing interval debulking surgery for advanced epithelial ovarian cancer

AbstractBackgroundOne of the primary treatment strategies for advanced epithelial ovarian cancers includes neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) and adjuvant chemotherapy. Compliance to treatment is important to possibly improve outcomes.AimTo audit treatment compliance and its effect on overall survival (OS) and disease free survival (DFS) in women undergoing IDS.Methods and ResultsWomen diagnosed with advanced epithelial ovarian cancer undergoing IDS were included. Details of compliance to chemotherapy and surgery as per standard guidelines were assessed, and correlation with survival was studied. Reasons for protocol deviation at various levels were documented and analysed.A total of 182 patients were included. The total number of deviations was 134 with deviation at any level being 89 (48.9%) and at all levels 5%. Both patient‐ and treatment‐related factors contributed towards deviation. Deviation or noncompliance towards treatment resulted in a significantly reduced 5‐year OS (34.4% vs 58.2%; P = .001) compared with compliant patients, which retained its significance on multivariate analysis (P = .024) as well.ConclusionDeviation from treatment guidelines resulted in a significantly lower 5‐year OS compared with those who remained treatment compliant. Both patient‐ and treatment‐related factors contributed towards noncompliance and hence towards lower survival.

Indocyanine green versus technetium‐99m with blue dye for sentinel lymph node detection in early‐stage cervical cancer: A systematic review and meta‐analysis

AbstractBackgroundThe fluorescent dye indocyanine green (ICG) has emerged as a promising tracer for intraoperative detection of sentinel lymph nodes (SLNs) in early‐stage cervical cancer. Although researchers suggest the SLN detection of ICG is equal to the more conventional combined approach of a radiotracer and blue dye, no consensus has been reached.AimsWe aimed to assess the differences in overall and bilateral SLN detection rates with ICG versus the combined approach, the radiotracer technetium‐99m (99mTc) with blue dye.Methods and ResultsWe searched MEDLINE, Embase, and the Cochrane Library from inception to January 1, 2020 and included studies reporting on a comparison of SLN detection with ICG versus 99mTc with blue dye in early‐stage cervical cancer. The overall and bilateral detection rates were pooled with random‐effects meta‐analyses.From 118 studies retrieved seven studies (one cross‐sectional; six retrospective cohorts) were included, encompassing 589 patients. No significant differences were found in the pooled overall SLN detection rate of ICG versus 99mTc with blue dye. Meta‐analyses of all studies showed ICG to result in a higher bilateral SLN detection rate than 99mTc with blue dye; 90.3% (95%CI, 79.8‐100.0%) with ICG versus 73.5% (95%CI, 66.4‐80.6%) with 99mTc with blue dye. This resulted in a significant and clinically relevant risk difference of 16.6% (95%CI, 5.3‐28.0%). With sensitivity analysis, the risk difference of the bilateral detection rate maintained in favor of ICG but was no longer significant (13.2%, 95%CI −0.8‐27.3%).ConclusionICG appears to provide higher bilateral SLN detection rates compared to 99mTc with blue dye in patients with early‐stage cervical cancer. However, in adherence with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines, the quality of evidence is too low to provide strong recommendations and directly omit the combined approach of 99mTc with blue dye.

Association of Medicaid expansion and insurance status, cancer stage, treatment and mortality among patients with cervical cancer

