Chiara Casprini

This systematic review aimed to summarize the available evidence on the associations between the female reproductive tract microbiota and endometrial cancer (EC). While gut microbiota has been studied extensively, microbial communities within the endometrium, cervix, and vagina remain relatively understudied. A systematic literature search was conducted in PubMed, Scopus, Web of Science, EMBASE, and the Cochrane Library for studies published up to January 2025. Predefined PECO-based criteria included studies on women or human cell models assessing genital tract microbiota in EC versus non-EC controls, focusing on composition, diversity, or function; reviews and non-microbiota studies were excluded. A total of 21 studies were included. Overall, there was a consistent depletion of protective Lactobacillus species and enrichment of anaerobic, pro-inflammatory bacteria like Prevotella, Atopobium, and Porphyromonas in EC tissues. Beta-diversity was significantly different between EC and controls across studies, indicating distinct microbial profiles. Some studies also identified fungal and viral taxa associated with EC, and functional assays demonstrated that certain species could modulate host immune responses or promote tumor growth. Despite methodological heterogeneity and the lack of evidence supporting causality due to the observational design, the findings support an association between altered genital tract microbiota and EC.