4.4 Review

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

Journal

CANCER CYTOPATHOLOGY
Volume 120, Issue 5, Pages 294-307

Publisher

WILEY
DOI: 10.1002/cncy.21205

Keywords

cervical cancer; cervical intraepithelial neoplasia; atypical squamous cells of undetermined significance; low-grade squamous intraepithelial lesions; triage; p16INK4a; cytoimmunochemistry; human papillomavirus testing; diagnostic accuracy; systematic review

Funding

  1. European Commission through the Prevention Strategies for HPV-Related Diseases in European Countries (PREHDICT) Network
  2. DG Research (Brussels, Belgium)
  3. European Cooperation on Development and Implementation of Cancer screening and prevention guidelines
  4. Directorate of SANCO (Luxembourg, Grand-Duchy of Luxembourg)
  5. Belgian Foundation Against Cancer (Brussels, Belgium)
  6. Gynaecological Cancer Cochrane Review Collaboration (Bath, United Kingdom)

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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. (c) 2012 American Cancer Society.

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