p16INK4a immunocytochemistry versus human papillomavirus testing for triage of women with minor cytologic abnormalities

A systematic review and meta-analysis

Authors

  • Jolien Roelens MSc,

    1. Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium
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  • Miriam Reuschenbach MD,

    1. Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany
    2. Clinical Cooperation Unit, German Cancer Research Center, Heidelberg, Germany
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  • Magnus von Knebel Doeberitz MD, PhD,

    1. Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany
    2. Clinical Cooperation Unit, German Cancer Research Center, Heidelberg, Germany
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  • Nicolas Wentzensen MD,

    1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
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  • Christine Bergeron MD, PhD,

    1. Laboratoire Cerba, Cergy Pontoise, France
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  • Marc Arbyn MD, MSc, DrTMH

    Corresponding author
    1. Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium
    • Scientific Institute of Public Health, Unit of Cancer Epidemiology, J. Wytsmanstraat 14, 1050 Brussels, Belgium
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    • Fax: (011) 32-2-6425410


  • The authors acknowledge M. Nasioutziki, M. Guo, A. Szarewski, J. Cuzick and J. Monsonego for the provision of additional data as well as L. Houthuys for bibliographic support.

  • See related Commentary on pages 291–293, this issue.

Abstract

The best method for identifying women who have minor cervical lesions that require diagnostic workup remains unclear. The authors of this report performed a meta-analysis to assess the accuracy of cyclin-dependent kinase inhibitor 2A (p16INK4a) immunocytochemistry compared with high-risk human papillomavirus DNA testing with Hybrid Capture 2 (HC2) to detect grade 2 or greater cervical intraepithelial neoplasia (CIN2+) and CIN3+ among women who had cervical cytology indicating atypical squamous cells of undetermined significance (ASC-US) or low-grade cervical lesions (LSIL). A literature search was performed in 3 electronic databases to identify studies that were eligible for this meta-analysis. Seventeen studies were included in the meta-analysis. The pooled sensitivity of p16INK4a to detect CIN2+ was 83.2% (95% confidence interval [CI], 76.8%-88.2%) and 83.8% (95% CI, 73.5%-90.6%) in ASC-US and LSIL cervical cytology, respectively, and the pooled specificities were 71% (95% CI, 65%-76.4%) and 65.7% (95% CI, 54.2%-75.6%), respectively. Eight studies provided both HC2 and p16INK4a triage data. p16INK4a and HC2 had similar sensitivity, and p16INK4a has significantly higher specificity in the triage of women with ASC-US (relative sensitivity, 0.95 [95% CI, 0.89-1.01]; relative specificity, 1.82 [95% CI, 1.57-2.12]). In the triage of LSIL, p16INK4a had significantly lower sensitivity but higher specificity compared with HC2 (relative sensitivity, 0.87 [95% CI, 0.81-0.94]; relative specificity, 2.74 [95% CI, 1.99-3.76]). The published literature indicated the improved accuracy of p16INK4a compared with HC2 testing in the triage of women with ASC-US. In LSIL triage, p16INK4a was more specific but less sensitive. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society.

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