{"doi":"10.1002/cncr.33504","title":"Genomic heterogeneity and copy number variant burden are associated with poor recurrence‐free survival and 11q loss in human papillomavirus‐positive squamous cell carcinoma of the oropharynx","abstract":"BACKGROUND: Human papillomavirus-positive (HPV+) squamous cell carcinoma of the oropharynx (OPSCC) is the most prevalent HPV-associated malignancy in the United States. Favorable treatment outcomes have led to increased interest in treatment de-escalation to reduce treatment morbidity as well as the development of prognostic markers to identify appropriately low-risk 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. METHODS: 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. RESULTS: High intratumorally genomic heterogeneity and high numbers of copy number alterations were strongly associated with worse recurrence-free survival. Tumors with higher heterogeneity and frequent copy number alterations were associated with loss of distal 11q, which encodes key genes related to double-strand break repair, including ATM and MRE11A. CONCLUSIONS: Both intratumor genomic heterogeneity and high-burden copy number alterations are strongly associated with poor recurrence-free 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-strand 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.","journal":"Cancer","year":2021,"id":190762,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9611,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":363724,"name":"Nicholas R. Lenze","orcid":"0000-0002-2126-6663","position":1,"is_corresponding":false},{"id":755579,"name":"Lee Landess","orcid":null,"position":2,"is_corresponding":false},{"id":13571,"name":"Alan P. Hoyle","orcid":"0000-0002-0664-8786","position":3,"is_corresponding":false},{"id":13902,"name":"Joel S. Parker","orcid":"0000-0003-2080-6901","position":4,"is_corresponding":false},{"id":755580,"name":"Asim Lal","orcid":null,"position":5,"is_corresponding":false},{"id":367424,"name":"Siddharth Sheth","orcid":"0000-0002-1923-2309","position":6,"is_corresponding":false},{"id":600748,"name":"Bhishamjit S. Chera","orcid":"0000-0002-6775-7986","position":7,"is_corresponding":false},{"id":755083,"name":"Samip Patel","orcid":"0000-0003-1575-4043","position":8,"is_corresponding":false},{"id":574887,"name":"Trevor Hackman","orcid":"0000-0001-9330-2398","position":9,"is_corresponding":false},{"id":18212,"name":"Michael B. Major","orcid":"0000-0002-6753-8513","position":10,"is_corresponding":false},{"id":755084,"name":"Natalia Issaeva","orcid":"0000-0001-5483-6610","position":11,"is_corresponding":false},{"id":452945,"name":"Wendell G. Yarbrough","orcid":"0000-0003-0855-6444","position":12,"is_corresponding":false},{"id":392097,"name":"Travis P. Schrank","orcid":"0000-0002-8297-3329","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T23:49:26.966524Z","pmid":"33819343","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}