title: Triaging Pap cytology negative, HPV positive cervical cancer screening results with p16/Ki-67 Dual-stained cytology.
abstract: OBJECTIVE
  Testing for human papillomavirus (HPV) has been shown to increase the sensitivity and negative predictive value for detection of high-grade cervical intraepithelial neoplasia (CIN2+), either when used in conjunction with Pap cytology testing or alone. However, there is no satisfying clinical management algorithm for women testing Pap negative/HPV positive. We therefore evaluated the clinical utility of a novel dual biomarker-based approach (p16/Ki-67 Dual-stained cytology) for the identification of CIN2+ in women with Pap negative/HPV positive screening results, without the need to refer all women to immediate colposcopy.
  
  
  METHODS
  All women aged ≥30 enrolled during 2007/2008 into a regional prospective Pap/HPV co-testing screening pilot project and tested Pap negative, but positive for HPV (n=425) were included in the analysis. p16/Ki-67 Dual-stained cytology was performed from residual cellular material available from the liquid-based cytology vial collected during the initial Pap/HPV co-testing screening visit. Results were correlated to the presence of CIN2+ confirmed during preliminary follow-up.
  
  
  RESULTS
  p16/Ki-67 Dual-stained cytology tested positive at baseline in 108 out of 425 (25.4%) Pap negative/HPV positive cases. Sensitivity of Dual-stain testing for the detection of biopsy-confirmed CIN2+ during preliminary follow-up within the group of Pap negative/HPV positive women was 91.9% for CIN2+ (34/37 cases), and 96.4% for CIN3+ (27/28 cases). Specificity was 82.1% for CIN2+ on biopsy, and 76.9% for CIN3+, respectively.
  
  
  CONCLUSIONS
  Triaging Pap negative/HPV positive screening test results with p16/Ki-67 Dual-stained cytology may identify women with a high probability of underlying CIN2+ and may efficiently complement HPV-based screening programs to prevent cervical cancer.
authors.affiliation: Klinikum der Stadt Wolfsburg, Department of Obstetrics and Gynecology, Wolfsburg, Germany.
authors.forename: K Ulrich
authors.initials: KU
authors.lastname: Petry
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmidt
authors.forename: Sarah
authors.initials: S
authors.lastname: Scherbring
authors.forename: Alexander
authors.initials: A
authors.lastname: Luyten
authors.forename: Axel
authors.initials: A
authors.lastname: Reinecke-Lüthge
authors.forename: Christine
authors.initials: C
authors.lastname: Bergeron
authors.forename: Friedrich
authors.initials: F
authors.lastname: Kommoss
authors.forename: Thomas
authors.initials: T
authors.lastname: Löning
authors.forename: Jaume
authors.initials: J
authors.lastname: Ordi
authors.forename: Sigrid
authors.initials: S
authors.lastname: Regauer
authors.forename: Ruediger
authors.initials: R
authors.lastname: Ridder
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D012680:Sensitivity and Specificity; D013194:Staining and Labeling / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology* / Q000821:virology*
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins