The association of smoking and outcomes in HPV-positive oropharyngeal cancer: A systematic review

While smoking is linked to worse outcomes for human papillomavirus (HPV)-related oropharyngeal squamous cell cancer (OPSCC), the magnitude of this association and the amount of smoking exposure necessary to confer clinically significant differences in outcomes is unclear. Recent studies suggested that greater tobacco exposure results in higher risk of cancer progression and death. Our study objective was to perform a systematic review of the association between smoking and HPV-related OPSCC outcomes. A literature search was conducted in April 2019 to identify relevant articles using Embase, Medline, Scopus, CENTRAL, and Cochrane databases. All studies were independently screened by two investigators to identify studies that assessed HPV-positive patients as an independent cohort, specified smoking measures, and reported locoregional recurrence (LRR), overall survival (OS), disease-specific survival (DSS), or disease-free survival (DFS) in association with smoking. Of 1130 studies identified, 10 met final inclusion criteria with 2321 total patients, mean age 57.5 years. Smoking measures included ever vs never, current vs never/former smokers, ≤10 vs >10 pack-year, and continuous pack-years. Of these studies, 8 (80%) showed a significant effect of smoking on increasing recurrence and mortality. Adjusted HRs for LRR ranged from 0.6 to 5.2, OS from 1.3 to 4.0, DSS from 2.3 to 7.2, and DFS from 1.02 to 4.2 among heavier smokers compared to lighter/non-smokers. While there was significant variability in smoking metrics and reported outcomes, all studies reporting statistically significant HRs showed that smoking was associated with worse outcomes. Further studies using uniform smoking measures are necessary to better understand this association.