Skip to main content

Advertisement

SpringerLink
Log in

Comparison of Epstein-Barr Virus Serological Tools for the Screening and Risk Assessment of Nasopharyngeal Carcinoma: a Large Population-based Study

  • Original Article
  • Published:
Pathology & Oncology Research

Abstract

Epstein-Barr virus (EBV)-based serologic antibody testing has been found to be a feasible alternative for nasopharyngeal carcinoma (NPC) screening in endemic areas. The purpose of this study was to evaluate the performance of ELISA based on VCA IgA antibody, EA-IgA and Rta-IgG antibody specific to EBV in the diagnosis of NPC. A total of 2155 untreated NPC patients and 6957 healthy volunteers without nasopharyngeal disorder were recruited, and all subjects received EBV VCA-IgA, EA-IgA and Rta-IgG antibody tests simultaneously. The diagnostic efficiency of three testing alone or in combination for the diagnosis of NPC was evaluated. The prevalence of IgA antibody against EBV-VCA, IgA antibody against EBV-EA and IgG antibody against EBV-Rta was 89.9%, 46.6% and 63.2%. The sensitivity, specificity, positive predictive value, negative predictive value and Youden index were 89.88%, 89.65%, 73.18%, 96.63% and 0.79 for the EBV VCA-IgA antibody test, 46.59%, 96.89%, 82.5%, 85.42% and 0.43 for the EA-IgA antibody test, and 63.25%, 94.87%, 79.48%, 89.29% and 0.58 for the Rta-IgG antibody test in the diagnosis of NPC, and ROC curve analysis revealed the greatest diagnostic efficiency for EBV VCA-IgA antibody test and the lowest efficiency for EBV EA-IgA antibody test in the diagnosis of NPC. In addition, the simultaneous triple positivity of VCA-IgA, EA-IgA and Rta-IgG antibodies specific to EBV indicated the highest risk of NPC, and the simultaneous triple negativity of the three types of anti-EBV antibodies suggested the lowest risk of NPC. Our data demonstrate that EBV VCA-IgA antibody test shows a higher diagnostic efficiency than EA-IgA and Rta-IgG antibody tests for the screening of NPC, and triple positivity of is a better biomarker for the diagnosis of NPC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Chua MLK, Wee JTS, Hui EP, Chan ATC (2016) Nasopharyngeal carcinoma. Lancet 387:1012–1024

    Article  Google Scholar 

  2. Tang LL, Chen WQ, Xue WQ, He YQ, Zheng RS, Zeng YX, Jia WH (2016) Global trends in incidence and mortality of nasopharyngeal carcinoma. Cancer Lett 374:22–30

    Article  CAS  Google Scholar 

  3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Article  Google Scholar 

  4. Fu ZT, Guo XL, Zhang SW, Zeng HM, Sun KX, Chen WQ, He J (2018) Incidence and mortality of nasopharyngeal carcinoma in China, 2014. Zhonghua Zhong Liu Za Zhi 40:566–571

    CAS  PubMed  Google Scholar 

  5. Petersson F (2015) Nasopharyngeal carcinoma: a review. Semin Diagn Pathol 32:54–73

    Article  Google Scholar 

  6. Kamran SC, Riaz N, Lee N (2015) Nasopharyngeal carcinoma. Surg Oncol Clin N Am 24:547–561

    Article  Google Scholar 

  7. Tsao SW, Tsang CM, Lo KW (2017) Epstein-Barr virus infection and nasopharyngeal carcinoma. Philos Trans R Soc Lond B Biol Sci 372:20160270

    Article  Google Scholar 

  8. Tsang CM, Tsao SW (2015) The role of Epstein-Barr virus infection in the pathogenesis of nasopharyngeal carcinoma. Virol Sin 30:107–121

    Article  CAS  Google Scholar 

  9. Lee AW, Ma BB, Ng WT, Chan AT (2015) Management of nasopharyngeal carcinoma: current practice and future perspective. J Clin Oncol 33:3356–3364

    Article  Google Scholar 

  10. Tabuchi K, Nakayama M, Nishimura B, Hayashi K, Hara A (2011) Early detection of nasopharyngeal carcinoma. Int J Otolaryngol. 2011:638058

