Improved Predictive Value Provided by ProExC™ Staining of HSIL Pap Smears Supports Leap to LEEP Clinical Management
C Rozelle, A Veyliotti, L Matsumura, M Berlin, R Krum, TK Morgan. OHSU, Portland, OR; Kaiser Northwest, Portland
Background: Management guidelines now allow for a “leap to LEEP” in non-adolescent women with a cervical pap smear diagnosis of high-grade dysplasia (HSIL). This change was due to an improved positive predictive value (PPV) of HSIL (70-80) provided by liquid-based paps sufficient to bypass inefficient colposcopy. In our experience, however, the consequence has been a reduction in the frequency of definitive HSIL diagnoses. Our clinicians are also hesitant to LEEP because of significant false positive rates. HPV testing is not useful because the PPV is no better than a HSIL diagnosis. Our objective was to test whether a marker of neoplastic transformation, such as ProExCTM, provides an improved PPV to better support “leap to LEEP.”
Design: SurePath™ cervical pap smears diagnosed as HSIL (n=118) at either OHSU or Kaiser Northwest were immunostained for ProExC (BD Tripath) using a Ventana Benchmark XT. A minimum of 5000 epithelial cells per slide were required to be adequate for immunostaining and cases were scored as positive or negative by a cytopathologist (TM) and resident (CR). Each specimen was tested for high-risk HPV by hybrid capture (Digene™) and all followup cervical LEEP biopsies were immunostained for ProExC to generate a “Clinical Consensus Diagnosis" as the gold standard surgical outcome. Outcomes were classified as either biopsy-proven high grade dysplasia (CIN 2+), or a minimum of two years negative followup (including CIN 1). Predictive values were calculated and associations determined by Chi-square analysis.
Results: We observed excellent agreement between pathologists' scoring of the immunostained pap smears and biopsies (kappa statistic 0.61, 0.78, respectively). Discordant scores occurred in paps with fewer than 10 positive cells (52% discordance, compared to 3-5% in negative or abundantly positive cases). The prevalence of CIN 2+ in this HSIL cohort was 81%. Chi-square analysis showed a significant association between positive ProExC staining and CIN2+ followup (p<.0001). Positive staining significantly improved the PPV (95%) and positive likelihood ratio (4.5 [CI:2-9]). The prevalence of high-risk HPV was 96% and the PPV of a positive test (81%) was no better than HSIL cytology.
Conclusions: Immunostaining cervical pap smears diagnosed as HSIL for ProExC significantly improves the PPV for CIN2+ surgical outcome, which may strengthen clinical confidence when leaping to LEEP in non-adolescent women.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 53, Monday Morning