OBJECTIVE: To quantify associations between pretreatment patient-reported health-related quality of life (HRQoL) domains and overall survival in head and neck cancer. DATA SOURCES: PubMed, Embase, and Web of Science were searched from inception through July 27, 2026. REVIEW METHODS: Longitudinal studies evaluating validated patient-reported HRQoL as a prognostic exposure were included. Adjusted hazard ratios (HRs) for overall survival were harmonized to a 10-point worsening and pooled by domain using restricted maximum-likelihood random-effects models. Risk of bias, multiplicity, leave-one-out stability, cohort overlap, residual-confounding sensitivity, and reporting completeness were evaluated. RESULTS: Thirty-two independent studies in 40 publications were included; 43 estimates contributed to meta-analyses of 10 domains. Worse Global QoL (HR, 1.11; 95% CI, 1.08-1.14), physical functioning (1.16; 1.13-1.20), role functioning (1.09; 1.07-1.11), and social functioning (1.09; 1.06-1.12) were consistently associated with higher mortality and remained leave-one-out stable. Swallowing was associated with mortality (1.15; 1.02-1.29) but was sensitive to one study. Dyspnea was associated with higher mortality in the primary analysis (4 studies; HR, 1.16; 95% CI, 1.01-1.33), but the estimate was heterogeneous and unstable. CONCLUSION: Pretreatment HRQoL provides multidimensional prognostic information, with Global QoL and physical, role, emotional, and social functioning showing the most consistent evidence. These domains may help prioritize pretreatment supportive-care assessment, whereas sensitivity-limited or very-low-certainty findings require further confirmation and should not be interpreted as actionable treatment targets. LEVEL OF EVIDENCE: N/A. TRIAL REGISTRATION: PROSPERO number: CRD420261461389.
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