AbstractBackgroundCurrently, little is known about the effect of the Patient Protection and Affordable Care Act's Medicaid expansion on care delivery and outcomes in cervical cancer.AimWe evaluated whether Medicaid expansion was associated with changes in insurance status, stage at diagnosis, timely treatment, and survival outcomes in cervical cancer.Methods and resultsUsing the National Cancer Database, we performed a difference‐in‐differences (DID) cross‐sectional analysis to compare insurance status, stage at diagnosis, timely treatment, and survival outcomes among cervical cancer patients residing in Medicaid expansion and nonexpansion states before (2011–2013) and after (2014–2015) Medicaid expansion. January 1, 2014 was used as the timepoint for Medicaid expansion. The primary outcomes of interest were insurance status, stage at diagnosis, treatment within 30 and 90 days of diagnosis, and overall survival. Fifteen thousand two hundred sixty‐five patients (median age 50) were included: 42% from Medicaid expansion and 58% from nonexpansion states. Medicaid expansion was significantly associated with increased Medicaid coverage (adjusted DID = 11.0%, 95%CI = 8.2, 13.8, p < .01) and decreased rates of uninsured (adjusted DID = −3.0%, 95%CI = −5.2, −0.8, p < .01) among patients in expansion states compared with non‐expansion states. However, Medicaid expansion was not associated with any significant changes in cancer stage at diagnosis or timely treatment. There was no significant change in survival from the pre‐ to post‐expansion period in either expansion or nonexpansion states, and no significant differences between the two (DID‐HR = 0.95, 95%CI = 0.83, 1.09, p = .48).ConclusionAlthough Medicaid expansion was associated with an increase in Medicaid coverage and decrease in uninsured among patients with cervical cancer, the effects of increased coverage on diagnosis and treatment outcomes may have yet to unfold. Future studies, including longer follow‐up are necessary to understand the effects of Medicaid expansion.

Knowledge on cervical cancer, attitude toward its screening, and associated factors among reproductive age women in Metu Town, Ilu Aba Bor, South West Ethiopia, 2018: community‐based cross‐sectional study

AbstractBackgroundCervical cancer is one of the major public health problems worldwide. Lack of awareness and unavailability of screening services are the major factors that contribute to the problem of cervical cancer in Ethiopia. The community‐based study conducted regarding the knowledge and attitude toward cervical cancer among women of reproductive age group is not enough to indicate the problem.AimTo assess the knowledge on cervical cancer, attitude toward its screening, and associated factors among women of reproductive age.MethodsA community‐based cross‐sectional study with a mixed approach method was conducted from April to May 2018. The sample size calculated for this study was 420. A systematic random sampling technique was used to select study participants. A binary logistic regression model was used to determine the association between the covariate and the dependent variable.ResultOf all participants, 31% have good knowledge of cervical cancer, and 57.8% have a positive attitude toward cervical cancer screening. In a multivariable analysis, educational status, occupation, visiting health facilities, and parity were significantly associated with knowledge and attitude toward cervical cancer screening.ConclusionThis study suggests increasing women's awareness, health education on cervical cancer in the community, and health institutions should be strengthened.Patient and public contributionFemale health workers were involved in the data collection process. Educated women and women who are community health leaders were involved as Interviewees for the qualitative part of the study. However, they have no direct contributions to authorship.

Meta‐analysis of microarray data to determine gene indicators involved in the cisplatin resistance in ovarian cancer

AbstractBackgroundSignificant miss‐expressed gene indicators contributing to cisplatin resistance in ovarian cancer have not been completely understood. It seems that several regulatory genes and signaling pathways are associated with the emergence of the chemo‐resistant phenotype.AimsHere, a meta‐analysis approach was adopted to assess deregulated genes involved in relapse after the first line of chemotherapy (cisplatin).Methods and ResultsTo do so, six ovarian cancer libraries were gathered from GEO repository. Batch effect removal and quality assessment, and boxplots and PCA were performed using SVA and ggplot2 packages in R, respectively. Cisplatin‐resistant and ‐sensitive ovarian cancer groups were compared with find genes with significant expression changes using linear regression models in the LIMMA R package. The significance threshold for DEGs was taken as adj p‐value < .05 and − 1 > logFC > 1. A total of 261 genes were identified to have significant differential expression levels in the cisplatin‐resistant versus cisplatin‐sensitive group. Among the 10 top up‐regulated and down‐regulated genes, PITX2, SNCA, and EPHA7 (up), as well as TMEM98 (down) are indirect upstream regulators of PI3K/AKT signaling pathway, contributing greatly to the development of chemo‐resistance in cancer via promoting cell proliferation, survival, and cell cycle progression as well as inhibiting apoptosis. Moreover, a comprehensive assessment of DEGs revealed the dysregulation of not only membrane ion channels KCa1.1, Kv4, and CACNB4, affecting cell excitability, proliferation, and apoptosis but also cell adhesion proteins COL4A6, EPHA3, and CD9, affecting the attachment of normal cells to ECM and apoptosis, introducing good options to reverse cisplatin resistance.ConclusionOur results predict and suggest that upstream regulators of PI3K/AKT signaling pathway, ion channels, and cell adhesion proteins play important roles in cisplatin resistance development in ovarian cancer.

