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

31 Citations (Scopus)

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

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Early Detection of Cancer
Uterine Cervical Neoplasms
Cell Biology
Coloring Agents
Sensitivity and Specificity
Cervical Intraepithelial Neoplasia
Biomarkers

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wentzensen, N., Fetterman, B., Tokugawa, D., Schiffman, M., Castle, P. E., Wood, S. N., ... 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

Interobserver reproducibility and accuracy of p16/Ki-67 dual-stain cytology in cervical cancer screening. / Wentzensen, Nicolas; Fetterman, Barbara; Tokugawa, Diane; Schiffman, Mark; Castle, Philip E.; Wood, Shannon N.; Stiemerling, Eric; Poitras, Nancy; Lorey, Thomas; Kinney, Walter.

In: Cancer cytopathology, Vol. 122, No. 12, 01.12.2014, p. 914-920.

Research output: Contribution to journalArticle

Wentzensen, N, Fetterman, B, Tokugawa, D, Schiffman, M, Castle, PE, Wood, SN, 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, vol. 122, no. 12, pp. 914-920. https://doi.org/10.1002/cncy.21473
Wentzensen, Nicolas ; Fetterman, Barbara ; Tokugawa, Diane ; Schiffman, Mark ; Castle, Philip E. ; Wood, Shannon N. ; Stiemerling, Eric ; Poitras, Nancy ; Lorey, Thomas ; Kinney, Walter. / Interobserver reproducibility and accuracy of p16/Ki-67 dual-stain cytology in cervical cancer screening. In: Cancer cytopathology. 2014 ; Vol. 122, No. 12. pp. 914-920.
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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.",
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AU - Wentzensen, Nicolas

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AU - Tokugawa, Diane

AU - Schiffman, Mark

AU - Castle, Philip E.

AU - Wood, Shannon N.

AU - Stiemerling, Eric

AU - Poitras, Nancy

AU - Lorey, Thomas

AU - Kinney, Walter

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N2 - 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.

AB - 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.

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