{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:14:13Z","timestamp":1789503253595,"version":"build-2803163510"},"reference-count":131,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Persistent high-risk human papillomavirus infection is a critical prerequisite for cervical intraepithelial neoplasia and cervical cancer, yet viral factors alone do not fully explain why most infections clear while a subset persists and progresses. Emerging longitudinal, multi-omics, and mechanistic evidence supports a plausible model in which the cervicovaginal microbiota is not a passive bystander but a functional determinant of mucosal immunity, epithelial barrier integrity, and local metabolic tone. Lactobacillus-dominant community states, particularly those enriched in Lactobacillus crispatus, are generally associated with lower pH, regulated inflammatory signaling, stronger barrier function, and a higher likelihood of HPV clearance. In contrast, anaerobe-enriched dysbiosis is linked to elevated pro-inflammatory cytokines, altered antigen presentation, immune checkpoint signatures consistent with T-cell dysfunction, and metabolic shifts involving lactate depletion and accumulation of short-chain fatty acids and other metabolites that can influence epithelial and immune-cell programs. Importantly, the interaction is bidirectional: hrHPV can remodel the microenvironment by suppressing host defense peptides and perturbing mucosal barriers, thereby reducing Lactobacillus fitness and reinforcing dysbiosis in a feed-forward loop that favors persistence and oncogenic progression. This review integrates functional ecology, longitudinal clinical evidence, immunological and metabolic mechanisms, and translational implications, highlighting opportunities for microbiome-informed risk stratification and adjunctive interventions, as well as key gaps requiring standardized longitudinal multi-omics and rigorously designed clinical trials.<\/jats:p>","DOI":"10.3390\/ijms27125616","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"5616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bidirectional Interactions Between Cervicovaginal Microbiota and Human Papillomavirus Drive Persistence and Disease Progression"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9237-213X","authenticated-orcid":false,"given":"Daniel Osmar","family":"Su\u00e1rez-Rico","sequence":"first","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Calle Sierra Mojada 950, Independencia Oriente, Guadalajara 44340, Mexico"},{"name":"Laboratorio de Microbiolog\u00eda Molecular II, Divisi\u00f3n de Medicina Molecular, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara 44100, Mexico"},{"name":"Instituto de Terap\u00e9utica Experimental y Cl\u00ednica (INTEC), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5482-1611","authenticated-orcid":false,"given":"Lourdes del Carmen","family":"Rizo de la Torre","sequence":"additional","affiliation":[{"name":"Laboratorio de Microbiolog\u00eda Molecular II, Divisi\u00f3n de Medicina Molecular, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara 44100, Mexico"},{"name":"Divisi\u00f3n de Gen\u00e9tica, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3631-0281","authenticated-orcid":false,"given":"Martin","family":"Zerme\u00f1o-Ruiz","sequence":"additional","affiliation":[{"name":"Departamento de Farmacobiolog\u00eda, Centro Universitario de Ciencias Exactas e Ingenier\u00edas (CUCEI), Universidad de Guadalajara, Guadalajara 44430, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1540-9365","authenticated-orcid":false,"given":"Luis Ricardo","family":"Balleza-Alejandri","sequence":"additional","affiliation":[{"name":"Instituto de Terap\u00e9utica Experimental y Cl\u00ednica (INTEC), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2120-1819","authenticated-orcid":false,"given":"Jes\u00fas Jonathan","family":"Garc\u00eda-Galindo","sequence":"additional","affiliation":[{"name":"Instituto de Terap\u00e9utica Experimental y Cl\u00ednica (INTEC), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor","family":"Montoya-Fuentes","sequence":"additional","affiliation":[{"name":"Laboratorio de Microbiolog\u00eda Molecular II, Divisi\u00f3n de Medicina Molecular, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara 44100, Mexico"},{"name":"Divisi\u00f3n de Gen\u00e9tica, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7892-9125","authenticated-orcid":false,"given":"Alberto","family":"Beltr\u00e1n-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Instituto de Terap\u00e9utica Experimental y Cl\u00ednica (INTEC), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Li, Y., Deng, J., Liu, Y., and Yu, S. 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