Changes in sex-specific incidence of lymphoid neoplasms across the lifespan - Letter to the editor

Sep 21, 2026

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This letter to the editor examines why lymphoid neoplasms show male predominance across age groups and quantifies sex-specific incidence patterns over the lifespan. Using SEER-16 population-based cancer registry data for first primary incident lymphoid neoplasms diagnosed from 2001–2017, the analysis estimates male-to-female incidence rate ratios within finely categorized 5-year age bands. Multivariable Poisson regression and joinpoint trend analyses evaluate changes across age, including sensitivity analyses restricted or un-restricted to HIV status.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages6

Reading Time15 min

AccessFree to download

Methods

Data sources and case selection

Statistical analyses

Results

Overall male predominance by subtype

Age-related shifts in male-to-female IRR

Female predominance in selected age groups

LETTER TO THE EDITOR Changes in sex-specific incidence of lymphoid neoplasms across the lifespan While male predominance for most subtypes of lymphoid neoplasms (LN) has been described,1 the underlying reasons for this observation are not well understood. Certain established LN risk factors (e.g., autoimmune diseases, infections, or occupational exposures) differ by sex but generally are rare and thus unlikely to explain the observed sex differences in LN incidence, and previous studies assessing hormonal factors have been inconclusive.2 Notably, however, there is substantial age variation in the prevalence of some lymphoma risk factors (e.g., viral infections), with certain risk factors and immune function known to vary substantially by age and sex.3 To date, the understanding of male predominance across age groups remains limited.3-5 To contribute novel epidemiologic insights, we explore sex-specific incidence rates and maleto-female incidence rate ratios (IRR) according to finely categorized age groups across the lifespan for common and rare LN subtypes by leveraging US population-based cancer registry data. We identified all first primary incident LN diagnosed during 2001-2017 in 16 Surveillance, Epidemiology, and End Results (SEER-16) registry areas. Cases with unknown age (N=21), unknown race and ethnicity (N=4,385), or those diagnosed through autopsy/death certificate only (N=4,775) were excluded. We also excluded human immunodeficiency virus (HIV)-positive cases (N=7,562) because of the known age-and sex-specific incidence patterns of HIV infection, which would potentially obscure other incidence patterns. Analysis was limited to cases diagnosed after the 2001 World Health Organization classification introduction (Online Supplementary Table S1) through 2017, the last available HIV status date. Three registries (Iowa, Hawaii, and Connecticut) lacking HIV data were included, assuming low HIV prevalence as previously described.6,7 We estimated age-adjusted incidence rates by sex and fitted multivariable Poisson regression models to estimate male-to-female IRR and 95% confidence intervals (CI) in each of the 18 5-year age groups (0-4, 5-9,…, and ≥85 years [yrs]) . Age groups with <16 cases for males or females were combined with the next oldest group. Models were adjusted for race and ethnicity, and population size was used as an offset. Using joinpoint models, we estimated the average percent change (APC) in the sex-specific incidence rates and the male-to-female IRR to evaluate the significance of trends across age groups. Additionally, we performed a sensitivity analysis by comparing the IRR from the main analysis (restricted to cases without known HIV) with those based on all cases regardless of HIV status at diagnosis using a Z-score.8 Analyses were performed using SEER*Stat (v [8.4.1.2](8.4.1.2)), Joinpoint (v4.9.0), and R (v4.1.1) . This study is not considered human subjects research and thus did not require review by an Institutional Review Board. We analyzed 492,948 incident LN (273,620 males and 219,328 females) (Table 1) . For all ages combined, males had a significantly higher incidence than females for most subtypes, with >2-fold IRR for hairy cell leukemia, mantle cell lymphoma (MCL), T-cell precursor leukemia/lymphoma (T-ALL), Burkitt leukemia/lymphoma (BL), and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) . In contrast, no male predominance was observed for nodular sclerosis Hodgkin lymphoma (NSCHL); primary mediastinal large B-cell lymphoma (PMBCL); marginal zone lymphoma (MZL), including nodal, extranodal, and splenic MZL; and adult T-cell leukemia/lymphoma. Male-to-female IRR increased considerably with age for lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM; IRR [age group], from 0.81 [0-39 yrs] to 2.47 [≥85 yrs]), T-cell large granular lymphocytic leukemia (LGLL, from 0.76 [0-49 yrs] to 2.83 [≥85 yrs]), and primary cutaneous anaplastic large cell lymphoma (PCALCL,

FAQs

What data and time period were used to assess sex-specific incidence?

The study used SEER-16 population-based cancer registry data for first primary incident lymphoid neoplasms diagnosed from 2001 to 2017.

How were male-to-female incidence rate ratios (IRR) estimated across age?

Age-adjusted incidence rates were modeled by sex using multivariable Poisson regression, estimating male-to-female IRR and 95% confidence intervals in 5-year age groups.

Were HIV-positive cases included, and how was this handled?

HIV-positive cases were excluded in the main analysis to avoid obscuring other patterns, and a sensitivity analysis compared IRR including all cases regardless of HIV status using a Z-score.

Sep 21, 2026

Upload by Rowan