From Dysbiosis to Malignancy: The Female Genital Tract Microbiome in Endometrial Cancer; Insights from a Systematic Review and Meta-Analysis.

Background/Aim: Emerging evidence suggests that alterations in the female genital tract microbiome may be associated with the development and progression of endometrial cancer (EC). Microbial dysbiosis may contribute to chronic inflammation, immune dysregulation, and metabolic disturbances within the endometrial microenvironment. This systematic review and meta-analysis aimed to evaluate alterations in the female genital tract microbiome in women with EC and to identify microbial patterns associated with benign, premalignant, and malignant endometrial conditions. Methods: A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Meta-analysis of Observational Studies in Epidemiology (MOOSE) recommendations. Ten eligible observational studies published between 2016 and 2026 were included, comprising 775 women: 329 with benign conditions, 121 with endometrial hyperplasia, and 325 with EC. Demographic, histopathological, anatomical sampling, and microbiological data were extracted and analyzed using Review Manager, SPSS version 23, and EPI-INFO. Risk of bias was assessed using the Cochrane Collaboration tool. Results: Women with EC were older than those with benign conditions (59.2 ± 5.3 vs. 52.7 ± 4.4 years) and had a higher mean body mass index (33.8 ± 3.8 vs. 27.5 ± 2.0 kg/m²). Endometrioid carcinoma was the predominant histological subtype, and most malignant cases were low-grade and early-stage tumors. EC was associated with significant alterations in the genital tract microbiome. Several commensal taxa, including Lactobacillus, Bacteroides, Prevotella, Staphylococcus, and Enterococcus, were decreased in malignant cases, whereas potentially pathogenic or infection-associated genera, particularly Stenotrophomonas, Streptococcus, and Porphyromonas, were increased (p < 0.001). The pooled analysis demonstrated a significant association between genital tract microbial dysbiosis and EC. Conclusions: Female genital tract microbial dysbiosis is associated with EC, characterized particularly by depletion of potentially protective microorganisms and enrichment of potentially pathogenic or infection-associated taxa. These microbial alterations may have potential as adjunctive biomarkers for EC risk stratification and early detection. However, the available observational evidence does not establish a causal role of microbial dysbiosis or infection in endometrial carcinogenesis. Large prospective studies using standardized sampling, sequencing, and analytical methods are required to clarify causality and determine the clinical utility of microbiome-based diagnostic and therapeutic approaches.