Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests

Multiplechromosomal aneuploidiesmay be associated with maternal malignancies and can cause failure of noninvasive prenatal screening ( NIPS) tests. However, multiplechromosomal aneuploidiesshow poor specificity and selectivity for diagnosing maternal malignancies. This multicenter retrospective analysis evaluated 639 pregnant women who tested positive for multiplechromosomal aneuploidieson initial NIPStest between January 2016 and December 2017. Women were assessed using genome profiling of copy-number variations, which was translated to cancer risk using a novel bioinformatics algorithm called the cancer detection pipeline (CDP). Sensitivity, specificity, and positive predictive value (PPV) of diagnosing maternal malignancies were compared for multiplechromosomal aneuploidies, the CDP model, and the combination of CDP and plasma tumor markers. Of the 639 subjects, 41 maternal malignant cancer cases were diagnosed. Multiplechromosomal aneuploidiespredicted maternal malignancies with a PPV of 7.6%. Application of the CDP algorithm to women with multiplechromosomal aneuploidiesallowed 34 of the 41 (83%) cancer cases to be identified, while excluding 422 of 501 (84.2%) of the false positive cases. Combining the CDP with plasma tumor markertesting gave PPV of 75.0%. The CDP algorithm can diagnose occult maternal malignancies with a reasonable PPV in multiplechromosomal aneuploidies–positive pregnant women in NIPStests. This performance can be further improved by incorporating findings for plasma tumor markers.