We investigated the p53 expression and the presence of HPV DNA in 90 patients with squamous cell carcinomas (SCCs) of the head and neck and the relation to clinicopathological parameters and patients' prognosis. Immunohistochemical analysis of p53 protein was conducted by using monoclonal anti-p53 antibody, clone 1801 and clone 240. The relationship between the overexpression of p53 and the duration of survival of patients was analyzed. The polymerase chain reaction (PCR) was carried out with consensus primers capable of detecting HPV16, 18, 31, 33, 52b and 58. In situ hybridization was performed in the mesopharyngeal carcinoma to confirm the presence of HPV genomes in cancer cells with a wide-spectrum cDNA probe capable of detecting HPV6, 11, 16, 18, 30, 31, 33, 35, 45, 51, 52. Forty-five tissue samples (50%) were immunohistochemically positive for p53. T-category, N-category, primary site of tumor, clinical stage and tumor differentiation did not correlate with p53 expression. Our finding that p53 overexpression occurred in 50% of head and neck tumor samples is similar to the frequency of p53 overexpression reported for both lung and esophageal cancer. The common risk factor is the same in these neoplasms, and therefore it is not surprising to find a similar percentage of p53 overexpression. The prevalence of metastasis was higher in the patients with p53-positive staining than in those with p53-negative staining (p < 0.10). Analysis of cumulative survival rates of patients by the Kaplan-Meier method showed a close correlation between p53 expression and survival time. The survival differences according to p53 immunostaining were significant (p 0.05). Our results indicate that p53 immunohistochemical evaluation may be useful as one of the new prognostic parameters in head and neck cancer patients. The HPV genomes were detected in 9 of 90 patients (10.0%); 8 of 9 patients with mesopharyngeal cancer and one with maxillary cancer, namely, 29.6% of mesopharyngeal cancers and 6.7% of maxillary cancer contained HPV DNA sequences. Seven of 8 patients had SCCs of tonsil origin. Almost all of the HPV infections in our study occurred in patients with mesopharyngeal cancer, and it has been suggested that this anatomic subsite may be more frequently infected by HPV than other sites within the head and neck region. Among the 27 patients with mesopharyngeal cancer, HPV DNA-positive patients experienced a higher incidence of complete remission than HPV DNA-negative patients (87.5% vs. 26.3%, p < 0.05).