{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:45:49Z","timestamp":1790667949108,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T00:00:00Z","timestamp":1617580800000},"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":["T32CA009156"],"award-info":[{"award-number":["T32CA009156"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005193","name":"American Academy of Otolaryngology-Head and Neck Surgery","doi-asserted-by":"publisher","award":["Translational Innovator Award"],"award-info":[{"award-number":["Translational Innovator Award"]}],"id":[{"id":"10.13039\/100005193","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Human papillomavirus\u2013positive (HPV+) squamous cell carcinoma of the oropharynx (OPSCC) is the most prevalent HPV\u2010associated malignancy in the United States. Favorable treatment outcomes have led to increased interest in treatment de\u2010escalation to reduce treatment morbidity as well as the development of prognostic markers to identify appropriately low\u2010risk patients. Intratumoral genomic heterogeneity and copy number alteration burden have been demonstrated to be predictive of poor outcomes in many other cancers; therefore, we sought to determine whether intratumor heterogeneity and genomic instability are associated with poor outcomes in HPV+ OPSCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Tumor heterogeneity estimates were made based on targeted exome sequencing of 45 patients with HPV+ OPSCC tumors. Analysis of an additional cohort of HPV+ OPSCC tumors lacking matched normal sequencing allowed copy number analysis of 99 patient tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>High intratumorally genomic heterogeneity and high numbers of copy number alterations were strongly associated with worse recurrence\u2010free survival. Tumors with higher heterogeneity and frequent copy number alterations were associated with loss of distal 11q, which encodes key genes related to double\u2010strand break repair, including ATM and MRE11A.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Both intratumor genomic heterogeneity and high\u2010burden copy number alterations are strongly associated with poor recurrence\u2010free survival in patients with HPV+ OPSCC. The drivers of genomic instability and heterogeneity in these tumors remains to be elucidated. However, 11q loss and defective DNA double\u2010strand break repair have been associated with genomic instability in other solid tumors. Copy number alteration burden and intratumoral heterogeneity represent promising avenues for risk stratification of patients with HPV+OPSCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.33504","type":"journal-article","created":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T16:36:28Z","timestamp":1617640588000},"page":"2788-2800","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Genomic heterogeneity and copy number variant burden are associated with poor recurrence\u2010free survival and 11q loss in human papillomavirus\u2010positive squamous cell carcinoma of the oropharynx"],"prefix":"10.1002","volume":"127","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8297-3329","authenticated-orcid":false,"given":"Travis P.","family":"Schrank","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery The University of North Carolina at Chapel Hill Chapel Hill North Carolina"},{"name":"Linberger Comprehensive Cancer Center The University of North Carolina at Chapel Hill Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Lenze","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery The University of North Carolina at Chapel Hill Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee P.","family":"Landess","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery The University of North Carolina at Chapel Hill Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0664-8786","authenticated-orcid":false,"given":"Alan","family":"Hoyle","sequence":"additional","affiliation":[{"name":"Linberger Comprehensive Cancer Center The University of North Carolina at Chapel Hill Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Parker","sequence":"additional","affiliation":[{"name":"Linberger Comprehensive Cancer Center The University of North Carolina at Chapel Hill Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asim","family":"Lal","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery The University of North Carolina at Chapel Hill Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1923-2309","authenticated-orcid":false,"given":"Siddharth","family":"Sheth","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology The University of North Carolina at Chapel Hill Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6775-7986","authenticated-orcid":false,"given":"Bhishamjit S.","family":"Chera","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology The University of North Carolina at Chapel Hill Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samip N.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery The University of North Carolina at Chapel Hill Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor G.","family":"Hackman","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery The University of North Carolina at Chapel Hill Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Ben","family":"Major","sequence":"additional","affiliation":[{"name":"Linberger Comprehensive Cancer Center The University of North Carolina at Chapel Hill Chapel Hill North Carolina"},{"name":"Department of Cell Biology and Physiology The University of North Carolina at Chapel Hill Chapel Hill North Carolina"},{"name":"Department of Cell Biology and Physiology Washington University in St. Louis St. Louis Missouri"},{"name":"Institute for Informatics School of Medicine Washington University in St. Louis St. Louis Missouri"},{"name":"Department of Otolaryngology School of Medicine Washington University in St. Louis St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Issaeva","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery The University of North Carolina at Chapel Hill Chapel Hill North Carolina"},{"name":"Linberger Comprehensive Cancer Center The University of North Carolina at 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