Increased rate of atypical squamous cells of undetermined significance and declining high-risk human papillomavirus rates following implementation of ThinPrep Imaging System are associated with increased nuclear chromasia

Abstract

The ThinPrep Imaging System ([Imager], Cytyc Corporation, Hologic, Inc.) for cervical cytology is commonly employed in laboratories. It uses a proprietary stain that allows measurement of cellular DNA content. We evaluated the initial effect of implementing the Imager stain on atypical squamous cells of undetermined significance (ASCUS) and squamous intraepithelial lesion (SIL) diagnoses, and high-risk human papillomavirus (hrHPV) rates. This study included 264 Imager-stained ASCUS cases from the first 5 months of Imager use. All cases were analyzed for hrHPV using Hybrid Capture II assay (Digene Corporation, Qiagen). ASCUS/SIL ratios and hrHPV-positive rates were calculated for the laboratory overall and for 3 cytopathologists. ASCUS/SIL ratios were also calculated for 5 cytotechnologists. These metrics were compared with those from the equivalent 5-month period 1 year prior. Slide review of all Imager-stained ASCUS cases was performed to assess for potential factors involved in ASCUS misinterpretation. The proportion of ASCUS diagnoses increased after Imager stain introduction, from 1.79% to 3.14% (P < 0.001). The proportion of SIL diagnoses also increased, from 0.69% to 1.1% (P < 0.001). However, the hrHPV-positive rate declined from 61.3% to 53.6% (P = 0.104). Review of Imager-stained ASCUS cases showed marked nuclear hyperchromasia, particularly in benign squamous metaplastic cells. Imager stain implementation, required for the ThinPrep Imaging System, led to significant increase in ASCUS rates while the hrHPV-positive rate declined. Cytopathologists will need to recalibrate thresholds for an ASCUS diagnosis when interpreting Imager-stained slides. In particular, nuclear hyperchromasia in squamous metaplastic cells should not be overdiagnosed as ASCUS.