Papillomavirus life cycle organization and biomarker selection

Abstract

Human papillomaviruses (HPVs) are a diverse group of viruses that cause epithelial lesions of varying severity. Of the 100 or so types that have been identified, around 40 can infect the cervix, with a subset of these causing lesions that can progress to high-grade neoplasia and cervical cancer. These high-risk types are prevalent in the general population, and can predispose to the development of cancer in women who cannot resolve their infection. Virus infection usually leads to the establishment of productive flat warts, or to maintenance of the viral genome in an asymptomatic or latent state. Virus synthesis depends on the ordered expression of viral gene products as the infected basal cell migrates towards the epithelial surface. E7 is expressed in the lower epithelial layers, and is followed eventually by the expression of E4 and L1 closer to the epithelial surface. This ordered pattern changes in characteristic ways during neoplastic progression and latency, and can be irreversibly fixed following integration of the viral genome into the host cell chromosome. Our understanding of expression patterns and their significance, is beginning to explain the nature of disease progression, and offers a rational basis for the selection of biomarkers that may be used to predict disease status and prognostic outcome.