Cancer neuroscience of head and neck cancer: killing two birds with one stone through integrated stress and symptom management

Head and neck cancer (HNC) is a highly prevalent and lethal carcinoma, with major risk factors including smoking, alcohol consumption, and HPV/EBV infection. Although immunotherapy has reshaped the treatment paradigm for HNC, patients with advanced disease still have a poor prognosis. Due to anatomical and functional complexities, patients with HNC often experience impairments in speech, swallowing, and respiration, together with appearance-related distress, resulting in severe psychosocial stress and psychological trauma. Emerging work in cancer neuroscience indicates that peripheral nerves and stress-responsive neuroendocrine pathways shape the tumor microenvironment to regulate tumor growth, angiogenesis, metastasis, immune evasion, and treatment response. Chronic stress drives cancer progression through sustained activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, elevating glucocorticoids and catecholamines that signal through glucocorticoid receptors and adrenergic receptors on tumor, stromal, and immune cells. This review explores the relationship between the nervous system and HNC, focusing on how stress affects cancer development and discussing innovative therapeutic strategies targeting neuroendocrine and neural components to improve HNC outcomes.