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Aim: The causative role of human papillomavirus (HPV) has been established into the aetiology of oral squamous cell carcinoma (OSCC). Some authors believe that HPV can determinate the prognosis and module treatment response from this kind of malignancies.Methods: Articles published in the last 10 years, focusing on the role of HPV in the development, molecular biology, prognosis and treatment of OSCC were reviewed.Results: Thirty-nine articles from 252 were selected, highlighting 4 meta-analysis, 3 prospective and 2 retrospective studies. According to its role in the development of cervical cancer, HPV is classified into a high risk for malignant lesions subtype and a low-grade malignant lesions subtype. Epidemiology and prevalence of HPV varies according to the published data: large studies tend to have lower rates of HPV (< 50%) than smaller ones (0-100%). Interestingly, HPV+ patients are usually diagnosed at a younger age, mainly those with oropharyngeal tumours. There is a predilection for the oropharynx and Waldeyer ring tumours. Regarding prognosis, OSCC HPV+ patients tend to have better outcome and treatment response.Conclusion: HPV divides OSCC in two types of tumours with different prognostic and therapeutic implications, with increased survival, better treatment response rates and lower risk of death and recurrences.