title: [Molecular mechanism of cervical carcinogenesis].
abstract: Cervical cancer is the second leading cause of cancer death in women worldwide; approximately 500,000 women develop cervical cancer every year, and more than half of them die from the disease. While the incidence of cervical cancer in developed countries is decreasing due to the widespread use of cervical cytology screening, the incidence among those in their 20's and 30's in Japan is rapidly increasing because of gradually younger sexual debut. High-risk human papilloma viruses (HPVs) such as HPV16 and 18 are thought to be responsible for more than 90% of cervical cancers. HPVs reach and infect the basal layer of the stratified epithelia via small epithelial injuries produced by sexual intercourse, and the viral DNAs are maintained as episomes in the basal cells. When the host cells initiate terminal differentiation, the viral DNAs start to replicate by reactivating the DNA synthesis machinery through degrading p53 by E6 and inactivating Rb by E7. Viral propagation results in the host cells' death, whereas on rare occasions HPV genomes are integrated into the host chromosomes. The cells constantly over expressing E6 and E7 from the integrated viral genomes develop multiple steps towards carcinogenesis through numerous E6 and E7 oncoprotein functions. However, the over-expressions of E6 and E7 are known to be insufficient for carcinogenesis; additional accumulation of genetic and epigenetic abnormalities in oncogenes and tumor suppressors are required. In this review, we outline the current understanding of the molecular mechanisms of high-risk HPV-induced cervical carcinogenesis.
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Minaguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshikawa
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics*