Subtype distribution and long-term titer luctuation patterns of serum anti-Epstein–Barr virus antibodies in a non-nasopharyngeal carcinoma population from an endemic area in South China： a cohort study

Background： Serum immunoglobulin A antibodies against Epstein–Barr virus（EBV）, viral capsid antigen（VCA-Ig A） and early antigen（EA-Ig A）, are used to screen for nasopharyngeal carcinoma（NPC） in endemic areas. However, their routine use has been questioned because of a lack of specificity. This study aimed to determine the distributions of different subtypes of antibody and to illustrate how the natural variation patterns affect the specificity of screening in non-NPC participants.Methods： The distribution of baseline VCA-IgA was analyzed between sexes and across 10-year age groups in 18,286 non-NPC participants using Chi square tests. Fluctuations in the VCA-IgA level were assessed in 1056 non-NPC participants with at least two retests in the first 5-year period（1987–1992） after the initial screening using the Kaplan–Meier method.Results： The titers of VCA-Ig A increased with age（P 〈 0.001）. Using a previous serological definition of high NPC risk, nasopharyngeal endoscopy and/or nasopharyngeal biopsy would be recommended in 55.5% of the non-NPC partici-pants with an initial VCA-Ig A-positive status and in 20.6% with an initial negative status during the 5-year follow-up. However, seroconversions were common; 85.2% of the participants with a VCA-Ig A-positive status at baseline con-verted to negative, and all VCA-Ig A-negative participants changed to positive at least once during the 5-year follow-up. The EA-Ig A status had a high seroconversion probability（100%） from positive to negative; however, it had a low probability（19.6%） from negative to positive.Conclusions： Age- and sex-specific cutoff titer values for serum anti-EBV antibodies as well as their specific titer fluc-tuation patterns should be considered when defining high NPC risk criteria for follow-up diagnostics and monitoring.