The role of the microbiome in gynecological cancers: implications for diagnosis and treatment

Gynecological malignancies such as cancer of the cervix, ovary, endometrium, vulva, and vagina pose a severe global health burden. Although conventionally attributed to genetic mutation, hormonal imbalance, and chronic viral infection, including high-risk human papillomavirus, recent evidence suggests that the human microbiome plays a central role in their pathogenesis and development. This review summarizes existing evidence that microbial dysbiosis, specifically the depletion of beneficial Lactobacillus species and overrepresentation of anaerobic organisms such as Fusobacterium, Atopobium, and Sneathia, is implicated in carcinogenesis pathways. These include chronic inflammation, immune modulation, loss of epithelial barrier integrity, microbial metabolite toxicity, and estrogen metabolism by the estrobolome. Dysbiosis in the gut and reproductive tract has been associated with HPV persistence, tumor microenvironment remodeling, and immune surveillance/therapy resistance. Consequently, microbial signatures are being investigated as a potentially successful non-invasive biomarker for early diagnosis, prognosis, and monitoring of therapy in gynecological oncology. In addition, emergent microbiome-based therapies are being considered as potential adjunct therapies, including probiotics, prebiotics, dietary manipulation, vaginal microbiota transplantation, and fecal microbiota transplantation. This review connects the basic research microbiome research to translational and clinical practice, identifies associated limitations, and highlights how it may transform gynecological cancer prevention, detection, and treatment.