{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T03:14:35Z","timestamp":1783307675045,"version":"3.54.6"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010751","name":"Fondo Nacional de Desarrollo Cient\u00edfico, Tecnol\u00f3gico y de Innovaci\u00f3n Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["1160741\/2016"],"award-info":[{"award-number":["1160741\/2016"]}],"id":[{"id":"10.13039\/501100010751","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012478","name":"Secretaria de Ciencia y Tecnolog\u00eda - Universidad Nacional de C\u00f3rdoba","doi-asserted-by":"publisher","award":["05\/J154"],"award-info":[{"award-number":["05\/J154"]}],"id":[{"id":"10.13039\/100012478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic mechanical irritation (CMI) has been proposed as a risk factor for oral cancer. Epigenetic alterations, particularly methylation, are early events in carcinogenesis, and it has been proposed that they can be prompted by CMI. Thus, the aim of this study was to describe p16 and MGMT methylation in chronic traumatic ulcer (CTU).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A case\u2013control split\u2010mouth study was performed. Two samples per individual (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200927) were taken using exfoliative cytology using a split\u2010mouth design, one from the CTU and the other from a contralateral site of clinically normal mucosa. DNA was extracted and bisulfite\u2010treated, and specific sites at the promoter region of p16 and MGMT genes were amplified by qPCR using validated primers. Then, the PCR product was sequenced. The statistical analysis was performed by McNemar and the Chi\u2010square test.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients had a mean age of 59.1\u2009years. CTU showed higher methylation than control sites for both p16 (85% vs. 20%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and MGMT (80% vs. 24%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0005).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Oral mucosa subjected to continuous exposure to CMI is associated with increased methylation of p16 and MGMT. Proper management of mechanical injury factors could be an important measure for OSCC prevention. In CMI, exfoliative cytology and the split\u2010mouth design could be useful tools to study biomarkers. However, the role of CMI in oral carcinogenesis needs more evidence focusing on the biological phenomenon.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jop.70128","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:22:07Z","timestamp":1771334527000},"page":"669-675","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["p16 and\n                    <scp>MGMT<\/scp>\n                    Methylation in Chronic Traumatic Ulcers: A Plausible Link Between Chronic Mechanical Irritation and Oral Carcinogenesis?"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0881-9614","authenticated-orcid":false,"given":"Jeronimo Pablo","family":"Lazos","sequence":"first","affiliation":[{"name":"Oral Medicine Department Dentistry College, Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Hernandez Rios","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology and Medicine &amp; Laboratory of Periodontal Biology Dentistry College, Universidad de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Astorga","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology and Medicine &amp; Laboratory of Periodontal Biology Dentistry College, Universidad de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene Luis","family":"Panico","sequence":"additional","affiliation":[{"name":"Oral Medicine Department Dentistry College, Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo David","family":"Piemonte","sequence":"additional","affiliation":[{"name":"Oral Medicine Department Dentistry College, Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Mar\u00eda","family":"Z\u00e1rate","sequence":"additional","affiliation":[{"name":"Oral Biology Department Dentistry College, Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.31053\/1853.0605.v78.n2.31247"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.4317\/medoral.22017"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/6784526"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.17305\/bjbms.2021.5577"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784\u2010022\u201004584\u2010w"},{"key":"e_1_2_9_7_1","first-page":"182","article-title":"Malignant Potential of Oral Submucous Fibrosis due to Intraoral Trauma","volume":"54","author":"Dayal","year":"2000","journal-title":"Indian Journal of Medical Sciences"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2021.105616"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784\u2010022\u201004710\u20108"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4317\/medoral.23729"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/248419"},{"key":"e_1_2_9_12_1","first-page":"892","article-title":"Gene Promoter Hypermethylation in Tumors and Serum of Head and Neck Cancer Patients","volume":"60","author":"Sanchez\u2010Cespedes M.","year":"2000","journal-title":"Cancer Research"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4103\/0970\u20109290.152208"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2011.1205"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(02)00932\u20104"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41432\u2010022\u20100248\u20109"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs\u20102016\u20100195"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2009.07.006"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/1010428317699113"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010024\u201001716\u20109"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698\u2010019\u20100079\u20100"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.7860\/JCDR\/2014\/9251.4949"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010020\u201000224\u20103"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1368\u20108375(03)00143\u2010X"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0959\u20108049(03)00550\u20101"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000336914"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280215601137"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/2057178X18791034"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652410790963303"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12642"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0030225"}],"container-title":["Journal of Oral Pathology &amp; 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