Clinical-Inspired Cytological Whole Slide Image Screening with Just Slide-Level Labels

Cytology test is effective, non-invasive, convenient, and inexpensive for clinical cancer screening. ThinPrep, a commonly used liquid-based specimen, can be scanned to generate digital whole slide images (WSIs) for cytology testing. However, WSIs classification with gigapixel resolutions is highly resource-intensive, posing significant challenges for automated medical image analysis. In order to circumvent this computational impasse, existing methods emphasize learning features at the cell or patch level, typically requiring labor-intensive and detailed manual annotations, such as labels at the cell or patch level. Here we propose a novel automated Label-Efficient WSI Screening method, dubbed LESS, for cytology-based diagnosis with only slide-level labels. Firstly, in order to achieve label efficiency, we suggest employing variational positive-unlabeled (VPU) learning, enhancing patch-level feature learning using WSI-level labels. Subsequently, guided by the clinical approach of scrutinizing WSIs at varying fields of view and scales, we employ a cross-attention vision transformer (CrossViT) to fuse multi-scale patch-level data and execute WSI-level classification. We validate the proposed label-efficient method on a urine cytology WSI dataset encompassing 130 samples (13,000 patches) and FNAC 2019 dataset with 212 samples (21,200 patches). The experiment shows that the proposed LESS reaches 84.79%, 85.43%, 91.79% and 78.30% on a urine cytology WSI dataset, and 96.53%, 96.37%, 99.31%, 94.95% on FNAC 2019 dataset in terms of accuracy, AUC, sensitivity and specificity. It outperforms state-of-the-art methods and realizes automatic cytology-based bladder cancer screening.