Detection of cervical high-grade squamous intraepithelial lesions from cytologic samples using a novel immunocytochemical assay (ProEx™ C)

Deidra Kelly, Erik Kincaid, Zoya Fansler, Dorothy Rosenthal, Douglas P. Clark

Research output: Contribution to journalArticle


BACKGROUND. Routine liquid-based cytology (LBC) provides excellent sensitivity for the detection of cervical high-grade squamous intraepithelial lesion (HSIL); however, its specificity is low. Consequently, many women who have atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL) cytology undergo unnecessary colposcopy. The authors hypothesized that a novel immunocytochemical assay (ProEx™ C) that can be performed on LBC slides had a significantly higher positive predictive value (PPV) for biopsy-proven HSIL compared with routine LBC. METHODS. The ProEx™ C immunocytochemical assay utilizes a cocktail of monoclonal antibodies directed against proteins associated with aberrant S-phase cell cycle induction (topoisomerase IIA, minichromosome maintenance protein 2). The ProEx™ C reagents were validated in the authors' laboratory for staining and scoring reproducibility, open-vial stability, and accuracy before a retrospective analysis using these reagents was performed on 317 residual cytology samples. Sensitivity, specificity, PPV, and negative predictive value (NPV) for the detection of biopsy-proven HSIL were determined. RESULTS. The ProEx™ C assay was validated successfully in the authors' cytology laboratory. Using biopsy-proven HSIL as an endpoint, the ProEx™ C assay yielded a sensitivity of 85.3%, specificity of 71.7%, PPV of 44.6%, and NPV of 94.8%. Compared with the routine LBC results in the same cohort, the ProEx™ C sensitivity for biopsy-proven HSIL was 70.6% greater than HSIL+ cytology (50% vs. 85.3%). ProEx™ C also showed a 114% increase in PPV relative to ASC-US cytology (21.1% vs. 44.6%). CONCLUSIONS. The ProEx™ C immunocytochemical assay can be integrated into a clinical cytology laboratory and may increase the PPV of LBC for biopsy-proven HSIL.

Original languageEnglish (US)
Pages (from-to)494-500
Number of pages7
Issue number6
Publication statusPublished - Dec 25 2006



  • Cervical cytology
  • High-grade squamous intraepithelial lesion
  • Immunocytochemistry
  • Liquid-based cytology

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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