{"doi":"10.21203/rs.2.22588/v2","title":"Tobacco exposure as a major modifier of oncologic outcomes in Human PapillomaVirus (HPV) associated oropharyngeal squamous cell carcinoma","abstract":"Abstract Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the US is rapidly increasing, driven largely by the epidemic of human papillomavirus (HPV)-mediated OPSCC. Although survival for patients with HPV mediated OPSCC (HPV+ OPSCC) is generally better than that of patients with non-viral HPV+ OPSCC, the improvement is not uniform. We hypothesized that tobacco exposure remains a critical modifier of survival for HPV+ OPSCC patients. Methods: We conducted a retrospective analysis of 611 OPSCC patients with concordant p16 and HPV testing treated at a single institute (2002-2013). Survival analysis was performed using Kaplan-Meier analysis and Cox regression. Recursive partitioning analysis (RPA) was used to define tobacco exposure associated with survival (p<0.05). Results: Tobacco exposure impacted overall survival (OS) for HPV+ patients on univariate and multivariate analysis (p=0.002, p=0.003 respectively). RPA identified 30 pack-years (PY) as a threshold at which survival became significantly worse in HPV+ patients. OS and disease-free survival (DFS) for HPV+ >30 PY patients didn’t differ significantly from HPV- group (p= 0.72, p= 0.27, respectively). HPV+ >30 PY patients had substantially lower 5-year OS when compared to their ≤30 PYs counterparts: 78.4% vs 91.6%; p= 0.03, 76% vs 88.3%; p= 0.07, and 52.3% vs 74%; p= 0.05, for stages I, II, and III (AJCC 8 th Edition Manual), respectively. Conclusions: Tobacco exposure can eliminate the survival benefit associated with HPV+ status in OPSCC patients. Until this effect can be clearly quantified using prospective datasets, de-escalation of treatment for HPV+OPSCC smokers should be avoided.","journal":"Research Square","year":2020,"id":134646,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":589210,"name":"Abdallah S.R. Mo","orcid":null,"position":1,"is_corresponding":false},{"id":351183,"name":"Baher Elgohari","orcid":"0000-0001-7694-6466","position":2,"is_corresponding":false},{"id":351184,"name":"Timothy A. Lin","orcid":"0000-0003-4183-9120","position":3,"is_corresponding":false},{"id":260512,"name":"Andrew G. Sikora","orcid":"0000-0002-8357-8435","position":4,"is_corresponding":false},{"id":351185,"name":"Stephen Y. Lai","orcid":"0000-0001-8301-7286","position":5,"is_corresponding":false},{"id":351186,"name":"Abdelrahman Abusaif","orcid":"0000-0002-7237-3098","position":6,"is_corresponding":false},{"id":351187,"name":"Jack Phan","orcid":"0000-0001-5977-6004","position":7,"is_corresponding":false},{"id":351188,"name":"William H. Morrison","orcid":"0000-0002-9546-0805","position":8,"is_corresponding":false},{"id":351189,"name":"G. Brandon Gunn","orcid":"0000-0001-8197-0380","position":9,"is_corresponding":false},{"id":32353,"name":"David I. Rosenthal","orcid":"0000-0001-7124-7447","position":10,"is_corresponding":false},{"id":299194,"name":"Adam S. Garden","orcid":"0000-0001-7926-2641","position":11,"is_corresponding":false},{"id":295555,"name":"Clifton D. Fuller","orcid":"0000-0002-5264-3994","position":12,"is_corresponding":false},{"id":260511,"name":"Vlad C. Sandulache","orcid":"0000-0002-9205-385X","position":13,"is_corresponding":false},{"id":295554,"name":"Hesham Elhalawani","orcid":"0000-0001-9848-2623","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-18T23:16:27.963294Z","pmid":null,"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":[]}