Herpes Zoster Is Associated with An Increased Risk of Subsequent Lymphoid Malignancies — A Population-Based Matched-Control Study in Taiwan
Authors: Liu Yi-Chang , Yang Yi-Hsin , Hsiao Hui-Hua , Yang Ming-Yu , Yang Wen-Chi , Lin Sheng-Fung 
Published: October 2019

Abstract
Abstract 1599
Infectious agents have been shown to contribute to the development of certain lymphoid malignancies. The different distribution of lymphoid malignancies in Asian and Western populations suggests possibly different etiologies in lymphomagenesis in Asian populations. Herpes zoster infection, commonly seen in immunocompromised persons, has been reported to be associated with lymphoid malignancies, but the results are controversial and large-scale studies from Asian populations are lacking. In this study we performed a population-based matched-controlled prospective study on Taiwanese patients using the National Health Insurance Research Database which provided 1,000,000 random subjects from 1996 to 2007. We defined herpes zoster by compatible ICD-9-CM (International Classification of Disease, 9th Revision, Clinical Modification) codes of herpes zoster (053.0–053.9) on at least one service claim for inpatient or outpatient care. The cases were identified by compatible ICD-9-CM codes including Hodgkin's disease (code 201.0–201.9), non-Hodgkin's lymphoma (code 200.0–200.8, 202.0–202.9), multiple myeloma (code 203.0–203.1), and lymphoid leukemia (code 204.0–204.9). Patients who had been diagnosed with any lymphoid malignancies or any cancers (code 140.0–199.1) before herpes zoster, and who had been diagnosed with other viral infections (code 045.0–052.9, 054.0–066.9, 071–079.9) and HIV infection (code 042) before the diagnosis of lymphoid malignancies were excluded. We randomly selected 169,983 control subjects (4 for every herpes zoster patient), matched with the study group in terms of age, sex and the year and month of index visit. Of 42,498 patients with herpes zoster prior to the diagnosis of any malignancies, the mean age was 48.92 years (± 20.67 years), with a mild female predominance (52.4%). Patients with herpes zoster infection had a lower monthly income (p < 0.001), and tended to live in urban areas (p < 0.001). Among the patients with herpes zoster, 2.42% subsequently developed cancer, and 0.11% lymphoid malignancy. Among the controls, 2.26% of the patients subsequently developed cancer, and 0.06% lymphoid malignancy. Patients with herpes zoster had a significantly increased risk of developing any cancers (excluding lymphoid malignancies, crude HR: 1.07, 95% CI: 1.01–1.15), and lymphoid malignancies (crude HR: 1.82, 95% CI: 1.29–2.55) compared with the control group. After adjusting for Charlson disease index, income category, and residence using Cox proportional hazard regressions, patients with herpes zoster had an increased risk of developing lymphoid malignancies (adjusted HR: 1.72, 95% CI: 1.22–2.42, p = 0.0019), but did not have an increased risk of developing non-lymphoid malignancies (adjusted HR: 1.00, 95% CI: 0.93–1.07, p = 0.895). These data suggest that preceding herpes zoster infection is an independent risk factor for the subsequent development of lymphoid malignancies in Taiwanese subjects. Further studies are warranted to explore the role of herpes zoster in the pathogenesis.

Disclosures:
No relevant conflicts of interest to declare.