Human papillomavirus (HPV) is responsible for approximately 25% of head and neck cancer (HNC) worldwide and appears to be associated with a better response to treatment and improved prognosis. Evidence suggests that HPV-induced HNC has steadily increased in the USA and some European countries in the last decades. However, whether this is a worldwide phenomenon and specific risk factors are associated with it remains to be proven. In addition, little is known on the natural history and risk factors of oral HPV infection. HPV-AHEAD network aims to address these and other unanswered questions on HNC etiology and epidemiology with a focus on the role of HPV. We will assemble and analyze a large collection of plasma/sera and HNC tissues from 42 centres in 16 European countries as well as HNC tissues from 7 Indian centres together with epidemiological and clinical data. HPV status in human specimens will be evaluated by different assays in central laboratories. Epidemiological studies will be conducted to establish the overall proportion and type distribution of HPV-positive HNC at different anatomical sites in European and Indian regions as well as the time trend of the proportion of HPV-positive HNC in recent decades. Using the follow-up information on HNC patients, we will further investigate whether HPV positivity confers a better prognosis and survival. We will also conduct a study in HPV-vaccinated and non-vaccinated women in order to determine risk factors and natural history of oral HPV infections. In addition, we will search for new surrogate markers for oral HPV infection to facilitate novel screening strategies. Finally, the HPV-AHEAD consortium aims to transfer technology to Indian centres as well as to develop several strategies for the training of European and Indian researchers in infections and cancers. This study will provide important insights for the screening, diagnosis, treatment and prophylaxis of HPV-associated HNC in Europe, India and elsewhere.