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; Jakob Schmidt Jensen; Steffen Wagner; Christian Dehlendorff; Jeppe Friborg; Elo Andersen; Claus Wittekindt; Nora Würdemann; Shachi Jenny Sharma; Stefan Gattenlöhner; Jens Peter Klussmann; Christian von Buchwald

doi:10.18632/oncotarget.27079

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

Oncotarget. 2019 Jul 23;10(45):4655-4663. doi: 10.18632/oncotarget.27079.

Authors

Affiliations

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.

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.

Keywords: human papillomavirus; oropharyngeal cancer; smoking; survival.