A significant proportion of squamous cell carcinomas (SCC) of the oropharynx are associated with high-risk human papillomavirus (HPV). These HPV-related carcinomas are prognostically and therapeutically different from traditional SCC of the head and neck. Cervical metastases from head and neck primary SCC are frequently investigated by fine-needle aspiration (FNA). HPV testing of cytologic samples from these lesions would potentially simplify diagnosis and therapeutic planning. This review summarizes current methodologies for HPV testing of FNA specimens and the role of HPV typing in diagnosis, prediction of prognosis, and selection of therapy. Diagn. Cytopathol. 2012;40:491–497. © 2012 Wiley Periodicals, Inc.