title: MicroRNA detection in cervical exfoliated cells as a triage for human papillomavirus-positive women.
abstract: BACKGROUND
  Papanicolaou (Pap) triage, with high specificity, has been recommended for primary Human papillomavirus (HPV) testing but is flawed by poor sensitivity and cytologist dependence. We evaluated the potential role of microRNA (miRNA) detection in cervical exfoliated cells in HPV-positive women from a clinic-based population.
  
  
  METHODS
  Primary HPV testing as well as Pap test were performed on all eligible women. Six miRNAs (miR-424/miR-375/miR-34a/miR-218/miR-92a/miR-93) were detected by RT-qPCR in cervical exfoliated cells. All HPV-positive women underwent colposcopy and further biopsy if indicated. Mann-Whitney U test, the receiver operating characteristic curve, logistic regression, and Pearson's Chi-square were used to assess data. All tests of statistical significance were two-sided.
  
  
  RESULTS
  A total of 1021 eligible HPV-positive women were enrolled. The expression of miR-424/miR-375/miR-34a/miR-218 in high-grade cervical intraepithelial neoplasia (CIN) and abnormal cytology was statistically significantly lower than that in low-grade CIN and normal cytology, respectively (all P < .05). Compared with the Pap test, both miR-424 and miR-375 detection achieved higher sensitivity (76.0% and 74.9% vs 63.8%, P < .05), higher negative predictive value (NPV) (85.7% and 85.4% vs 79.3%, P < .05), and comparable specificity while identifying CIN2 or worse (CIN2+). Similar results were achieved while identifying CIN3+. Multi-marker panels based on miR-424, miR-375, and miR-218 further improved the performance over any single miRNA test or Pap test.
  
  
  CONCLUSIONS
  Single miR-424 or miR-375 detection and miR-424/miR-375/miR-218-based multimarker panels in cervical exfoliated cells show superior performance over Pap triage for high-grade CIN identification in a clinic-based population. Detection of miRNA may provide a new triage option for HPV-positive women.
authors.affiliation: Department of Gynecologic Oncology (QT, YS, XinW, XC, YC, XiaW, WL, XX) and Women's Reproductive Health Laboratory of Zhejiang Province (YaL, FW, YiL, JX, FY), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Qifang
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Department of Gynecologic Oncology (QT, YS, XinW, XC, YC, XiaW, WL, XX) and Women's Reproductive Health Laboratory of Zhejiang Province (YaL, FW, YiL, JX, FY), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gynecologic Oncology (QT, YS, XinW, XC, YC, XiaW, WL, XX) and Women's Reproductive Health Laboratory of Zhejiang Province (YaL, FW, YiL, JX, FY), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Fenfen
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Gynecologic Oncology (QT, YS, XinW, XC, YC, XiaW, WL, XX) and Women's Reproductive Health Laboratory of Zhejiang Province (YaL, FW, YiL, JX, FY), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gynecologic Oncology (QT, YS, XinW, XC, YC, XiaW, WL, XX) and Women's Reproductive Health Laboratory of Zhejiang Province (YaL, FW, YiL, JX, FY), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Junfen
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Gynecologic Oncology (QT, YS, XinW, XC, YC, XiaW, WL, XX) and Women's Reproductive Health Laboratory of Zhejiang Province (YaL, FW, YiL, JX, FY), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Gynecologic Oncology (QT, YS, XinW, XC, YC, XiaW, WL, XX) and Women's Reproductive Health Laboratory of Zhejiang Province (YaL, FW, YiL, JX, FY), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Gynecologic Oncology (QT, YS, XinW, XC, YC, XiaW, WL, XX) and Women's Reproductive Health Laboratory of Zhejiang Province (YaL, FW, YiL, JX, FY), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Gynecologic Oncology (QT, YS, XinW, XC, YC, XiaW, WL, XX) and Women's Reproductive Health Laboratory of Zhejiang Province (YaL, FW, YiL, JX, FY), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Gynecologic Oncology (QT, YS, XinW, XC, YC, XiaW, WL, XX) and Women's Reproductive Health Laboratory of Zhejiang Province (YaL, FW, YiL, JX, FY), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yaxia
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Gynecologic Oncology (QT, YS, XinW, XC, YC, XiaW, WL, XX) and Women's Reproductive Health Laboratory of Zhejiang Province (YaL, FW, YiL, JX, FY), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Gynecologic Oncology (QT, YS, XinW, XC, YC, XiaW, WL, XX) and Women's Reproductive Health Laboratory of Zhejiang Province (YaL, FW, YiL, JX, FY), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Gynecologic Oncology (QT, YS, XinW, XC, YC, XiaW, WL, XX) and Women's Reproductive Health Laboratory of Zhejiang Province (YaL, FW, YiL, JX, FY), Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China. xiex@zju.edu.cn.
authors.forename: Xing
authors.initials: X
authors.lastname: Xie
mesh_terms: D000328:Adult; D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification*; D002584:Cervix Uteri / Q000821:virology*; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000302:isolation & purification*; D065006:Papanicolaou Test; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D014218:Triage; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology*; D014626:Vaginal Smears
chemical_list: C547471:MIRN218 microRNA, human; C522425:MIRN34 microRNA, human; C540933:MIRN375 microRNA, human; C554214:MIRN424 microrna, human; C541874:MIRN92 microRNA, human; C543350:MIRN93 microRNA, human; D035683:MicroRNAs