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Association between p53 and Human Papillomavirus in Head and Neck Cancer Survival

¹ Department of Epidemiology, College of Public Health, and ² Veterans Affairs Medical Center, Iowa City, Iowa; and ³ Department of Pathology, College of Medicine, University of Iowa

Requests for reprints: Elaine M. Smith, Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242. Phone: 319-338-0581, ext. 7503; Fax: 319-339-7178. E-mail: elaine-smith{at}uiowa.edu

Background: High-risk human papillomavirus (HPV-HR) is a significant risk factor for head and neck cancer (HNC), abrogating normal p53 function. In addition, HPV and p53 have been associated with prognosis of these tumors but the findings have been inconsistent. We examined p53 expression and HPV-HR individually and jointly for differences in predicting HNC survival.

Methods: HNC patients (n = 294) were evaluated for p53 by immunohistochemical staining. HPV was detected by PCR/dot blot hybridization and sequencing.

Results: HNC tumors showed 48% with p53 overexpression and 27% with HPV-HR. Multivariate analyses showed that p53 positivity was significantly associated with higher risk of disease-specific [hazard ratio (HR); 2.0; 95% confidence interval (95% CI), 1.1-3.7] and recurrence-free mortality (HR, 2.8; 95% CI, 1.4-5.3). HPV– cases had significantly worse disease-specific survival (HR, 2.8; 95% CI, 1.3-6.3) compared with HPV-HR cases. When analyzed jointly, with p53^–/HPV-HR tumors as the reference group, p53⁺/HPV^– patients had the worst disease-specific (HR, 5.3; 58% versus 15%, P = 0.006) and recurrence-free survival rates (HR, 9.5; 17% versus 89%, P = 0.001), in contrast to the p53^–/HPV^– and p53⁺/HPV-HR groups, which had less elevated and different risks for disease-specific survival (HR, 2.5 and 1.7, respectively) and recurrence-free survival (HR, 4.2 and 7.2, respectively).

Conclusion: Joint assessment of p53/HPV status provides different HRs for each clinical outcome in the four biomarker groups that are distinct from the individual biomarkers. These findings suggest that joint assessment of p53/HPV provides a better indicator of prognosis and potentially different types of treatments. (Cancer Epidemiol Biomarkers Prev 2008;17(2):421–7)