Adult T-Cell Leukemia/Lymphoma and Targeted Maternal Screening.
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IMPORTANCE: Adult T-cell leukemia/lymphoma (ATLL) is a rare but highly aggressive malignant disease caused by lifelong infection with human T-cell leukemia virus type 1 (HTLV-1), typically acquired through mother-to-child transmission. In southwestern Japan, the world's highly documented HTLV-1 endemic region, maternal HTLV-1 screening and breastfeeding counseling have reduced vertical transmission. Because of the long latency between infection and disease, reductions in ATLL burden are expected to occur over time. In the US, HTLV-1 screening is limited to blood donors, while mother-to-child transmission remains unaddressed, despite growing immigrant populations from HTLV-1-endemic regions. OBJECTIVE: To estimate ATLL incidence in the US by race, ethnicity, and birthplace, and to assess whether incidence in specific populations approaches levels observed in historically endemic regions with established maternal HTLV-1 screening programs. DESIGN, SETTING, AND PARTICIPANTS: A population-based incidence and survival analysis was performed using cancer registries from all 50 US states. Individuals 15 years or older diagnosed with ATLL between 2005 and 2022 were included. Data analysis was conducted from December 2024 to November 2025. EXPOSURES: Race, ethnicity, and country of birth, with focused analyses of non-Hispanic Caribbean-born US residents originating from HTLV-1-endemic regions, were examined. MAIN OUTCOMES AND MEASURES: The main outcomes were age-adjusted incidence rates, incidence rate ratios, temporal trends, sensitivity analyses accounting for misclassification with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), and cause-specific survival. RESULTS: A total of 3228 individuals with ATLL were identified. Among these individuals diagnosed with ATLL between 2005 and 2022, 1662 (51.5%) were male and 1566 (48.5%) were female, with a mean (SD) age at diagnosis of 61.1 (17.3) years, estimated from 5-year age group data. A total of 126 (3.9%) were non-Hispanic Asian or Pacific Islander, 1300 (40.3%) were non-Hispanic Black, 364 (11.3%) were Hispanic, 1394 (43.2%) were non-Hispanic White, and 44 (1.4%) were another race (including American Indian or Alaska Native, other or multiple race, and unknown race). Incidence varied by birthplace. Among non-Hispanic Caribbean-born US residents, the ATLL incidence rate was 14.1 per million, compared with 0.4 per million among US- or Canada-born populations (incidence rate ratio [IRR], 32.0; 95% CI, 27.9-36.8). Rates reached 33.7 per million among individuals born in Grenada. Sensitivity analyses redistributing excess PTCL-NOS incidence under a misclassification framework increased ATLL incidence among Caribbean-born populations to levels approaching or exceeding those reported in HTLV-1 endemic regions. Five-year survival was poor (23.8%; 95% CI, 21.1%-26.5%) and lowest among Caribbean-born individuals. CONCLUSIONS AND RELEVANCE: This cross-sectional analysis found that ATLL incidence among non-Hispanic Caribbean-born US residents approached that of historically endemic regions. Since 2000, more than 300 000 births to Caribbean-born mothers have occurred in Florida alone, underscoring the scale of unaddressed early-life HTLV-1 exposure in the absence of maternal screening. These findings identify early-life infection as an actionable target for cancer prevention, with implications for reducing future ATLL burden.