Search

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 EBV-ve HL, when compared with children infected at older ages; the interpretation of these latter results is unclear.

The epidemiology of young adult Hodgkin lymphoma (HL) suggests that delayed exposure to a common childhood pathogen may be involved in disease pathogenesis. The Epstein-Barr virus (EBV) is associated with a proportion of cases but cases of young adult HL in westernized countries are less frequently EBV-associated than cases in other age groups and geographical locales. This study investigated the possibility that polyomaviruses might be involved in the etiology of HL by analysing a series of 35 cases of classical HL using both specific and degenerate PCR assays for polyomavirus genomes. No positive results were obtained, indicating that it is highly unlikely that this virus family is directly involved in the pathogenesis of HL.

The association between tumor Epstein-Barr virus (EBV) status and clinical outcome in Hodgkin lymphoma (HL) is controversial. This population-based study assessed the impact of EBV status on survival in age-stratified cohorts of adults with classic HL (cHL). Data from 437 cases were analyzed with a median follow-up of 93 months. Overall survival (OS) was significantly better for EBV-negative compared with EBV-positive patients (P < .001), with 5-year survival rates of 81% and 66%, respectively; disease-specific survival (DSS) was also greater for EBV-negative patients (P = .03). The impact of EBV status varied with age at diagnosis. In patients aged 16 to 34 years, EBV-associated cases had a survival advantage compared with EBV-negative cases, but differences were not statistically significant (P = .21). Among patients 50 years or older, EBV positivity was associated with a significantly poorer outcome (P = .003). Excess deaths occurred in EBV-positive patients with both early- and advanced-stage disease. In multivariate analysis of OS in the older patients, EBV status retained statistical significance after adjusting for the effects of sex, stage, and B symptoms (P = .01). Impaired immune status may contribute to the development of EBV-positive cHL in older patients, and strategies aimed at boosting the immune response should be investigated in the treatment of these patients. (Blood. 2005;106:2444-2451)

Aims: The epidemiological and pathological features of Hodgkin lymphoma (HL) are complex. The Epstein-Barr virus (EBV) is consistently associated with a proportion of cases, and these cases are thought to represent a distinct aetiological subgroup of HL. The aim of the present analysis was to determine the age and sex specific incidence of EBV associated and non-associated HL, analysed separately, using data derived from a population based study–the Scotland and Newcastle epidemiological study of Hodgkin’s disease (SNEHD). This study also provided a unique opportunity to evaluate accuracy in the current diagnosis and classification of HL. Methods: SNEHD analysed consecutive cases of HL diagnosed in the study area between 1993 and 1997. Diagnostic biopsy material was retrieved, EBV status of tumours was determined, and histological review was performed. Results: In total, 622 cases were eligible for the study, and EBV studies and histopathological review were performed on biopsy material from 537 and 549 cases, respectively. Accuracy in the overall diagnosis of HL and classification of nodular sclerosis HL was good, but diagnosis of HL in the elderly and classification of other subtypes was less reliable. One third of classic HL cases were EBV associated, and age specific incidence curves for EBV associated and non-associated cases were distinct. Conclusions: Comparison of age specific incidence curves for EBV associated and non-associated HL supports the hypothesis that these are two distinct aetiological entities. Accuracy in the diagnosis of HL is generally good, but certain subgroups of cases continue to present diagnostic difficulties.

An epidemiologic study of index and family infectious mononucleosis and adult Hodgkin's disease (HD): Evidence for a specific association with EBV+ve HD in young adults. Infectious mononucleosis (IM) is an established risk factor for Hodgkin's disease (HD). A substantial minority (33%) of cases of HD have. Epstein-Barr virus (EBV) DNA within the malignant cells (are EBV+ve). It is unclear whether risk after IM applies specifically to EBV+ve HD. We report the results of a population-based case-control study of HD in adults (n = 408 cases of classical H D, 513 controls) aged 16-74 years; the case series included 113 EBV+ve and 243 EBV-ve HD. Analyses compared total HD, EBV+ve HD and EBV-ve HD with the controls and EBV+ve HD with EBV-ve HD cases using, mainly, logistic regression. Regression analyses were adjusted for gender, age-group and socioeconomic status, and were per formed for the whole age range and separately for young (< 35 years) and old adults ( greater than or equal to 35 years); formal tests of effect modification by age were included. For the young adults, reported 1M in index or relative was strongly and significantly associated with EBV+ve HD when compared to controls (odds ratio [OR] = 2.94, 95% confidence interval [Cl]: 1.08-7.98 and OR = 5.22, 95% Cl: 2.15-12.68, respectively). These results may be interpreted as indications that late first exposure to EBV increases risk of HD, especially in young adults; this applies primarily to EBV+ve HD. (C) 2003 Wiley-Liss, Inc.

