p16INK4a immunoexpression:: surrogate marker of high-risk HPV and high-grade cervical intraepithelial neoplasia

p16(INK4a) has emerged as a valuable surrogate marker for high-risk human papillomavirus infection and shows increased immunoexpression with worsening grades of cervical intraepithelial neoplasia (CIN). Numerous studies have emerged in recent years supporting its role in the detection of high-grade dysplasia and have lead to the use of p16(INK4a) immunohistochemistry in many laboratories. However, only a few studies have examined the possible predictive or prognostic value of p16(INK4a) in CIN or cervical cancer. This review addresses some of the practical issues in the application of p16(INK4a) in everyday practice, with an emphasis on integrating the extensive data that have emerged in the literature on p16(INK4a) immunoreactivity in CIN. The potential role of p16(INK4a) immunohistochemistry in the prediction of CIN progression is also discussed.