Impact on survival of tobacco smoking for cases with oropharyngeal squamous cell carcinoma and known human papillomavirus and p16-status: a multicenter retrospective study

// Christian Grønhøj 1 , Jakob Schmidt Jensen 1 , Steffen Wagner 2 , Christian Dehlendorff 3 , Jeppe Friborg 4 , Elo Andersen 5 , Claus Wittekindt 2 , Nora Würdemann 2 , 6 , Shachi Jenny Sharma 2 , 6 , Stefan Gattenlöhner 7 , Jens Peter Klussmann 2 , 6 and Christian von Buchwald 1 1 Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 2 Department of Otorhinolaryngology, Head and Neck Surgery, University of Giessen, Giessen, Germany 3 Department of Statistics and Pharmacoepidemiology, Danish Cancer Society Research Center, Copenhagen, Denmark 4 Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 5 Department of Oncology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark 6 Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Cologne, Cologne, Germany 7 Department of Pathology, University of Giessen, Giessen, Germany Correspondence to: Christian Grønhøj, email: christian.groenhoej@regionh.dk Keywords: oropharyngeal cancer; human papillomavirus; smoking; survival Received: May 01, 2019 Accepted: June 29, 2019 Published: July 23, 2019 ABSTRACT 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.