title: Epstein-Barr virus as a marker of survival after Hodgkin's lymphoma: a population-based study.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Northern California Cancer Center, 2201 Walnut Ave, Ste 300, Fremont, CA 94538-2334, USA. tkeegan@nccc.org
authors.forename: Theresa H M
authors.initials: TH
authors.lastname: Keegan
authors.forename: Sally L
authors.initials: SL
authors.lastname: Glaser
authors.forename: Christina A
authors.initials: CA
authors.lastname: Clarke
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Gulley
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Craig
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Digiuseppe
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Dorfman
authors.forename: Risa B
authors.initials: RB
authors.lastname: Mann
authors.forename: Richard F
authors.initials: RF
authors.lastname: Ambinder
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D006689:Hodgkin Disease / Q000453:epidemiology / Q000401:mortality / Q000821:virology; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor