Immunocytochemical detection of p16INK4a protein for the identification of patients at risk of cervical cancer

INTRODUCTION p16 INK4a is a cyclin–dependent kinase (CDK) inhibitor that inhibits cyclin dependent kinase 4 and 6, product of the INK4a gene, involved in the phosphorylation of the retinoblastoma protein (pRB). HPV E7 oncoprotein binds specifically to pRB (inactivation of Prb). PRB inhibits transcription of the cyclin dependent kinase inhibitor gene p16INK4a. The inactivation of pRB leads to enhanced p16INK4a protein levels in the affected cells. Increased expression of the p16INK4a is a result of active expression of the hrHPV oncogenes in cervical cells and it is well known that cervical dysplasia and carcinoma are caused by persistent infections with high risk type human papilloma viruses (1,2). The deregulated expression of two viral oncogenes E6 and E7, which both interact with various cell cycle-regulating proteins, in undifferentiated basal or parabasal cells, induce neoplastic transformation of the cervical epithelium. p16 INK4a has been proposed as a specific biomarker for the identification of dysplastic lesions in histologic and cervical smears or liquid-based cytologic slides. The aim of this study was to evaluate whether p16INK4a could be used as an additional marker in the detection of patients with cervical intraepithelial lesions at risk of progression to invasive cancer.