{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:35:22Z","timestamp":1786977322281,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,1,26]],"date-time":"2015-01-26T00:00:00Z","timestamp":1422230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA131648"],"award-info":[{"award-number":["CA131648"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA115243"],"award-info":[{"award-number":["CA115243"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE023941"],"award-info":[{"award-number":["DE023941"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2015,3]]},"abstract":"Abstract<\/jats:title>\n \n Human papillomavirus (\n HPV<\/jats:styled-content>\n )\u2010positive oropharyngeal squamous cell carcinoma (\n OPSCC<\/jats:styled-content>\n ) is recognized as a distinct disease entity associated with improved survival.\n DNA<\/jats:styled-content>\n hypermethylation profiles differ significantly by\n HPV<\/jats:styled-content>\n status suggesting that a specific subset of methylated\n CpG<\/jats:styled-content>\n loci could give mechanistic insight into\n HPV<\/jats:styled-content>\n \u2010driven\n OPSCC<\/jats:styled-content>\n . We analyzed genome\u2010wide\n DNA<\/jats:styled-content>\n methylation of primary tumor samples and adjacent normal mucosa from 46\n OPSCC<\/jats:styled-content>\n patients undergoing treatment at Montefiore Medical Center, Bronx,\n NY<\/jats:styled-content>\n using the Illumina HumanMethylation27 beadchip. For each matched tissue set, we measured differentially methylated\n CpG<\/jats:styled-content>\n loci using a change in methylation level (M value). From these analyses, we identified a 22\n CpG<\/jats:styled-content>\n loci panel for\n HPV<\/jats:styled-content>\n +\n OPSCC<\/jats:styled-content>\n that included four\n \n CDKN2A<\/jats:styled-content>\n <\/jats:italic>\n loci downstream of the p16(\n INK4A<\/jats:styled-content>\n ) and p14(\n ARF<\/jats:styled-content>\n ) transcription start sites. This panel was significantly associated with overall\n HPV<\/jats:styled-content>\n detection (\n P<\/jats:italic>\n \u00a0<\u00a00.05;\n ROC<\/jats:styled-content>\n area under the curve\u00a0=\u00a00.96, 95% CI: 0.91\u20131.0) similar to the subset of four\n \n CDKN2A<\/jats:styled-content>\n <\/jats:italic>\n \u2010specific\n CpG<\/jats:styled-content>\n loci (0.90, 95% CI: 0.82\u20130.99) with equivalence to the full 22\n CpG<\/jats:styled-content>\n panel.\n DNA<\/jats:styled-content>\n hypermethylation correlated with a significant increase in alternative open reading frame (\n ARF<\/jats:styled-content>\n ) expression in\n HPV<\/jats:styled-content>\n +\n OPSCC<\/jats:styled-content>\n primary tumors, but not to the other transcript variant encoded by the\n \n CDKN2A<\/jats:styled-content>\n <\/jats:italic>\n locus. Overall, this study provides evidence of epigenetic changes to the downstream region of the\n \n CDKN2A<\/jats:styled-content>\n <\/jats:italic>\n locus in\n HPV<\/jats:styled-content>\n + oropharyngeal cancer that are associated with changes in expression of the coded protein products.\n <\/jats:p>","DOI":"10.1002\/cam4.374","type":"journal-article","created":{"date-parts":[[2015,1,26]],"date-time":"2015-01-26T01:36:24Z","timestamp":1422236184000},"page":"342-353","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Epigenetic changes in the\n CDKN2A<\/i>\n locus are associated with differential expression of P16INK4A and P14ARF in HPV\u2010positive oropharyngeal squamous cell carcinoma"],"prefix":"10.1002","volume":"4","author":[{"given":"Nicolas F.","family":"Schlecht","sequence":"first","affiliation":[{"name":"Department of Epidemiology & Population Health Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx New York 10461"},{"name":"Department of Medicine (Oncology) Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Ben\u2010Dayan","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Anayannis","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto A.","family":"Lleras","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard V.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx New York 10461"},{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Montefiore Medical Center Medical Arts Pavilion, 3400 Bainbridge Avenue Bronx New York 10467"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Burk","sequence":"additional","affiliation":[{"name":"Department of Epidemiology & Population Health Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx New York 10461"},{"name":"Department of Pediatrics (Genetics), Microbiology & Immunology; Obstetrics, Gynecology & Women's Health Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"Childs","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Ow","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx New York 10461"},{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Montefiore Medical Center Medical Arts Pavilion, 3400 Bainbridge Avenue Bronx New York 10467"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Prystowsky","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Belbin","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912217"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2007.08.004"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004941"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11389"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0966-842X(94)90667-X"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24842"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2011.91"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28876"},{"key":"e_1_2_7_10_1","first-page":"1519","article-title":"Frequent promoter hypermethylation of tumor\u2010related genes in head and neck squamous cell carcinoma","volume":"22","author":"Steinmann K.","year":"2009","journal-title":"Oncol. Rep."},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2012.02.018"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3280"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djh183"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-4-546"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.25.14863"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11404"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.26881"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67010"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm419"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2008.10.012"},{"key":"e_1_2_7_21_1","first-page":"1114","article-title":"A systematic profile of DNA methylation in human cancer cell lines","volume":"63","author":"Paz M. F.","year":"2003","journal-title":"Cancer Res."},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.6.6.16216"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2010.07.003"},{"key":"e_1_2_7_24_1","first-page":"4620","article-title":"E7 protein of human papilloma virus\u201016 induces degradation of retinoblastoma protein through the ubiquitin\u2010proteasome pathway","volume":"56","author":"Boyer S. N.","year":"1996","journal-title":"Cancer Res."},{"key":"e_1_2_7_25_1","first-page":"3590","article-title":"E2F\u20101 up\u2010regulates c\u2010Myc and p14(ARF) and induces apoptosis in colon cancer cells","volume":"7","author":"Elliott M. J.","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-3483"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90409-8"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-48"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2006.19.468"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcam4.374","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.374","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.374","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.374","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T03:31:42Z","timestamp":1696563102000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.374"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,26]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1002\/cam4.374"],"URL":"https:\/\/doi.org\/10.1002\/cam4.374","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1,26]]},"assertion":[{"value":"2014-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-09-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-01-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}