title: Subtype distribution and long-term titer fluctuation patterns of serum anti-Epstein-Barr virus antibodies in a non-nasopharyngeal carcinoma population from an endemic area in South China: a cohort study.
abstract: Serum immunoglobulin A antibodies against Epstein-Barr virus (EBV), viral capsid antigen (VCA-IgA) and early antigen (EA-IgA), 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.
  
  
  
  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.
  
  
  
  The titers of VCA-IgA 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 participants with an initial VCA-IgA-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-IgA-positive status at baseline converted to negative, and all VCA-IgA-negative participants changed to positive at least once during the 5-year follow-up. The EA-IgA status had a high seroconversion probability (100%) from positive to negative; however, it had a low probability (19.6%) from negative to positive.
  
  
  
  Age- and sex-specific cutoff titer values for serum anti-EBV antibodies as well as their specific titer fluctuation patterns should be considered when defining high NPC risk criteria for follow-up diagnostics and monitoring.
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Cancer Prevention Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China.|School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong, P. R. China.
authors.forename: Jin-Lin
authors.initials: JL
authors.lastname: Du
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Cancer Prevention Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China.
authors.forename: Sui-Hong
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Sihui Cancer Institute, Sihui, 526200, Guangdong, P. R. China.
authors.forename: Qi-Hong
authors.initials: QH
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Cancer Prevention Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Shang-Hang
authors.initials: SH
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Cancer Prevention Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Cancer Prevention Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Cancer Prevention Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Cancer Prevention Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Meng-Jie
authors.initials: MJ
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Cancer Prevention Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China. hongmh@sysucc.org.cn.|Department of Cancer Prevention Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China. hongmh@sysucc.org.cn.|Department of Clinical Trial Center, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China. hongmh@sysucc.org.cn.
authors.forename: Ming-Huang
authors.initials: MH
authors.lastname: Hong
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China. caosm@sysucc.org.cn.|Department of Cancer Prevention Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China. caosm@sysucc.org.cn.
authors.forename: Su-Mei
authors.initials: SM
authors.lastname: Cao
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D000956:Antigens, Viral / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D036022:Capsid Proteins / Q000276:immunology; D002681:China / Q000453:epidemiology; D004279:DNA, Viral / Q000235:genetics; D019353:Endemic Diseases / Q000706:statistics & numerical data*; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000453:epidemiology / Q000473:pathology* / Q000821:virology; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000453:epidemiology / Q000473:pathology* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D015415:Biomarkers; D036022:Capsid Proteins; D004279:DNA, Viral; C041788:Epstein-Barr viral capsid antigen
keywords: Cohort study; Epstein–Barr virus; Fluctuation; Mass screening; Nasopharyngeal carcinoma