title: Prognostic Importance of Comorbidity and the Association Between Comorbidity and p16 in Oropharyngeal Squamous Cell Carcinoma.
abstract: Comorbidity affects the prognosis of patients with cancer through the direct effects of the comorbid illness and by influencing the patients' ability to tolerate treatment and mount a host response. However, the prognostic importance of comorbidity in oropharyngeal squamous cell carcinoma is not well characterized in the era of human papillomavirus infection.
  
  
  
  To determine the prognostic importance of comorbidity in both p16-positive and p16-negative oropharyngeal squamous cell carcinoma and to explore the relationship between comorbidity and p16.
  
  
  
  Retrospective cohort study of 305 patients at a single tertiary referral center diagnosed as having oropharyngeal squamous cell carcinoma between June 1996 and June 2010, but without a history of head and neck cancer or distant metastasis at time of diagnosis. The data were analyzed from August 1, 2014, through April 30, 2015.
  
  
  
  Patients were grouped according to p16 status.
  
  
  
  Overall survival, defined as the time from diagnosis to death from any cause. Disease-free survival, defined as the time from diagnosis to either death from any cause or the first documented local, regional, or distant recurrence.
  
  
  
  Of the 305 patients who met eligibility criteria, 230 were p16-positive, 70 were p16-negative, and 5 were not evaluable for p16 status. The final cohort of 300 patients had a mean (SD) age of 56.3 (9.3) years and 262 (87%) were male. In Kaplan-Meier analysis, the 5-year overall survival rates were 71% (95% CI, 65%-76%) for 232 patients with no comorbidity to mild comorbidity and 49% (95% CI, 36%-61%) for 63 patients with moderate to severe comorbidity. In multivariate Cox proportional hazards analysis, moderate to severe comorbidity was associated with an increased risk of death from any cause (adjusted hazards ratio [aHR], 1.52 [95% CI, 0.99-2.32]) and increased risk of death or recurrence (aHR, 1.71 [95% CI, 1.13-2.59]). After stratifying by p16 status and controlling for other variables, moderate to severe comorbidity was significantly associated with increased risk of death from any cause among p16-negative patients (aHR, 1.90 [95% CI, 1.03-3.50]) but not among p16-positive patients (aHR, 1.11 [95% CI, 0.61-2.02]).
  
  
  
  Comorbidity is important to consider when assessing the prognosis of patients with oropharyngeal squamous cell carcinoma and is of greater prognostic value in p16-negative than p16-positive cancer.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.
authors.forename: S Andrew
authors.initials: SA
authors.lastname: Skillington
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.
authors.forename: Dorina
authors.initials: D
authors.lastname: Kallogjeri
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine in St Louis, St Louis, Missouri3Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: James S
authors.initials: JS
authors.lastname: Lewis
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri4Editor, JAMA Otolaryngology-Head & Neck Surgery.
authors.forename: Jay F
authors.initials: JF
authors.lastname: Piccirillo
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000473:pathology / Q000628:therapy / Q000821:virology*; D015331:Cohort Studies; D015897:Comorbidity; D018572:Disease-Free Survival; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009959:Oropharyngeal Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy / Q000821:virology*; D011379:Prognosis; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects; D014861:Washington / Q000453:epidemiology