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The vaginal microbiome, particularly the transition from <jats:italic>Lactobacillus crispatus<\/jats:italic>\u2013dominated communities to dysbiotic states enriched in <jats:italic>Gardnerella<\/jats:italic>, <jats:italic>Fannyhessea<\/jats:italic>, and <jats:italic>Sneathia<\/jats:italic>, has emerged as a key modulator of HPV persistence, local inflammation, and epithelial transformation. First, community state type IV (CST IV) microbiota strongly predict persistent HR-HPV infection and progression to high-grade lesions, highlighting their potential as non-invasive biomarkers for early risk stratification. Second, cervicovaginal dysbiosis alters mucosal immunity and promotes epigenetic reprogramming of both host and viral genomes, facilitating immune evasion and oncogenesis. Third, restoring <jats:italic>Lactobacillus<\/jats:italic> dominance through probiotics or microbial engineering holds translational promise for enhancing HPV vaccine efficacy and reducing cervical cancer burden. These findings position the vaginal microbiome not as a passive bystander, but as an active determinant of HPV-driven carcinogenesis and underscore its diagnostic and therapeutic potential in cervical cancer prevention.<\/jats:p>","DOI":"10.3389\/fcimb.2025.1634251","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T05:34:52Z","timestamp":1759815292000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":33,"title":["The vaginal microbiome in HPV persistence and cervical cancer progression"],"prefix":"10.3389","volume":"15","author":[{"given":"Jhommara","family":"Bautista","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Altamirano-Colina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"L\u00f3pez-Cort\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.currproblcancer.2022.100877","article-title":"The vaginal microbiome: A complex milieu affecting risk of human papillomavirus persistence and cervical cancer","volume":"46","author":"Alimena","year":"2022","journal-title":"Curr. 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