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Evidence from genome-wide association studies (GWAS) is discussed, highlighting the contribution of specific genetic loci, predominantly within the HLA region, to susceptibility to HPV infection and disease progression. In parallel, the review examines the molecular mechanisms by which the viral oncoproteins E6 and E7 promote genetic instability and epigenetic reprogramming, including histone modifications and dysregulation of non-coding RNAs. Particular emphasis is placed on DNA methylation, affecting both the viral genome and host genes such as FAM19A4, CADM1, PAX1, and MAL, as a promising biomarker for triage and detection of high-grade intraepithelial lesions (CIN2+). Finally, the review evaluates currently available methylation-based assays and self-sampling devices, highlighting their potential to enhance diagnostic accuracy and increase participation in cervical cancer screening programs.<\/jats:p>","DOI":"10.3390\/ijms27020803","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T18:40:09Z","timestamp":1768329609000},"page":"803","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["HPV-Driven Cervical Carcinogenesis: Genetic and Epigenetic Mechanisms and Diagnostic Approaches"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4261-2745","authenticated-orcid":false,"given":"Evangelia","family":"Legaki","sequence":"first","affiliation":[{"name":"Laboratory of Biology, Department of Basic Biological Science, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8083-4402","authenticated-orcid":false,"given":"Theofania","family":"Lappa","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Department of Basic Biological Science, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6907-1654","authenticated-orcid":false,"given":"Konstantina-Lida","family":"Prasoula","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Department of Basic Biological Science, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9577-5249","authenticated-orcid":false,"given":"Zoi","family":"Kardasi","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Department of Basic Biological Science, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1444-6161","authenticated-orcid":false,"given":"Emmanouil","family":"Kalampokas","sequence":"additional","affiliation":[{"name":"Unit of Gynecologic Oncology, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1379-894X","authenticated-orcid":false,"given":"Theodoros","family":"Kalampokas","sequence":"additional","affiliation":[{"name":"Unit of Obstetrics and Gynecology, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5790-6581","authenticated-orcid":false,"given":"Maria G.","family":"Roubelakis","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Department of Basic Biological Science, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Charvalos","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnosis, Reprogenetica, Dios 44, 15235 Vrilissia, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3295-6811","authenticated-orcid":false,"given":"Maria","family":"Gazouli","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Department of Basic Biological Science, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Medina-Rivero, A.S., Ratkovich-Gonzalez, S., Ruiz-Brise\u00f1o, M.D.R., and Rosas-Gonz\u00e1lez, V.C. 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