Prognostic Impact of p16, p53, Epidermal Growth Factor Receptor, and Human Papillomavirus in Oropharyngeal Cancer in a Betel Nut-Chewing Area

Objective: To evaluate the prevalence of human papillomavirus (HPV) and the prognostic significance of epidermal growth factor receptor (EGFR), p53, and p16 among patients with oropharyngeal carcinoma. Design: Retrospective study. Setting: Academic Institute of Otolaryngology, Kaohsiung, Taiwan. Patients: Two hundred seventy-four patients who were diagnosed as having oropharyngeal carcinoma underwent testing for the presence of the HPV genome in the nuclei of their tumor cells from January 1, 1992, through March 31, 2008. Interventions: The HPV genome was detected by performing polymerase chain reaction-based assays and in situ hybridization on tumor tissue from paraffin blocks. Immunohistochemistry staining for p16, p53, and EGFR was also performed. Main Outcome Measures: We used the Fisher exact test to evaluate the correlation between the clinicopathological variables and the presence of HPV in tumor cells. Survival analysis was based on the Kaplan-Meier method. Results: We detected HPV in 45 of the 274 patients (16.4%); of these, HPV-16 and -18 were identified in 42 (93.3%) of the HPV-positive tumors. The HPV-positive oropharyngeal cancers were more likely to occur in females, nonsmoking individuals, and those who did not chew betel quid. The HPV-positive tumors significantly expressed p16 and were inversely associated with EGFR and p53 expression (all, P < .001). In addition, patients with tumor tissue that was positive for HPV (P = .008) and had negative expression of EGFR (P = .01), low expression of p53 (P = .01), and high expression of p16 (P = .04) had a better prognosis. Conclusion: Our results suggest that HPV, EGFR, p53, and p16 are useful biomarkers in predicting the clinical outcomes of oropharyngeal cancer.