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The majority (75%) of all newly diagnosed cases are observed in patients with locally advanced and aggressive disease, associated with significant relapse rates (30%) and poor prognostic outcomes, despite advances in multimodal treatment. Consequently, there is an unmet need for the identification and application of tools that would enable diagnosis at the earliest possible stage, accurately predict prognostic outcomes, contribute to the timely detection of relapses, and aid in the decision for therapy selection. Recent evidence suggests that DNA methylation can alter the expression of genes in a way that it favors tumorigenesis and tumor progression in HNSCC, and therefore represents a potential source for biomarker identification. This study summarizes the current knowledge on how abnormally methylated DNA profiles in HNSCC patients may contribute to the pathogenesis of HNSCC and designate the methylation patterns that have the potential to constitute clinically valuable biomarkers for achieving significant advances in the management of the disease and for improving survival outcomes in these patients.<\/jats:p>","DOI":"10.3390\/ijms24032996","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T03:36:57Z","timestamp":1675395417000},"page":"2996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["DNA Methylation as a Diagnostic, Prognostic, and Predictive Biomarker in Head and Neck Cancer"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2625-5728","authenticated-orcid":false,"given":"Galateia","family":"Liouta","sequence":"first","affiliation":[{"name":"Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8779-4485","authenticated-orcid":false,"given":"Maria","family":"Adamaki","sequence":"additional","affiliation":[{"name":"Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonis","family":"Tsintarakis","sequence":"additional","affiliation":[{"name":"Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Zoumpourlis","sequence":"additional","affiliation":[{"name":"Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0314-9981","authenticated-orcid":false,"given":"Anastasia","family":"Liouta","sequence":"additional","affiliation":[{"name":"Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Agelaki","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University General Hospital of Heraklion, Vassilika Vouton, 71110 Heraklion, Greece"},{"name":"Laboratory of Translational Oncology, School of Medicine, University of Crete, Vassilika Vouton, 71003 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilis","family":"Zoumpourlis","sequence":"additional","affiliation":[{"name":"Biomedical Applications Unit, Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1080\/14737159.2017.1404906","article-title":"Serum, Plasma and Saliva Biomarkers for Head and Neck Cancer","volume":"18","author":"Arantes","year":"2018","journal-title":"Expert Rev. 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