Papillomaviruses and assays for transforming genes

Human papillomavirus (HPV) research dates back to the turn of the century, when Ciuffo demonstrated that human warts are caused by an infectious agent, only later identified as a virus (1). More recently, the HPVs have generated particular interest, since they include some of the few viruses clearly involved in the development of certain human cancers (2). Although most papillomaviruses give rise to benign, self-limiting proliferations, a number of human and animal papillomaviruses have also been shown to have oncogenic potential. This link between papillomaviruses and malignant disease was first recognized more than 50 years ago, when it was shown that benign lesions induced by the cottontail rabbit papillomavirus could progress to invasive carcinoma (3). The change from benign lesions to malignancy and the identification of factors that contribute to this conversion has been extremely useful as a model for tumor progression. However, following the initial studies that so elegantly identified the oncogenic potential of papillomaviruses, research into these viruses slowed considerably for many years. Further investigation has been hampered by the failure to develop an in vitro culture system for viral propagation. In general, papillomaviruses are limited to a single host and show strong tropism with respect to the cell type that they infect. Most papillomaviruses infect only cutaneous or mucosal epithelial cells at specific anatomical sites. Viral DNA replication and transcription of some viral sequences occurs in cells throughout the epithelium.