title: Identification of high-grade cervical dysplasia by the detection of p16INK4a in cell lysates obtained from cervical samples.
abstract: BACKGROUND
  Current cervical cancer screening approaches are based on cytology supplemented by human papillomavirus (HPV) testing in some settings. Whereas cytology is laborious and depends on the cytologists' experience, HPV testing has limited specificity when it is used to detect high-grade lesions. A dichotomous test to identify high-grade lesions with greater specificity may be a useful tool for cervical cancer screening. p16(INK4a) is a cell-cycle regulator that has demonstrated strong overexpression in cervical precancer cells and cervical cancer induced by the deregulated expression of HPV oncogenes.
  
  
  METHODS
  The authors used a sandwich enzyme-linked immunosorbent assay (ELISA) to quantify the amount of solubilized p16(INK4a) protein in lysates that were prepared from cervical samples to detect high-grade cervical lesions. In total, 187 specimens that were obtained after sampling for conventional cytology in women who attended a cervical colposcopy clinic were analyzed. Seventy-six women underwent a biopsy, and 45 of those women showed histologically confirmed, high-grade cervical intraepithelial neoplasia.
  
  
  RESULTS
  For 76 women with biopsy-proven diagnoses, receiver operating characteristic (ROC) analysis of different cutoff values showed an area under the ROC curve of 0.89 for the detection of high-grade cervical dysplasia. At a cutoff value of 8 U/mL, the sensitivity of the p16(INK4a) ELISA for detecting high-grade dysplastic cervical lesions was 96%.
  
  
  CONCLUSIONS
  The data obtained in this study suggested that ELISA-based quantification of solubilized p16(INK4a) protein may have high sensitivity for detecting cervical precancer. Further population-based studies will be necessary to analyze the specificity and predictive values of p16(INK4a) protein quantification in cervical samples.
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.forename: Monika
authors.initials: M
authors.lastname: Hampl
authors.forename: Matthias
authors.initials: M
authors.lastname: Herkert
authors.forename: Anja
authors.initials: A
authors.lastname: Reichert
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Trunk
authors.forename: Christopher
authors.initials: C
authors.lastname: Poremba
authors.forename: Ruediger
authors.initials: R
authors.lastname: Ridder
authors.forename: Magnus
authors.initials: M
authors.lastname: von Knebel Doeberitz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002584:Cervix Uteri / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D015854:Up-Regulation; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis*; D014626:Vaginal Smears
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16