Dynamic, transition and variation of cervicovaginal microbiome and HPV infection and cervical dysplasia and cancer: a systematic review

BACKGROUND: Cervical cancer is the fourth most common malignancy in women worldwide, with approximately 660,000 new cases and 350,000 deaths annually. The burden falls disproportionately on low- and middle-income countries. Although persistent infection with high-risk HPV (hrHPV) is the necessary cause, most infected women clear the virus spontaneously, implicating additional cofactors, including the cervicovaginal microbiome in determining oncogenic outcomes. METHODS: PubMed was searched through September 10, 2024, to identify longitudinal studies assessing cervicovaginal microbiota in relation to HPV infection or cervical lesion outcomes at two or more time points. Methodological quality was evaluated using the Newcastle-Ottawa Scale (NOS). Given the substantial heterogeneity, a structured thematic synthesis was performed across three predefined domains: (a) baseline microbiome composition and clinical outcomes; (b) community state type (CST) dynamics and temporal stability; and (c) microbiome changes following treatment. RESULTS: Twelve studies enrolling 1,663 women across 11 countries met inclusion criteria. NOS scores ranged from 4 to 9. Lactobacillus-dominated CSTs at baseline were consistently associated with HPV clearance and CIN regression, while Lactobacillus-depleted states showed higher transition rates and unfavourable outcomes. Prior L.iners (CST III) dominance was repeatedly linked to favourable outcomes, although evidence on this species remains conflicting. Cervicovaginal dysbiosis frequently preceded HPV persistence or lesion progression. CONCLUSION: Sustained Lactobacillus-dominated CST stability, rather than dominance by any single species, is the most consistent microbiome factor associated with favourable HPV and cervical lesion outcomes. Standardized longitudinal designs incorporating metagenomic sequencing, frequent sampling intervals, and rigorous confounder adjustment are needed to advance mechanistic understanding. CLINICAL TRIAL REGISTRATION NUMBER: Not applicable.