There is accumulating evidence that oropharyngeal squamous cell carcinomas (SCCs) that harbour oncogenic human papillomavirus (HPV) are biologically distinct and have a better prognosis. This information is a persuasive argument for the identification of these cancers in clinical practice. The concept of 'HPV related' SCC should be underpinned by knowledge that the malignant cells harbour a high risk HPV genotype and there is evidence of oncogenic viral protein expression with effects on cell signalling pathways. For satisfactory classification in clinical practice HPV tests should reliably work on fixed cells and tissue. There is evidence that detection of high risk HPV by consensus polymerase chain reaction (PCR) alone is insufficient to accurately classify tumours. However, there is convincing evidence that the detection of p16 protein by immunohistochemistry can be used as a surrogate marker for the elaboration of oncogenic HPV proteins. Recently, there have been calls for standardisation of HPV testing in head and neck cancers and two diagnostic algorithms have emerged: the first advocates screening for p16 by immunohistochemistry followed by detection of HPV DNA by in situ hybridisation: the second recommends detection of p16 followed by consensus PCR. The majority of pathology laboratories have the capability of delivering the first algorithm. Furthermore, the techniques employed are automated and are subject to stringent quality assurance measures; features that can deliver routine, accurate and cost effective HPV testing for oropharyngeal cancers.