Abstract

BackgroundInfectious agents have been shown to contribute to the development of lymphoid malignancies. The different distribution of lymphoid malignancies in Asian and Western populations suggests possibly different etiologies in Asian populations. Herpes zoster infection, commonly seen in immunocompromised persons, has been reported to be associated with lymphoid malignancies in retrospective case–control studies from Western populations, but the results are controversial and large-scale prospective studies from Asian populations are lacking.MethodsA nationwide population-based matched-controlled prospective study on Taiwanese patients was performed using the National Health Insurance Research Database from 1996 to 2007. Herpes zoster and malignancies were defined by compatible ICD-9-CM (International Classification of Disease, 9th Revision, Clinical Modification) codes. Patients who had been diagnosed with any malignancies before herpes zoster, with known viral infections including human immunodeficiency virus, and duration from herpes zoster to diagnosis of malignancies less than 6 months were excluded.ResultsOf 42,498 patients with herpes zoster prior to the diagnosis of any malignancies, the cumulative incidence for lymphoid malignancies was 0.11% (n = 48), compared with 0.06% (n = 106) in 169,983 age- and gender-matched controls (univariate hazard ratio (HR): 1.82, 95%CI: 1.29-2.55). The most common lymphoid malignancy was non-Hodgkin’s lymphoma (60.4%, n = 29), followed by multiple myeloma (27.1%, n = 13). Risk for developing lymphoid malignancies is significantly higher in herpes zoster patients (log rank P = 0.005). After adjusting for presence of any comorbidities in Charlson comorbidity index, time-dependent covariate for herpes group, and income category using Cox proportional hazard regressions, herpes zoster patients had an increased risk of developing lymphoid malignancies (adjusted HR: 1.68, 95%CI: 1.35-2.42, P = 0.0026), but did not have an increased risk of developing non-lymphoid malignancies (adjusted HR: 1.00, 95%CI: 0.91-1.05, P = 0.872).ConclusionPreceding herpes zoster infection is an independent risk marker for subsequent lymphoid malignancies in Taiwanese subjects. Further studies are warranted for pathogenesis exploration and preventive strategies in Asian populations.

Highlights

  • Infectious agents have been shown to contribute to the development of lymphoid malignancies

  • Some viral infections have been found to be associated with the development of certain lymphoid malignancies, such as Epstein-Barr virus (EBV) and Burkitt’s lymphoma, extranodal NK/T cell lymphoma, human T-cell leukemia virus type 1 (HTLV-1) and adult T cell leukemia/lymphoma, human herpes virus-8 (HHV-8) and primary effusion lymphoma, and hepatitis C virus (HCV) and some B cell lymphomas [4,5,6,7]

  • Because the National Health Insurance Research Database (NHIRD) database provided by the official National Health Insurance (NHI) program consists of totally de-identified, encrypted, secondary data released to the public for research purposes without personal or institutional identification or contact with the study patients, the study was exempt from full review by the institutional review board (IRB) of Kaohsiung Medical University

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Summary

Introduction

Infectious agents have been shown to contribute to the development of lymphoid malignancies. The different distribution of lymphoid malignancies in Asian and Western populations suggests possibly different etiologies in Asian populations. Commonly seen in immunocompromised persons, has been reported to be associated with lymphoid malignancies in retrospective case–control studies from Western populations, but the results are controversial and large-scale prospective studies from Asian populations are lacking. Some host factors, including inherited genetic factors, infections, autoimmune diseases, and environmental or medication exposure have been found to be associated with the development of lymphoid malignancies [4]. Some viral infections have been found to be associated with the development of certain lymphoid malignancies, such as Epstein-Barr virus (EBV) and Burkitt’s lymphoma, extranodal NK/T cell lymphoma, human T-cell leukemia virus type 1 (HTLV-1) and adult T cell leukemia/lymphoma, human herpes virus-8 (HHV-8) and primary effusion lymphoma, and hepatitis C virus (HCV) and some B cell lymphomas [4,5,6,7]. The association between herpes zoster and subsequent lymphoid malignancies is still unclear

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