Epstein-Barr virus directed screening for nasopharyngeal carcinoma in individuals with positive family history: A systematic review

Oral Oncol. 2022 Oct:133:106031. doi: 10.1016/j.oraloncology.2022.106031. Epub 2022 Jul 28.


Objectives: Evidence to support Epstein-Barr virus (EBV)-directed population nasopharyngeal carcinoma (NPC) screening has been growing. Familial aggregation is a well-recognized phenomenon in endemic regions. This systematic review summarizes the role of EBV-directed screening in individuals with a positive family history (FH+) of NPC.

Methods: We searched four electronic databases from their inception to October 2021. We included studies on individuals with FH+ of NPC who had undergone EBV-directed investigations, with no restriction in the testing methods or analytic techniques. The primary and secondary outcomes were EBV positivity rates and NPC incidence rates, respectively. Meta-analyses were performed using the random-effect model.

Results: Ten cross-sectional studies (n = 7436) and three cohort studies (n = 4306) were included. The pooled relative risk (RR) of EBV positivity between individuals with and without FH+ of NPC were 2.79 (95 % CI 1.37-5.68, p = 0.005) for viral capsid antigen (VCA) IgA, 3.09 (95 % CI 0.65-14.83, p = 0.16) for Epstein-Barr nuclear antigen (EBNA1) IgA, and 1.76 (95 % CI 1.04-2.96, p = 0.03) for combined EBNA1/VCA IgA. In the three cohort studies, the NPC incidence rates ranged from 90.2 to 266 per 100 000 person-years with high proportions of early-stage diseases. FH+ individuals who were EBV-positive had a 2.5 to 30.7-fold risk of NPC development compared to their EBV-negative counterparts.

Conclusion: Family members of NPC patients had significantly higher EBV positivity rates than the general population. FH+ individuals who are EBV-positive had high risks of developing NPC. Familial screening using EBV serology may facilitate early NPC detection in endemic areas.

Keywords: Cancer screening; Epstein-Barr virus; Family; Nasopharyngeal carcinoma; Systematic review.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Viral
  • Cross-Sectional Studies
  • Epstein-Barr Virus Infections* / complications
  • Herpesvirus 4, Human / genetics
  • Humans
  • Immunoglobulin A
  • Nasopharyngeal Carcinoma / complications
  • Nasopharyngeal Neoplasms*


  • Antibodies, Viral
  • Immunoglobulin A