title: Evaluation of p16/Ki-67 dual staining in detection of cervical precancer and cancers: a multicenter study in China.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Yu
authors.affiliation: Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Lei
authors.affiliation: Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Ze-Ni
authors.initials: ZN
authors.lastname: Wu
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Qin-Jing
authors.initials: QJ
authors.lastname: Pan
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Bai-Feng
authors.initials: BF
authors.lastname: Chang
authors.affiliation: Department of Cancer Epidemiology, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Henan Office for Cancer Control and Research, Zhengzhou, P. R. China.
authors.forename: Shao-Kai
authors.initials: SK
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Hui-Qin
authors.initials: HQ
authors.lastname: Guo
authors.affiliation: Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Qiao
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism / Q000821:virology; D000328:Adult; D065309:Atypical Squamous Cells of the Cervix / Q000378:metabolism / Q000473:pathology / Q000821:virology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism / Q000821:virology; D002681:China; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D019942:Genes, p16; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D027383:Papillomaviridae / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen
keywords: Chinese women; Pathology Section; cervical cancer; human papillomavirus; p16/Ki-67 dual staining