Incidence Trends of Vulvar Cancer in the United States: A 20‐Year Population‐Based Study

ABSTRACTBackgroundDespite being uncommon, vulvar cancer is a serious health concern with a 5‐year relative survival rate of 71%.AimsThe objective was to investigate the incidence rates of this disease across different racial, ethnic, and histological subgroups in the United States, as well as the effects of the COVID‐19 pandemic on this cancer.MethodsWe used the Surveillance, Epidemiology, and End Results (SEER) 22 database. The International Classification of Diseases for Oncology Version 3 topologic code C51 was assigned for vulvar cancer. Average annual percent change (AAPC) and the pairwise comparison with the parallelism and coincidence were reported. Counts and age‐adjusted incidence rates per 100 000 individuals with their corresponding 95% confidence intervals (CIs) were reported.ResultsThe age‐adjusted incidence rate of vulvar cancer was 2.40 (95% CI, 2.38–2.43) over the period 2000–2019, with an AAPC of 0.80 (95% CI, 0.63–0.99). By race/ethnicity, only non‐Hispanic Whites had an increasing trend over 2000–2019 (AAPC: 1.30; 95% CI, 1.07–1.54). The highest age‐adjusted incidence rate of vulvar cancer in the United States was for squamous cell carcinoma (SCC). There was a significant decrease in the age‐standardized incidence rate of vulvar cancer in all races/ethnicities in all age groups (AAPC: −10.15; 95% CI, −15.35 to −4.94) over 2019–2020. Also, the incidence rates and incident numbers of vulvar cancer increased with aging and peaked at the 85+ age group.ConclusionThere was an increase in the incidence rate of vulvar cancer in all races, with a significantly increased trend in non‐Hispanic White women from 2000 to 2019. SCC displayed the highest incidence rate among vulvar cancer histological types. It is recommended to conduct further research to identify the relevant risk factors of vulvar cancer in the United States.

Verrucous carcinoma of the vulva: Patterns of care and treatment outcomes

AbstractBackgroundVerrucous vulvar carcinoma (VC) is an uncommon and distinct histologic subtype of squamous cell carcinoma (SCC). The available literature on VC is currently limited to case reports and small single institution studies.AimsThe goals of this study were to analyze data from the National Cancer Database (NCDB) to quantitate the incidence of VC and to investigate the effects of patient demographics, tumor characteristics, and treatment regimens on overall survival (OS) in women with verrucous vulvar carcinoma.Methods and resultsPatients diagnosed with vulvar SCC or VC between the years of 2004 and 2016 were identified in the NCDB. OS was assessed with Kaplan–Meier curves and the log‐rank test. Construction of a Cox model compared survival after controlling for confounding variables. The reported incidence of SCC of the vulva has significantly increased since 2004 (p < .0001). In contrast, the incidence of VC has remained stable (p = .344) since 2004. Compared to SCC, VC was significantly more likely to be diagnosed in older women (p < .0001) and treated with surgery alone (p < .0001). However, on propensity score weighted analysis there was a trend toward improved 5‐year OS in women with VC compared to those with SCC (63.4% vs. 57.7%, p = .0794). Multivariable Cox survival analysis showed an improvement in OS in VC patients treated with both primary site and regional lymph node surgery compared to primary site surgery alone (adjusted hazard ratio [aHR] 0.67, 95% confidence interval [CI] 0.46–0.97, p = .0357).ConclusionVerrucous carcinoma is more likely to present in older women. Regional lymph node surgery in addition to primary site surgery significantly improves OS in VC patients.

