Established associations between human papillomavirus (HPV) and lower genital tract cancers provide a framework from which to evaluate a possible pathogenic role for the virus in cancers at nongenital sites. Proposed associations must fit coherently within the context of our current knowledge of the epidemiology and biology of HPV. In this article, insights obtained from studies of the etiologic link between mucosal-type HPV infection and four specific human cancers are described briefly. Specific characteristics, shared among cancers caused by HPV, are then used by extrapolation to discuss possible associations between certain other nongenital cancers and mucosal HPV infections in a manner intended to supplement, and in no way to supplant, the classic Hill criteria for causal inference.