Epidemiological evidence suggests that human papillomavirus(HPV) infection is a high risk factor for the development of oral cancers. Many oncogenes, especially p53 suppressor gene, have a critical role of carcinogenesis in several human cancers including oral cancers. To investigate the prevalence of HPV infection and subtyping of high risk group(HPV-16, -18 and -33) HPV in oral cancers, the author studied 31 cases of squamous cell carcinomas arising from the oral cavity using polymerase chain reaction (PCR). The author also demonstrated the overexpression of p53 oncoprotein in the oral cancers using immunohistochemical methods. The correlation between HPVs infection and p53 overexpression in tumorigenesis of the oral cancers was evaluated. 1. Twenty-one cases(66.7%) among 31 cases of oral squamous cell carcinomas were positive for HPV-DNA. Among them, 16 cases were positive for HPV-16, 4 cases for HPV-18, and 2 cases for HPV-33. Two cases were coinfected with HPV-16 and HPV-18, and HPV-18 and HPV-33. 2. The prevalence of HPV infection appeared not correlated with tumor differentiation and clinical stages of oral squamous cell carcinomas. 3. The overexpression of p53 oncoprotein was present in 24 of 31 cases(77% ). In 21 HPV positive tumors 18 cases were positive for overexpression of p53 oncoprotein. Six cases were positive for p53 in ten HPV negative tumors. There was no correlation between HPV DNA detection rate and p53 overexpression. The above results suggest that HPV infection and p53 oncogene mutation play different roles in tumorigenesis of oral squamous cell carcinomas. No coexpression of p53 oncoprotein with HPV-DNA detection suggests that another etiologic mechanism other than HPV infection may be operative.