Clinical predictors and disparities in second primary malignancy risk and survival after index head and neck cancer: A SEER population analysis.

Abstract

e18090 Background: Survivors of head and neck squamous cell carcinoma (HNSCC) carry a substantial lifelong risk of developing second primary malignancies (SPMs) driven by carcinogenic exposures, field cancerization, treatment effects, and underlying behavioral or environmental factors. Previous studies suggest sociodemographic disparities in cancer outcomes; however, population-level analyses evaluating disparities in SPM survival among HNSCC survivors remain limited. Methods: We conducted a retrospective cohort study of adults (≥18 years) diagnosed with first-primary HNSCC from 2000–2015 to allow for follow-up through at least 2020 using SEER. Exclusions included autopsy-only diagnoses, synchronous tumors, and third-or-greater primaries. Key variables included sociodemographic indicators, primary cancer characteristics, and survival outcomes. Kaplan–Meier survival curves assessed racial/ethnic differences in overall survival (OS), cancer-specific survival (CSS), SPM-specific survival, and other-cause mortality. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) for SPM-specific death. Results: Among 28,608 HNSCC survivors, SPMs exhibited substantial variation in SPM histology, with squamous cell neoplasms (39.7%), adenocarcinomas (29.8%), epithelial neoplasms (8.0%), and melanomas (4.2%) representing major categories. Patients developing SPMs were older, with a median age shifting toward 65–84 years. Treatment patterns differed between primary and secondary cancers as SPM patients were less likely to receive chemotherapy (24.8% vs. 37.1%) or radiation (27.9% vs. 66.8%). The Black race was independently associated with higher SPM-specific mortality (aHR 1.41; 95% CI 1.35–1.48; p < 0.001). Non-White/Other race also conferred elevated risk (aHR 1.28; 95% CI 1.13–1.46). Patients residing in low-income counties (<$50,000 median household income) had 37% higher adjusted mortality risk from SPMs compared to the highest-income regions (p < 0.001). Non-metropolitan residence remained an independent predictor of mortality (aHR 1.07; p = 0.004). Increasing age at SPM diagnosis strongly predicted worse outcomes, with a stepwise rise in mortality from ages 45–54 through 85+ (aHRs 1.33–3.61; all p < 0.001). Conclusions: SPMs affected nearly 30% of HNSCC survivors, underscoring SPMs as a major late driver of mortality. Black survivors, residents of low-income counties, and non-metropolitan populations experienced significantly worse SPM-specific survival independent of tumor and treatment factors. The parallel excess in both cancer-specific and non-cancer mortality among Black survivors highlights the contribution of structural and health-system inequities beyond tumor biology alone. These support a shift towards risk-adapted survivorship care and targeted early detection strategies.