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One-third of the cases of oropharyngeal squamous cell carcinoma (OSCC) contain oncogenic human papillomavirus (HR-HPV). Epidemiologic and molecular evidence underlines the causal role of HR-HPV in these tumors, which can be defined as HPV-related OSCC. These tumors differ from chemical/toxin-induced OSCC in several biological aspects, including specific molecular and genetic alterations. This leads to a characteristic clinical profile of HPV-related OSCC. Sexual risk factors play a role; however, the knowledge about natural infection and the rate of persistence of HR-HPV in the oropharynx is marginal. It is shown that the distinct biological behavior of the HPV-related subset of oropharyngeal tumors results in a more favorable prognosis. This might be the result of a better response to chemotherapy and radiotherapy. However, further studies are needed to show whether it will be possible to reliably select patients for individualized therapy depended on the HPV status of their tumors. Therefore, we think it will be mandatory to consider and stratify HPV status in the design of prospective clinical trials in the future.

The major risk factors for head and neck squamous cell carcinomas (HNSCC) are considered to be tobacco and alcohol. A link between oncogenic types of the human papilloma virus (HPV) and the risk of HNSCC has been suggested in the literature. However, the causal link is now becoming more firmly established on the basis of recent analyses. About 20% of all HNSCC and more than 50% of tonsillar cancers contain HR-HPV. The causal role of HPV-infection in carcinogenesis and the molecular mechanisms involved could thus far be best elucidated in the case of cervical carcinomas. New insights and increasing evidence for the analogy of HPV-positive HNSCC with cervical cancer are discussed. The definition of HPV-positive HNSCC has become more important due to the implications for risk factors and prognosis.