{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T13:01:54Z","timestamp":1789909314591,"version":"4.0.1"},"reference-count":33,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T00:00:00Z","timestamp":1559174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA008748"],"award-info":[{"award-number":["P30CA008748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:p>The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing due to high\u2010risk HPV infection. We explored the significance of genetic alterations in HPV\u2010positive (HPV\u2010P) and HPV\u2010negative (HPV\u2010N) OPSCC patients on long\u2010term outcome. A total of 157 cases of primary resected OPSCC diagnosed from 1978 to 2005 were subjected to a targeted exome sequencing by MSK\u2010IMPACT\u2122 interrogating somatic mutations in 410 cancer\u2010related genes. Mutational profiles were correlated to recurrence and survival outcomes. OPSCC included 47% HPV\u2010positive (HPV\u2010P) and 53% HPV\u2010negative (HPV\u2010N) tumors arising in the base of tongue (BOT, 43%), palatine tonsil (30%) and soft palate (SP, 27%). HPV negative status, SP location and smoking were associated with poorer outcome. Poorer overall survival was found in <jats:italic>NOTCH1<\/jats:italic>\u2010mutated HPV\u2010P (<jats:italic>p<\/jats:italic> = 0.039), and in <jats:italic>SOX2\u2010<\/jats:italic>amplified HPV\u2010N cases (<jats:italic>p<\/jats:italic> = 0.036). Chromosomal arm gains in 8p and 8q, and 16q loss were more common in HPV\u2010P (<jats:italic>p<\/jats:italic> = 0.005, 0.04 and 0.01, respectively), while 9p, 18q and 21q losses were more frequent in HPV\u2010N OPSCC (<jats:italic>p<\/jats:italic> = 0.006, 0.002 and 0.01, respectively). Novel, potentially functional <jats:italic>JAK3<\/jats:italic>, <jats:italic>MYC<\/jats:italic> and <jats:italic>EP300<\/jats:italic> intragenic deletions were found in HPV\u2010P, and <jats:italic>FOXP1<\/jats:italic>, <jats:italic>CDKN2A<\/jats:italic>, <jats:italic>CCND1<\/jats:italic> and <jats:italic>RUNX1<\/jats:italic> intragenic deletions and one <jats:italic>FGFR3<\/jats:italic> inversion were detected in HPV\u2010N tumors. HPV\u2010N\/<jats:italic>TP53<\/jats:italic>\u2010wild\u2010type OPSCC harbored recurrent mutations in <jats:italic>NOTCH1\/3\/4<\/jats:italic> (39%), <jats:italic>PIK3CA<\/jats:italic>, <jats:italic>FAT1<\/jats:italic> and <jats:italic>TERT<\/jats:italic>. In comparison to their oral and laryngeal counterparts, HPV\u2010N OPSCC were genetically distinct. In OPSCC, HPV status, tumor subsite and smoking determine outcome. Risk\u2010stratification can be further refined based on the mutational signature, namely, <jats:italic>NOTCH1<\/jats:italic> and <jats:italic>SOX2<\/jats:italic> mutation status.<\/jats:p>","DOI":"10.1002\/ijc.32412","type":"journal-article","created":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T07:40:11Z","timestamp":1557992411000},"page":"3152-3162","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Identification of prognostic molecular biomarkers in 157 HPV\u2010positive and HPV\u2010negative squamous cell carcinomas of the oropharynx"],"prefix":"10.1002","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4905-8946","authenticated-orcid":false,"given":"Snjezana","family":"Dogan","sequence":"first","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center  New York 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