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. Cancer (Cancer Cytopathol) 2006. © 2006 American Cancer Society.

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Screening for HPV-driven cervical dysplasia and neoplasia is a significant public health concern in the developing world. The purpose of this study was to use a manual, low-cost liquid-based Pap preparation to determine HPV prevalence in HIV-positive and HIV-negative young women in Kampala, Uganda and to correlate cervical cytopathology with HPV-DNA genotype. About 196 post-partum women aged 18-30 years underwent rapid HIV testing and pelvic examination. Liquid-based cervical cytology samples were processed using a low-cost manual technique. A DNA collection device was used to collect specimens for HPV genotyping. HIV and HPV prevalence was 18 and 64%, respectively. Overall, 49% of women were infected with a high-risk HPV genotype. The most common high-risk HPV genotypes were 16 (8.2%), 33 (7.7%), 35 (6.6%), 45 (5.1%), and 58 (5.1%). The prevalence of HPV 18 was 3.6%. HIV-positive women had an HPV prevalence of 86% compared to 59% in HIV-negative women (P = 0.003). The prevalence of HPV 16/18 did not differ by HIV status. HIV-positive women were infected with a significantly greater number of HPV genotypes compared to HIV-negative women. By multivariate analysis, the main risk factor for HPV infection was coinfection with HIV. HIV-positive women were four times more likely to have abnormal cytology than HIV-negative women (43% vs. 11.6%, P < 0.001). These data highlight that HIV infection is a strong risk factor for HPV infection and resultant abnormal cervical cytology. Notably, the manual low-cost liquid-based Pap preparation is practical in this setting and offers an alternate method for local studies of HPV vaccine efficacy.