Cancer incidence among people living with HIV in Zimbabwe: A record linkage study

AbstractBackgroundPeople living with HIV (PLWH) are at increased risk of developing cancer. Cancer diagnoses are often incompletely captured at antiretroviral therapy (ART) clinics.AimTo estimate the incidence and explore risk factors of cancer in a cohort of PLWH in Harare using probabilistic record linkage (PRL).MethodsWe conducted a retrospective cohort study that included PLWH aged ≥16 years starting ART between 2004 and 2017. We used PRL to match records from the Zimbabwe National Cancer Registry (ZNCR) with electronic medical records from an ART clinic in Harare to investigate the incidence of cancer among PLWH initiating ART. We matched records based on demographic data followed by manual clerical review. We followed PLWH up until first cancer diagnosis, death, loss to follow‐up, or 31 December 2017, whichever came first.ResultsWe included 3442 PLWH (64.9% female) with 19 346 person‐years (PY) of follow‐up. Median CD4 count at ART initiation was 169 cells/mm3 (interquartile range [IQR]: 82–275), median age was 36.6 years (IQR: 30.6–43.4). There were 66 incident cancer cases for an overall incidence rate of 341/100 000 PY (95% confidence interval [CI]: 268–434). Twenty‐two of these cases were recorded in the ZNCR only. The most common cancers were cervical cancer (n = 16; 123/100 000 PY; 95% CI: 75–201), Kaposi sarcoma, and lymphoma (both n = 12; 62/100 000 PY; 95% CI: 35–109). Cancer incidence increased with age and decreased with higher CD4 cell counts at ART initiation.ConclusionPRL was key to correct for cancer under‐ascertainment in this cohort. The most common cancers were infection‐related types, reinforcing the role of early HIV treatment, human papillomavirus vaccination, and cervical cancer screening for cancer prevention in this setting.

Evaluation of elderly women with uterin cervical cancer

AbstractBackgroundUterine cervical cancer rates also increase with aging. Especially, the primary treatments of patients with cervical cancer include surgery, chemotherapy, and radiotherapy.AimOur aim is to discuss the effect of clinical and histopathological risk factors on survival in patients over 65 years old with invasive cervical cancer in the light of the literature.Methods and ResultsThe files of 60 patients aged 65 and over who were diagnosed, examined, and treated for invasive cervical uteri cancer between 2004 and 2021 by the gynecological oncology clinic of Akdeniz University were analyzed retrospectively after obtaining approval from the Akdeniz University ethics committee with the number KAEK‐110. Detailed written consent was obtained from all patients and their relatives for data analysis. Patients aged 65 and over who were diagnosed with invasive cervical uteri cancer at all stages who accepted treatment were included in the study. The patients who were not included in the study were those who did not accept treatment, did not continue their follow‐up regularly, were under 65 years of age, had preinvasive cervical lesion, had a second primary cancer, had an unknown stage, and died due to accidents or similar reasons.When the demographic data of 60 cases were examined, the mean age was 70.5, the youngest age was 65, and the oldest age was 84. When we divided them into two groups by age groups, 76.7% were between 65 and 75 years old and 23.3% were over 75 years old. When the data of 60 patients who were referred to our hospital, which was a tertiary center in the 15 years duration, were examined, the mean disease‐progression free survival (PFS) of patients with locally advanced stage was 45 months, however, it was 4 months for metastatic patients, this difference was significant and a statistically significant difference was found between the two groups (p: .001). When the total survival was examined, the mean was 108.7 months in the locally advanced stage group, while it was 2.9 months in metastatic cases, and this difference was also statistically significant between the two groups (p: .001). When we divide the cases into two groups as between 65 and 75 and over 75 years of age, the mean age of disease‐free survival is 76.9 months in the 65–75 years old group, while 16 months in the 76–85 years old group, however, the p value of this difference in PFS between the two groups was not significant (p: 0.154). However, when the total survival was examined, it was seen that the mean was 140.4 in the 65–75 years old group, while it was 56 months in the 76–85 years old group and this difference was significant between the two groups (p: .046).ConclusionIn parallel with the increased population worldwide, advanced age cancer rates are increasing. In parallel with the population growth, it should be remembered that the patients over 65 years of age who were diagnosed with invasive uterine cervical cancer had difficulty in accessing screening tests, late diagnosis and inadequate treatment regimens due to concomitant diseases, resulting in recurrence in a short time and poor clinical symptoms due to short total survival.

