Diagnostics of nasopharyngeal carcinoma with Epstein-Barr virus (Herpesviridae, Lymphocryptovirus, HHV-4) serological and molecular markers in cases of undetected primary tumor location

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Abstract

Introduction. The reasons of late diagnosis of nasopharyngeal carcinoma (NPC) are the long asymptomatic course of the pathological process, the anatomical structure of the nasopharynx, often small, visually and endoscopically undetectable tumor and other factors. It is proved that the Epstein-Barr virus (EBV) is an etiological agent in the most common undifferentiated non-keratinizing histological type of NPC (uNPC).

The aim of the work was to assess the significance of diagnostic markers of EBV (titers of humoral antibodies to the virus and the concentration of viral DNA in plasma) for the diagnosis of uNPC in a group of patients with metastatic lesions of the cervical lymph nodes without an identified localization of the primary tumor focus.

Material and methods. The material for the study was blood plasma of 83 patients with metastatic lesions of the cervical lymph nodes and not established localization of the primary tumor. Plasma samples were tested for the anti-EBV IgG and IgA antibody content and titers and the concentration of viral DNA.

Results and discussion. The data obtained indicate that the parallel testing of blood plasma for EBV-specific antibodies and viral load is a useful tool for preliminary screening of uNPC patients. The final diagnosis is confirmed by the data of subsequent morphological and instrumental studies. Several examples also show that the concentration of viral DNA in the blood plasma of patients with uNPC reflects the effect of the therapy and the prognosis of the disease: remission, stabilization of the tumor process, relapse or metastasis.

Conclusion. Although the titers of virus-specific antibodies are found to reflect clinical manifestations of the disease less accurately than the plasma concentrations of viral DNA, serological markers are extremely important for the preliminary diagnostics of uNPC in cases of undetected primary tumor location. They are also useful for primary screening of this neoplasm among individuals at risk.

About the authors

N. B. Senyuta

N.N. Blokhin National Medical Research Center of Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0001-8915-8274
Moscow, 115478, Russia Russian Federation

K. V. Smirnova

N.N. Blokhin National Medical Research Center of Oncology; N.I. Pirogov Russian National Research Medical University

Email: fake@neicon.ru
ORCID iD: 0000-0001-6209-977X
Moscow, 115478, Russia; Moscow, 117997, Russia Russian Federation

V. N. Kondratova

N.N. Blokhin National Medical Research Center of Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0003-0614-8789
Moscow, 115478, Russia Russian Federation

A. V. Ignatova

N.N. Blokhin National Medical Research Center of Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0002-6796-0968
Moscow, 115478, Russia Russian Federation

A. M. Mudunov

N.N. Blokhin National Medical Research Center of Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0002-0918-3857
Moscow, 115478, Russia Russian Federation

T. E. Dushenkina

N.N. Blokhin National Medical Research Center of Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0002-3066-1606
Moscow, 115478, Russia Russian Federation

A. V. Liechtenstein

N.N. Blokhin National Medical Research Center of Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0002-0190-5069
Moscow, 115478, Russia Russian Federation

V. E. Gurtsevich

N.N. Blokhin National Medical Research Center of Oncology

Author for correspondence.
Email: gurtsevitch-vlad-88@yandex.ru
ORCID iD: 0000-0003-1840-4364
Vladimir E. Gurtsevitch, Dr. Med. Sci., leading researcher of the laboratory of viral carcinogenesis, Moscow, 115478, Russia Russian Federation

