Measles virus and classical Hodgkin lymphoma: No evidence for a direct association

Abstract

A proportion of Hodgkin lymphoma (HL) cases are causally associated with the Epstein-Barr virus (EBV) but the aetiology of the remaining cases remains obscure. Over the last 3 decades several studies have found an association between HL and measles virus (MV) including a recent cohort study describing the detection of MV antigens in Hodgkin and Reed-Sternberg cells, the tumour cells in HL. In the present study we looked at the relationship between history of MV infection and risk of developing HL in a population-based, case/control study of HL. In addition we used immunohistochemistry and RT-PCR to look for direct evidence of MV in HL biopsies. There was no significant difference in the proportion of cases reporting previous measles compared to controls in the entire data set or when young adults were considered separately. Using a robust immunohistochemical assay for MV infection, we failed to find evidence of MV in biopsies from 97 cases of HL and RT-PCR studies similarly gave negative results. This study therefore provides no evidence that MV is directly involved in the development of HL. However, when age at first reported MV infection was investigated, significant differences emerged with children infected before school-age having higher risk, especially of EBV2ve HL, when compared with children infected at older ages; the interpretation of these latter results is unclear. ' 2007 Wiley-Liss, Inc.Key words: Hodgkin lymphoma; measles virus; PCR; epidemiology The term Hodgkin lymphoma (HL) encompasses 2 entities, nodular lymphocyte predominant HL and classical HL (cHL), which are now recognised as distinct disease processes.1 The pathology and epidemiology of cHL, which accounts for almost 95% of cases, also suggest that this is a heterogeneous entity that is likely to have more than one aetiology.2 Histologically, cHL is divided into 4 subtypes on the basis of the appearance of the rare tumour cells, the Hodgkin and Reed-Sternberg (HRS) cells, and the composition of the more plentiful background infiltrate.3 The most common subtypes are nodular sclerosis (NSHL) and mixed cellularity (MCHL).3 cHL generally shows a bimodal age-specific incidence curve but there is marked geographical variation in the shape of the curve and the age at which the incidence peaks occur. 4,5 It is the most common lymphoma in young adults in the Western world and the most common childhood malignancy in some developing countries.6,7 Epstein-Barr virus (EBV) is present in the HRS cells in a proportion of cHL cases and is believed to contribute to disease causation.8 EBV-associated cases (EBV1ve cHL) are not evenly distributed across all patient subgroups; cases of the MCHL subtype are more likely to be EBV-associated than NSHL cases, as are cases diagnosed in early childhood (<10 years) and older adulthood (>50 years).2 Consistent with this, a higher proportion of cases in developing countries are EBV-associated compared to developed countries, in which around 33% of cHL cases are EBV-positive. 9,10An increased risk of developing young...

A protective role for early oral exposures in the etiology of young adult Hodgkin lymphoma

“…31 Extensive studies based on serology or viral load have not yet identified an association between any specific known infectious agent and EBV-negative YAHL. [11][12][13][14][15][16] Although our study could not rule out a protective advantage after specific childhood exanthemata or other infections, risk was strongly reduced in the member of the twin pair who had more behaviors associated with oral-oral or fecal-oral exposure. Behaviors that increase oral exposures are risk factors for all infections transmitted by the fecal-oral or oral-oral route including but not limited to hepatitis A, Helicobacter pylori, Salmonella, and herpes simplex type 1.…”

“…8 However, extensive searches have yet to identify a viral agent that could account for the majority of YAHL. [11][12][13][14][15][16] Epstein-Barr virus is etiologically linked only to that small proportion of YAHL with EBV evident in the malignant cells. 4,10 An alternative hypothesis was first offered to explain the recent increase in the prevalence of atopic disease.…”

Interleukin-2, interleukin-12, and interferon-γ levels and risk of young adult Hodgkin lymphoma

“…[29][30][31][32] An alternative explanation for the YAHL risk pattern (which is similar to that for atopy) is that relative social isolation in early childhood results in a deficit of generic microbial signals (ie, endotoxin) necessary for the normal maturation of the immune response ("hygiene hypothesis"). 33 In the gut lymphoid tissue, these microbial signals are thought to bind to toll-like receptors resulting in secretion of IL-12, which in turn induces the differentiation of Th1 lymphocytes necessary to mount cellmediated, cytotoxic responses.…”

Epidemiology of Lymphoid Malignancy in Asia

“…Also detection of EBV in HL in most Asian countries are less in young adults and are more detectable in children and older ages. Because of these differences infectious cofactors other than EBV have been suggested, but no consensus in support of any other particular association have emerge (Wilson, et al, 2007). …”