Stress, inflammation, and resilience among patients with oral squamous cell carcinoma undergoing multimodal therapy: Current knowledge and future directions

Oral squamous cell carcinoma represents a significant public health challenge in Asia, where multimodal therapies, while extending survival, impose substantial biologic and psychosocial stress. Sustained activation of the sympathetic-adrenal-medullary axis and dysregulation of the hypothalamic-pituitary-adrenal axis increase catecholamines, cortisol, interleukin-6, and C-reactive protein, accelerating tumor progression, impairing treatment tolerance, and increasing cardiovascular risk. Betel quid chewing, prevalent in the region, exacerbates inflammation and contributes to cardiovascular comorbidities. Resilience, defined as the ability to restore physiologic and emotional homeostasis, modulates these pathways, with higher resilience linked to improved recovery, quality of life, and survival. Current evidence supports interventions including structured psychoeducation, cognitive-behavioral therapy, and peer mentoring to reduce anxiety and enhance treatment adherence. Smoking and betel quid cessation, alongside cardiometabolic optimization, mitigate inflammatory burden. Nonopioid strategies, including acupuncture, transcutaneous vagus nerve stimulation, and mindfulness, recalibrate neuro-immune signaling while minimizing opioid reliance. Enhanced recovery surgical protocols and omega-3 supplementation attenuate inflammatory responses and preserve lean mass. Emerging biomarkers such as heart rate variability and neutrophil-lymphocyte ratio show promise for real-time stress and inflammation monitoring. Digital health technologies and telerehabilitation extend intervention benefits postdischarge. Future research should focus on validating predictive biomarkers, developing resilience-stratified trials, integrating cardio-oncology surveillance, and implementing precision supportive care models that incorporate stress, inflammation, and resilience metrics to optimize oncologic and cardiovascular outcomes in this high-risk population.