Conjunctive p16INK4a Testing Significantly Increases Accuracy in Diagnosing High-Grade Cervical Intraepithelial Neoplasia

• Published in: American journal of clinical pathology Vol. 133; no. 3; pp. 395 - 406
• Main Authors: Bergeron, Christine, Ordi, Jaume, Schmidt, Dietmar, Trunk, Marcus J., Keller, Thomas, Ridder, Ruediger
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Society of Clinical Pathologists 01.03.2010
• Subjects: Adult; Analysis of Variance; Biological and medical sciences; Cervical Intraepithelial Neoplasia - diagnosis; Cervical Intraepithelial Neoplasia - metabolism; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Observer Variation; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Predictive Value of Tests; Reference Standards; Reproducibility of Results; Tumors; Uterine Cervical Neoplasms - diagnosis; Uterine Cervical Neoplasms - metabolism; Immunohistochemistry; Premalignant lesion; Cervical biopsy; Increase; Medical screening; CDKN2 gene; Female genital diseases; High grade; Interrater reliability; Anatomic pathology; Accuracy; Cervical dysplasia; p16; Biopsy; Cervical intraepithelial neoplasia; Diagnostic accuracy; Interindividual comparison; Diagnosis; Reliability; Uterine cervix diseases; Tumor suppressor gene; High malignancy
• ISSN: 0002-9173; 1943-7722; 1943-7722
• DOI: 10.1309/AJCPXSVCDZ3D5MZM

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 p16INK4a-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 p16INK4a-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 κ values advanced from 0.566 to 0.749; P < .0001). Reproducibility of p16INK4a stain interpretation was excellent (κ = 0.899). Our results show that conjunctive interpretation of p16INK4a-stained slides could significantly improve the routine interpretation of cervical histopathology.