Interobserver reproducibility and accuracy of p16/Ki-67 dual-stain cytology in cervical cancer screening

Nicolas Wentzensen, Barbara Fetterman, Diane Tokugawa, Mark Schiffman, Philip E. Castle, Shannon N. Wood, Eric Stiemerling, Nancy Poitras, Thomas Lorey, Walter Kinney

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

BACKGROUND Dual-stain cytology for p16 and Ki-67 has been proposed as a biomarker in cervical cancer screening. The authors evaluated the reproducibility and accuracy of dual-stain cytology among 10 newly trained evaluators. METHODS In total, 480 p16/Ki-67-stained slides from human papillomavirus-positive women were evaluated in masked fashion by 10 evaluators. None of the evaluators had previous experience with p16 or p16/Ki-67 cytology. All participants underwent p16/Ki-67 training and subsequent proficiency testing. Reproducibility of dual-stain cytology was measured using the percentage agreement, individual and aggregate κ values, as well as McNemar statistics. Clinical performance for the detection of cervical intraepithelial neoplasia grade 2 or greater (CIN2+) was evaluated for each individual evaluator and for all evaluators combined compared with the reference evaluation by a cytotechnologist who had extensive experience with dual-stain cytology. RESULTS The percentage agreement of individual evaluators with the reference evaluation ranged from 83% to 91%, and the κ values ranged from 0.65 to 0.81. The combined κ value was 0.71 for all evaluators and 0.73 for cytotechnologists. The average sensitivity and specificity for the detection of CIN2+ among novice evaluators was 82% and 64%, respectively; whereas the reference evaluation had 84% sensitivity and 63% specificity, respectively. Agreement on dual-stain positivity increased with greater numbers of p16/Ki-67-positive cells on the slides. CONCLUSIONS Good to excellent reproducibility of p16/Ki-67 dual-stain cytology was observed with almost identical clinical performance of novice evaluators compared with reference evaluations. The current findings suggest that p16/Ki-67 dual-stain evaluation can be implemented in routine cytology practice with limited training.

Original languageEnglish (US)
Pages (from-to)914-920
Number of pages7
JournalCancer Cytopathology
Volume122
Issue number12
DOIs
StatePublished - Dec 1 2014
Externally publishedYes

Keywords

  • Ki-67
  • Papanicolaou test
  • cervical cancer screening
  • cytology
  • human papillomavirus
  • p16
  • reproducibility

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Interobserver reproducibility and accuracy of p16/Ki-67 dual-stain cytology in cervical cancer screening'. Together they form a unique fingerprint.

  • Cite this

    Wentzensen, N., Fetterman, B., Tokugawa, D., Schiffman, M., Castle, P. E., Wood, S. N., Stiemerling, E., Poitras, N., Lorey, T., & Kinney, W. (2014). Interobserver reproducibility and accuracy of p16/Ki-67 dual-stain cytology in cervical cancer screening. Cancer Cytopathology, 122(12), 914-920. https://doi.org/10.1002/cncy.21473