J Cancer 2020; 11(24):7176-7183. doi:10.7150/jca.47260

Research Paper

Efficacy of Chemiluminescence Immunoassays on VCA-IgA and EBNA1-IgA Antibodies of Epstein-Barr Virus in Diagnosing Nasopharyngeal Carcinoma

Xia Yu1, Fugui Li1, Weimin Cheng1, Biaohua Wu1, Huiyun Fang1, Fuzhen Xia2, Yijun Gong2, Wenjing Yu3, Pu Liao4, Youde Cao5, Fenghua Yang6, Hong Zhu7, Jiang Li8, Yajun Huang9, Liying Gan10, Lei Zhang11, Yonggang Lou12, Mingfang Ji1✉

1. Cancer Research Institute of Zhongshan City, Zhongshan City People's Hospital, Zhongshan, Guangdong, China
2. Guangdong Provincial Engineering Technology Research Center for Autoimmune Laboratory Diagnostic Products, Shenzhen, Guangdong, China
3. Department of Clinical Laboratory, First Hospital of Jilin University, Changchun, Jilin, China
4. Department of Clinical Laboratory, Chongqing General Hospital, Chongqing, China
5. Department of Clinical Laboratory, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China
6. Department of Clinical Laboratory, Fushun Central Hospital, Fushun, Liaoning, China
7. Department of Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
8. Department of Clinical Laboratory, Shenzhen Sixth People's Hospital (Nanshan Hospital), Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong, China
9. Department of Clinical Laboratory, The Second Affiliated Hospital of Fujian Medical University (Donghai Hospital District), Quanzhou, Fujian, China
10. Department of Clinical Laboratory, Guangxi International Zhuang Medicine Hospital, Nanning, Guangxi, China
11. Department of Clinical Laboratory, Capital Medical University Daxing Teaching Hospital, Beijing, China
12. Department of Clinical Laboratory, Dongyang People's Hospital, Dongyang, Zhejiang, China

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Citation:
Yu X, Li F, Cheng W, Wu B, Fang H, Xia F, Gong Y, Yu W, Liao P, Cao Y, Yang F, Zhu H, Li J, Huang Y, Gan L, Zhang L, Lou Y, Ji M. Efficacy of Chemiluminescence Immunoassays on VCA-IgA and EBNA1-IgA Antibodies of Epstein-Barr Virus in Diagnosing Nasopharyngeal Carcinoma. J Cancer 2020; 11(24):7176-7183. doi:10.7150/jca.47260. Available from https://www.jcancer.org/v11p7176.htm

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Abstract

Background: IgA antibodies against Epstein-Barr virus (EBV) capsid antigen (VCA) and nuclear antigen 1 (EBNA1) have been proposed to facilitate the diagnosis and early detection of nasopharyngeal carcinoma (NPC) in high-incidence regions. However, while new methodologies and new platforms for the detection of VCA-IgA and EBNA1-IgA have become available, proper interassay simultaneous comparisons have not been carried out. The study was to compare the performance of the chemiluminescent immunoassays (CLIA) and enzyme-linked immunosorbent assay (ELISA) for VCA-IgA and EBNA1-IgA antibodies, and to evaluate the levels of EBV antibodies in healthy population from different areas of China.

Methods: CLIA and ELISA for VCA-IgA and EBNA1-IgA were performed in NPC and healthy populations from high-incidence areas of NPC in South China (N=555), medium-incidence areas of NPC in Central China (N=318) and low-incidence areas of NPC in North China (N=379), and the results were compared and analyzed.

Results: (1) The highest sensitivity in total, early and advanced NPC were 91.5% (CLIA for VCA-IgA), 86.4% (CLIA and ELISA-2 for EBNA1-IgA) and 93.6% (CLIA for VCA-IgA). However, the specificity of EBV-IgA measured by CLIA was relatively lower than ELISA. The top three seromarkers with the largest AUC was CLIA for VCA-IgA (AUC: 0.929, 95% CI: 0.905-0.953), ELISA-2 for EBNA1-IgA (AUC: 0.922, 95% CI: 0.896-0.947) and CLIA for EBNA1-IgA (AUC:0.919, 95% CI: 0.893-0.945), respectively. The positive and negative coincidence rates of the two EBNA1-IgA kits were 69.5% and 91.9%, respectively. However, the coincidence rates of VCA-IgA were relatively low. CLIA kits had good repeatability between different laboratories. (2) The positive rates of EBV-IgA antibodies were relatively high in high-incidence areas of NPC (P < 0.017), while there was no significant difference in the antibody positive rates between medium-incidence areas and low-incidence areas of NPC (P > 0.05).

Conclusions: The performance of EBV-IgA antibodies measured by CLIA has good repeatability, higher sensitivity and similar specificity. The higher EBV-IgA positive rate in healthy subjects by CLIA raises concern about its suitability for NPC-risk screening and requires further analysis.

Keywords: nasopharyngeal carcinoma, VCA-IgA, EBNA1-IgA, CLIA, ELISA