title: Value of P16 expression in the triage of liquid-based cervical cytology with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions.
abstract: BACKGROUND
  The management of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions (ASCUS/LSIL) is still controversial and it is advisable to make a triage for these two cytological abnormalities. P16(INK4) (P16) has been shown to be a potential biomarker for predicting high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer. The aim of the study was to determine the value of P16 expression by immunostaining method compared with high-risk human papillomavirus (HR-HPV) DNA test in the triage of ASCUS/LSIL women.
  
  
  METHODS
  Totally 86 eligible residual liquid-based cytological specimens with ASCUS and 45 with LSIL were obtained. All specimens were submitted to HR-HPV DNA test (HC2) and P16 immunocytochemical staining simultaneously. And all women underwent colposcopy and biopsy after cytology.
  
  
  RESULTS
  The positive rate of P16 staining was 32.6% in ASCUS and 42.2% in LSIL, which was significantly lower than that of HR-HPV test in both ASCUS (P < 0.05) and LSIL (P < 0.05). Moreover, the positive rate of P16 staining was 12.7% in normal histology, 61.5% in CIN 1, 87.0% in CIN 2-3, and 100.0% in cancer, in which P16 positive rate was significantly lower than HR-HPV positive rate in normal group. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of P16 staining for predicting CIN 2 or more were 87.5%, 68.6%, 38.9%, 96.0%, and 72.1%, respectively in the ASCUS; while 90.0%, 71.4%, 47.4%, 96.2% and 54.7%, respectively in the LSIL, in which the specificity and accuracy of P16 staining were significantly higher than those of HR-HPV test in both ASCUS and LSIL (P < 0.05).
  
  
  CONCLUSIONS
  P16 immunostaining had significantly higher specificity and accuracy than HR-HPV DNA test for predicting for high-grade CIN and cervical cancer in ASCUS and LSIL and can be used for the triage of women with ASCUS/LSIL cytological abnormality.
authors.affiliation: Department of Women's Health Care, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China.
authors.forename: Yuan-Ying
authors.initials: YY
authors.lastname: Ma
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Cheng
authors.forename: Cai-Yun
authors.initials: CY
authors.lastname: Zhou
authors.forename: Li-Qian
authors.initials: LQ
authors.lastname: Qiu
authors.forename: Xiao-Duan
authors.initials: XD
authors.lastname: Chen
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Lü
authors.forename: Xing
authors.initials: X
authors.lastname: Xie
mesh_terms: D000328:Adult; D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000821:virology; D014218:Triage / Q000379:methods*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D014626:Vaginal Smears; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000378:metabolism*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral