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In recent years, there has been mounting epidemiologic and experimental evidence of a role for human papillomavirus (HPV) as the etiologic agent of a subset of head and neck cancers. The association is strongest for oropharyngeal cancers, especially those of the tonsil. HPV 16 is invariably the predominant type. HPV\u2010positive cancers have been shown to be biologically distinct, clustering among nonsmokers and light drinkers, and have been associated with a favorable prognosis. This review examines the current findings of HPV in head and neck cancers and discusses implications for developing new treatments. \u00a9 2006 Wiley Periodicals, Inc. 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