Microbiological and Histopathological Features of Gynecologic Cancers: A Systematic Review of Current Evidence and Future Directions.

Gynecologic cancers are a diverse group of malignancies with distinct microbiological, histopathological, and molecular characteristics. This systematic review examined the available evidence on these features in gynecologic cancers and premalignant lesions. A total of 46 studies involving 18,742 patients or samples were included. Because the studies differed considerably in design, sampling methods, laboratory techniques, histopathological classification, and reported outcomes, the findings were synthesized narratively. The strongest and most consistent evidence was found for persistent high-risk human papillomavirus (HPV) infection, particularly HPV-16 and HPV-18, in cervical cancer and other lower genital tract neoplasms. Cervicovaginal dysbiosis, marked by reduced Lactobacillus dominance, increased microbial diversity, and anaerobic bacterial overgrowth, was frequently associated with HPV persistence and higher-grade cervical lesions. However, current evidence suggests that dysbiosis acts as a contributing factor rather than an independent cause of malignancy. Histopathology remained central to tumour diagnosis, classification, and risk assessment. Squamous cell carcinoma was the predominant histological type in cervical, vulvar, and vaginal cancers. Endometrioid adenocarcinoma was commonly reported in endometrial cancer, while high-grade serous carcinoma was the main ovarian cancer subtype. Evidence regarding uterine, endometrial, and ovarian tumour-associated microbiota was limited and exploratory because of low microbial biomass, methodological variation, and the risk of contamination. Combining microbiological findings with histopathological and molecular classification may improve understanding of gynecologic carcinogenesis and support future risk-stratification approaches. Standardized sampling, strict contamination control, and well-designed longitudinal studies are needed before microbiome-based markers can be introduced into routine clinical practice.