Cervicovaginal microbiome alterations across HPV infection

Abstract

Introduction The cervicovaginal microbiome is a proposed modifier of HPV-associated cervical disease, yet its relationship with viral type heterogeneity, cytological grade, and community state type (CST) remains incompletely understood. Methods This cross-sectional study characterized cervicovaginal microbiome composition and functional potential across HPV infection status, viral type categories (No HPV, HPV High Risk, HPV16, HPV18, HPV Other), cervical cytological grades, and CSTs in 311 non-pregnant women using whole-genome shotgun metagenomic sequencing, integrated diversity analyses, MaAsLin2 differential abundance testing, and HUMAnN 3.0 functional pathway profiling. Results HPV-positive samples showed increased bacterial species richness, and a reciprocal Lactobacillus-to-Gardnerella dominance shift compared to HPV-negative samples. HPV Other showed the highest bacterial species richness and distinct taxonomic and predicted functional associations, including higher inferred abundance of siderophore- and lipopolysaccharide-biosynthesis pathways; however, overall species-level community composition did not differ significantly across HPV type groups. CST I and CST II exhibited compositional stability regardless of HPV status, while CST IV showed pronounced Lactobacillus depletion in HPV-positive women. LSIL was associated with lower Fannyhessea vaginae and Alloscardovia omnicolens abundance and higher Phocaeicola vulgatus abundance relative to NILM. Discussion These findings indicate that oncogenic potential and dysbiosis severity are not aligned, and that CST type modifies HPV–microbiome interactions.