Vaginal Microbial Risk Factors Associated with Human Papillomavirus-Induced Cervical Intraepithelial Neoplasia: A Systematic Review.

Human papillomavirus (HPV) drives cervical carcinogenesis, but viral infection alone is insufficient for malignant transformation. The vaginal microbiome may modulate HPV persistence and cervical intraepithelial neoplasia (CIN) progression, yet existing reviews remain inconclusive. This systematic review identifies specific vaginal microbiome risk factors associated with HPV and CIN and proposes plausible mechanisms linking dysbiosis to disease progression. Following (PRISMA) guidelines, databases were searched for studies published through October 2025. Thirty-three studies from 2013 to 2025 across 10 countries met the inclusion criteria, with 87.9% exhibiting low risk of bias. Most studies demonstrated marked Lactobacillus depletion alongside Prevotella and Gardnerella enrichment in HPV/CIN cases. Disease severity correlated with shifts toward high-diversity anaerobe communities, though alpha and beta diversity metrics varied across cohorts. Importantly, longitudinal data suggests a temporal sequence where baseline dysbiosis precedes clinical progression. Crucially, although the included cohorts directly observed and quantified these taxonomic shifts, the underlying mechanisms of disease progression, such as enzymatic degradation of mucosal barriers mediated by Gardnerella and immunosuppression driven by Fusobacterium, remain largely inferred from external in vitro literature. Lactobacillus iners emerged as a notable species-level risk factor in HPV persistence. Vaginal dysbiosis, characterised by Lactobacillus depletion and anaerobic expansion, is strongly correlated with HPV persistence and CIN progression, potentially facilitated through convergent barrier degradation and immune subversion. These findings highlight targets for microbiome-based risk stratification and therapeutic intervention.