    Article  Google Scholar 

  11. Hildesheim A (2013) Epstein-Barr virus-based screening for the early detection of nasopharyngeal carcinoma: a new frontier. Am J Epidemiol 177:251–253

    Article  Google Scholar 

  12. Ng MH, Chan KH, Ng SP, Zong YS (2006) Epstein-Barr virus serology in early detection and screening of nasopharyngeal carcinoma. Ai Zheng 25:250–256

    PubMed  Google Scholar 

  13. Cao SM, Liu Z, Jia WH, Huang QH, Liu Q, Guo X, Huang TB, Ye W, Hong MH (2011) Fluctuations of epstein-barr virus serological antibodies and risk for nasopharyngeal carcinoma: a prospective screening study with a 20-year follow-up. PLoS One 6:e19100

    Article  CAS  Google Scholar 

  14. Lee AWM, Ng WT, Chan LK, Chan OSH, Hung WM, Chan CC, Cheng PTC, Sze H, Lam TS, Yau TK (2012) The strength/weakness of the AJCC/UICC staging system (7th edition) for nasopharyngeal cancer and suggestions for future improvement. Oral Oncol 48:1007–1013

    Article  Google Scholar 

  15. Chan AT, Grégoire V, Lefebvre JL, Licitra L, Hui EP, Leung SF, Felip E, EHNS–ESMO–ESTRO Guidelines Working Group (2012) Nasopharyngeal cancer: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 23:vii83–vii85

  16. Gurtsevitch VE, Senyuta NB, Ignatova AV, Lomaya MV, Kondratova VN, Pavlovskaya AI, Dushenkina TE, Maximovich DM, Smirnova KV, Mudunov AM, Lichtenstein AV (2017) Epstein-Barr virus biomarkers for nasopharyngeal carcinoma in non-endemic regions. J Gen Virol 98:2118–2127

    Article  CAS  Google Scholar 

  17. Anghel I, Anghel AG, Dumitru M, Soreanu CC (2012) Nasopharyngeal carcinoma -- analysis of risk factors and immunological markers. Chirurgia (Bucur) 107:640–645

    CAS  Google Scholar 

  18. Wong MM, Lye MS, Cheng HM, Sam CK (2005) Epstein-Barr virus serology in the diagnosis of nasopharyngeal carcinoma. Asian Pac J Allergy Immunol 23:65–67

    PubMed  Google Scholar 

  19. Chen Y, Xin X, Cui Z, Zheng Y, Guo J, Chen Y, Lin Y, Su G (2016) Diagnostic value of serum Epstein-Barr virus capsid antigen-IgA for nasopharyngeal carcinoma: a meta-analysis based on 21 Studies. Clin Lab 62:1155–1166

    CAS  PubMed  Google Scholar 

  20. Li Y, Wang K, Yin SK, Zheng HL, Min DL (2016) Expression of Epstein-Barr virus antibodies EA-IgG, Rta-IgG, and VCA-IgA in nasopharyngeal carcinoma and their use in a combined diagnostic assay. Genet Mol Res 15:gmr7368

    Google Scholar 

  21. Cai YL, Li J, Lu AY, Zheng YM, Zhong WM, Wang W, Gao JQ, Zeng H, Cheng JR, Tang MZ (2014) Diagnostic significance of combined detection of Epstein-Barr virus antibodies, VCA/IgA, EA/IgA, Rta/IgG and EBNA1/IgA for nasopharyngeal carcinoma. Asian Pac J Cancer Prev 15:2001–2006

    Article  Google Scholar 

  22. Xia C, Zhu K, Zheng G (2015) Expression of EBV antibody EA-IgA, Rta-IgG and VCA-IgA and SA in serum and the implication of combined assay in nasopharyngeal carcinoma diagnosis. Int J Clin Exp Pathol 8:16104–16110

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Sun P, Chen C, Cheng YK, Zeng ZJ, Chen XL, Liu LZ, Gu MF (2014) Serologic biomarkers of Epstein-Barr virus correlate with TNM classification according to the seventh edition of the UICC/AJCC staging system for nasopharyngeal carcinoma. Eur Arch Otorhinolaryngol 271:2545–2554

