Serologic markers of Epstein-Barr virus infection and nasopharyngeal carcinoma in Taiwanese men

N Engl J Med. 2001 Dec 27;345(26):1877-82. doi: 10.1056/NEJMoa011610.


Background: It is probable but unproven that Epstein-Barr virus (EBV) has a role in nasopharyngeal carcinoma. We determined whether antibodies against EBV are present before the development of nasopharyngeal carcinoma.

Methods: A total of 9699 men were enrolled between 1984 and 1986. Blood samples were examined for IgA antibodies against EBV capsid antigen and neutralizing antibodies against EBV-specific DNase. During 131,981 person-years of follow-up, 22 pathologically confirmed new cases of nasopharyngeal carcinoma that were diagnosed more than one year after recruitment were ascertained through linkage with the National Cancer Registry of Taiwan.

Results: The cumulative risk of nasopharyngeal carcinoma per 100,000 person-years was 11.2 for subjects who tested positive for neither serologic marker, 45.0 for those who had one marker, and 371.0 for those who had both markers. After adjustment for age and the presence or absence of a family history of nasopharyngeal carcinoma, the relative risk of nasopharyngeal carcinoma was 32.8 for subjects with both markers (95 percent confidence interval, 7.3 to 147.2; P<0.001) and 4.0 for subjects with one marker (95 percent confidence interval, 1.6 to 10.2; P=0.003), as compared with subjects with neither marker. The longer the duration of follow-up, the greater the difference in the cumulative incidence of nasopharyngeal carcinoma between seropositive and seronegative subjects.

Conclusions: IgA antibodies against EBV capsid antigen and neutralizing antibodies against EBV DNase are predictive of nasopharyngeal carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / blood
  • Antibodies, Viral / blood*
  • Capsid / immunology
  • Cohort Studies
  • Deoxyribonucleases / immunology
  • Epstein-Barr Virus Infections / complications*
  • Follow-Up Studies
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immunoglobulin A / blood
  • Incidence
  • Life Tables
  • Male
  • Multivariate Analysis
  • Nasopharyngeal Neoplasms / epidemiology*
  • Nasopharyngeal Neoplasms / etiology
  • Risk Factors
  • Taiwan / epidemiology


  • Antibodies
  • Antibodies, Viral
  • Immunoglobulin A
  • Deoxyribonucleases