Abstract
BackgroundThe 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.MethodsWe 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).ResultsTobacco 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 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 8th Edition Manual), respectively.ConclusionsTobacco 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.
Highlights
The incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the United States (US) is rapidly increasing, driven largely by the epidemic of human papillomavirus (HPV)-mediated OPSCC
Tobacco remains a critical driver of survival and treatment response in HPV+ OPC
Oropharyngeal squamous cell carcinoma (OPSCC), a disease traditionally associated with tobacco and alcohol exposure, is overwhelmingly a disease associated with HPV [1,2,3,4]
Summary
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. Oropharyngeal squamous cell carcinoma (OPSCC), a disease traditionally associated with tobacco and alcohol exposure, is overwhelmingly a disease associated with HPV [1,2,3,4] This change in the epidemiology of the disease has resulted in dramatic improvements in treatment efficacy along with disease specific and overall survival [1,2,3,4,5,6]. The principal distinction between the two risk categories was a reduced survival in patients who were smokers This observation has been confirmed in subsequent studies, the interaction between HPV and cigarette smoking remains poorly characterized both from a biological perspective and with respect to clinical outcomes [8]. Smoking rates have decreased over the last two decades, evidence suggests that tobacco exposure remains a significant consideration for OPSCC patients throughout the United States and varies widely based on race/ethnicity and socioeconomic strata [3, 9]
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