As has been previously highlighted by leading researchers, progress is being made in understanding biological responses to engineered nanomaterial (ENM), however, we do not yet understand the full consequences of occupational exposure, to these substances, or the resulting health risks fully enough, to develop science-based health and safety risk assessment guidelines which would support regulatory decision. To address this, national and international efforts have been made to provide guidance using new and existing regulations to support research and development to limit and prevent worker exposure and these are based on our current knowledge of toxicology data. Improving our understanding of ENM toxicity is crucial for informing the responsible development of nanotechnology and fully implementing risk control measures. In particular, research workers face unknown risks from exposure to new and innovative ENMs in occupational settings and as such are not fully informed of the risk. This chapter looks at the global concerted efforts and subsequent guidance and policies currently being produced to control occupational exposure and prevent potential ill health on a national and international level.

A UK population-based case–control study of Hodgkin's disease (HD) in young adults (16–24 years) included 118 cases and 237 controls matched on year of birth, gender and county of residence. The majority (103) of the cases were classified by Epstein–Barr virus (EBV) status (EBV present in Reed–Stenberg cells), with 19 being EBV-positive. Analyses using conditional logistic regression are presented of subject reports of prior infectious disease (infectious mononucleosis (IM), chicken pox, measles, mumps, pertussis and rubella). In these analyses HD cases are compared with matched controls, EBV-positive cases and EBV-negative cases are compared separately with their controls and formal tests of differences of association by EBV status are applied. A prior history of IM was positively associated with HD (odds ratio (OR) = 2.43, 95% confidence interval (CI) = 1.10–5.33) and with EBV-positive HD (OR = 9.16, 95% CI = 1.07–78.31) and the difference between EBV-positive and EBV-negative HD was statistically significant (P = 0.013). The remaining infectious illnesses (combined) were negatively associated with HD, EBV-positive HD and EBV-negative HD (in the total series, for ≥2 episodes compared with ≤1, OR = 0.45, 95% CI = 0.25–0.83). These results support previous evidence that early exposure to infection protects against HD and that IM increases subsequent risk; the comparisons of EBV-positive and EBV-negative HD are new and generate hypotheses for further study. © 2000 Cancer ResearchCampaign

Summary An accumulating body of data suggests that the Epstein–Barr virus (EBV), a lymphotropic herpesvirus, is involved in the pathogenesis of a proportion of cases of Hodgkin lymphoma (HL). In this study, we showed that the frequency of circulating EBV-infected cells was significantly higher (P

The Epstein-Barr virus (EBV) is associated with a proportion of Hodgkin lymphoma (HL) cases, and this association is believed to be causal. The aetiology of cases lacking EBV in the tumour cells (EBV HRS-ve), which make up the majority of cases in western countries, is obscure. It has been suggested that EBV may also cause these tumours by using a hit-and-run mechanism. Support for this idea comes from the finding that most young adult patients, who are likely to have a good immune response to EBV, have EBV HRS-ve HL. We investigated this possibility using a combined serologic and molecular approach. Analysis of EBV seroprevalence rates in an epidemiologic study of young adult HL revealed that cases with EBV HRS-ve HL were more likely to be EBV-seronegative than controls. Furthermore, additional studies clearly showed that some HL patients have never been infected by EBV. Quantitative PCR was used to look for the presence of deleted EBV genomes in a series of adult cases with both EBV HRS+ve and HRS-ve HL. Subgenomic fragments were detected in equimolar proportions. This study, therefore, found no evidence to support the idea that a hit-and-run mechanism involving EBV plays a role in the pathogenesis of HL.

The Epstein-Barr virus (EBV) is associated with a proportion of cases of Hodgkin disease (HD) and this association is believed to be causal. Epidemiological studies suggest that an infectious agent is involved in the aetiology of young adult HD, however, cases in this age group are less likely to have EBV-associated disease than cases diagnosed in early childhood or older adult years. Molecular studies have failed to find a consistent association between HD and other candidate viruses, and the aetiology of non-EBV-associated cases remains obscure. We looked for evidence of herpesvirus infection in samples of non-EBV-associated HD using a highly sensitive, degenerate PCR assay. Despite exhaustive sequence analysis of PCR products, no novel herpesviruses were identified. These results suggest that it is extremely unlikely that a novel herpesvirus is involved in the pathogenesis of non-EBV-associated HD.