The relation between HPV and head and neck cancer has recently and extensively been investigated. The purpose of this study was to indentify HPV genotypes, as well as E6/E7 mRNA expression of high-risk HPVs (16, 18, 31, 33 and 45) in oral squamous cell carcinomas (OSCCs) from 45 Greek patients. The overall prevalence of HPV DNA positive OSCCs was 11.1% (5/45), while high-risk HPV DNA was found in 6.7% (3/45) of OSCCs. E6/E7 mRNA expression was detected in 8.9% (4/45) of the oral cavity samples. Our data indicated that HPV 16 was the commonest genotype identified in HPV-positive OSCCs by both DNA and RNA tests. This study confirms the prevalence of HPV infections among patients with OSCCs. Future analysis and followup of more OSCCs will enable us to correlate HPV detection and clinical outcome.