Epstein-Barr virus-associated Hodgkin's disease: Epidemiologic characteristics in international data

Abstract

Hodgkin's disease (HD) has long been suspected to have an infectious precursor, and indirect evidence has implicated Epstein-Barr virus (EBV), a ubiquitous herpesvirus, as a causal agent. Recent molecular studies using EBER in situ hybridization or latency membrane protein-1 (LMP-1) immunohistochemistry have identified EBV latent infection in up to 50% of HD tumors. However, the epidemiologic features of these cases have not been examined in detail. To explore the epidemiology of EBV-positive HD so as to understand the role of EBV in HD etiology more clearly, this project accumulated patient data from 14 studies that had applied these EBV assays to HD tumors. With information on age at diagnosis, sex, ethnicity, histologic subtype, country of residence, clinical stage and EBV tumor status from 1,546 HD patients, we examined risk for EBV-positive disease using logistic regression. Forty percent of subjects had EBV-positive tumors, and EBV prevalence varied significantly across groups defined by the study variables. Odds ratios (OR) for EBV-associated HD were significantly elevated for Hispanics vs. whites (OR 5 4.1), mixed cellularity vs. nodular sclerosis histologic subtypes (OR 5 7.3, 13.4, 4.9 for ages 0-14, 15-49, 501 years), children from economically less-developed vs. more-developed regions and young adult males vs. females (OR 5 2.5). These findings suggest that age, sex, ethnicity and the physiologic effects of poverty may represent biologic modifiers of the EBV association and confirm that this association is strongly but variably linked to histologic subtype. The data augment biologic evidence that EBV is actively involved in HD pathogenesis in some cases but describe epidemiologic complexity in this process. Int.

Cancer incidence patterns by region and socioeconomic deprivation in teenagers and young adults in England

“…HL in early childhood is related to Epstein Barr virus (EBV) infections, but in TYAs the predominant subtype is nodular sclerosis, which is associated with a much lower incidence of EBV inclusion within the tumour (Jarrett et al, 1996). HL in older childhood has been related to delayed exposure to infection arising from improved socioeconomic conditions (Glaser et al, 1997). Law et al (2003) found marginal evidence for higher NHL incidence in under-15 year olds in less deprived areas in England and Wales, but was not found here.…”

Molecular Diagnosis of Epstein-Barr Virus-Related Diseases

“…27 Nearly half of all classical Hodgkin's disease and T cell lymphomas have EBER-positive tumor cells, whereas only 5% of diffuse large B cell or anaplastic large cell lymphomas express EBER. 4,5,28 Certain subsets of these lymphomas are more likely than others to harbor EBV, such as nasal T/NK lymphoma ( Table 2). In classes of tumors that are only fractionally associated with EBV, further investigation of the prognostic value of EBV testing is warranted.…”

“…Nasopharyngeal carcinomas and posttransplant lymphoproliferative disorders are nearly always EBV-associated, whereas several other tumors, such as Hodgkin's disease, nonHodgkin's lymphoma, lymphoepithelioma-like carcinoma, gastric adenocarcinoma, and several types of sarcoma, are less uniformly EBV-associated. [2][3][4][5][6][7] EBV causes benign transient lymphoproliferative lesions at the time of primary infection, and it is found in a benign lesion of the tongue called oral hairy leukoplakia. 8,9 Patients affected by these benign or malignant diseases may benefit from laboratory detection of EBV to confirm their diagnosis or to monitor disease burden after the initiation of therapy.…”

Exposure to childhood infections and risk of Epstein‐Barr virus–defined Hodgkin's lymphoma in women

“…38 (ii) Differences in gender composition among studies may be relevant. Although primary infection with EBV affects males and females similarly, 39 women are less likely than men to develop EBV-positive HL [8][9][10] and other EBV-related cancers, possibly due to heightened immunologic sensitivity following the transient reactivation of latent EBV in pregnancy. 30,40,41 If such a mechanism impacts control of other etiologically relevant infections, risk patterns could differ between our data and data from populations including males.…”

“…7 Nevertheless, the role of EBV in HL etiology remains unresolved as present methods detect evidence of EBV in the tumor cells of only a proportion of HL patients, and this evidence is least common in young adults, for whom the epidemiologic support for a viral association is strongest. [8][9][10] Yet, only a few studies have attempted to reconcile the patterns of EBV tumor-cell presence with factors suggestive of viral etiology, such as childhood social class or infection history. One case series analysis found no association of EBV-defined HL with several childhood social class characteristics, 11 while another identified neighborhood poverty as a risk factor but only in women.…”