Background: Human papilloma virus (HPV) and tobacco smoking are important risk factors for development of oropharyngeal squamous cell carcinoma (OPSCC).

Aims/objectives: To evaluate the impact of tobacco smoking on survival for cases with OPSCC with known HPV- and p16INK4A(p16)-status.

Materials and Methods: OPSCC cases at the University Hospital of Copenhagen, Rigshospitalet, Denmark (2000-2014) and at University Hospital of Giessen, Germany (2000-2009) were included. Survival was illustrated with Kaplan-Meier plots. The effect of smoking exposure on survival was evaluated by Cox-regression models. HPV-positivity was defined as positivity for both HPV-DNA and p16.

Results: We included 1316 OPSCC cases from 2000-2014 (48% HPV-positive). Smokers had a poorer outcome compared to non-smokers. Considering continuous smoking exposure, adding 10 pack-years of smoking increased hazard ratios irrespective of HPV-status.We observed a tendency to a greater impact on survival for cases with HPV-neg. tumours compared to cases with HPV-pos. tumours at low numbers of pack-years, yet the survival was similar at high numbers of pack-years. There was no significant difference in the impact of HPV-status on survival for non-smokers, however a highly significant difference for smokers.

Conclusions and Significance: Smoking-status and number of pack-years at time of diagnosis impact survival for cases with OPSCC independent of HPV-status.