Cervicovaginal Virome Restructuring Associated with HPV Status, Bacterial Dysbiosis, and Cervical Cytological Abnormalities

The cervicovaginal virome remains poorly characterized in relation to human papillomavirus (HPV) infection and bacterial community structure. We performed shotgun metagenomic sequencing of 311 cervicovaginal specimens from a Kazakhstani cohort spanning seven groups defined by HPV status and cervical cytology. Viral community composition differed according to HPV status, with increasing representation of the oncogenic Alphapapillomavirus 9 clade across more abnormal cytological categories. Predicted phage functional profiles also differed between NILM HPV-positive and NILM HPV-negative women. Integrase, excisionase, transcriptional repressor, anti-repressor Ant, and amidase annotations showed differential prevalence after false-discovery-rate correction. Auxiliary metabolic and host-interaction genes associated with nucleotide metabolism, DNA modification, anti-restriction functions, and toxin–antitoxin systems were also differentially represented. Stratification by bacterial community state type revealed contrasting predicted functional repertoires, with toxin–antitoxin-associated annotations enriched in Lactobacillus crispatus-dominated communities and anti-restriction-associated annotations enriched in Gardnerella vaginalis-dominated communities. These findings identify associations between HPV status, bacterial community structure, and cervicovaginal viral composition and predicted phage functions. Longitudinal and experimental studies are required to determine the directionality and biological activity of these associations.