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

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.

• Authors: Nicolas Wentzensen, Barbara Fetterman, Diane Tokugawa, Mark Schiffman, Philip E Castle, Shannon N Wood, Eric Stiemerling, Nancy Poitras, Thomas Lorey, Walter Kinney
• Journal: Cancer cytopathology (Cancer Cytopathol) Vol. 122 Issue 12 Pg. 914-20 (Dec 2014) ISSN: 1934-6638 [Electronic] United States
• PMID: 25132656 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 American Cancer Society.

Chemical References

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

Topics

• Adult
• Biomarkers, Tumor (metabolism)
• Carcinoma, Squamous Cell (diagnosis, metabolism, virology)
• Colposcopy
• Cyclin-Dependent Kinase Inhibitor p16
• Cytodiagnosis
• Early Detection of Cancer
• Female
• Follow-Up Studies
• Humans
• Ki-67 Antigen (metabolism)
• Neoplasm Grading
• Neoplasm Proteins (metabolism)
• Observer Variation
• Papillomaviridae (isolation & purification)
• Papillomavirus Infections (diagnosis, metabolism, virology)
• Prognosis
• Reference Standards
• Reproducibility of Results
• Sensitivity and Specificity
• Staining and Labeling
• Uterine Cervical Neoplasms (diagnosis, metabolism, virology)
• Vaginal Smears
• Uterine Cervical Dysplasia (diagnosis, metabolism, virology)