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p16INK4a is superior to high-risk human papillomavirus testing in cervical cytology for the prediction of underlying high-grade dysplasia
Article first published online: 5 MAY 2010
Copyright © 2010 American Cancer Society
Volume 118, Issue 3, pages 146–156, 25 June 2010
How to Cite
Samarawardana, P., Dehn, D. L., Singh, M., Franquemont, D., Thompson, C., Gaido, L., Torkko, K. C., Homer, P., Burke, S., Titmus, M. A., Nayi, V. and Shroyer, K. R. (2010), p16INK4a is superior to high-risk human papillomavirus testing in cervical cytology for the prediction of underlying high-grade dysplasia. Cancer Cytopathology, 118: 146–156. doi: 10.1002/cncy.20078
- Issue published online: 11 JUN 2010
- Article first published online: 5 MAY 2010
- Manuscript Accepted: 26 JAN 2010
- Manuscript Revised: 8 JAN 2010
- Manuscript Received: 21 SEP 2009
- National Institutes of Health. Grant Numbers: R21CA110519, R33CA110519
Vol. 118, Issue 5, 303, Article first published online: 24 AUG 2010
- cervical cytology;
- cervical cancer screening;
- human papillomavirus
The primary goal of this study was to compare the clinical performance of an optimized and rigorously controlled immunocytochemical (ICC) assay for p16INK4a to high-risk (HR) human papillomavirus (HPV) detection by polymerase chain reaction (PCR) as diagnostic adjuncts for cytology specimens from colposcopy patients.
The study included 403 cervical cytology specimens collected within 3 months of colposcopy. The colposcopic impression and cervical biopsy diagnosis served as the standards for correlation with cytological, p16INK4a, and HPV data. p16INK4a was evaluated using an immunoperoxidase-based assay that was linear over 4 logs for the detection of HeLa-spiked positive control cytology specimens, using a threshold for positive test results that was based on receiver operating characteristic curve analysis. HR-HPV was detected by multiplex PCR using genotype-specific primers.
In all combined diagnostic categories (negative for intraepithelial lesion and malignancy, atypical glandular cells, atypical squamous cells of undetermined significance, atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion), the p16INK4a ICC and HR-HPV assays, respectively, had sensitivity of 81.7% and 83.3% (P = .81) and specificity of 78.1% and 50.9% (P < .001) for the detection of underlying ≥grade 2 cervical intraepithelial neoplasia (CIN) lesions on biopsy. Furthermore, the positive predictive value of p16INK4a ICC was greater than that of HR-HPV for patients with biopsies ≥CIN-2 (41.2% and 24.2%, respectively, P = .001).
This p16INK4a immunocytochemical assay has superior specificity but similar sensitivity to HR-HPV testing to predict underlying high-grade dysplastic lesions in patients who are referred for colposcopy. The determination of the overall performance characteristics of p16INK4a immunocytochemistry, as an independent test or in combination with HPV testing in low-risk screening populations, however, will require subsequent large-scale prospective clinical trials. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.