title: Biomarkers for cervical cancer screening: the role of p16(INK4a) to highlight transforming HPV infections.
abstract: Biomarkers indicating the initiation of neoplastic transformation processes in human papillomavirus (HPV)-infected epithelial cells are moving into the focus of cancer prevention research, particularly for anogenital cancer, including cancer of the uterine cervix. Based on the in-depth understanding of the molecular events leading to neoplastic transformation of HPV-infected human cells, the cyclin-dependent kinase inhibitor p16(INK4a) turned out to be substantially overexpressed in virtually all HPV-transformed cells. This finding opened novel avenues in diagnostic histopathology to substantially improve the diagnostic accuracy of cervical cancer and its precursor lesions. Furthermore, it provides a novel technical platform to substantially improve the accuracy of cytology-based cancer early-detection programs. Here, we review the molecular background and the current evidence for the clinical utility of the p16(INK4a) biomarker for HPV-related cancers, and cervical cancer prevention in particular.
authors.affiliation: Department of Applied Tumor Biology, Clinical Cooperation Unit, German Cancer Research Center & Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220, Heidelberg, Germany. knebel@med.uni-heidelberg.de
authors.forename: Magnus
authors.initials: M
authors.lastname: von Knebel Doeberitz
authors.forename: Miriam
authors.initials: M
authors.lastname: Reuschenbach
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmidt
authors.forename: Christine
authors.initials: C
authors.lastname: Bergeron
mesh_terms: D052685:Alphapapillomavirus / Q000201:enzymology / Q000502:physiology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000378:metabolism* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16