Successful pregnancy with stage IB2 uterine cervical cancer: A case report

AbstractBackgroundAlthough cervical cancer is one of the most common malignancies in pregnancy, its management mainly follows the guidelines for nonpregnant disease state. Within the limited time, patients, and healthcare workers must make difficult decisions to either delay treatment until documented fetal maturity or start immediate treatment based on the disease stage.CaseThe patient was a 37‐year‐old woman: gravida 1, para 0. Her cervical cytology revealed a high‐grade squamous intraepithelial lesion at 8 weeks' gestation. Moreover, invasive squamous cell carcinoma was suspected based on the findings of uterine cervix biopsy. Cervical conization was performed at 11 weeks' gestation, confirming a histopathological diagnosis of squamous cell carcinoma, pT1b2. Cervical cytology findings continued to be negative for intraepithelial lesion or malignancy from 2 weeks after conization until 2 weeks before a cesarean section. In addition, we performed abdominal pelvic lymphadenectomy at 16 weeks' gestation to determine whether the patient could continue her pregnancy. No lymph node metastasis or local recurrence was observed. Finally, a cesarean section and modified radical hysterectomy were performed at 35 weeks' gestation. There was no carcinoma invasion or metastasis. A baby girl weighing 2056 g was delivered with 1‐ and 5‐min Apgar scores of 8 and 9, respectively. Five years postoperatively, there was no evidence of cancer recurrence.ConclusionManagement of cervical cancer during pregnancy by using a combination strategy of deep conization and pelvic lymphadenectomy could be an effective strategy for carefully and safely assessing risks of recurrence and metastasis.

Factors influencing cervical cancer screening practice among female health workers in Nigeria: A systematic review

AbstractBackgroundCervical cancer is the most prevalent gynaecologic cancer in Nigeria. Despite being largely preventable through screening, cervical cancer is the second leading cause of cancer morbidity and mortality in Nigeria. To reduce the burden of cervical cancer in Nigeria, female health workers (FHWs) are expected to play an influential role in leading screening uptake and promoting access to cervical cancer education and screening.AimThe aim of this systematic review is to assess the factors influencing cervical cancer screening (CCS) practice among FHWs in Nigeria.MethodsWe conducted a systematic literature search across six (6) electronic databases namely MEDLINE, Embase, Scopus, African Index Medicus, CINAHL, and Web of Science between May 2020 and October 2020. Reference list and grey literature search were conducted to complement database search. Four reviewers screened 3171 citations against the inclusion criteria and critically appraised the quality of eligible studies. Narrative synthesis was used in summarising data from included studies.ResultsOverall, 15 studies met the inclusion criteria and were all quantitative cross‐sectional studies. Included studies sampled a total of 3392 FHWs in Nigeria. FHWs had a high level of knowledge and positive attitude towards CCS. However, CCS uptake was poor. Predominant barriers to CCS uptake were the cost of screening, fear of positive results, lack of test awareness, reluctance to screen, low‐risk perception, and lack of time. In contrast, being married, increasing age, awareness of screening methods, and physician recommendation were the most documented facilitators.ConclusionThis study revealed that a complex interplay of socioeconomic, structural, and individual factors influences CCS among FHWs in Nigeria. Therefore, implementing holistic interventions targeting both health system factors such as cost of screening and infrastructure and individual factors such as low‐risk perception and fear of positive result affecting FHWs in Nigeria is critical to reducing the burden of cervical cancer.

Knowledge, attitude, and practice of cervical cancer screening among women living with HIV in the Kilimanjaro region, northern Tanzania

AbstractBackgroundCervical cancer is the fourth most common cancer globally among women in incidence and mortality. Women living with HIV (WLHIV) are disproportionately at a higher risk of developing the disease.AimTo determine the knowledge, attitude, and practice of cervical cancer screening among WLHIV in the Kilimanjaro region, northern Tanzania, following the integration of these services in routine HIV care in the country.Methods and resultsA cross‐sectional study was conducted in the Kilimanjaro region among 297 WLHIV attending care and treatment centers (CTC) in Hai district and Mawenzi regional hospitals in northern Tanzania between 21 August and 3 September 2020. A questionnaire was used for data collection using face‐to‐face interviews. Data were analyzed using SPSS version 20.0. Frequencies and percentages summarized categorical variables and numerical variables summarized using median and interquartile range (IQR). About half (50.2%) of 297 WLHIV in this study had ever screened for cervical cancer, and 64% screened within the past 12 months preceding the survey. Although 90% ever heard of cervical cancer screening, only 20.5% knew when WLHIV should start screening. Over half (52.5%) had adequate knowledge of prevention, 38.4% on risk factors, and 27.9% of cervical cancer signs and symptoms. Two‐thirds (66.7%) had positive attitudes toward cervical cancer screening. A major source of cervical cancer screening information was the health care providers (80.1%) and the mass media (66%), particularly radio.ConclusionsThe WLHIV in this study had inadequate knowledge but favorable attitudes toward cervical cancer screening, while half had screened for cervical cancer. Efforts should be directed to capacity building of health care providers at CTC and scaling up the mass media campaigns as relevant interventions to promote the uptake of cervical cancer screening programs among WLHIV in Tanzania.

