Human papillomavirus (HPV) infection with high-risk types 16 and 18 has widely been reported as one of the prominent mechanisms behind the development of cervical squamous cell carcinoma. Links between HPV and oral cavity cancer have been suggested as well, based on epidemiologic and molecular means, though the association is less well-established. It is likely that HPV plays a role in oral cavity carcinogenesis, though only in a small subset of cases. The difficulty in providing true causal evidence of HPV's role in oral cancer lies in our lack of understanding of the significance of mechanisms by which HPV leads to oral carcinogenesis, as well as limitations in the molecular analysis of HPV. Further studies are necessary for the contribution of HPV in oral cavity malignancy to be better demonstrated.