Role of p16 Immunohistochemistry in Cervical Intraepithelial Neoplasia

Abstract

Introduction: p16 or p16/INK4a is a Cyclin Dependant Kinase Inhibitor 2 (CDKN2) and is upregulated in HPV-related lesions. Therefore, p16 can be considered an indirect marker for altered HR-HPV and growth cycle transformation. Aim: To study p16 Immunohistochemistry (IHC) in spectrum of Cervical Intraepithelial Neoplasia (CIN) and access the possible utility of p16 IHC in differentiating Low grade Squamous Intraepithelial Lesions (CIN1/L-SIL) from High Grade Lesions (CIN2,3/H-SIL). Materials and Methods: Retrospective Hospital Based study of 50 consecutive biopsies with CIN changes was conducted from January 2016 to March 2017. Routine Hematoxylin and Eosin (H&E) and IHC with p16 was performed. p16 IHC was scored according to a scoring system by a previous study. HPV status wherever present was correlated. Statistical analysis was done using SPSS 18.0 software and Fisher’s-exact test was used for comparison between p16 IHC and CIN. Association of p16 IHC and HPV DNA was calculated using the Phi co-efficient test. Results: The age range of CIN cases was 24-50 years and mean age was 35.9 years. The percentage of p16 positive cells, the intensity of IHC reaction, cellular reaction pattern and p16 IHC positivity, all increased with increasing grades of dysplasia. The use of p16 was statistically significant to differentiate between CIN1/L-SIL and CIN2, 3/H-SIL but not between CIN2 and CIN3. In p16 IHC intracellular pattern, weak cytoplasmic positivity of p16 was seen in L-SIL while strong cytoplasmic positivity was seen in H-SIL cases. High risk HPV positivity increased with increase in grade of dysplasia. Conclusion: p16 can be used as an adjunct to histopathology and will definitely improve reporting of grades of CIN.

Keywords

• cervical biopsies
• immunohistochemistry
• squamous intraepithelial neoplasia