Histopathology Foundation Models Enable Accurate Ovarian Cancer Subtype Classification

Large pretrained transformers are increasingly being developed as generalised foundation models which can underpin powerful task-specific artificial intelligence models. Histopathology foundation models show promise across many tasks, but analyses have been limited by arbitrary hyperparameters that were not tuned to the specific task/dataset. We report the most rigorous single-task validation conducted to date of a histopathology foundation model, and the first performed in ovarian cancer subtyping. Attention-based multiple instance learning classifiers were compared using vision transformer and ResNet features generated through varied preprocessing and pretraining procedures. The training set consisted of 1864 whole slide images from 434 ovarian carcinoma cases at Leeds Hospitals. Five-class classification performance was evaluated through five-fold cross-validation, and these cross-validation models were ensembled for evaluation on a hold-out test set and an external set from the Transcanadian study. Reporting followed the TRIPOD+AI checklist. The vision transformer-based histopathology foundation model, UNI, performed best in every evaluation, with five-class balanced accuracies of 88% and 93% in hold-out internal and external testing, compared to the best ResNet model scores of 68% and 81%, respectively. Normalisations and augmentations aided the generalisability of ResNet-based models, but these still did not match the performance of UNI, which gave the best external performance in any ovarian cancer subtyping study to date. Histopathology foundation models offer a clear benefit to subtyping, improving classification performance to a degree where clinical utility is tangible, albeit with an increased computational burden. Such models could provide a second opinion in challenging cases and may improve the accuracy, objectivity, and efficiency of pathological diagnoses overall.