title: The clinical impact of using p16(INK4a) immunochemistry in cervical histopathology and cytology: an update of recent developments.
abstract: Cervical cancer screening test performance has been hampered by either lack of sensitivity of Pap cytology or lack of specificity of Human Papillomavirus (HPV) testing. This uncertainty can lead to unnecessary referral and treatment, which is disturbing for patients and increases costs for health care providers. The identification of p16(INK4a) as a marker for neoplastic transformation of cervical squamous epithelial cells by HPVs allows the identification of HPV-transformed cells in histopathology or cytopathology specimens. Diagnostic studies have demonstrated that the use of p16(INK4a) immunohistochemistry substantially improves the reproducibility and diagnostic accuracy of histopathologic diagnoses. p16(INK4a) cytology has substantially higher sensitivity for detection of cervical precancer in comparison to conventional Pap tests. Compared to HPV DNA tests, immunochemical detection of p16(INK4a) -stained cells demonstrates a significantly improved specificity with remarkably good sensitivity. About 15 years after the initial observation that p16(INK4a) is overexpressed in HPV-transformed cells we review the accumulated clinical evidence suggesting that p16(INK4a) can serve as a useful biomarker in the routine diagnostic work up of patients with HPV infections and associated lesions of the female anogenital tract.
authors.affiliation: Laboratoire Cerba, 95066 Cergy Pontoise Cedex 9, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Bergeron
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Ronco
authors.forename: Miriam
authors.initials: M
authors.lastname: Reuschenbach
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.forename: Marc
authors.initials: M
authors.lastname: Arbyn
authors.forename: Mark
authors.initials: M
authors.lastname: Stoler
authors.forename: Magnus
authors.initials: M
authors.lastname: von Knebel Doeberitz
mesh_terms: D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D003581:Cytodiagnosis / Q000379:methods; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D027383:Papillomaviridae / Q000502:physiology; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000378:metabolism* / Q000821:virology; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000821:virology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: HPV; cervical cancer; cervical pathology; early detection; p16INK4a