p16/ki-67 dual-stain cytology in the triage of ASCUS and LSIL papanicolaou cytology: results from the European equivocal or mildly abnormal Papanicolaou cytology study

Cancer Cytopathol. 2011 Jun 25;119(3):158-66. doi: 10.1002/cncy.20140. Epub 2011 Mar 25.

Abstract

Background: The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-stain protocol, which simultaneously detects p16(INK4a) and Ki-67 expression in cervical cytology samples, for identifying high-grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL).

Methods: Residual liquid-based cytology material from 776 retrospectively collected ASCUS/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki-67 dual staining. The presence of 1 or more double-immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow-up.

Results: Sensitivity of p16/Ki-67 dual-stain cytology for biopsy-confirmed CIN2+ was 92.2% (ASCUS) and 94.2% (LSIL), while specificity rates were 80.6% (ASCUS) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged <30 years versus women aged ≥30 years. Dual-stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing.

Conclusions: The results of this study show that p16/Ki-67 dual-stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with ASCUS or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single-stain cytology. However, the specificity of this morphology-independent interpretation of p16/Ki-67 dual-stain cytology testing was further improved compared with the earlier p16 single-stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / metabolism*
  • Cervical Intraepithelial Neoplasia / metabolism
  • Cervical Intraepithelial Neoplasia / pathology*
  • Cyclin-Dependent Kinase Inhibitor p16
  • Europe
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism*
  • Neoplasm Proteins / metabolism*
  • Papanicolaou Test*
  • Retrospective Studies
  • Sensitivity and Specificity
  • Vaginal Smears*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Ki-67 Antigen
  • Neoplasm Proteins