Outcomes for patients with locally advanced head and neck cancer (HNC) remain suboptimal, with 5-year survival rates around 50%. Recognizing molecular residual disease (MRD) early is crucial, as most recurrences occur within two years post-treatment. A new study has clinically validated a tissue-agnostic, genome-wide methylome enrichment assay for MRD detection in HNC patients, demonstrating high sensitivity and specificity.
The study, published in Annals of Oncology, enrolled 325 patients with stage I-IVB HNC, including both HPV-positive and HPV-negative cases. Longitudinal peripheral blood plasma samples were collected at diagnosis and approximately 3, 12, and 24 months after curative-intent treatment. These samples were used to train and validate a classifier designed to identify MRD using the methylome enrichment platform. Recurrence-free survival (RFS) was the primary endpoint.
Significant Improvement in Recurrence-Free Survival
After a median follow-up of 60 months, patients in the blinded validation set who tested positive for MRD experienced significantly worse RFS, with a hazard ratio (HR) of 35.7 [95% CI 10.8-117.8; P < 0.0001]. For HPV-negative patients, the HR was 42.3 (95% CI 9.8-182.3; P < 0.0001), and for HPV-positive oropharyngeal cancer patients, the HR was 24.1 (95% CI 3.0-196.8; P < 0.0001).
Early Detection of Recurrence
Notably, the lead time between MRD positivity and clinical recurrence reached up to 14.9 months, with a mean lead time of 4.1 months. The surveillance sensitivity was 91% (95% CI 77% to 97%), and specificity was 88% (95% CI 80% to 93%). These results highlight the potential for early intervention based on MRD detection.
Broad Applicability Across HNC Subtypes
The MRD detection test demonstrated high sensitivity and specificity across different anatomical sites, HPV status, and treatment regimens, underscoring its broad applicability for MRD detection in HNC patients. This is particularly important given the challenges in obtaining tissue samples for analysis in this patient population.
This study validates the clinical performance of a tissue-agnostic genome-wide methylome enrichment assay for MRD detection in HNC, offering a promising tool for improving patient outcomes through early detection and intervention.
