Role of p16, CK17, p63, and Human Papillomavirus in Diagnosis of Cervical Intraepithelial Neoplasia and Distinction From Its Mimics

Abstract

Diagnosis of cervical intraepithelial neoplasia (CIN), the precursor forms of cervical cancer, can be tricky and it has led to discrepancy between pathologists in distinguishing them from its mimics such as atypical immature metaplasia (AIM), immature squamous metaplasia (ISM), reactive atypia (RA), atrophy, and basal cell hyperplasia (BCH). To overcome this problem this study aims at using immunohistochemical (IHC) markers p16, p63, CK17, and human papillomavirus (HPV) to differentiate CIN from its mimics. This study analyzed 350 cervical samples with histomorphological diagnosis of CIN and its mimics and the utility of IHC markers p16, p63, CK17, and HPV in distinction was analyzed. p16 showed 67.76% sensitivity and 99.4% specificity whereas HPV showed 57.9% sensitivity and 91.6% specificity in detecting CIN. CK17 and p63 did not show any significance in distinguishing CIN from its mimics. After IHC of AIM cases, 66.7% were reclassified as CIN III, 27.8% as ISM with reactive atypia (ISMRA), and 5.5% case as immature condyloma. In total, 3.7% of diagnosis was upgraded to CIN and 0.6% of pre-IHC diagnosis was downgraded from CIN to reactive lesions. IHC panel comprising p16, p63, CK17, and HPV are useful adjuncts in distinguishing CIN from its mimics particularly when histomorphology has overlapping morphological features.