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. 2020 May;128(5):323-332.
doi: 10.1002/cncy.22248. Epub 2020 Feb 12.

Interlaboratory concordance of p16/Ki-67 dual-staining interpretation in HPV-positive women in a screening population

Maria Benevolo  1 , Pamela Mancuso  2 , Elena Allia  3 , Daniela Gustinucci  4 , Simonetta Bulletti  4 , Elena Cesarini  4 , Francesca Maria Carozzi  5 , Massimo Confortini  5 , Simonetta Bisanzi  5 , Gabriele Carlinfante  6 , Teresa Rubino  6 , Francesca Rollo  1 , Natalina Marchi  7 , Angelo Farruggio  7 , Teresa Pusiol  8 , Francesco Venturelli  2   9 , Paolo Giorgi Rossi  2 ; New Technologies for Cervical Cancer 2 Working Group
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Free article

Interlaboratory concordance of p16/Ki-67 dual-staining interpretation in HPV-positive women in a screening population

Maria Benevolo et al. Cancer Cytopathol. 2020 May.
Free article

Abstract

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+.

Keywords: cervical cancer; dual immunostaining; human papillomavirus; interrater agreement; p16ink4a/Ki-67.

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References

    1. Ronco G, Biggeri A, Confortini M, et al. Health technology assessment report: HPV DNA based primary screening for cervical cancer precursors [in Italian]. Epidemiol Prev. 2012;36:e1-e72.
    1. Ronco G, Arbyn M, Meijer CJLM, Snijders PJF, Cuzick J. Screening for cervical cancer with primary testing for human papillomavirus. In: Anttila A, Arbyn M, de Vuyst H, et al, eds. European Guidelines for Quality Assurance in Cervical Cancer Screening. 2nd ed, suppl. Office for Official Publications of the European Communities; 2015:1-68.
    1. Anttila A, Arbyn M, de Vuyst H, et al, eds. European Guidelines for Quality Assurance in Cervical Cancer Screening. 2nd ed, suppl. Office for Official Publications of the European Communities; 2015.
    1. Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. Am J Clin Pathol. 2012;137:516-542.
    1. Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Obstet Gynecol. 2015;125:330-337.

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