Cervicovaginal microbiome modulates HPV genotype-specific clearance/persistence: role of bacterial dysbiosis in cervical carcinogenesis

This study focuses on the distinct epidemiological features of high-risk human papillomavirus (hrHPV) genotypes in Asian populations: HPV52/56/58 show uniquely high prevalence and strong correlation with cervical intraepithelial neoplasia, but their detection rates drop sharply in invasive cervical cancer, a pattern clearly different from the persistent dominance of HPV16/18 throughout malignant progression. To further elucidate the potential host-microbe interactions underlying these epidemiological observations, we integrated a 16S rRNA-sequenced cross-sectional discovery cohort and an independent longitudinal validation cohort from a Chinese population, with strict experimental quality control throughout the workflow. The preliminary analytical results demonstrate that a Lactobacillus-dominant cervicovaginal microbiome (CVM) is significantly and positively associated with HPV viral clearance, while enriched abundance of Gardnerella, Saccharofermentans and Atopobium exhibits a robust correlation with persistent HPV52/56/58 infection. Three undercharacterized microbial taxa-Chryseobacterium, Sphingobacterium and Enhydrobacter are closely linked to sustained HPV16/18 prevalence across advanced disease stages, and show negative correlation with the above obligate anaerobes, which aligns with the sharp decline of HPV52/56/58 in tumor tissues. A hormone-linked Chryseobacterium enrichment were also identified, a taxon with previously reported progesterone-degrading functional properties. While further longitudinal studies are required to establish causal relationships, our results indicate that CVM dysbiosis may modulate the natural history of these high-burden HPV genotypes, and provide a foundational rationale for subsequent development of genotype-specific, microbiota-targeted cervical disease intervention strategies.