Molecular biology of human papillomavirus infection and cervical cancer.
HPVs (human papillomaviruses) infect epithelial cells and cause a variety of lesions ranging from common warts/verrucas to cervical neoplasia and cancer. Over 100 different HPV types have been identified so far, with a subset of these being classified as high risk. High-risk HPV DNA is found in almost all cervical cancers (>99.7%), with HPV16 being the most prevalent type in both low-grade disease and cervical neoplasia. Productive infection by high-risk HPV types is manifest as cervical flat warts or condyloma that shed infectious virions from their surface. Viral genomes are maintained as episomes in the basal layer, with viral gene expression being tightly controlled as the infected cells move towards the epithelial surface. The pattern of viral gene expression in low-grade cervical lesions resembles that seen in productive warts caused by other HPV types. High-grade neoplasia represents an abortive infection in which viral gene expression becomes deregulated, and the normal life cycle of the virus cannot be completed. Most cervical cancers arise within the cervical transformation zone at the squamous/columnar junction, and it has been suggested that this is a site where productive infection may be inefficiently supported. The high-risk E6 and E7 proteins drive cell proliferation through their association with PDZ domain proteins and Rb (retinoblastoma), and contribute to neoplastic progression, whereas E6-mediated p53 degradation prevents the normal repair of chance mutations in the cellular genome. Cancers usually arise in individuals who fail to resolve their infection and who retain oncogene expression for years or decades. In most individuals, immune regression eventually leads to clearance of the virus, or to its maintenance in a latent or asymptomatic state in the basal cells.
Doorbar
John
J
Division of Virology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. jdoorba@nimr.mrc.ac.uk
D018450:Disease Progression; D005260:Female; D006801:Humans; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics* / Q000502:physiology; D030361:Papillomavirus Infections / Q000150:complications*; D011230:Precancerous Conditions / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D017735:Virus Latency