Impact of Smoking on Outcomes of HPV-related Oropharyngeal Cancer Treated with Primary Radiation or Surgery

Int J Radiat Oncol Biol Phys. 2019 Apr 1;103(5):1125-1131. doi: 10.1016/j.ijrobp.2018.11.046. Epub 2018 Dec 1.


Purpose: Tobacco exposure is known to affect the biological behavior of human papilloma virus (HPV)-positive oropharyngeal carcinoma (OPC) with intermediate outcomes relative to tumors that are HPV associated with no smoking exposure and smoking-related HPV-negative tumors. We aim to evaluate the impact of smoking on the outcomes of patients with HPV-associated locally advanced OPC when stratified by treatment modality.

Methods and materials: A retrospective chart review was undertaken for 352 patients with known p16-overexpressing locally advanced OPC who were managed with curative-intent therapy from 2006 to 2015. The impact of smoking status on overall survival (OS) and recurrence-free survival were compared using the Kaplan-Meier method.

Results: Of the 352 patients, 67.6% (n = 238) were managed with primary chemoradiation therapy (CRT) and 32.4% (n = 114) with primary surgery ± adjuvant therapy. The median smoking pack-year was 15. Twenty-seven percent of patients were active smokers at the time of presentation, with 40.3% identifying as former smokers and 32.7% having never smoked. Median follow-up for surviving patients was 4.2 years. Current smokers had a significantly worse relapse-free survival and OS compared with never and former smokers (P = .03 and P = .0001, respectively), with outcomes significantly worsening with increasing smoking exposure. The 5-year OS for more than 10, 20, and 30 pack-year smoking history was 73.2%, 64.7%, and 59.1%, respectively. Current smokers managed with CRT had a 5-year OS of 64.2% compared with former and never smokers (93.1% and 78.2%, respectively). For current smokers managed primarily by surgery the 5-year OS was 57.6% compared with former and never smokers (69.6% and 73.5%, respectively).

Conclusions: Current smokers and those with higher smoking exposure had poorer outcomes irrespective of their primary modality of treatment. Although not the specific focus of the study, definitive CRT appeared to at least be equivalent to surgery with respect to disease outcomes for patients with HPV-associated oropharyngeal cancer, regardless of smoking status.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chemoradiotherapy / statistics & numerical data*
  • Disease-Free Survival
  • Ex-Smokers / statistics & numerical data
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Non-Smokers / statistics & numerical data
  • Oropharyngeal Neoplasms / mortality*
  • Oropharyngeal Neoplasms / surgery
  • Oropharyngeal Neoplasms / therapy*
  • Oropharyngeal Neoplasms / virology*
  • Papillomavirus Infections / complications*
  • Radiotherapy Dosage
  • Retrospective Studies
  • Smokers
  • Smoking / adverse effects*
  • Smoking / epidemiology
  • Smoking / mortality*
  • Time Factors
  • Treatment Outcome