This article reviews the role of human papilloma virus (HPV) in oral squamous cell carcinomas (OSCCs), including the history, epidemiology, risk factors, molecular biology of oral HPV infection, and the prognostic role of HPV detection in patients with OSCC. The review showed that HPV is involved in the pathogenesis OSCCs; it determines the prognosis and modulates treatment response. Studies show a link between HPV and mouth cavity carcinoma: HPV preferentially infects the pre-cancer cells of the oropharynx; HPV prevalence is higher in pre-cancerous and cancerous oropharyngeal lesions. These may eventually develop into oropharyngeal cancer. It has been suggested the necessity of testing for papilloma virus in healthy and in individuals with different risk factors to identify whether a high-risk type of HPV is present.