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p16 and p53 Protein Expression as Prognostic Indicators of Survival and Disease Recurrence from Head and Neck Cancer¹

Department of Epidemiology, School of Public Health [S. A. G., A. F. O., J. S., K. V.], Department of Biostatistics, School of Public Health [J. C.], Division of Ear, Nose and Throat/Head and Neck Surgery, Department of Surgery, School of Medicine [A.F.O., M.C.W.]; and Department of Pathology, School of Medicine [W.K.F.], University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Purpose: Markers of somatic mutation such as p16 and p53 remain controversial prognostic indicators for patients with squamous cell carcinoma of the head and neck (SCCHN). The relationship between p53 protein expression and radiation therapy is also unclear.

Experimental Design: We made a prospective cohort study (n = 171) of incident cases receiving standardized therapy for SCCHN.

Results: Patients whose tumors showed increased p53 protein expression had over twice the risk of all-cause mortality after 550 days [hazard ratio (HR), 2.7; 95% confidence interval (CI), 1.07–6.66] and three times the risk of dying from cancer-specific causes after 550 days (HR, 3.09; 95% CI, 1.15–8.30) after adjustment for age, therapy, and stage. Tumors demonstrating alteration of both p16 and p53 did not confer any additional diagnostic information over p53 alone. Patients whose tumors expressed increased levels of p53 protein and received radiation were almost three times more likely to die as compared with those who received radiation but whose tumors did not express increased p53 protein after adjustment for age and stage (HR, 2.6; 95% CI, 1.03–6.50).

Conclusions: p53 protein expression was found to violate the proportional hazards assumption for our cohort, which may explain the controversial prognostic ability of this protein in the literature. p53 protein expression, but not p16 protein expression, was related to poor survival in general for men and women. In addition, an interaction between p53 expression and radiation therapy was demonstrated. Additional studies are needed to confirm and extend our results.

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