Conjunctive p16INK4a testing significantly increases accuracy in diagnosing high-grade cervical intraepithelial neoplasia.
The histopathologic interpretation of cervical intraepithelial neoplasia (CIN) is subject to a high level of interobserver variability and a substantial number of false-positive and false-negative results. We assessed the impact of the conjunctive interpretation of p16(INK4a)-immunostained slides on the accuracy of community-based pathologists in diagnosing high-grade cervical intraepithelial neoplasia (CIN; CIN 2 and CIN 3) in biopsy specimens. Twelve pathologists rendered independent diagnoses on a set of 500 H&E-stained cervical punch and conization specimens. Results were compared with a dichotomized "gold standard" established by consensus of 3 gynecopathology experts. When p16(INK4a)-immunostained slides were added and conjunctively interpreted with the H&E-stained slides, a significant increase in diagnostic accuracy for the detection of high-grade CIN was observed (P = .0004). Sensitivity for high-grade CIN was increased by 13%, cutting the rate of false-negative results in half. Agreement of community-based pathologists in diagnosing high-grade CIN was significantly improved (mean kappa values advanced from 0.566 to 0.749; P < .0001). Reproducibility of p16(INK4a) stain interpretation was excellent (kappa = 0.899). Our results show that conjunctive interpretation of p16(INK4a)-stained slides could significantly improve the routine interpretation of cervical histopathology.
Laboratoire Cerba, Cergy Pontoise, France.
Christine
C
Bergeron
Jaume
J
Ordi
Dietmar
D
Schmidt
Marcus J
MJ
Trunk
Thomas
T
Keller
Ruediger
R
Ridder
D000328:Adult; D000704:Analysis of Variance; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D015588:Observer Variation; D011237:Predictive Value of Tests; D012015:Reference Standards; D015203:Reproducibility of Results; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000378:metabolism
D019941:Cyclin-Dependent Kinase Inhibitor p16