Send to

Choose Destination
See comment in PubMed Commons below
Br J Cancer. 2014 Mar 18;110(6):1579-86. doi: 10.1038/bjc.2014.34. Epub 2014 Feb 11.

Triaging borderline/mild dyskaryotic Pap cytology with p16/Ki-67 dual-stained cytology testing: cross-sectional and longitudinal outcome study.

Author information

  • 1Department of Pathology, VU University Medical Center, PO BOX 7057, 1000 MB Amsterdam, The Netherlands.
  • 2Department of Epidemiology and Biostatistics, VU University Medical Center, PO BOX 7057, 1000 MB Amsterdam, The Netherlands.
  • 3Department of Pathology, Erasmus University Medical Center, PO BOX 2040, 3000 CA Rotterdam, The Netherlands.
  • 4Department of Obstetrics and Gynaecology, VU University Medical Center, PO BOX 7057, 1000 MB Amsterdam, The Netherlands.
  • 5Ventana Medical Systems, Inc., 1910 E Innovation Park Drive, Tucson, AZ 85755, USA.
  • 6Saltro Diagnostic Centre, PO BOX 9300, 3506 GH Utrecht, The Netherlands.



Women with borderline/mildly dyskaryotic (BMD) cytology smears are currently followed up with repeat testing at 6 and 18 months. The objective of this study is to analyse the cross-sectional and longitudinal performance of p16/Ki-67 dual-stained cytology for the detection of cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) and CIN2+ in women with BMD, and to compare the results with baseline human papillomavirus (HPV) testing.


Conventional Pap cytology specimens of 256 women with BMD were dual stained for p16/Ki-67 retrospectively, and compared with baseline HPV results and long-term follow-up results.


p16/Ki-67 dual-stained cytology showed a sensitivity of 100%, a specificity of 64.4% and a negative predictive value (NPV) of 100.% for CIN3+. Human papillomavirus testing demonstrated similar sensitivity (96.3%), and NPV (99.1%), but a significantly lower specificity (57.6%; P=0.024) for CIN3+. Sensitivity, specificity and NPV for CIN2+ of dual-stained cytology were 89.7%, 73.1% and 95.1%, respectively, which was similar when compared with HPV testing. Dual-stained cytology showed a significant lower referral rate than HPV testing (43.6% vs 49.1%; P=0.043). During long-term follow-up, no CIN3+ lesions developed in HPV-positive, dual-stained negative women.


Comparable sensitivity and NPV of dual-stained cytology for CIN3+, combined with a significantly higher specificity, makes p16/Ki-67 dual-stained cytology a viable alternative to HPV testing for triaging BMD.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center