References

  1. Young L.S., Rickinson A.B. Epstein-Barr virus: 40 years on. Nat. Rev. Cancer. 2004; 4(10): 757-68. Doi: https://doi.org/10.1038/nrc1452
  2. Brennan B. Nasopharyngeal carcinoma. Orphanet J. Rare Dis. 2006; 1: 23. Doi: https://doi.org/10.1186/1750-1172-1-23
  3. Marks J.E., Phillips J.L., Menck H.R. The National Cancer Data Base report on the relationship of race and national origin to the histology of nasopharyngeal carcinoma. Cancer. 1998; 83(3): 582-8. Doi: https://doi.org/10.1002/(SICI)1097-0142-(19980801)83:3<582::AID-CNCR29>3.0.CO;2-R
  4. Pathmanathan R., Prasad U., Sadler R., Flynn K., Raab-Traub N. Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma. N. Engl. J. Med. 1995; 333(11): 693-8. Doi: https://doi.org/10.1056/NEJM199509143331103
  5. Chien Y.C., Chen J.Y., Liu M.Y., Yang H.I., Hsu M.M., Chen C.J., et al. Serologic markers of Epstein-Barr virus infection and nasopharyngeal carcinoma in Taiwanese men. N. Engl. J. Med. 2001; 345(26): 1877-82. Doi: https://doi.org/10.1056/NEJMoa011610
  6. Song C., Yang S. A meta-analysis on the EBV DNA and VCA-IgA in diagnosis of Nasopharyngeal Carcinoma. Pak. J. Med. Sci. 2013; 29(3): 885-90. Doi: https://doi.org/10.12669/pjms.293.2907
  7. Niedobitek G. Epstein-Barr virus infection in the pathogenesis of nasopharyngeal carcinoma. Mol. Pathol. 2000; 53(5): 248-54. Doi: https://doi.org/10.1136/mp.53.5.248
  8. Chang C.M., Yu K.J., Mbulaiteye S.M., Hildesheim A., Bhatia K. The extent of genetic diversity of Epstein-Barr virus and its geographic and disease patterns: a need for reappraisal. Virus Res. 2009; 143(2): 209-21. Doi: https://doi.org/10.1016/j.virusres.2009.07.005
  9. Yu M.C., Yuan J.M. Epidemiology of nasopharyngeal carcinoma. Semin. Cancer Biol. 2002; 12(6): 421-9. Doi: https://doi.org/10.1016/s1044579x02000858
  10. Каприн А.Д., Старинский В.В., Петрова Г.В., ред. Злокачественные новообразования в России в 2017 году (заболеваемость и смертность). М.; 2018.
  11. Hildesheim A., Apple R.J., Chen C.J., Wang S.S., Cheng Y.J., Klitz W., et al. Association of HLA class I and II alleles and extended haplotypes with nasopharyngeal carcinoma in Taiwan. J. Natl. Cancer Inst. 2002; 94(23): 1780-9. Doi: https://doi.org/10.1093/jnci/94.23.1780
  12. Jia W.H., Qin H.D. Non-viral environmental risk factors for nasopharyngeal carcinoma: a systematic review. Semin. Cancer Biol. 2012; 22(2): 117-26. Doi: https://doi.org/10.1016/j.semcancer.2012.01.009
  13. Chang E.T., Adami H.O. The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol. Biomarkers Prev. 2006; 15(10): 1765-77. Doi: https://doi.org/10.1158/1055-9965.EPI-06-0353
  14. Shivappa N., Hebert J.R., Zucchetto A., Montella M., Libra M., Garavello W., et al. Increased Risk of Nasopharyngeal Carcinoma with Increasing Levels of Diet-Associated Inflammation in an Italian Case-Control Study. Nutr. Cancer. 2016; 68(7): 1123-30. Doi: https://doi.org/10.1080/01635581.2016.1216137
  15. Xiong G., Zhang B., Huang M.Y., Zhou H., Chen L.Z., Feng Q.S., et al. Epstein-Barr virus (EBV) infection in Chinese children: a retrospective study of age-specific prevalence. PLoS One. 2014; 9(6): e99857. Doi: https://doi.org/10.1371/journal.pone.0099857
  16. Wu L., Li C., Pan L. Nasopharyngeal carcinoma: A review of current updates. Exp. Ther. Med. 2018; 15(4): 3687-92. Doi: https://doi.org/10.3892/etm.2018.5878
  17. Gallicchio L., Matanoski G., Tao X.G., Chen L., Lam T.K., Boyd K., et al. Adulthood consumption of preserved and nonpreserved vegetables and the risk of nasopharyngeal carcinoma: a systematic review. Int. J. Cancer. 2006; 119(5): 1125-35. Doi: https://doi.org/10.1002/ijc.21946
  18. Tiwawech D., Srivatanakul P., Karalak A., Ishida T. Glutathione S-transferase M1 gene polymorphism in Thai nasopharyngeal carcinoma. Asian Pac. J. Cancer Prev. 2005; 6(3): 270-5.