Evidence for disseminated tumor cells in lymphatic vessels afferent to sentinel lymph nodes in patients diagnosed with cervical cancer

AbstractBackgroundIn patients diagnosed with cervical cancer, the purpose of lymphadenectomy is the removal of lymph nodes for diagnosis and potential treatment of metastasized tumor cells. It is unclear if afferent lymphatic vessels harbor tumor cells and, thus, may pose additional risk for recurrence or progression if not removed.AimIn this feasibility study, we analyzed the lymphatic vessels afferent to sentinel lymph node (SLN) using a highly sensitive and specific molecular marker for cervical cancer cells.Methods and ResultsTwenty patients diagnosed with cervical cancer of FIGO stage IA1 to IIB2 underwent laparoscopic SLN removal. Labeling was done using patent blue and the afferent lymphatic vessels were harvested from the parametric tissue and frozen at −80°C. HPV DNA type was evaluated in the primary tumor. Lymphatic vessels afferent to the sentinel lymph nodes were analyzed for the presence of viral oncogene transcripts of the respective HPV type. In one of 18 patients, all with tumor stage ≤IBI and pN0 by conventional histopathology, HPV mRNA could be detected in two of four lymphatic vessels, whereas at least one of the lymphatic vessel biopsies of both patients with tumors ˃4 cm and pN1 status was HPV mRNA positive. No clinical correlation with recurrence after a median follow‐up of 9 years was noticed.ConclusionHPV mRNA indicative of disseminated tumor cells could be detected in lymphatic vessels. The relevance of harvesting lymphatic vessels afferent to SLN in order to increase oncologic safety will have to be investigated in a future prospective study.

To study the role of pre‐treatment microRNA (micro ribonucleic acid) expression as a predictor of response to chemoradiation in locally advanced carcinoma cervix

AbstractBackgroundConcurrent chemoradiotherapy followed by brachytherapy is the standard of care in locally advanced carcinoma cervix. There is no prognostic factor at present to predict the outcome of disease in locally advanced carcinoma cervix.AimDifferential expression of microRNAs can be used as biomarkers to predict clinical response in locally advanced carcinoma cervix patients.MethodsThirty‐two patients of locally advanced carcinoma cervix with International Federation of Gynecology and Obstetrics Stage IB‐IVA were enrolled from 2017 to 2018. Expression of microRNA‐9 5p, ‐31 3p, ‐100 5p, ‐125a 5p, ‐125b‐5p, and –200a 5p in formalin‐fixed paraffin embedded (FFPE) biopsied tissue were analyzed by real time quantitative reverse transcriptase polymerase chain reaction (RT qPCR). Pretreatment evaluation was done with clinical examination and MRI pelvis. All patients received concurrent chemoradiotherapy followed by brachytherapy. Patients were evaluated for the clinical response after 3 months of treatment, with clinical examination and MRI pelvis scan using RECIST 1.1 criteria. Patients with no residual disease were classified as Complete responders (CR) and with residual or progressive disease were classified as Nonresponders (NR). Results were statistically analyzed using Mann Whiney U test to examine significant difference between the expression of microRNA between complete responders (CR) and nonresponders (NR).ResultsmicroRNA‐100 5p was upregulated in complete responders (CR) which showed a trend towards statistical significance (p value = 0.05).ConclusionmicroRNA‐100 5p can serve as a potential molecular biomarker in predicting clinical response to chemoradiation in locally advanced Carcinoma cervix. Its role should be further investigated in a larger study population.

Publisher

Wiley

ISSN

2573-8348