Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

M H Uijterwaal  1 , B I Witte  2 , F J Van Kemenade  3 , D Rijkaart  4 , R Ridder  5 , J Berkhof  2 , G A M A Balfoort-van der Meij  6 , M C G Bleeker  1 , P J F Snijders  1 , C J L M Meijer  1
Affiliations
Free PMC article

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

M H Uijterwaal et al. Br J Cancer. .
Free PMC article

Abstract

Background: 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.

Methods: 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.

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.

Conclusions: 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 Disclaimer

Figures

Figure 1
Figure 1
Flowchart design of VUSA-Screen study including p16/Ki-67 dual-stain cytology test results in 256 women with BMD – 3-years follow-up.
Figure 2
Figure 2
(A) Pap-stained BMD smear ( × 40) without p16/Ki-67 dual staining. (B) The same smear as in picture A dual stained for p16/Ki-67. Brown cytoplasmic signal for p16 overexpression and red nuclear signal for Ki-67 expression within the same cell points to dysplasia.
Figure 3
Figure 3
(A) Cumulative incidence risk (CIR) of CIN3+ in women with BMD Pap cytology stratified by p16/Ki-67 dual-stained cytology or HPV or both. (B) Cumulative incidence risk (CIR) of CIN2+ in women with BMD Pap cytology stratified by p16/Ki-67 dual-stained cytology or HPV or both. For comparison, the cumulative disease in the whole cohort is also shown. BMD=borderline/mildly dyskaryotic cytology smears; HPV=human papillomavirus; CIN2+=cervical intraepithelial neoplasia grade 2 or worse.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Anderson MC.2013Premalignant and malignant squamous lesions of the cervix Obstetrical and Gynaecological PathologyFox H, Wells M Haines Taylor, (eds) pp292–297.Churchill Livingstone: New York, USA
    1. Arbyn M, Sasieni P, Meijer CJ, Clavel C, Koliopoulos G, Dillner J. Chapter 9: Clinical applications of HPV testing: a summary of meta-analyses. Vaccine. 2006;24 (Suppl 3:S3/78–89. - PubMed
    1. Berkhof J, de Bruijne MC, Zielinski GD, Bulkmans NW, Rozendaal L, Snijders PJ, Verheijen RH, Meijer CJ. Evaluation of cervical screening strategies with adjunct high-risk human papillomavirus testing for women with borderline or mild dyskaryosis. Int J Cancer. 2006;118 (7:1759–1768. - PubMed
    1. Bulk S, Bulkmans NW, Berkhof J, Rozendaal L, Boeke AJ, Verheijen RH, Snijders PJ, Meijer CJ. Risk of high-grade cervical intra-epithelial neoplasia based on cytology and high-risk HPV testing at baseline and at 6-months. Int J Cancer. 2007;121 (2:361–367. - PubMed
    1. Bulkmans NW, Berkhof J, Rozendaal L, van Kemenade FJ, Boeke AJ, Bulk S, Voorhorst FJ, Verheijen RH, van GK, Boon ME, Ruitinga W, van BM, Snijders PJ, Meijer CJ. Human papillomavirus DNA testing for the detection of cervical intraepithelial neoplasia grade 3 and cancer: 5-year follow-up of a randomised controlled implementation trial. Lancet. 2007;370 (9601:1764–1772. - PubMed

MeSH terms