Tobacco exposure as a major modifier of oncologic outcomes in human papillomavirus (HPV) associated oropharyngeal squamo
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RESEARCH ARTICLE
Open Access
Tobacco exposure as a major modifier of oncologic outcomes in human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma Hesham Elhalawani1, Abdallah S. R. Mohamed1,2, Baher Elgohari1, Timothy A. Lin1, Andrew G. Sikora3,4, Stephen Y. Lai5,6, Abdelrahman Abusaif1, Jack Phan1, William H. Morrison1, G. Brandon Gunn1, David I. Rosenthal1, Adam S. Garden1, Clifton D. Fuller1,7* and Vlad C. Sandulache3,4,8*
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-virally mediated OPSCC, this effect 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- patients (p = 0.72, p = 0.27, respectively). HPV+ > 30 PY patients had substantially lower 5year 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 8th 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. Keywords: Oropharyngeal carcinoma, Radiotherapy, Tobacco, Human papillomavirus
* Correspondence: [email protected]; [email protected] 1 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, 0097, FCT10.6002, Houston, TX 77030, USA 3 ENT Section, Operative Care Line, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this
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