TY - JOUR
T1 - Interobserver reproducibility of cytologic p16INK4a/Ki-67 dual immunostaining in human papillomavirus-positive women
AU - Benevolo, Maria
AU - Allia, Elena
AU - Gustinucci, Daniela
AU - Rollo, Francesca
AU - Bulletti, Simonetta
AU - Cesarini, Elena
AU - Passamonti, Basilio
AU - Giovagnoli, Rosaria Maria
AU - Carico, Elisabetta
AU - Carozzi, Francesca M.
AU - Mongia, Alessandra
AU - Fantacci, Giulia
AU - Confortini, Massimo
AU - Rubino, Teresa
AU - Fodero, Cristina
AU - Prandi, Sonia
AU - Marchi, Natalina
AU - Farruggio, Angelo
AU - Coccia, Anna
AU - Macrì, Luigia
AU - Ghiringhello, Bruno
AU - Ronco, Guglielmo
AU - Bragantini, Emma
AU - Polla, Enzo
AU - Maccallini, Vincenzo
AU - Negri, Giovanni
AU - Giorgi Rossi, Paolo
PY - 2016
Y1 - 2016
N2 - BACKGROUND: The accumulation of cyclin-dependent kinase inhibitor 2A (p16ink4a) protein in a cell is associated with neoplastic progression in precancerous cervical lesions. Dual staining for p16ink4a 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 κ value was 0.612 (95% confidence interval [CI], 0.523-0.701), it was higher for the positive and negative categories (κ=0.692 and κ=0.641, respectively), and it was almost null for the inconclusive category (κ=0.058). Considering only readers from laboratories with documented experience, the κ value was higher (κ=0.747; 95% CI, 0.643-0.839) compared with nonexperienced centers (κ=0.498; 95% CI, 0.388-0.616). The results were similar in both sets of slides (κ=0.505 [95% CI, 0.358-0.642] and κ=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, κ=0.616 [95% CI, 0.384-0.866]; second evaluation, κ=0.403 [95% CI, 0.182-0.643]). CONCLUSIONS: Dual staining for p16 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.
AB - BACKGROUND: The accumulation of cyclin-dependent kinase inhibitor 2A (p16ink4a) protein in a cell is associated with neoplastic progression in precancerous cervical lesions. Dual staining for p16ink4a 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 κ value was 0.612 (95% confidence interval [CI], 0.523-0.701), it was higher for the positive and negative categories (κ=0.692 and κ=0.641, respectively), and it was almost null for the inconclusive category (κ=0.058). Considering only readers from laboratories with documented experience, the κ value was higher (κ=0.747; 95% CI, 0.643-0.839) compared with nonexperienced centers (κ=0.498; 95% CI, 0.388-0.616). The results were similar in both sets of slides (κ=0.505 [95% CI, 0.358-0.642] and κ=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, κ=0.616 [95% CI, 0.384-0.866]; second evaluation, κ=0.403 [95% CI, 0.182-0.643]). CONCLUSIONS: Dual staining for p16 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.
KW - Cervical cancer
KW - Cyclin-dependent kinase inhibitor 2A (p16)/Ki-67
KW - Dual immunostaining
KW - Human papillomavirus
KW - Inter-rater agreement
UR - http://www.scopus.com/inward/record.url?scp=85008262661&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85008262661&partnerID=8YFLogxK
U2 - 10.1002/cncy.21800
DO - 10.1002/cncy.21800
M3 - Article
AN - SCOPUS:85008262661
JO - Cancer cytopathology
JF - Cancer cytopathology
SN - 1934-662X
ER -