    Article  Google Scholar 

  24. Sun R, Wang X, Li X (2015) Correlation Analysis of Nasopharyngeal Carcinoma TNM Staging with Serum EA IgA and VCA IgA in EBV and VEGF-C and -D. Med Sci Monit 21:2105–2109

    Article  CAS  Google Scholar 

  25. Luo YL, Ou GP, Chi PD, Liang YN, Liu YH, Huang MY (2009) Combined determination of Epstein-Barr virus-related antibodies and antigens for diagnosis of nasopharyngeal carcinoma. Ai Zheng 28:76–78

    PubMed  Google Scholar 

  26. Li S, Deng Y, Li X, Chen QP, Liao XC, Qin X (2010) Diagnostic value of Epstein-Barr virus capsid antigen-IgA in nasopharyngeal carcinoma: a meta-analysis. Chin Med J (Engl) 123:1201–1205

    Google Scholar 

  27. Shao JY, Li YH, Gao HY, Wu QL, Cui NJ, Zhang L, Cheng G, Hu LF, Ernberg I, Zeng YX (2004) Comparison of plasma Epstein-Barr virus (EBV) DNA levels and serum EBV immunoglobulin A/virus capsid antigen antibody titers in patients with nasopharyngeal carcinoma. Cancer 100:1162–1170

    Article  CAS  Google Scholar 

  28. Song C, Yang S (2013) A meta-analysis on the EBV DNA and VCA-IgA in diagnosis of Nasopharyngeal Carcinoma. Pak J Med Sci 29:885–890

    PubMed  PubMed Central  Google Scholar 

  29. Leung SF, Tam JS, Chan AT, Zee B, Chan LY, Huang DP, Van Hasselt A, Johnson PJ, Lo YM (2004) Improved accuracy of detection of nasopharyngeal carcinoma by combined application of circulating Epstein-Barr virus DNA and anti-Epstein-Barr viral capsid antigen IgA antibody. Clin Chem 50:339–345

    Article  CAS  Google Scholar 

  30. Chan KH, Gu YL, Ng F, Ng PS, Seto WH, Sham JS, Chua D, Wei W, Chen YL, Luk W, Zong YS, Ng MH (2003) EBV specific antibody-based and DNA-based assays in serologic diagnosis of nasopharyngeal carcinoma. Int J Cancer 105:706–709

    Article  CAS  Google Scholar 

  31. Zhao FP, Liu X, Zhong ZM, Lu J, Yu BL, Zeng FY, Chen XM, Chen HH, Peng XH, Wang F, Peng Y, Li XP (2014) Positivity of both plasma Epstein-Barr virus DNA and serum Epstein-Barr virus capsid specific immunoglobulin A is a better prognostic biomarker for nasopharyngeal carcinoma. BBA Clin 2:88–93

    Article  Google Scholar 

Download references

Funding

This study was funded by the grants from the Natural Science Foundation of Fujian Province (grant nos. 2016J01511, 2017J05120 and 2018J01273), the Science and Technology Program of Fujian Province (grant no. 2018Y2003) and the Joint Funds for the Innovation of Science and Technology, Fujian Province (grant no. 2017Y9072).

Author information

Authors and Affiliations

  1. Department of Clinical Laboratory, Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, No. 420 Fuma Road, 350014, Fuzhou City, Fujian Province, China

    Junying Guo, Zhaolei Cui, Yuhong Zheng, Xiaoli Li & Yan Chen

Authors
  1. Junying Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhaolei Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuhong Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoli Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yan Chen.

Ethics declarations

Conflict of Interest

The authors declare no conflict of interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guo, J., Cui, Z., Zheng, Y. et al. Comparison of Epstein-Barr Virus Serological Tools for the Screening and Risk Assessment of Nasopharyngeal Carcinoma: a Large Population-based Study. Pathol. Oncol. Res. 26, 2185–2190 (2020). https://doi.org/10.1007/s12253-020-00808-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-020-00808-0

Keywords

Search

Navigation