Abstract B027: Early-Onset Head and Neck Cancer: Implications for Risk Stratification and Survival

Introduction: Head and neck cancers (HNC) represent nearly 4% of all cancers in the U.S., with established risk factors including tobacco, alcohol, and human papillomavirus (HPV) infection. While the mean age at diagnosis is 64 years, ∼20% of cases occur in adults <55, and 4–6% in those <40. Reports suggest rising incidence of early-onset HNC. A subset of younger patients without previously established risk factors indicates alternative etiologies. We aimed to describe demographic determinants of early-onset HNC and evaluate survival differences by age of onset. Methods: We analyzed data from the National Cancer Database (NCDB) from 2004–2022, including adults with HNC diagnosis codes (n=816,747). The NCDB is a clinical registry with data abstracted from patient records at Commission on Cancer–accredited facilities. Multivariable logistic regression estimated adjusted odds ratios (aORs) for early-onset HNC (<50 years) vs. traditional onset (≥50 years), adjusting for sex, race, ethnicity, Great Circle distance, Charlson-Deyo comorbidity (CDCC) score, and HPV-tumor status. Distance was analyzed in quartiles. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) by age of onset, adjusting for the same variables plus tumor stage. Results: In adjusted models, several demographics were significantly associated with early-onset HNC. Males were linked to slightly lower odds than females (aOR: 0.92, 95% CI: 0.86–0.99). White adults had reduced odds compared to Black adults (aOR: 0.52, 95% CI: 0.48–0.57), as did Non-Hispanic vs. Hispanic adults (aOR: 0.56, 95% CI: 0.51–0.63). Greater distance from reporting facility showed a dose-response association, with higher quartiles linked to increased odds (Quartile 4 vs. 1 aOR: 1.25, 95% CI: 1.15–1.35). Higher comorbidity burden was associated with lower odds (CDCC 1 aOR: 0.54, 95% CI: 0.49–0.59; CDCC 2 aOR: 0.28, 95% CI: 0.23–0.34; CDCC 3 aOR: 0.29, 95% CI: 0.23–0.35). HPV-positive tumors were more common in early-onset cases (aOR: 1.25, 95% CI: 1.17–1.33). In survival analyses, adults aged 40–49 had improved survival vs. those ≥50 (aHR: 0.89, 95% CI: 0.82–0.97), while survival among those 18–39 was similar (aHR: 0.96, 95% CI: 0.78–1.19). Male sex (aHR: 0.95, 95% CI: 0.91–0.99) and White race (aHR: 0.94, 95% CI: 0.89–0.99) were associated with modest survival benefits. Increasing comorbidity burden was linked to worse survival (CDCC 1 vs. 0 aHR: 1.09, 95% CI: 1.04–1.14; CDCC 2 vs. 0 aHR: 1.19, 95% CI: 1.11–1.27; CDCC 3 vs. 0 aHR: 1.24, 95% CI: 1.16–1.33), as was advanced stage. HPV-positive tumors were associated with improved survival (aHR: 0.87, 95% CI: 0.84–0.91). Conclusions: These findings underscore the need to investigate non-traditional risk factors and biological mechanisms underlying early-onset HNC, especially in subgroups not explained by conventional exposures. Citation Format: Morgan C. Byrd, Joab O. Odera, Trisha Kibugi, Rong Jiang, Tammara Watts, Nosayaba Osazuwa-Peters. Early-Onset Head and Neck Cancer: Implications for Risk Stratification and Survival [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr B027.