The interesting history of papillomavirus (PV) research has been reviewed before. The history of human papillomavirus (HPV) in head and neck region starts in 1901 when the contagious transmission of warty lesions into the mouth via oral sex was described, although the confirmation of their viral etiology had to wait until 1907. Ullman was the first to associate the human wart virus with laryngeal warts. Parsons and Kidd described the natural history of oral PV infections in rabbits already in 1942, but these findings were corroborated in humans only recently. Koilocytotic atypia described by Koss and Durfee in 1956 was recognized as a sign of HPV infection in cervical precancer lesions only in 1976-1977 (Meisels and Fortin; Purola and Savia). This prompted systematic surveys of head and neck lesions for the detection of koilocytosis since the late 1970s, and the authors of this communication were the first to propose the HPV involvement in a subgroup of head and neck cancers. Brandsma and Abramson demonstrated HPV16 DNA in tonsillar SCCs in 1989. Since the early 2000s, HPV research of head and neck squamous cell carcinomas (HNSCC) has made impressive progress, confirming that the specific anatomic site plays a key role in determining the susceptibility to HPV infection. The most likely cancer sites associated with HPV are the base of the tongue and palatine tonsils, followed by oral cavity, larynx, and sinonasal mucosa. There is substantial geographic variation in HPV association with HNSCC. Patients with HPV-associated HNSCC are younger, and survival is better than in the absence of HPV.