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Original Investigation |

Prognostic Importance of Comorbidity and the Association Between Comorbidity and p16 in Oropharyngeal Squamous Cell Carcinoma

S. Andrew Skillington, BA1; Dorina Kallogjeri, MD, MPH1; James S. Lewis Jr, MD2,3; Jay F. Piccirillo, MD1,4
[+] Author Affiliations
1Department of Otolaryngology–Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri
2Department of Pathology and Immunology, Washington University School of Medicine in St Louis, St Louis, Missouri
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
4Editor, JAMA Otolaryngology–Head & Neck Surgery
JAMA Otolaryngol Head Neck Surg. 2016;142(6):568-575. doi:10.1001/jamaoto.2016.0347.
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Importance  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.

Objective  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.

Design, Setting, and Participants  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.

Exposures  Patients were grouped according to p16 status.

Main Outcomes and Measures  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.

Results  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]).

Conclusions and Relevance  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.

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Figure 1.
Effect of Comorbidity on Survival

A, Kaplan-Meier overall survival curves. B, Disease-free survival curves. Patients with no comorbidity and those with mild, moderate, and severe comorbidity are compared. The reported P values indicate the differences among groups by log-rank test.

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Figure 2.
Effect of Comorbidity on Survival as a Function of p16 Status and Adjustment for Other Prognostic Factors

A, Adjusted overall survival curves for none to mild comorbidity and moderate to severe comorbidity among p16-positive patients. B, Adjusted overall survival curves for none to mild comorbidity and moderate to severe comorbidity among p16-negative patients. C, Adjusted disease-free survival curves for no comorbidity to mild comorbidity and moderate to severe comorbidity among p16-positive patients. D, Adjusted disease-free survival curves for no comorbidity to mild comorbidity and moderate to severe comorbidity among p16-negative patients. aHR indicates adjusted hazards ratio.

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