HUMAN PAPILLOMA-VIRUS AND P53 IN HEAD AND NECK-CANCER - CLINICAL CORRELATES AND SURVIVAL

Recent studies have shown that p53 mutations are frequently found in c ancer of the head and neck, whereas others have indicated that human p apilloma virus (HPV) infection may be involved, Thus far, no studies h ave examined both p53 and HPV in the same patient population and corre lated the results with clinical characteristics and outcome. The purpo se of this study was to examine any interrelationship between p53 and HPV in patients with squamous cell carcinoma (SCC) of the head and nec k, We also planned to correlate the experimental findings with clinica l characteristics, known risk factors, and treatment outcome to determ ine whether any prognostic factors could be detected, Archival materia l from 66 patients with SCC of the head and neck were selected for stu dy based on the availability of tissue from the primary tumors prior t o treatment, A data base was constructed containing all clinical param eters at the time of diagnosis and risk factors. Genomic DNA was isola ted and amplified using PCR, followed by SSCP analysis and direct geno mic sequencing of all variants to detect p53 mutations, Two independen t methods were used for HPV detection: (a) PCR amplification using pri mers homologous to the Ed region of HPV 16, 18, and 33, followed by RF LP analysis; and (b) PCR amplification with HPV L1 consensus primers, followed by triple restriction enzyme digestion, The results were ente red into the data base for statistical analysis, Twenty-four percent o f patients were found to have p53 mutations, and 18% were positive for HPV infection, Only one patient was positive for both, Tonsilar cance r was strongly correlated with HPV (P = 0.0001) and inversely correlat ed with p53 (P = 0.03), The only clinical parameter associated with p5 3 mutation was a trend toward a heavier smoking history, A subset anal ysis of the patients with tonsilar cancer revealed inverse correlation s with smoking (P = 0.015) and alcohol use (P = 0.05), Also, white pat ients with SCC of the tonsil were more likely to be HPV positive (P = 0.015), No significant relationships with outcome were detected with e ither p53 or HPV in the entire population. A subset analysis of patien ts with stage IV disease revealed that HPV infection was correlated wi th overall survival. This is the largest study to date to examine both p53 and HPV in patients with SCC of the head and neck. Our results su ggest that HPV may be involved in the development of these cancers in patients without traditional risk factors and that HPV-related cancers are more prevalent in the white race.