Longitudinal evaluation of interobserver and intraobserver agreement of cervical intraepithelial neoplasia diagnosis among an experienced panel of gynecologic pathologists.
Histologic diagnoses of cervical intraepithelial neoplasia grades 2 and 3 (CIN 2/3) are the key end points in clinical trials that evaluate the efficacy of a prophylactic quadrivalent human papillomavirus vaccine against cervical cancer. Adjudication of end points uses a panel of 4 pathologists. Quality control slides (n=185) from a nonclinical trial study with preestablished gold standard CIN diagnoses were used to characterize the panel's agreement on CIN diagnoses and monitor performance longitudinally. At 3-month intervals over 2 years, 1 of 6 different batches of quality control slides (n=30-31) was included with clinical trial slides for independent review by each of the 4 panelists. Unweighted kappas (kappa) were estimated within each panelist pair by dichotomizing the diagnoses as CIN+ versus non-CIN+ (including normal, unsatisfactory, and atypical immature metaplasia) or CIN 2/3+ versus non-CIN 2/3+ (including normal, unsatisfactory, atypical immature metaplasia, and CIN 1). Quadratic weighted kappa was calculated within each panelist pair using 4 diagnostic categories: normal, CIN 1, CIN 2, and CIN 3 or worse. Substantial interobserver agreement was observed (weighted kappa=0.765 to 0.865). Agreement with weighted kappa=0.779 to 0.887 was observed between the individual panelists and the gold standard, which is almost perfect agreement by Landis-defined categories. Intraobserver agreement was very high (weighted kappa=0.756 to 0.883). Some fluctuation in intraobserver and interobserver agreement was observed over the study period but there was no decreasing time trend. These data indicate that the interpretation of histologic end points used in the quadrivalent vaccine clinical trial program is highly valid and reliable.
Cai
Bing
B
Department of Epidemiology, Merck and Co., Inc., North Wales, PA 19454-1099, USA. bing_cai@merck.com
Ronnett
Brigitte M
BM
Stoler
Mark
M
Ferenczy
Alex
A
Kurman
Robert J
RJ
Sadow
David
D
Alvarez
Fran
F
Pearson
Jay
J
Sings
Heather L
HL
Barr
Eliav
E
Liaw
Kai-Li
KL
D005260:Female; D006176:Gynecology / Q000592:standards; D006801:Humans; D015588:Observer Variation; D030361:Papillomavirus Infections / Q000517:prevention & control; D010338:Pathology, Clinical / Q000592:standards*; D011785:Quality Assurance, Health Care; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000453:epidemiology* / Q000821:virology; D014611:Vaccination; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000453:epidemiology* / Q000821:virology