Head and neck cancer in older adults: biological aging, treatment tolerance, and survivorship

Abstract

Head and neck squamous cell carcinoma (HNC) is increasingly diagnosed in older adults, a population characterized by substantial heterogeneity in physiologic reserve, comorbidity burden, functional status, and social support. Chronological age alone is an inadequate predictor of treatment tolerance and outcomes, yet it continues to influence therapeutic decision-making despite growing evidence supporting individualized assessment. This review summarizes the current evidence on aging and HNC, emphasizing the impact of comorbidities, frailty, comprehensive geriatric assessment (CGA), and biological aging on treatment selection, toxicity, and survival. We review validated geriatric assessment tools, including frailty measures and evaluation of cognitive, nutritional, and social domains, which consistently provide prognostic information beyond age and conventional performance status. Emerging data on immunologic aging and other biomarkers of biological aging suggest promising avenues for improving risk stratification, although these approaches remain investigational. We also discuss evidence from contemporary clinical trials, treatment adaptation and de-escalation strategies, implementation science, and the persistent underrepresentation of older adults in oncology research. Survivorship challenges, including late toxicities, functional decline, rehabilitation, and multidisciplinary long-term care, are reviewed alongside disparities in access to care that disproportionately affect older patients. Collectively, the available evidence supports a shift from age-based treatment decisions toward individualized care guided by physiologic reserve, geriatric assessment, and patient-centered goals. Future progress will depend on integrating geroscience, validated biomarkers of biological aging, geriatric-informed clinical trial design, and implementation strategies that improve equitable access to evidence-based care for the growing population of older adults with HNC.