{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:04:42Z","timestamp":1780625082587,"version":"3.54.1"},"reference-count":148,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Persistence of human papillomavirus (HPV) infection leading to cervical carcinogenesis can be attributed to the action of high-risk HPVs, but there are still some unclear factors involved in the mechanisms of either viral clearance or persistence. Although many infections may be self-limiting and cleared successfully by the immune response of the infected individuals, other infections result in persistent HPV infection. Recent studies indicate that microbiota in the gut and cervicovaginal tract modulate host immune status, mucosal inflammation, and epithelial barrier integrity. All these factors determine susceptibility to persistent infection. Inflammation, overproduction of reactive oxygen species (ROS), genomic instability, and impaired antiviral transcription pathways are associated with dysbiosis. In parallel, redox imbalance contributes to mitochondrial dysfunction, impairing mitochondrial antiviral signaling (MAVS)-dependent interferon responses and attenuating induction of interferon-stimulated genes. Additionally, extracellular vesicles (EVs) further promote immune evasion, metabolic programming, and epigenetic regulation by facilitating the intercellular exchange of viral constituents, microRNAs, and signaling molecules. Through this interconnected network of mechanisms, microbial dysbiosis, mitochondrial disruption, and EV signaling collectively shape a niche conducive to persistence. Unlike previous reviews that primarily examine microbiome alterations, oxidative stress (OS), mitochondrial dysfunction, extracellular vesicles, or immune responses as separate processes, this review integrates clinical and omics findings into a systems-based conceptual framework of HPV persistence. By emphasizing the potential interactions among these interconnected biological systems, we aim to identify points of biological convergence, generate mechanistic hypotheses, and highlight opportunities for future biomarker development and therapeutic intervention.<\/jats:p>","DOI":"10.3390\/genes17060655","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:58:38Z","timestamp":1780473518000},"page":"655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Microbiome\u2013Mitochondria\u2013Extracellular Vesicle Axis in HPV Persistence and Cervical Carcinogenesis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3333-2620","authenticated-orcid":false,"given":"Efthalia","family":"Moustakli","sequence":"first","affiliation":[{"name":"Department of Nursing, School of Health Sciences University of Ioannina, 4th Kilometer National Highway Street Ioannina-Athens, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9981-7488","authenticated-orcid":false,"given":"Stylianos","family":"Makrydimas","sequence":"additional","affiliation":[{"name":"Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9227-1365","authenticated-orcid":false,"given":"Emmanouil D.","family":"Oikonomou","sequence":"additional","affiliation":[{"name":"Human Computer Interaction Laboratory, Department of Informatics and Telecommunications, University of Ioannina, Kostakioi, 47150 Arta, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agni","family":"Nakou","sequence":"additional","affiliation":[{"name":"Department of Nursing, School of Health Sciences University of Ioannina, 4th Kilometer National Highway Street Ioannina-Athens, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9698-8276","authenticated-orcid":false,"given":"Eleni","family":"Albani","sequence":"additional","affiliation":[{"name":"Laboratory of Child Care and Family Resilience, Department of Nursing, University of Patras, 26334 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3036-7212","authenticated-orcid":false,"given":"Nektaria","family":"Zagorianakou","sequence":"additional","affiliation":[{"name":"Scientific Laboratory for Innovative Technologies in Internal Medicine, Preventive Medicine and Overall Care, Department of Nursing, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"W\u0142oszek, E., Krupa, K., Skrok, E., Budzik, M.P., Depta\u0142a, A., and Badowska-Kozakiewicz, A. 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