Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck

Oncogenic human papillomaviruses (HPVs), especially HPV type 16, cause anogenital epithelial cancers and are suspected of causing epithelial cancers of the head and neck. In several studies, tonsillar and oropharyngeal carcinomas contained HPV DNA more commonly than cancers at other head and neck sites, in line with findings that patients with a history of anogenital cancer have 4.3 times the risk for tonsillar cancer of the general population. How HPV infects the upper respiratory tract is not firmly established, but epidemiologic evidence suggests sexual transmission. In three case-control studies, patients with oral cancer had more sexual partners than controls. The increasing incidence of oropharyngeal squamous cell carcinomas is believed to be due to the growing proportion of HPV-positive oropharyngeal squamous cell carcinoma. Oropharyngeal squamous cell carcinomas incidence is on the rise and it is a distinct subset of head and neck squamous cell carcinoma with a well-established etiologic link to HPV; in epidemiologic studies, anatomical site of tumor origin (ie, oropharynx) is used as a surrogate marker of HPV status. Changing patterns of sexual behavior represent the most widely accepted explanation for the increase in HPV-positive oropharyngeal squamous cell carcinomas. Also, in a 50-year period, the predominant morphologic oropharyngeal squamous cell carcinomas type changed from keratinizing to nonkeratinizing, and the incidence of HPV in oropharyngeal squamous cell carcinomas doubled, most significantly in men.