title: Evaluation of p16(INK4a)/Ki-67 dual stain in comparison with an mRNA human papillomavirus test on liquid-based cytology samples with low-grade squamous intraepithelial lesion.
abstract: BACKGROUND
  The objective of the current study was to investigate the clinical performance of detecting high-grade lesions with the CINtec PLUS p16(INK4a)/Ki-67 dual stain and the APTIMA human papillomavirus (HPV) Assay in a cohort of women with low-grade squamous intraepithelial lesion (LSIL) cytology. The authors also assessed the reproducibility of the evaluation of immunocytochemical staining.
  
  
  METHODS
  The 2 tests were performed on liquid-based residual material from 469 women with LSILs. The samples had at least 5 years of follow-up and the gold standard used was high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) proven on histology.
  
  
  RESULTS
  Approximately 69% of all the women included in the study had a positive test for HPV mRNA and 56% was positive for the dual stain. The 2 tests demonstrated high sensitivities. When examining the specificities, the APTIMA HPV Assay performed with significantly lower values than the CINtec PLUS test. For patients with CIN2+, the APTIMA HPV Assay had a specificity of 36.1% versus 51.3% for the CINtec PLUS test, and for women with CIN3+, the specificity was 33.8% versus 48.2%, respectively. The difference was even more pronounced when analyzing women aged < 30 years separately. The kappa values between the 3 observers in scoring the dual stain ranged from 0.43 to 0.49 and improved in a second evaluation round to values ranging from 0.50 to 0.66.
  
  
  CONCLUSIONS
  The CINtec PLUS p16(INK4a)/Ki-67 dual-staining test in LSIL cytology samples demonstrated high sensitivity that was similar to that of the APTIMA HPV Assay in the detection of underlying high-grade disease but with enhanced specificity, especially among women aged < 30 years. The kappa value for the evaluation of the CINtec PLUS dual-staining test was moderate but could be improved through training.
authors.affiliation: Department of Clinical Pathology, Vejle Hospital, Vejle, Denmark. marianne.waldstroem@slb.regionsyddanmark.dk
authors.forename: Marianne
authors.initials: M
authors.lastname: Waldstrøm
authors.forename: Rikke Kølby
authors.initials: RK
authors.lastname: Christensen
authors.forename: Dorthe
authors.initials: D
authors.lastname: Ørnskov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D003581:Cytodiagnosis; D004279:DNA, Viral / Q000235:genetics; D003955:Diagnostic Tests, Routine; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000235:genetics / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics*; D012680:Sensitivity and Specificity; D013194:Staining and Labeling; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000235:genetics / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000821:virology; D014626:Vaginal Smears; D055815:Young Adult
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D012333:RNA, Messenger