Head & Neck Cancer (HNC) is one of the most common malignancies worldwide and among oral neoplasias about 90-92% are squamous cell carcinomas (OSCC). Alcohol and tobacco consumption have been recognized as the main risk factors for development of OSCC. However, 10 to 20% of patients suffering from OSCC have no history of use of these substances. Clinico-pathological evidence suggests that we are dealing with virally-induced cancers, and that HPV should not be a relevant candidate. A systematic search of HPV in OSCC has no real relevance in current clinical practice even although it is still relevant in organized research protocols. Further studies are ongoing, with the aim of identifying other infectious agents, including viruses, in OSCC.