The vaginal microbiome is associated with endometrial cancer grade and histologyOriginal paper
What was studied?
This study asked whether the vaginal microbiome differs by endometrial cancer grade and histology. Researchers prospectively collected vaginal swabs at hysterectomy from women with benign disease or endometrial carcinoma. Extracted DNA underwent shotgun metagenomic sequencing. The team calculated alpha and beta diversity, defined community state types by hierarchical clustering, ran differential abundance analysis, and built machine-learning classifiers. The goal was to see if microbial patterns could separate benign disease from cancer and distinguish low-grade from high-grade tumors.
Who was studied?
The cohort was 61 racially and ethnically diverse women having hysterectomy at hospitals affiliated with the University of Miami, USA. They fell into three groups: 11 benign controls, 30 low-grade endometrial carcinomas, and 20 high-grade carcinomas. About 37% of participants were Black, and both Hispanic and non-Hispanic women were included. High-grade patients were older (mean 61.9 years) and had higher body mass index (mean 37.3) than benign patients. Women with recent antibiotics, douching, or active infection were excluded.
What were the most important findings?
Microbial diversity rose with tumor grade. Alpha diversity differed across all three groups (ANOVA p 0.024), with a significant increase from benign to high-grade disease (p 0.025). Tumor grade also drove beta diversity (p 0.042), while race, ethnicity, and BMI did not. Four community state types were identified. Benign disease clustered in CST1, low-grade in CST2, and high-grade split across CST3 and CST4 (p 0.036). Fusobacterium ulcerans was the only species significantly enriched in high-grade versus benign tumors, and Prevotella bivia was also higher in high-grade versus low-grade. A three-species random-forest model separated cancer from benign disease with a mean AUC of 0.878.
What are the greatest implications of this study?
The vaginal microbiome may serve as a noninvasive marker of endometrial cancer, a disease with no routine screening test. Microbial signatures separated benign from malignant disease and even distinguished tumor grade and histology. These findings are exploratory and associative, not causal. The single-institution cohort was small, so larger prospective studies are needed before clinical use. The results suggest microbial patterns, rather than single species, could refine future risk-stratification and early-detection tools.