[Aspects of molecular pathogenesis of cervical cancer in establishing new tumor markers for early detection and diagnosis].
The mortality rates of cervical cancer could be drastically reduced by the implementation of population wide cytological screening test for women (Pap-Test). However, these screening tests are hampered by high rates of false positive and false negative results, pointing to the urgent demand for improved screening technologies. High risk human papillomaviruses were identified as the causal agents of cervical cancer. The detection of the viral infection allows to identify patients at risk, however, about 5-30% of the normal female population harbours these viruses and only very few of these develop clinically relevant lesions. The activity of two viral oncogenes E6 and E7 initiates in a long term process neoplastic transformation in few of the HPV harbouring cells. As consequence of the expression of E7 a cellular marker protein (p16) is increasingly expressed in dysplastic cells. Monoclonal antibodies directed against p16 allow therefore to specifically identify dysplastic cells and derived invasive cancers in histological slides but also cytological smears (CINtec Assay). In advanced preneoplastic lesions HPV genomes are often integrated into cellular chromosomes. This leads to enhanced expression of the viral oncogenes. The detection of specific viral mRNA transcripts derived from integrated HPV genomes allows to identify preneoplastic lesions with a particularly high risk for progression to invasive cancers (APOT-assay). These findings will allow to establish highly sensitive, but specific and cost efficient new cancer early detection assays.
von Knebel Doeberitz
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Sektion für Molekulare Diagnostik und Therapie, Chirurgische Universitätsklinik Heidelberg. knebel@med.uni-heidelberg.de
D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D012367:RNA, Viral / Q000032:analysis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000821:virology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000235:genetics / Q000821:virology*
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009856:Oncogene Proteins, Viral; D012367:RNA, Viral