An evaluation of p16 expression in cervical intraepithelial neoplasia specimens, including women with HIV-1

P16INK4a is a cyclin-dependent kinase inhibitor that regulates the transition from the G1 to S phase and negatively influences cell proliferation in conjunction with other tumour suppressor proteins, such as the retinoblastoma gene (pRb) (Tringler et al. 2004). As pRb is functionally inactivated by the high-risk human papilloma virus (HPV) oncoprotein E7, there is a concomitant overexpression of p16INK4a. New data suggest that p16 overexpression in E7-expressing cells does not appear to result from pRB degradation, but from the induction of histone demethylases by HPV E7 (McLaughlin-Drubin et al. 2011). Although p16INK4a immunostaining has been correlated with the severity of cytological and histological abnormalities in cervical lesions, variations in interpretation and a lack of standardised methodologies has resulted in uncertainty regarding the most appropriate cut-offs for the analysis of P16INK4a levels (Branca et al. 2004, Wentzensen et al. 2005, Valasoulis et al. 2011). This dilemma is underscored by the fact that P16INK4a expression can be upregulated in non-dysplastic cervical lesions, including common squamous metaplasia. Moreover, published studies for the diagnostic performance of P16INK4a in human immunodeficiency virus (HIV)infected patients remain limited (Queiroz et al. 2006, Kreuter et al. 2010). In the present study, we assessed the expression of p16INK4a in normal and abnormal cervical epithelium in HIV-positive and negative women and determined the diagnostic performance [receiving operating characteristics curve (ROC), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)] of P16INK4a for detecting cervical intraepithelial neoplasia (CIN) and invasive cervical cancer in tissue microarray (TMA) samples in each group.