Generalizable Cervical Cancer Screening via Large-scale Pretraining and Test-Time Adaptation

Cervical cancer is a leading malignancy in female reproductive system. While AI-assisted cytology offers a cost-effective and non-invasive screening solution, current systems struggle with generalizability in complex clinical scenarios. To address this issue, we introduced Smart-CCS, a generalizable Cervical Cancer Screening paradigm based on pretraining and adaptation to create robust and generalizable screening systems. To develop and validate Smart-CCS, we first curated a large-scale, multi-center dataset named CCS-127K, which comprises a total of 127,471 cervical cytology whole-slide images collected from 48 medical centers. By leveraging large-scale self-supervised pretraining, our CCS models are equipped with strong generalization capability, potentially generalizing across diverse scenarios. Then, we incorporated test-time adaptation to specifically optimize the trained CCS model for complex clinical settings, which adapts and refines predictions, improving real-world applicability. We conducted large-scale system evaluation among various cohorts. In retrospective cohorts, Smart-CCS achieved an overall area under the curve (AUC) value of 0.965 and sensitivity of 0.913 for cancer screening on 11 internal test datasets. In external testing, system performance maintained high at 0.950 AUC across 6 independent test datasets. In prospective cohorts, our Smart-CCS achieved AUCs of 0.947, 0.924, and 0.986 in three prospective centers, respectively. Moreover, the system demonstrated superior sensitivity in diagnosing cervical cancer, confirming the accuracy of our cancer screening results by using histology findings for validation. Interpretability analysis with cell and slide predictions further indicated that the system's decision-making aligns with clinical practice. Smart-CCS represents a significant advancement in cancer screening across diverse clinical contexts.