p16INKa and Ki67 expression in different grades of cervical intraepithelial neoplasm in relation to HPV genotypes

Abstract

Background: Early diagnosis of cervical intraepithelial neoplasia and prevention of its malignant progression is very important. The interaction between human papillomavirus (HPV) oncogenic proteins and the cellular regulatory proteins leads to the upregulation of p16INK4a. Overexpression of p16INK4a is a surrogate biomarker of HPV infection leading to premalignant or malignant cervical lesions. Aim: In this study, we evaluated the expression of p16INK4a/Ki67 in correlation with HPV genotypes to find out their correlation with dysplasia grading. Patients and Methods: Pap cytology and HPV genotyping were performed from 101 women referred to colposcopy. Biopsy specimens were stained with haematoxylin-eosin, then sections were used for subsequent p16INK4a and Ki67 immunohistochemical analysis. Results: There was a significant correlation between the staining score of p16INK4a and Ki67 and increase the severity of the cervical lesion. A significant positive correlation was found between HPV type and cervical lesion severity. A significant correlation was found between HPV genotypes and the expression of either p16INK4a or Ki67. Conclusion: There is a strong association between the degree of dysplasia and combined p16INK4a/Ki67 immunoreactivity which could be explained by cervical malignant transformation associated with high-risk HPV infections.