Markers of Biological Aging and Survival in Recurrent and Metastatic Head and Neck Cancer Patients Receiving Immunotherapy

Background/Objectives: Immunotherapy has become a cornerstone in the treatment of recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC), but reliable noninvasive biomarkers of prognosis remain limited. We investigated the associations between markers of biological aging and survival outcomes among patients with R/M HNSCC treated with immune checkpoint inhibitors (ICIs). Methods: Peripheral blood samples collected prior to ICI initiation from 100 patients with R/M HNSCC underwent DNA methylation profiling using the Illumina Infinium MethylationEPIC array. Four epigenetic age acceleration measures were estimated from DNA methylation levels and evaluated for associations with progression-free survival (PFS) and overall survival (OS). Results: Greater intrinsic and extrinsic epigenetic age acceleration were each associated with longer PFS (p = 0.025 and p = 0.048, respectively) and OS (p = 0.024 and p = 0.029, respectively). Significant interactions between GrimAge acceleration and chronological age were observed for both PFS (p = 0.010) and OS (p < 0.001). Greater GrimAge acceleration was associated with improved PFS among patients less than 65 years of age but shorter OS among patients 65 years of age or older. Conclusions: In this exploratory study, pretreatment epigenetic aging measures were associated with survival outcomes among patients with R/M HNSCC receiving ICIs. These findings suggest biological aging metrics may have clinical relevance and warrant further investigation as potential noninvasive prognostic biomarkers.