The Vaginal Microbiome Across the Continuum from HPV Infection to Cervical Cancer: A Narrative Review

Abstract

Persistent high-risk human papillomavirus (HR-HPV) infection serves as the core prerequisite for cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. Accumulated translational evidence confirms that vaginal microecological homeostasis dominated by protective Lactobacillus strains fundamentally governs the initiation, persistence, and spontaneous clearance of HR-HPV infection, while microbial dysbiosis featuring depleted lactobacilli and overgrown anaerobic pathogens creates a pro-inflammatory, immune-suppressive mucosal niche that accelerates viral retention and cervical malignant transformation. We conducted a narrative review of studies published primarily between January 2021 and April 2026. PubMed, Web of Science, CNKI, Wanfang Data, and VIP were searched using terms related to the vaginal microbiome, HR-HPV infection, CIN, cervical cancer, underlying mechanisms, microbial biomarkers, and microbiome-modulating interventions. Relevant peer-reviewed epidemiological, mechanistic, and clinical studies were prioritized, and the manuscript was prepared with reference to the Scale for the Assessment of Narrative Review Articles (SANRA). This review systematically delineates the bidirectional regulatory crosstalk between vaginal microbiota and HR-HPV across the cervical cancer continuum. Dysbiosis disrupts vaginal acidic barriers, reshapes local cytokine networks, impairs antiviral innate immunity, and modulates HPV E6/E7 oncogenic transcription; reciprocally, HR-HPV oncoproteins remodel microbial community structures to sustain a dysbiotic feedback loop. Three core carcinogenic cascades induced by dysbiotic flora are elaborated: epithelial barrier erosion, metabolic reprogramming, and epigenetic rewiring of host and viral genomes. Dynamic microbial characteristics corresponding to all stages of progressive cervical lesions, from transient HPV infection to high-grade CIN and carcinoma, are sorted out. The bench-to-bedside translational progress of microbiome-targeted interventions is summarized, including single/multi-strain probiotic supplementation, engineered lactic acid bacterial therapeutic vaccines, vaginal microbiota transplantation, and traditional Chinese medicine therapy that reconstructs vaginal eubiosis. The clinical application of microbial diversity, strain-level single-nucleotide variants, and taxonomic biomarkers for early screening, efficacy prediction, and postoperative recurrence risk stratification is illustrated. This comprehensive framework with the vaginal microbiome as the core clarifies the internal mechanism of HR-HPV progression along the entire pathway to cervical cancer and provides practical clinical means to block this cascade. Current bottlenecks, including inconsistent probiotic standards, preclinical model limitations, and unresolved gut–vagina microbiome interactions, require further investigation before widespread clinical translation.