The Role of Biomarkers (p16INK4a and Ki-67) in Cervical Cancer Screening: An Appraisal

Abstract

Cervical cancer is a common and important public health problem in developing countries. Even though many developed countries have achieved significant successes in reducing invasive cervical cancer burden, the burden in developing countries is still worrisome. Currently, cervical examinations and Papanicolaou (Pap) tests remain the screening method of choice for most women in many parts of Africa. Molecular diagnostic tests for human papillomavirus (HPV) can augment screening for cervical cancer when used in conjunction with the Pap smear. Due to the inherent limitations of morphologic interpretation and borderline cases, the atypical squamous cells (Atypical Squamous Cells of Undetermined Significance [ASCUS] and Atypical Squamous Cells cannot rule out High Grade [ASC‑H]) were introduced and this led to significant colposcopic follow-up and/or treatment of these women. p16^INK4a is an efficient triage method; the dual staining with Ki‑67 was introduced mainly to increase reproducibility and specificity compared with stand‑alone p16INK4a staining. Diffuse p16INK4a immunostaining is the hallmark of high‑grade squamous intraepithelial lesions regardless of HPV status.