title: Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer.
abstract: OBJECTIVE
  Tobacco smoking is associated with oropharynx cancer survival, but to what extent cancer progression or death increases with increasing tobacco exposure is unknown.
  
  
  METHODS
  Patients with oropharynx cancer enrolled onto a phase III trial of radiotherapy from 1991 to 1997 (Radiation Therapy Oncology Group [RTOG] 9003) or of chemoradiotherapy from 2002 to 2005 (RTOG 0129) were evaluated for tumor human papillomavirus status by a surrogate, p16 immunohistochemistry, and for tobacco exposure by a standardized questionnaire. Associations between tobacco exposure and overall survival (OS) and progression-free survival (PFS) were estimated by Cox proportional hazards models.
  
  
  RESULTS
  Prevalence of p16-positive cancer was 39.5% among patients in RTOG 9003 and 68.0% in RTOG 0129. Median pack-years of tobacco smoking were lower among p16-positive than p16-negative patients in both trials (RTOG 9003: 29 v 45.9 pack-years; P = .02; RTOG 0129: 10 v 40 pack-years; P < .001). After adjustment for p16 and other factors, risk of progression (PFS) or death (OS) increased by 1% per pack-year (for both, hazard ratio [HR], 1.01; 95% CI, 1.00 to 1.01; P = .002) or 2% per year of smoking (for both, HR, 1.02; 95% CI, 1.01 to 1.03; P < .001) in both trials. In RTOG 9003, risk of death doubled (HR, 2.19; 95% CI, 1.46 to 3.28) among those who smoked during radiotherapy after accounting for pack-years and other factors, and risk of second primary tumors increased by 1.5% per pack-year (HR, 1.015; 95% CI, 1.005 to 1.026).
  
  
  CONCLUSIONS
  Risk of oropharyngeal cancer progression and death increases directly as a function of tobacco exposure at diagnosis and during therapy and is independent of tumor p16 status and treatment.
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA. maura.gillison@osumc.edu
authors.forename: Maura L
authors.initials: ML
authors.lastname: Gillison
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Richard
authors.initials: R
authors.lastname: Jordan
authors.forename: Weihong
authors.initials: W
authors.lastname: Xiao
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.forename: Andy
authors.initials: A
authors.lastname: Trotti
authors.forename: Sharon
authors.initials: S
authors.lastname: Spencer
authors.forename: Jonathan
authors.initials: J
authors.lastname: Harris
authors.forename: Christine H
authors.initials: CH
authors.lastname: Chung
authors.forename: K Kian
authors.initials: KK
authors.lastname: Ang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D016016:Proportional Hazards Models; D012306:Risk; D012907:Smoking / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16