Retrospective cohort study on cervicovaginal swabs for the non-invasive molecular detection of ovarian and endometrial cancers

Background Ovarian and endometrial cancers together account for nearly 10% of all female cancer-related deaths worldwide, with ovarian cancer being the deadliest gynecologic malignancy. We aimed to evaluate the diagnostic performance of genetic mutations and DNA methylation markers detected from cervicovaginal swabs for identifying ovarian and endometrial cancers. Methods We conducted a retrospective multicenter cohort study including 238 women (127 ovarian/endometrial cancers; 111 benign controls) from three tertiary hospitals between 2018 and 2023. Targeted sequencing was performed for TP53, PTEN, BRCA1, and BRCA2; DNA methylation profiling was analyzed using quantitative methylation-specific PCR (qMSP). Logistic regression and ROC analyses assessed diagnostic accuracy. Survival was evaluated by Kaplan–Meier methods and Cox regression. Results TP53 and PTEN mutations were identified in 68% and 47% of cancer samples, respectively, versus <5% among controls. The combined molecular panel (mutations + methylation markers) achieved an AUC of 0.91 (95% CI 0.87–0.95), with sensitivity = 86.5% and specificity = 90.1%. Stratified analysis showed AUC 0.93 in premenopausal and 0.89 in postmenopausal women. TP53 mutation independently predicted 1-year mortality (HR 1.78, 95% CI 1.14–2.64; p = 0.008). The addition of methylation markers improved overall model performance (ΔAUC +0.05, p = 0.02). Conclusions Genetic and epigenetic alterations detectable in cervicovaginal swabs can accurately identify ovarian and endometrial cancers, demonstrating feasibility for non-invasive molecular triage. Incorporation of TP53 and PTEN sequencing with methylation profiling warrants further prospective investigation as a potential adjunct to upper-tract oncologic surveillance.