The association between tumor EpsteinBarr 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 EBVnegative compared with EBV-positive patients (P < .001), with 5-year survival rates of 81% and 66%, respectively; diseasespecific 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 ‫؍‬ .

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

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 ؉veAbundant epidemiologic evidence supports the hypothesis that Hodgkin's disease (HD) aetiology differs for cases diagnosed in the young adult peak and diagnosed in older people (aged Ն 50). 1 Under the late host-response model, 2 HD in the young adult peak arises as a sequel to relatively late first infection with a common infectious agent-a similar pattern to that seen for infectious mononucleosis (IM) in relation to the Epstein-Barr virus (EBV). Large cohort studies 3,4 have demonstrated that HD risk is increased around 3-fold in the followup of subjects with IM compared to the general population. This could indicate that EBV is causally implicated in HD or, alternatively, that IM is a marker of a type of lifestyle that predisposes to late first exposure to many infectious agents. A direct link seemed probable when EBV viral DNA was identified within the HD tumour cells. 5,6 It is now established that EBV is associated with a substantial minority (referred to here as EBV ϩve ) of cases of HD, and IARC has recently classified EBV as a probable human carcinogen in relation to HD. 7 Subsequent research has indicated the complexity of the association between EBV and HD. For example, the proportion of cases that are EBV ϩve is markedly lower in the young adult peak (16 -34 years) than for HD in children or older people. 8 Because the late host-response model applies to the young adult peak, this suggests that EBV is not the elusive agent involved in that model, if indeed there is just 1 agent.One key question is whether IM is associated specifically with EBV ϩve HD or, alternatively, associated as strongly with the cases that lack EBV (the EBV -ve cases) that constitute the majority of cases in the young adult peak. Very few studies have looked at epidemiologic risk factors for HD with cases classified as EBV ϩve or EBV -ve . Only 2 studies have collected personal data to address this question: a US case-series that compared EBV ϩve and EBV -ve HD and included cases aged 16 -55 years at diagnosis, 9 and a UK case-control study 10,11 that was restricted to subjects aged 16 -24 years and analysed as both a case-series and case-control study. These 2 studies generated results that are potentially inconsistent, and suggest different answers to the key question. Sleckman et al. 9 found no evidence that a history of IM conveyed specific risk for EBV ϩve compared to EBV -ve HD. In contrast, Alexander et al. 10,11 reported evidence that increased risk after IM was specific to EBV ϩve HD, although there was also a small excess risk of EBV -ve HD after IM. These 2 results are consistent only if the age at diagnosis of HD becomes critical to the association of IM with subsequent HD.The study of Alexander and colleagues also found that family history of IM was a significant risk factor for EBV ϩve HD in the age range 16 -24 ye...

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 < 0·001) in pretreatment blood samples from EBV‐associated cases when compared with non‐EBV‐associated cases. We further showed that in patients with EBV‐associated disease, the virus persisted in the peripheral blood in memory B cells. This phenotype is consistent with that seen in healthy seropositive controls, post‐transplant patients and patients with acute infectious mononucleosis. The data suggest that an increased frequency of EBV carrying B cells in peripheral blood is associated with EBV‐associated HL.