title: [Molecular pathogenesis of cervical cancer and its first steps].
abstract: Specific types of the human papillomaviruses (high risk human papillomaviruses) play an essential role in the pathogenesis of cervical cancer. Although infections by these viruses are very common in the general population, only few result in clinically relevant lesions. Continuous and deregulated expression of two viral oncoproteins E6 and E7 in basal or parabasal cells are required to induce and maintain neoplastic growth. In the course of an acute HPV-infection these genes are exclusively expressed in cell cycle arrested, terminally differentiated cells in the intermediate or superficial layers of the epithelium. Accidental activation of these genes in proliferating cells in the basal or parabasal cell layers results in interference with the cell cycle regulation, disturbances of the mitotic spindle apparatus and centrosome functions. This results in numerical and structural chromosome aberrations, chromosomal instability, increasing aneuploidy and initiates cervical carcinogenesis. The deregulated expression of the viral oncogene E7 is indicated by strong over-expression of the cellular p16(INK4a) gene product. This finding may have significant influence on novel strategies in cervical cancer diagnosis and screening. This review summarizes the basic molecular mechanisms of how papillomaviruses contribute to cellular transformation and how this can influence future diagnostic applications.
authors.affiliation: mtm laboratories AG, Heidelberg.
authors.forename: M J
authors.initials: MJ
authors.lastname: Trunk
authors.forename: N
authors.initials: N
authors.lastname: Wentzensen
authors.forename: M
authors.initials: M
authors.lastname: von Knebel Doeberitz
mesh_terms: D002453:Cell Cycle; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology; D014412:Tumor Virus Infections / Q000235:genetics / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000821:virology