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Oncogenic human papillomavirus (HPV)\u2010positive disease is often associated with a good prognosis compared with HPV\u2010negative disease. However, some HPV\u2010positive HNSCC recurs, often with distant metastases and significant treatment resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>We performed p16 immunohistochemistry (IHC), in situ hybridization (ISH) for high\u2010risk HPV, and comprehensive genomic profiling on oropharyngeal HNSCC with basaloid features and particularly aggressive disease course, noting a rare genetic event: a deleting mutation (exons 5\u201317) of the tumor suppressor and dominant cell cycle regulator retinoblastoma 1 (RB1). Genomic and transcriptomic data available through FoundationOne and The Cancer Genome Atlas (TCGA) were reviewed for additional HNSCC cases with RB1 alterations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>RB1 alterations may have important prognostic implications, particularly in the context of high p16 expression, in both HPV\u2010positive and HPV\u2010negative HNSCC. \u00a9 2016 Wiley Periodicals, Inc. <jats:italic>Head Neck<\/jats:italic> 39: E34\u2013E39, 2017<\/jats:p><\/jats:sec>","DOI":"10.1002\/hed.24604","type":"journal-article","created":{"date-parts":[[2016,11,8]],"date-time":"2016-11-08T14:53:40Z","timestamp":1478616820000},"source":"Crossref","is-referenced-by-count":13,"title":["Head and neck squamous cell carcinoma: Ambiguous human papillomavirus status, elevated p16, and deleted retinoblastoma 1"],"prefix":"10.1002","volume":"39","author":[{"given":"Tim N.","family":"Beck","sequence":"first","affiliation":[{"name":"Program in Molecular Therapeutics Fox Chase Cancer Center Philadelphia Pennsylvania"},{"name":"Molecular and Cell Biology &amp; Genetics Program Drexel University College of Medicine Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chad H.","family":"Smith","sequence":"additional","affiliation":[{"name":"Program in Molecular Therapeutics Fox Chase Cancer Center Philadelphia Pennsylvania"},{"name":"Department of Medical Oncology Fox Chase Cancer Center Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas B.","family":"Flieder","sequence":"additional","affiliation":[{"name":"Department of Pathology Fox Chase Cancer Center Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Galloway","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Fox Chase Cancer Center Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Ridge","sequence":"additional","affiliation":[{"name":"Program in Molecular Therapeutics Fox Chase Cancer Center Philadelphia Pennsylvania"},{"name":"Department of Surgical Oncology Fox Chase Cancer Center Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica A.","family":"Golemis","sequence":"additional","affiliation":[{"name":"Program in Molecular Therapeutics Fox Chase Cancer Center Philadelphia Pennsylvania"},{"name":"Molecular and Cell Biology &amp; Genetics Program Drexel University College of Medicine Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranee","family":"Mehra","sequence":"additional","affiliation":[{"name":"Program in Molecular Therapeutics Fox Chase Cancer Center Philadelphia Pennsylvania"},{"name":"Department of Medical Oncology Fox Chase Cancer Center Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,11,8]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.58.6412"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2012.06.019"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2015.0102"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.61.2358"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2010.078154"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoto.2013.5308"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2009.11.015"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2014.192"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv344"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-8815-6_1"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djn025"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2011.91"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318253a2d1"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djn011"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.53.5633"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.44.0164"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4321"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.4358"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-3000"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14129"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004088"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0095"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051862"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt417"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.6.6.953"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1747-1028-7-10"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.7.4032"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/36038"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2982"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1208130"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2907"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-8815-6_2"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009933108"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03486-14"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.510809"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm453"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.61.1509"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa1348"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500596"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3051"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.00.3335"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu167"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.54.5228"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912217"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.53.9163"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.57.9268"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2940"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2764"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1015027108"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209616"}],"container-title":["Head &amp; 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