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Interlaboratory concordance of p16/Ki‐67 dual‐staining interpretation in HPV‐positive women in a screening population
Author(s) -
Benevolo Maria,
Mancuso Pamela,
Allia Elena,
Gustinucci Daniela,
Bulletti Simonetta,
Cesarini Elena,
Carozzi Francesca Maria,
Confortini Massimo,
Bisanzi Simonetta,
Carlinfante Gabriele,
Rubino Teresa,
Rollo Francesca,
Marchi Natalina,
Farruggio Angelo,
Pusiol Teresa,
Venturelli Francesco,
Giorgi Rossi Paolo
Publication year - 2020
Publication title -
cancer cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.29
H-Index - 57
eISSN - 1934-6638
pISSN - 1934-662X
DOI - 10.1002/cncy.22248
Subject(s) - medicine , concordance , cervical intraepithelial neoplasia , confidence interval , gynecology , positive predicative value , population , reproducibility , cervical cancer , biomarker , cancer , oncology , predictive value , biochemistry , statistics , chemistry , mathematics , environmental health
Background p16/Ki‐67 dual staining is a candidate biomarker for triaging human papillomavirus (HPV)–positive women. Reproducibility is needed for adopting a test for screening. This study assessed interlaboratory reproducibility in HPV‐positive women. Methods All women positive for HPV from the Italian New Technologies for Cervical Cancer 2 study, were included in this study. ThinPrep slides were immunostained for p16/Ki‐67 in 4 laboratories and were interpreted in 7 laboratories. Each slide had 3 reports from different laboratories. Slides were classified as valuable or inadequate, and valuable slides were classified as positive (at least 1 double‐stained cell) or negative. Interlaboratory reproducibility was evaluated with κ values. Results Overall, we obtained 9300 reports for 3100 cases; 905 reports (9.7%) were inadequate. The overall adequacy concordance was poor (κ = 0.224; 95% confidence interval [CI], 0.183‐0.263). The overall positivity concordance was moderate (κ = 0.583; 95% CI, 0.556‐0.610). Of the 176 cervical intraepithelial neoplasia 2+ (CIN‐2+) lesions found in HPV DNA–positive women, 158 had a valid result: 107 were positive in all 3 reports (sensitivity for CIN‐2+, 67.7%; 95% CI, 59.8%‐74.9%), 23 were positive in 2 reports (sensitivity of the majority report, 82.3%; 95% CI, 75.4%‐87.9%), and 15 were positive in 1 report (sensitivity of at least 1 positive result, 91.8%; 95% CI, 86.3%‐95.5%). Thirteen CIN‐2+ cases were negative in all 3 reports. The overall positivity concordance in CIN‐2+ samples was κ = 0.487 (95% CI, 0.429‐0.534), whereas in the non–CIN‐2+ samples, it was κ = 0.558 (95% CI, 0.528‐0.588). Conclusions The p16/Ki‐67 assay showed poor reproducibility for adequacy and good reproducibility for positivity comparable to that of cervical cytology. Nevertheless, the low reproducibility does not affect the sensitivity for CIN‐2+.