P16INK4a is superior to high-risk human papillomavirus testing in cervical cytology for the prediction of underlying high-grade dysplasia

Panduka Samarawardana, Donna L. Dehn, Meenakshi Singh, Douglas Franquemont, Chesney Thompson, Loretta Gaido, Kathleen C. Torkko, Petra Homer, Stephanie Burke, Matthew A. Titmus, Vipul Nayi, Kenneth R. Shroyer

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


BACKGROUND 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. METHODS: 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. RESULTS: 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 p16 INK4a ICC was greater than that of HR-HPV for patients with biopsies ≥CIN-2 (41.2% and 24.2%, respectively, P=.001). CONCLUSIONS: This p16 INK4a 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.

Original languageEnglish (US)
Pages (from-to)146-156
Number of pages11
JournalCancer Cytopathology
Issue number3
StatePublished - 2010
Externally publishedYes


  • Cervical cancer screening
  • Cervical cytology
  • Human papillomavirus
  • P16

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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