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Recent data demonstrate that human papillomavirus also plays a role in cancers other than ano-genital cancers, specifically head and neck cancers, and non-cancerous conditions such as recurrent respiratory papillomatosis. As more and more information about the role of infection in non-cervical diseases is amassed, additional questions about whether prophylactic human papillomavirus vaccines will effectively prevent these conditions are raised. This article reviews the epidemiology of oral human papillomavirus infection and the role of human papillomavirus in head and neck cancers. In addition, it will review the known clinical indications for human papillomavirus vaccination, and highlight other potential clinical targets for the vaccine that have not yet been demonstrated in clinical trials but for which there is biologic plausibility.