부산대학교 도서관

Byline: Maria Benevolo,Elena Allia, Daniela Gustinucci, Francesca Rollo, Simonetta Bulletti, Elena Cesarini, Basilio Passamonti, Maria Rosaria Giovagnoli, Elisabetta Carico, Francesca M. Carozzi, Alessandra Mongia, Giulia Fantacci, Massimo Confortini, Teresa Rubino, Cristina Fodero, Sonia Prandi, Natalina Marchi, Angelo Farruggio, Anna Coccia, Luigia Macri, Bruno Ghiringhello, Guglielmo Ronco, Emma Bragantini, Enzo Polla, Vincenzo Maccallini, Giovanni Negri, Paolo Giorgi Rossi, Keywords: cervical cancer; cyclin-dependent kinase inhibitor 2A (p16.sub.ink4a)/Ki-67; dual immunostaining; human papillomavirus; inter-rater agreement BACKGROUND The accumulation of cyclin-dependent kinase inhibitor 2A (p16.sub.ink4a) protein in a cell is associated with neoplastic progression in precancerous cervical lesions. Dual staining for p16.sub.ink4a and Ki-67 has been proposed as a triage test in cervical cancer screening for women who test positive for human papillomavirus DNA. In this study, interobserver reproducibility of the interpretation of this test was assessed. METHODS Forty-two immunostained, liquid-based cytology slides were divided into 2 sets and were interpreted by 17 to 21 readers from 9 different laboratories, yielding a total of 816 reports. Immunostaining results were classified as positive, negative, inconclusive, or inadequate. After evaluation of the first set of slides and before circulation of the second set, the results were discussed in a plenary meeting. The 10 slides with the most discordant results were evaluated again by selected expert cytopathologists. RESULTS The overall I* value was 0.612 (95% confidence interval [CI], 0.523-0.701), it was higher for the positive and negative categories (I*=0.692 and I*=0.641, respectively), and it was almost null for the inconclusive category (I*=0.058). Considering only readers from laboratories with documented experience, the I* value was higher (I*=0.747; 95% CI, 0.643-0.839) compared with nonexperienced centers (I*=0.498; 95% CI, 0.388-0.616). The results were similar in both sets of slides (I*=0.505 [95% CI, 0.358-0.642] and I*=0.521 [95% CI, 0.240-0.698] for the first and second sets, respectively). Reinterpretation of the slides with the most discordant results did not provide any improvement (first evaluation, I*=0.616 [95% CI, 0.384-0.866]; second evaluation, I*=0.403 [95% CI, 0.182-0.643]). CONCLUSIONS Dual staining for p16 .sub.ink4a and Ki-67 demonstrated good reproducibility, confirming its robustness, which is a necessary prerequisite for its adoption as a triage test in cervical cancer screening programs that use human papillomavirus DNA as a primary test. Cancer Cytopathol 2017;125:212-220. [c] 2016 American Cancer Society. Article Note: The following are participants in the New Technologies for Cervical Cancer 2 (NTCC2) Working Group: Regione Lazio (Alessandra Barca and Francesco Quadrino); Regina Elena National Cancer Institute, Rome (Maria Benevolo, Amina Vocaturo, Francesca Rollo, Manuela Scalfari, and Giulia Fabbri); Reggio Emilia Local Health Trust (Paolo Giorgi Rossi and Laura Bonvicini); Institute for Cancer Study and Prevention, Florence (Francesca Maria Carozzi, Karin Andersson, Simonetta Bisanzi, Stefania Capassoni, Massimo Confortini, Carmelina Di Pierro, Giulia Fantacci, Anna Iossa, Marzia Matucci, Paola Mantellini, Alessandra Mongia, GiamPaolo Pompeo, Donella Puliti, and Andrea Baldini); Center for Cancer Epidemiology and Prevention, Turin (Guglielmo Ronco, Raffaella Rizzolo, Anna Gillio-Tos, Laura De Marco, Elena Allia, and Bruno Ghiringhello); Provincial Health Care Service, Trento (Mattia Barbareschi, Paolo Dalla Palma, Salvatore Girlando, Enzo Polla, Teresa Pusiol, Sara Condini, and Emma Bragantini); Local Health Authority-Umbria 1, Perugia (Basilio Passamonti, Daniela Gustinucci, Simonetta Bulletti, Elena Cesarini, Nadia Martinelli, Gabriella Vinti, Graziella Principi, Arturo Fabra, Antonella Lucaccioni, Angela Carlani, and Maria Donata Giaimo); Local Health and Social Care Facility 17, Este Monselice (Maria Gabriella Penon, Natalina Marchi, Angelo Farruggio, and Alessandra Bertazzo); Veneto Oncology Institute (Annarosa Del Mistro, Helena Frayle, Martina Rizzi, and Silvia Gori); Veneto Tumor Registry (Manuel Zorzi); and Veneto Regional Coordinated Screening Oncology (Chiara Fedato and Adriana Montaguti). The manufacturers of CINtec PLUS and ThinPrep kits did not have any influence on the study design, conduct, data analysis, or the decision to publish data.