TY - JOUR
T1 - Interlaboratory concordance of p16/Ki-67 dual-staining interpretation in HPV-positive women in a screening population
AU - Benevolo, Maria
AU - Mancuso, Pamela
AU - Allia, Elena
AU - Gustinucci, Daniela
AU - Bulletti, Simonetta
AU - Cesarini, Elena
AU - Carozzi, Francesca Maria
AU - Confortini, Massimo
AU - Bisanzi, Simonetta
AU - Carlinfante, Gabriele
AU - Rubino, Teresa
AU - Rollo, Francesca
AU - Marchi, Natalina
AU - Farruggio, Angelo
AU - Pusiol, Teresa
AU - Venturelli, Francesco
AU - Giorgi Rossi, Paolo
AU - New Technologies for Cervical Cancer 2 Working Group
N1 - © 2020 American Cancer Society.
PY - 2020/5
Y1 - 2020/5
N2 - 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+.
AB - 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+.
KW - Adult
KW - Biomarkers, Tumor/metabolism
KW - Cervical Intraepithelial Neoplasia/diagnosis
KW - Cyclin-Dependent Kinase Inhibitor p16/metabolism
KW - Early Detection of Cancer/standards
KW - Female
KW - Humans
KW - Ki-67 Antigen/metabolism
KW - Laboratories/standards
KW - Middle Aged
KW - Observer Variation
KW - Papillomaviridae/isolation & purification
KW - Papillomavirus Infections/complications
KW - Prognosis
KW - Uterine Cervical Neoplasms/diagnosis
U2 - 10.1002/cncy.22248
DO - 10.1002/cncy.22248
M3 - Article
C2 - 32168431
VL - 128
SP - 323
EP - 332
JO - Cancer cytopathology
JF - Cancer cytopathology
SN - 1934-662X
IS - 5
ER -