title: Prognostic utility of anti-EBV antibody testing for defining NPC risk among individuals from high-risk NPC families.
abstract: OBJECTIVE
  Epstein-Barr virus (EBV) infection and a family history of nasopharyngeal carcinoma (NPC) are associated with NPC risk. We examined the risk associated with EBV markers and their clinical utility to identify NPC susceptibles within high-risk NPC families.
  
  
  METHODS
  We evaluated antibody titers against viral capsid antigen (VCA) IgA, EBV nuclear antigen-1 (EBNA1) IgA, and DNase among unaffected relatives of NPC cases from 358 multiplex families in Taiwan. Incident NPC cases were identified via linkage to the National Cancer Registry. Clinical examinations of 924 individuals were also done to identify occult, asymptomatic NPC. Baseline EBV serology was used to estimate NPC risk using rate ratios with 95% CI. Associated sensitivity/specificity and receiver operating characteristic (ROC) curves were calculated.
  
  
  RESULTS
  A total of 2,444 unaffected individuals with 15,519 person-years (6.5 years median follow-up) yielded 14 incident NPC cases (nearly 11 times the general population rate). The absolute rate of NPC among anti-EBV EBNA1 IgA seropositives using a standard positivity cutoff versus an optimized cutoff point defined by ROC analyses was 265/100,000 person-years with a 4.7-fold increased risk of NPC (95% CI: 1.4-16) and 166/100,000 person-years with a 6.6-fold increase (95% CI: 1.5-61), respectively. Sensitivity and specificity using the optimized positivity cutoff points were 85.7% and 51.2%, respectively. It is estimated that active evaluation of 49% of individuals from high-risk NPC families seropositive for this marker could lead to earlier detection of up to 86% of NPC cases. Risks associated with the other three EBV markers were weaker.
  
  
  CONCLUSIONS
  Future efforts are needed to identify susceptibility markers among high-risk NPC families that maximize both sensitivity and specificity.
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA. yuke@mail.nih.gov
authors: Kelly J
authors: KJ
authors: Yu
authors: Wan-Lun
authors: WL
authors: Hsu
authors: Ruth M
authors: RM
authors: Pfeiffer
authors: Chun-Ju
authors: CJ
authors: Chiang
authors: Cheng-Ping
authors: CP
authors: Wang
authors: Pei-Jen
authors: PJ
authors: Lou
authors: Yu-Juen
authors: YJ
authors: Cheng
authors: Patti
authors: P
authors: Gravitt
authors: Scott R
authors: SR
authors: Diehl
authors: Alisa M
authors: AM
authors: Goldstein
authors: Chien-Jen
authors: CJ
authors: Chen
authors: Allan
authors: A
authors: Hildesheim
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood*; D000956:Antigens, Viral / Q000097:blood / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology; D002277:Carcinoma / Q000175:diagnosis* / Q000209:etiology / Q000821:virology; D003851:Deoxyribonucleases / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000821:virology; D016017:Odds Ratio; D011379:Prognosis; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; C041788:Epstein-Barr viral capsid antigen; D007070:Immunoglobulin A; D003851:Deoxyribonucleases; C417029:EBV-encoded nuclear antigen 1