Blood-Based MCED Test Enables Early-Stage Detection for Multiple Cancer Types

Thirteen malignancies linked to excess body weight now account for roughly 40% of U.S. cancer diagnoses, yet most, such as pancreatic, hepatic, and endometrial cancers, lack population-wide screening programs. New clinical evidence now shows the robust performance of a blood-based multi-cancer early-detection (MCED) assay across several high-incidence, high-mortality tumor types, including those that disproportionately affect people with obesity.

The reflex MCED blood test developed by Harbinger Health (Cambridge, MA, USA) uses specific proprietary methylation signatures in circulating tumor DNA (ctDNA) to detect the presence of cancer. The company’s technology platform integrates biological insights into cancer initiation with artificial-intelligence methods and analytical advances to deliver novel screening and diagnostic products for multiple settings and indications. The reflex workflow employs two tiers: an initial methylome-profiling assay tuned for high sensitivity to “rule out” disease, followed by a confirmatory test that uses an expanded methylation panel to enhance positive predictive value (PPV), “rule in” cancer, and pinpoint the tissue of origin (TOO).

A multicenter, case-control study designed to validate and refine Harbinger’s platform enrolled about 8,095 participants at 126 U.S. sites. The cancer arm included treatment-naïve patients with confirmed diagnoses spanning more than 20 solid and hematologic tumors, while the control arm comprised individuals with no clinical suspicion of cancer at enrollment; control participants were monitored for a year to verify their cancer-free status. The analysis cohort evaluated here consisted of 762 adults with obesity (mean age 57.1 ± 13.4 years; 63.3% female; 22.4% Black or African American; 67.8% White). Tumor types represented were breast, uterine, lung, lymphoid lineage, prostate, colorectal, pancreatic, upper gastrointestinal (esophageal, esophagogastric junction, and gastric), head and neck, liver, biliary tract, and others.

With specificity set at 98.3%, the reflex assay demonstrated conventional sensitivities of 25.8% for early-stage (I–II) cancers and 80.3% for late-stage (III–IV) cancers. Using the same specificity, the test achieved a 50.9% conventional sensitivity for malignancies lacking established U.S. screening programs. Among cases that generated a tissue-of-origin readout, the overall accuracy of the TOO assignment was 36%. Tumor-specific PPVs for the TOO call were 15% for hepatobiliary, 22% for upper GI, 33% for colorectal, and 25% for lung cancers.

“The results from our study demonstrate the robust early-stage performance of our test across multiple cancer types,” said Hutan Ashrafian, M.D., Ph.D., M.B.A., Chief Medical Officer of Harbinger Health. “While the obesity-associated subset demonstrates our ability to target high-risk groups, the broader results underscore the platform’s potential across a wide range of deadly cancers that lack mechanisms for effective, large-scale early detection via routine screening.”

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