Conjunctive p16INK4a testing significantly increases accuracy in diagnosing high-grade cervical intraepithelial neoplasia

Am J Clin Pathol. 2010 Mar;133(3):395-406. doi: 10.1309/AJCPXSVCDZ3D5MZM.

Abstract

The histopathologic interpretation of cervical intraepithelial neoplasia (CIN) is subject to a high level of interobserver variability and a substantial number of false-positive and false-negative results. We assessed the impact of the conjunctive interpretation of p16(INK4a)-immunostained slides on the accuracy of community-based pathologists in diagnosing high-grade cervical intraepithelial neoplasia (CIN; CIN 2 and CIN 3) in biopsy specimens. Twelve pathologists rendered independent diagnoses on a set of 500 H&E-stained cervical punch and conization specimens. Results were compared with a dichotomized "gold standard" established by consensus of 3 gynecopathology experts. When p16(INK4a)-immunostained slides were added and conjunctively interpreted with the H&E-stained slides, a significant increase in diagnostic accuracy for the detection of high-grade CIN was observed (P = .0004). Sensitivity for high-grade CIN was increased by 13%, cutting the rate of false-negative results in half. Agreement of community-based pathologists in diagnosing high-grade CIN was significantly improved (mean kappa values advanced from 0.566 to 0.749; P < .0001). Reproducibility of p16(INK4a) stain interpretation was excellent (kappa = 0.899). Our results show that conjunctive interpretation of p16(INK4a)-stained slides could significantly improve the routine interpretation of cervical histopathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Observer Variation
  • Predictive Value of Tests
  • Reference Standards
  • Reproducibility of Results
  • Uterine Cervical Dysplasia / diagnosis*
  • Uterine Cervical Dysplasia / metabolism
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / metabolism

Substances

  • Cyclin-Dependent Kinase Inhibitor p16