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Life sciences · Journal article
Frontiers in Oncology · October 22, 2026
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Background Persistent high-risk human papillomavirus (hrHPV) infection causes virtually all high-grade squamous intraepithelial lesions (HSIL) and cervical cancer, but only a minority progress, implicating host and microenvironmental cofactors. The cervicovaginal microbiome (CVM), particularly Lactobacillus-dominated communities, may influence hrHPV persistence, clearance, and response to HSIL treatment. Objective To map evidence linking the CVM with hrHPV clearance and outcomes after HSIL treatment, including loop electrosurgical excision procedure (LEEP) and conization, using PRISMA-ScR and Arksey and O’Malley frameworks. Methods Literature on cervicovaginal microbiota, community state types (CSTs), HPV natural history, HSIL/CIN treatment, probiotics, microbiome-directed interventions, and predictive biomarkers was systematically searched and narratively synthesized using a Population-Concept-Context framework. Results Sixty-six sources were charted. Lactobacillus crispatus -dominated communities (CST-I) were associated with hrHPV clearance and favorable post-treatment outcomes, whereas CST-IV, bacterial vaginosis, and increased alpha-diversity were associated with hrHPV persistence, greater HSIL severity, and treatment failure. Proposed mechanisms include lactic acid-mediated pH regulation, D-lactic acid signaling, and modulation of viral oncoproteins and immune responses. Excision altered the CVM, with restoration of Lactobacillus dominance accompanying viral clearance. Microbial-signature machine-learning models showed promising but preliminary predictive performance. Oral and intravaginal probiotics showed inconsistent but generally favorable trends, with strongest evidence for intravaginal L. crispatus transplantation. Gut microbiome diversity may also influence chemoradiotherapy outcomes in invasive cervical cancer. Conclusion The CVM is a promising predictor of hrHPV clearance and HSIL treatment response. However, methodological heterogeneity, small cohorts, and limited prospective evidence restrict clinical translation. Large prospective studies and rigorously designed trials are needed to validate predictive signatures and determine whether microbiome profiling or targeted modulation can improve HSIL management and outcomes.