Epstein-Barr virus serology as a potential screening marker for nasopharyngeal carcinoma among high-risk individuals from multiplex families in Taiwan

Cancer Epidemiol Biomarkers Prev. 2014 Jul;23(7):1213-9. doi: 10.1158/1055-9965.EPI-13-1262. Epub 2014 Apr 27.

Abstract

Background: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer that is highly treatable when diagnosed early, with 5-year disease-free survival of approximately 90%. However, NPC is typically diagnosed at advanced stages, in which disease-free survival is <50%. There is, therefore, a need for clinical tools to assist in early NPC detection, particularly among high-risk individuals.

Methods: We evaluated the ability of anti-EBV IgA antibodies to detect incident NPC among high-risk Taiwanese individuals. NPC cases (N = 21) and age- and sex-matched controls (N = 84) were selected. Serum collected before NPC diagnosis was tested for ELISA-based IgA antibodies against the following EBV peptides: EBNA1, VCAp18, EAp138, Ead_p47, and VCAp18 + EBNA1 peptide mixture. The sensitivity, specificity, and screening program parameters were calculated.

Results: EBNA1 IgA had the best performance characteristics. At an optimized threshold value, EBNA1 IgA measured at baseline identified 80% of the high-risk individuals who developed NPC during follow-up (80% sensitivity). However, approximately 40% of high-risk individuals who did not develop NPC also tested positive (false positives). Application of EBNA1 IgA as a biomarker to detect incident NPC in a previously unscreened, high-risk population revealed that 164 individuals needed to be screened to detect 1 NPC and that 69 individuals tested positive per case detected.

Conclusions: EBNA1 IgA proved to be a sensitive biomarker for identifying incident NPC, but future work is warranted to develop more specific screening tools to decrease the number of false positives.

Impact: Results from this study could inform decisions about screening biomarkers and referral thresholds for future NPC early-detection program evaluations.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / blood*
  • Area Under Curve
  • Carcinoma
  • Early Detection of Cancer / methods*
  • Enzyme-Linked Immunosorbent Assay
  • Epstein-Barr Virus Infections / blood
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Nuclear Antigens / blood
  • False Positive Reactions
  • Humans
  • Immunoglobulin A
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / blood*
  • Nasopharyngeal Neoplasms / virology
  • ROC Curve
  • Sensitivity and Specificity
  • Taiwan

Substances

  • Antibodies, Viral
  • Epstein-Barr Virus Nuclear Antigens
  • Immunoglobulin A
  • EBV-encoded nuclear antigen 1