The Role of p16 Immunohistochemistry in the Diagnosis of Pre-Invasive Cervical Lesions and its Applications in a Low Resource Setting

Abstract

Cervical cancer is caused by the sexually transmitted Human Papilloma virus (HPV) which is the most common viral infection of the reproductive tract. Long standing infection with specific types of HPV (especially types 16 and 18) may lead to pre-invasive lesions. The importance of detecting preinvasive lesions is that progression to full blown invasive carcinoma can be prevented. Recently, attention has been focused on p16^INK4a (p16) as a biomarker with potential utility in the identification of pre-invasive cervical lesions. We assessed the application of p16 in the detection of pre-invasive cervical lesions on cervical samples seen between 2009 and 2013.A total number of 61 blocks were retrieved from the tissue repository out of which 45 were suitable for the purposes of this study. The age range of the patients was from 24 to 76 years with a mean age of 42 years. The initial diagnosis was as follows: chronic nonspecific cervicitis: 20 (44.4%), CIN1: 10 (22.2%), CIN2: 6 (13.3%), CIN3: 4 (8.9%), CIS: 2 (4.4%), and normal cervix: 3 (6.7%). p16 was adjudged to be positive when there was uniform, intense staining of the epithelium. Patchy or background staining was interpreted as negative. After p16 staining, 39 (86. 7%) were interpreted as negative for p16, atrophy: 1 (2.2%), CIN1: 2 (4.4%), CIN2: 2 (4.4%) and CIN3: 1 (2.2%). There were discrepancies in 17 results out of which nine (52.9%) were considered significant. We conclude that p16 is of great importance especially in differentiating between reactive/chronically inflamed cervix and CIN and also in differentiating the various CIN types. We propose that with the limited resources available, p16 staining should be done on a case by case basis after peer review of the H&E diagnosis.

Keywords: CIN, cervix, dysplasia