Evaluation of p16/Ki-67 dual staining in detection of cervical precancer and cancers: a multicenter study in China

Abstract

// Lu-Lu Yu 1 , Wen Chen 1 , Xiao-Qin Lei 1 , Yu Qin 1 , Ze-Ni Wu 1 , Qin-Jing Pan 2 , Xun Zhang 2 , Bai-Feng Chang 2 , Shao-Kai Zhang 3 , Hui-Qin Guo 2 and You-Lin Qiao 1 1 Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China 2 Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China 3 Department of Cancer Epidemiology, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Henan Office for Cancer Control and Research, Zhengzhou, P. R. China Correspondence to: Hui-Qin Guo, email: // You-Lin Qiao, email: // Keywords : cervical cancer; p16/Ki-67 dual staining; human papillomavirus; Chinese women; Pathology Section Received : December 23, 2015 Accepted : March 10, 2016 Published : March 23, 2016 Abstract Purpose: To analyze the clinical performance of p16/Ki-67 dual-stained cytology identifying high-grade cervical intraepithelial neoplasia (CIN2+) in Chinese women. Methods: 1079 women attending ongoing cervical cancer screening and 211 “enriched” women aged ≥30yrs with biopsy-confirmed CIN2+ from five Chinese hospitals were enrolled during year 2014-2015. Cervical specimens were collected for high-risk human papillomavirus (HR-HPV) DNA analysis, Liquid-based cytology (LBC) and p16/Ki-67 dual staining. Colposcopy and biopsy were performed on women with any abnormal result. Results: p16/Ki-67 positivity increased with histologic severity. It was 18.4%(183/996) in normal histology, 54.0%(34/63) in CIN1, 81.0%(34/42) in CIN2, 93.3%(111/119) in CIN3, 71.4% (5/7) in adenocarcinoma and 95.2%(60/63) in squamous cell carcinoma. Compared with the HR-HPV negatives, p16/Ki-67 expression was significantly higher in the HPV16/18 positive (OR: 35.45(95%CI: 23.35-53.84)) and other 12 HR-HPV types positive group (OR: 8.01(95%CI: 5.81-11.05). The sensitivity and specificity of p16/Ki-67 to detect CIN2+ in the entire population were 90.9% and 79.5%, respectively. In women with ASC-US and LSIL, sensitivity and specificity for detection of CIN2+ were 87.5% and 66.4%, respectively, with a referral rate of 43.8%. In women who tested positive for HR-HPV, sensitivity and specificity of dual-staining for detection of CIN2+ were 92.7% and 52.7%, respectively, and the referral rate was 68.7%. Conclusions: p16/Ki-67 dual-stained cytology provided a high sensitivity and moderate specificity to detect underlying cervical precancer and cancers in various settings, and might be considered as an efficient screening tool in China.