The prevalence of oropharyngeal squamous cell carcinoma (OPSCC) has increased to epidemic proportions in Europe and the United States of America over the last three decades. Most of this increase has been attributed to an exponential rise in the incidence of Human Papilloma Virus (HPV) associated OPSCC: HPV-16 being the most common genotype. HPV associated tumours constitute a discrete disease entity, with non-smoking, non-heavy drinking patients presenting at an earlier age than their counterparts presenting with HPV negative tumours. This article highlights evidence of this increased incidence and describes the genetic make-up of HPV. In addition, we explain the mechanisms underlying the ability of HPV to transform normal epithelial cells into cancer cells. Finally, we describe the current methods employed to detect HPV infection and conclude by highlighting a diagnostic algorithm which has been proposed as a pragmatic strategy to maximise the detection of HPV infection in oropharyngeal tumour tissue.