The aim of this study was to ascertain the prevalence of HPV 16/18 DNA in oral squamous cell carcinoma (OSCC) vs. normal oral mucosa, and to correlate the virologic data with other factors obtained from the patients' records. One hundred and thirteen paraffin embedded tissue samples (73 OSCC and 40 normal oral mucosa) were studied using HPV type specific primer-mediated polymerase chain reaction (PCR). Seventy-four per cent (54/73) of OSCC and 55% (22/44) of normal oral mucosa were positive for HPV 16/18 DNA. Statistical analysis indicated there was a significant difference between HPV16/18 positive OSCC vs. normal oral mucosa (P=0.040), and that age (<60 years) and gender (male) were correlated with the presence of HPV16/18 in the tumour. No significant association was found between the presence of HPV and other risk factors, including tobacco use, alcohol use, tumour location, histologic grade or TNM staging. We found a significant association of HPV16/18 with oral squamous cell carcinoma. Also, HPV16/18 is a co-factor in oral carcinogenesis, particularly in male patients and patients under the sixth decade. In addition, we found that HPV infection is a common event in the normal oral mucosa.