Jan F Nygård

Hierarchical continuous-time inhomogeneous hidden Markov model for cancer screening with extensive followup data

Continuous-time hidden Markov models are an attractive approach for disease modeling because they are explainable and capable of handling both irregularly sampled, skewed and sparse data arising from real-world medical practice, in particular to screening data with extensive followup. Most applications in this context consider time-homogeneous models due to their relative computational simplicity. However, the time homogeneous assumption is too strong to accurately model the natural history of many diseases including cancer. Moreover, cancer risk across the population is not homogeneous either, since exposure to disease risk factors can vary considerably between individuals. This is important when analyzing longitudinal datasets and different birth cohorts. We model the heterogeneity of disease progression and regression using piece-wise constant intensity functions and model the heterogeneity of risks in the population using a latent mixture structure. Different submodels under the mixture structure employ the same types of Markov states reflecting disease progression and allowing both clinical interpretation and model parsimony. We also consider flexible observational models dealing with model over-dispersion in real data. An efficient, scalable Expectation-Maximization algorithm for inference is proposed with the theoretical guaranteed convergence property. We demonstrate our method’s superior performance compared to other state-of-the-art methods using synthetic data and a real-world cervical cancer screening dataset from the Cancer Registry of Norway. Moreover, we present two model-based risk stratification methods that identify the risk levels of individuals.

Cross-population evaluation of cervical cancer risk prediction algorithms

Cervical cancer is a preventable disease, despite being one of the most common types of female cancers worldwide. Integrating existing programs for cervical cancer screening with personalized risk prediction algorithms can improve population-level cancer prevention by enabling more targeted screening and contrive preventive healthcare innovations. While algorithms developed for cervical cancer risk prediction have shown promising performance in internal validation on more homogeneous populations, their ability to generalize to external populations remains to be assessed. To address this gap, we perform a cross-population comparative study of personalized prediction algorithms for more personalized cervical cancer screening. Using data from the Norwegian and Estonian populations, the algorithms are validated on internal and external datasets to study their potential biases and limitations when applied to different populations. We evaluate the algorithms in predicting progression from low-grade precancerous cervical lesions, simulating a clinically relevant application of more personalized risk stratification. As expected, our numerical experiments show that algorithm performance varies depending on the population. However, some algorithms show strong generalization capacity across different data sources. Using Kaplan-Meier estimates, we demonstrate the strengths and limitations of the algorithms in detecting cancer progression over time by comparing to the trends observed from data. We assess their overall discrimination performance in personalized risk predictions by analyzing the accuracy and confidence in individual risk estimates. This study examines the effectiveness of personalized prediction algorithms across different populations. Our results demonstrate the potential for generalizing risk prediction algorithms to external populations. These findings highlight the importance of considering population diversity when developing risk prediction algorithms.