Prevalence of human papilloma virus DNA in head and neck cancers carrying wild-type or mutant p53 tumor suppressor genes.

The normal function of the p53 tumor suppressor protein can be perturbed by non-mutational mechanisms. The E6 protein encoded by high risk strains of human papilloma virus (HPV) targets the p53 protein resulting in enhanced degradation via the ubiquitin pathway. We have used nested PCR for detecting the presence of HPV DNA in 58 primary head and neck tumors and 15 metastatic lymph nodes, which had been prescreened for p53 mutations in exons 5 to 8. HPV DNA sequences were detected in 12 tumors (20.6%) and 4 metastatic lymph nodes (21%). HPV type 16 DNA was predominantly found in tumors (n = 11) and lymph nodes (n = 4), one tumor was positive for HPV type 18 sequences. Five of 12 HPV-positive tumors (41%) carried a p53 mutation. Of 46 HPV-negative tumors, 16 (34.8%) carried a p53 mutation. Thus, HPV positivity and p53 mutations were not mutually exclusive in head-and-neck cancer. Three of 6 normal tissues adjacent to the tumor were positive for HPV type 16, while no viral DNA was found in the corresponding tumors. Thus, the presence of HPV type 16 DNA did not directly confer a growth advantage on the population of emerging tumor cells. Instead, these tumors lack normal p53 function due to mutation.