Fig. (1) Different Outcomes of Papillomavirus Infection. (A) Papillomavirus DNA can be detected in epithelial tissues because of its presence as virus particles on the epithelial surface. The detection of papillomavirus DNA in such situations can be misinterpreted as papillomavirus latency. To cause a lesion and/or to initiate a latent infection, the virus particles have to gain access to the epithelial basal cells at sufficiently high levels. Each papillomavirus type has specific epithelial sites where it can initiate a productive life cycle, as well as sites where virus entry occurs in the absence of lesion formation. Such epithelial tropisms are not yet understood at the molecular level. (B) Depending on the epithelial site, the virus titre, and the tropism of the particular papillomavirus, it appears that several outcomes can result. At low titres and/or at non-permissive epithelial sites, an asymptomatic or silent infection may ensue, in which viral genomes may persist in the basal layer without appropriate gene expression or lesion formation. While this is a form of latency, such silent infections do not necessarily involve the immune system, and are distinguished here from latency mediated by the immune-system Alternatively a productive infection may develop, in which viral gene expression is properly regulated as the infected cell migrates through the epithelium. With some HPV types (e.g. high-risk types) and at particular epithelial sites, deregulated viral gene expression can lead to neoplasia. Cervical Intraepithelial Neoplasia (CIN) of different grades can occur following high-risk HPV infection of the cervix. (C) Persistent high-risk HPV infection can predispose to the accumulation of genetic errors and the progression to cancer at certain epithelial sites (e.g. the cervical transformation zone). Most infections are transient however and are resolved by the host immune system. Although immune surveillance may suppress viral gene expression in the epithelium, failure of the immune system to clear viral genomes from the epithelial basal layer would explain papillomavirus latency.