J Cancer 2019; 10(12):2654-2660. doi:10.7150/jca.32743

Review

Application of p16/Ki-67 dual-staining cytology in cervical cancers

Li Yu1,✉, Lingyan Fei1, Xubin Liu1, Xufang Pi1, Liantang Wang1, Shangwu Chen2,✉

1. Department of Pathology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
2. State Key Laboratory for Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, Key Laboratory of Gene Engineering of the Ministry of Education, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Yu L, Fei L, Liu X, Pi X, Wang L, Chen S. Application of p16/Ki-67 dual-staining cytology in cervical cancers. J Cancer 2019; 10(12):2654-2660. doi:10.7150/jca.32743. Available from http://www.jcancer.org/v10p2654.htm

File import instruction

Abstract

Cytology-based Papanicolaou test on and primary HPV screening have been widely used in the identification of cervical cancer and precancerous lesions, which is of great significance for the prevention and treatment of cervical cancer. Patients diagnosed as ASCUS/LSIL usually need follow-up because some of them may develop into CIN2+. The consequences of women positive for HPV vary from person to person; some of them may progress into cervical dysplasia, reversible forms of precancerous lesions, and eventually invasive cervical cancer. Therefore, it is necessary to establish an effective biomarker to triage different patients according to the preliminary screening results. p16 acts as a cell cycle regulatory protein that induces cell cycle arrest, and Ki-67 is a cell proliferation marker. Under physiological conditions, they could not co-express in the same cervical epithelial cells. The co-expression of these two molecules suggests a deregulation of the cell cycle mediated by HR-HPV infection and predicts the presence of high-grade cervical epithelial lesions. There is increasing evidence that p16/Ki-67 dual-staining cytology can be used as an alternative biomarker, showing overall high sensitivity and specificity for identifying high-grade CIN and cervical cancer. In this review, we discuss the significance of p16/Ki-67 dual-staining and summarize its application in the screening and triaging of cervical cancer and precancerous lesions.

Keywords: p16/Ki-67 dual-staining, cytology, HPV, cervical cancer screening, CIN