E. Kydyrbayeva, Y. Iztleuov, G. Iztleuova
Relevance: Cervical cancer remains a major medical and social problem, while persistent infection with high-risk human papillomavirus is a necessary but insufficient condition for neoplastic transformation. The cervicovaginal microbiome is considered a key modifying factor.The study aimed to summarize contemporary evidence from 2020 to 2026 on taxonomic, metabolic, and immune alterations in the cervicovaginal microbiota in HPV-positive conditions, including cervical intraepithelial neoplasia (CIN) and cervical cancer. Materials and Methods: A systematic review of publications indexed in PubMed/MEDLINE, Scopus, and Web of Science was conducted using PRISMA 2020 principles. The qualitative synthesis included clinical, metagenomic, interventional, and fundamental studies that assessed microbiota composition, HPV status, and the morphological stage of cervical lesions.Results: A protective profile is associated with Lactobacillus crispatus dominance, D-lactate and H2O2 production, and preservation of the epithelial barrier. CST IV dysbiosis, expansion of Gardnerella, Fannyhessea, Prevotella, Sneathia, and Fusobacterium, and depletion of lactobacilli are associated with HPV persistence, chronic inflammation, activation of MMP-8/MMP-9, TLR9/NF-κB, and Wnt/β-catenin pathways, and an increased risk of CIN2+/HSIL.Conclusion: Current evidence supports the cervicovaginal microbiome as an important modifier of HPV persistence and cervical lesion progression, rather than as an independent diagnostic criterion. Microbiome signatures may complement HPV testing, cytology, and colposcopy for risk stratification, but their clinical implementation requires prospective validation, standardized sampling protocols, and harmonized metagenomic analysis.