TY - JOUR
T1 - Determinants of p16/Ki-67 adequacy and positivity in HPV-positive women from 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 - Rubino, Teresa
AU - Rollo, Francesca
AU - Marchi, Natalina
AU - Farruggio, Angelo
AU - Pusiol, Teresa
AU - Venturelli, Francesco
AU - Giorgi Rossi, Paolo
AU - for the New Technologies for Cervical Cancer 2 (NTCC2) Working Group
AU - Barca, Alessandra
AU - Quadrino, Francesco
AU - Benevolo, Maria
AU - Rollo, Francesca
AU - Giorgi Rossi, Paolo
AU - Bonvicini, Laura
AU - Mancuso, Pamela
AU - Venturelli, Francesco
AU - Carlinfante, Gabriele
AU - Rubino, Teresa
AU - Carozzi, Francesca Maria
AU - Bisanzi, Simonetta
AU - Confortini, Massimo
AU - Di Pierro, Carmelina
AU - Fantacci, Giulia
AU - Iossa, Anna
AU - Andersson, Karin Louise
AU - Mongia, Alessandra
AU - Pompeo, Giampaolo
AU - Sani, Cristina
AU - Puliti, Donella
AU - Baldini, Andrea
AU - Ronco, Guglielmo
AU - Rizzolo, Raffaella
AU - Gillio Tos, Anna
AU - De Marco, Laura
AU - Allia, Elena
AU - Pusiol, Teresa
AU - Barbareschi, Mattia
AU - Bragantini, Emma
AU - Passamonti, Basilio
AU - Gustinucci, Daniela
AU - Bulletti, Simonetta
AU - Cesarini, Elena
N1 - Funding Information:
This work was supported by the Italian Ministry of Health, data owner (grant RF‐2009‐1536040).
Funding Information:
Maria Benevolo and Paolo Giorgi Rossi, as principal investigator and former principal investigator, respectively, of the New Technologies for Cervical Cancer 2 (NTCC2) study report nonfinancial support from Roche Diagnostics and Hologic Srl, which provided part of the reagents for free or at a reduced price. Maria Benevolo, Paolo Giorgi Rossi, and Simonetta Bisanzi are negotiating with Becton Dickinson to obtain financial and nonfinancial support for genotyping stored NTCC2 samples. Maria Benevolo also reports financial and nonfinancial support from Arrow Diagnostics Srl, outside the submitted work. The remaining authors made no disclosures.
Publisher Copyright:
© 2020 American Cancer Society
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Background: The objective of this study was to describe the determinants of adequacy and positivity of the p16/Ki-67 assay in a human papillomavirus (HPV)-positive screening population enrolled within the New Technologies for Cervical Cancer 2 (NTCC2) study. Methods: ThinPrep slides were immunostained for p16/Ki-67; each slide had 3 reports from different laboratories. The authors included population-related, sampling-related/staining-related, and interpretation-related variables in the analyses. Adequacy and positivity proportions were stratified by variables of interest. Univariate and multivariate logistic models were used to identify determinants of adequacy and positivity. Results: In total, 3100 consecutive HPV-positive cases were analyzed. Because every slide was interpreted by 3 centers, 9300 reports were obtained, including 905 (9.7%) that were inadequate and 2632 (28.3%) that were positive. The percentage of cases in which all 3 reports were inadequate increased with increasing age of the women and with inadequate cytology. The highest percentage of adequacy in all 3 reports and of cases with all 3 reports positive was observed in specimens from women who had grade ≥2 cervical intraepithelial neoplasia (CIN2+), atypical squamous cells of undetermined significance or more severe (ASC-US+) cytology, or mRNA positivity. The number of inadequate reports was significantly associated with increasing age, inadequate cytology, mRNA negativity, and scant cellularity. A positive p16/Ki-67 report was associated with an ASC-US+ result and with a positive mRNA result in cases both with and without CIN2+ but was associated with an HPV type 16 and/or 18 infection only in CIN2+ cases. The presence of CIN2+ was strongly associated with dual staining positivity. Conclusions: The interpretation of p16/Ki-67 results may be influenced by several different variables, all of which are part of the steps in the procedure, and by the characteristics of the screened population.
AB - Background: The objective of this study was to describe the determinants of adequacy and positivity of the p16/Ki-67 assay in a human papillomavirus (HPV)-positive screening population enrolled within the New Technologies for Cervical Cancer 2 (NTCC2) study. Methods: ThinPrep slides were immunostained for p16/Ki-67; each slide had 3 reports from different laboratories. The authors included population-related, sampling-related/staining-related, and interpretation-related variables in the analyses. Adequacy and positivity proportions were stratified by variables of interest. Univariate and multivariate logistic models were used to identify determinants of adequacy and positivity. Results: In total, 3100 consecutive HPV-positive cases were analyzed. Because every slide was interpreted by 3 centers, 9300 reports were obtained, including 905 (9.7%) that were inadequate and 2632 (28.3%) that were positive. The percentage of cases in which all 3 reports were inadequate increased with increasing age of the women and with inadequate cytology. The highest percentage of adequacy in all 3 reports and of cases with all 3 reports positive was observed in specimens from women who had grade ≥2 cervical intraepithelial neoplasia (CIN2+), atypical squamous cells of undetermined significance or more severe (ASC-US+) cytology, or mRNA positivity. The number of inadequate reports was significantly associated with increasing age, inadequate cytology, mRNA negativity, and scant cellularity. A positive p16/Ki-67 report was associated with an ASC-US+ result and with a positive mRNA result in cases both with and without CIN2+ but was associated with an HPV type 16 and/or 18 infection only in CIN2+ cases. The presence of CIN2+ was strongly associated with dual staining positivity. Conclusions: The interpretation of p16/Ki-67 results may be influenced by several different variables, all of which are part of the steps in the procedure, and by the characteristics of the screened population.
KW - cervical cancer screening
KW - dual immunostaining
KW - human papillomavirus
KW - immunocytochemistry
KW - p16/Ki-67
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U2 - 10.1002/cncy.22385
DO - 10.1002/cncy.22385
M3 - Article
C2 - 33142029
AN - SCOPUS:85096852536
JO - Cancer cytopathology
JF - Cancer cytopathology
SN - 1934-662X
ER -