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

Cancer Cytopathol. 2013 Mar;121(3):136-45. doi: 10.1002/cncy.21233. Epub 2012 Sep 17.

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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cohort Studies
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cytodiagnosis
  • DNA, Viral / genetics
  • Diagnostic Tests, Routine
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Ki-67 Antigen / metabolism*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Proteins / genetics*
  • Papillomaviridae / genetics*
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / virology
  • RNA, Messenger / genetics*
  • Sensitivity and Specificity
  • Staining and Labeling
  • Uterine Cervical Dysplasia / diagnosis
  • Uterine Cervical Dysplasia / genetics
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears
  • Young Adult

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • Ki-67 Antigen
  • Neoplasm Proteins
  • RNA, Messenger