Originally published as JCO Early Release 10.1200/JCO.2005.02.6310 on September 26 2005

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Epstein-Barr Virus As a Marker of Survival After Hodgkin's Lymphoma: A Population-Based Study

From the Northern California Cancer Center, Fremont; Stanford University Medical Center, Stanford, CA; University of North Carolina, Chapel Hill, NC; University of Pittsburgh, Pittsburgh, PA; Hartford Hospital, Hartford, CT; and Johns Hopkins University, Baltimore, MD

Address reprint requests to Theresa H.M. Keegan, PhD, Northern California Cancer Center, 2201 Walnut Ave, Ste 300, Fremont, CA 94538-2334; e-mail: tkeegan{at}nccc.org

PURPOSE: Epstein-Barr virus (EBV) in Hodgkin's lymphoma (HL) cells has been considered as a prognostic marker for this heterogeneous disease, but studies have yielded mixed findings, likely because of selected patient series and failure to acknowledge an effect of age on outcome. This study assessed survival after HL in a population-based cohort large enough to examine the joint effects of EBV with other factors including age, sex, and histologic subtype.

PATIENTS AND METHODS: Included were 922 patients with classical HL diagnosed between mid-1988 and 1997 in the Greater San Francisco Bay Area, with archived biopsy specimens assayed for EBV with immunohistochemistry and in situ hybridization. Vital status was followed through December 30, 2003 (median follow-up time, 97 months). Overall and disease-specific survival were analyzed with the Kaplan-Meier method and Cox proportional hazards regression models.

RESULTS: In children less than 15 years old, EBV presence was suggestively associated (P = .07) with favorable survival. In adults aged 15 to 44 years, EBV did not affect HL outcome, although a protective effect was suggested. In older adults (45 to 96 years), EBV presence nearly doubled the risk of overall and HL-specific mortality but only for patients with nodular sclerosis (NS) histologic subtype (hazard ratio for death = 2.5; 95% CI, 1.5 to 4.3).

CONCLUSION: In HL, EBV tumor cell presence is associated with better survival in young patients and poorer survival in older patients with NS, independent of other factors. Variation in outcome by age and histology could indicate biologically distinct disease entities. Evidence that EBV is a meaningful prognostic marker may have therapeutic relevance.

Supported by National Cancer Institute (NCI) Grants No. NCI R29 CA-50381 (S.L.G.), NCI RO3 CA-63245 (S.L.G., R.F.A.), and N01-CN-65107 (S.L.G.). The collection of Cancer incidence data used in this study was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's Nationals Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the authors, and endorsement by the state of California, Department of Health Services, the National Cancer Institute, and the Centers for Disease Control and Prevention or their contractors and subcontractors is not intended, nor should it be inferred.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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