20 pack-year smoking history as strongest smoking metric predictive of HPV-positive oropharyngeal cancer outcomes

Objectives: While smoking is associated with worse outcomes in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), the magnitude of this association is unclear given the heterogenous smoking definitions and outcomes. Our objective was to investigate the association between smoking, survival, and recurrence in HPV-related OPSCC using multiple smoking metrics reported in the literature. Materials and methods: This was a retrospective cohort study of 375 adults with p16+ OPSCC undergoing surgical resection (n = 272) or definitive chemoradiation (n = 103) at a tertiary academic institution from 2006 to 2017. The primary outcome was overall survival (OS). Secondary outcomes included disease-free survival (DFS), disease-specific survival (DSS), and recurrence. We used multiple smoking metrics commonly cited in previous studies, including ever versus never smokers, current versus former/never smokers, ≤10 versus >10 pack-year, ≤20 versus >20 pack-year, and continuous pack-year. Results: There were 375 patients, median age 58 years, with 326 (87%) males, and median follow-up of 52 months. Of all smoking metrics, >20 pack-year history was the strongest predictor of both OS (HR 2.24, 95% CI: 1.19–4.20) and DFS (HR 1.67, 95% CI: 1.04–2.66) on univariable and multivariable analysis after adjusting for age, overall stage, and comorbidities. Patients with >20 pack-year smoking history were also more likely to have recurrence (HR 1.59, 95% CI: 0.95–2.67) after adjusting for overall stage. Conclusion: Heavier smoking >20 pack-years was the strongest smoking metric associated with 2-times worse survival and recurrence. Our findings suggest that >20 pack-year smoking history may be a more useful cutoff for risk stratification models but requires further validation.