title: Herpes zoster is associated with an increased risk of subsequent lymphoid malignancies - a nationwide population-based matched-control study in Taiwan.
abstract: BACKGROUND
  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. 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  Of 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).
  
  
  CONCLUSIONS
  Preceding 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.
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100, Tzyou 1st Road, Kaohsiung 807, Taiwan.
authors.forename: Yi-Chang
authors.initials: YC
authors.lastname: Liu
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Yang
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Hsiao
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Yang
authors.forename: Ta-Chih
authors.initials: TC
authors.lastname: Liu
authors.forename: Chao-Sung
authors.initials: CS
authors.lastname: Chang
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Yang
authors.forename: Pai-Mei
authors.initials: PM
authors.lastname: Lin
authors.forename: Jui-Feng
authors.initials: JF
authors.lastname: Hsu
authors.forename: Pi-Yu
authors.initials: PY
authors.lastname: Chang
authors.forename: Sheng-Fung
authors.initials: SF
authors.lastname: Lin
mesh_terms: D000328:Adult; D000367:Age Factors; D016022:Case-Control Studies; D005260:Female; D006562:Herpes Zoster / Q000453:epidemiology*; D014645:Herpesvirus 3, Human / Q000302:isolation & purification; D006801:Humans; D008223:Lymphoma / Q000453:epidemiology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk; D013624:Taiwan / Q000453:epidemiology