Trend dynamics of non-Hodgkin lymphoma and primary ocular adnexal lymphoma incidence in the United States from 1992 to 2021 using age-period-cohort and joinpoint analysis

BACKGROUND: This U.S. population-based study analyzed incidence trends of non-Hodgkin lymphoma (NHL) and its subtype, primary ocular adnexal lymphoma (POAL), from 1992 to 2021, and explored their underlying drivers. METHODS: Data were extracted from the SEER-12 registries. Joinpoint regression identified significant changes in age-standardized incidence rates (ASIR). Age-period-cohort (APC) modeling estimated net drifts, local drifts, age curves, and period/cohort relative risks. Sex-stratified analyses were performed. RESULTS: Both NHL and POAL exhibited a biphasic incidence pattern: an initial increase followed by a decline. NHL incidence peaked in 2009 (ASIR: 28.4 per 100,000, annual percent change: 0.41%, P < 0.001) and subsequently declined to 24.94 per 100,000 by 2021 (annual percent change: -1.04%, P < 0.001). POAL incidence rose until 2003 (ASIR: 0.46 per 100,000, annual percent change: 3.19%, P = 0.01) and then decreased to 0.30 per 100,000 (annual percent change: -2.41%, P < 0.001). APC analysis revealed similar age effects (increased risk with age) for both cancers, but significant divergences in period and cohort effects. Period effects strongly influenced POAL risk, while NHL risk was additionally shaped by birth cohort exposures. Notably, sex disparities were evident in NHL, with higher incidence and distinct cohort effects in males, whereas no significant sex difference was observed in POAL. CONCLUSIONS: Despite similar biphasic incidence trends, NHL and POAL differed in their underlying temporal dynamics: age effects were similar for both diseases, whereas period and cohort effects differed substantially. Sex disparities were present in NHL but not in POAL. These findings highlight the need for subtype-specific approaches in lymphoma epidemiology.