  19. Guo X., O’Brien S.J., Zeng Y., Nelson G.W., Winkler C.A. GSTM1 and GSTT1 gene deletions and the risk for nasopharyngeal carcinoma in Han Chinese. Cancer Epidemiol. Biomarkers Prev. 2008; 17(7): 1760-3. Doi: https://doi.org/10.1158/1055-9965.EPI-08-0149
  20. Vaughan T.L., Stewart P.A., Teschke K., Lynch C.F., Swanson G.M., Lyon J.L., et al. Occupational exposure to formaldehyde and wood dust and nasopharyngeal carcinoma. Occup. Environ. Med. 2000; 57(6): 376-84. Doi: https://doi.org/10.1136/oem.57.6.376
  21. Hildesheim A., Wang C.P. Genetic predisposition factors and nasopharyngeal carcinoma risk: a review of epidemiological association studies, 2000-2011: Rosetta Stone for NPC: genetics, viral infection, and other environmental factors. Semin. Cancer Biol. 2012; 22(2): 107-16. Doi: https://doi.org/10.1016/j.semcancer.2012.01.007
  22. Gurtsevitch V., Ruiz R., Stepina V., Plachov I., Le Riverend E., Glazkova T., et al. Epstein-Barr viral serology in nasopharyngeal carcinoma patients in the USSR and Cuba, and its value for differential diagnosis of the disease. Int. J. Cancer. 1986; 37(3): 375-81. Doi: https://doi.org/10.1002/ijc.2910370308
  23. Ho H.C., Ng M.H., Kwan H.C. Factors affecting serum IgA antibody to Epstein-Barr viral capsid antigens in nasopharyngeal carcinoma. Br. J. Cancer. 1978; 37(3): 356-62. Doi: https://doi.org/10.1038/bjc.1978.54
  24. Ho H.C., Kwan H.C., Ng M.H., de The G. Serum IgA antibodies to Epstein-Barr virus capsid antigen preceding symptoms of nasopharyngeal carcinoma. Lancet. 1978; 1 (8061): 436. Doi: https://doi.org/10.1016/s0140-6736(78)91220-5
  25. Hou X., Zhao C., Guo Y., Han F., Lu L.X., Wu S.X., et al. Different Clinical Significance of Pre- and Post-treatment Plasma Epstein- Barr Virus DNA Load in Nasopharyngeal Carcinoma Treated with Radiotherapy. Clin. Oncol. (R. Coll. Radiol.). 2011; 23(2): 128-33. Doi: https://doi.org/10.1016/j.clon.2010.09.001
  26. Wang W.Y., Twu C.W., Chen H.H., Jan J.S., Jiang R.S., Chao J.Y., et al. Plasma EBV DNA clearance rate as a novel prognostic marker for metastatic/recurrent nasopharyngeal carcinoma. Clin. Cancer Res. 2010; 16(3): 1016-24. Doi: https://doi.org/10.1158/1078-0432.CCR-09-2796
  27. Fan H., Nicholls J., Chua D., Chan K.H., Sham J., Lee S., et al. Laboratory markers of tumor burden in nasopharyngeal carcinoma: a comparison of viral load and serologic tests for Epstein-Barr virus. Int. J. Cancer. 2004; 112(6): 1036-41. Doi: https://doi.org/10.1002/ijc.20520
  28. Cao S.M., Liu Z., Jia W.H., Huang Q.H., Liu Q., Guo X., et al. Fluctuations of epstein-barr virus serological antibodies and risk for nasopharyngeal carcinoma: a prospective screening study with a 20-year follow-up. PLoS One. 2011; 6(4): e19100. Doi: https://doi.org/10.1371/journal.pone.0019100
  29. Белоусова Н.В., Поддубный Б.К., Унгиадзе Г.В., Кондратьева Т.Т., Архипов В.В., Пробатова Н.А. и др. Современная диагностика рака носоглотки. Современная онкология. 2000; 2(3): 78-82.
  30. Lawrence J.B., Villnave C.A., Singer R.H. Sensitive, high-resolution chromatin and chromosome mapping in situ: presence and orientation of two closely integrated copies of EBV in a lymphoma line. Cell. 1988; 52(1): 51-61. Doi: https://doi.org/10.1016/0092-8674(88)90530-2
  31. Гурцевич В.Э., Степина В.Н., Сенюта Н.Б., Гончаров Е.В., Щербак Л.Н., Душенькина Т.Е. и др. Гуморальный иммунный ответ к вирусу Эпштейна-Барр в диагностике рака носоглотки (обзор литературы и 30-летний опыт собственных исследований). Вестник РОНЦ им. Н.Н. Блохина РАМН. 2011; 22(2): 20-30.
  32. Zhao F.P., Liu X., Chen X.M., Lu J., Yu B.L., Tian W.D., et al. Levels of plasma Epstein-Barr virus DNA prior and subsequent to treatment predicts the prognosis of nasopharyngeal carcinoma. Oncol. Lett. 2015; 10(5): 2888-94. Doi: https://doi.org/10.3892/ol.2015.3628
  33. Leung S.F., Tam J.S., Chan A.T., Zee B., Chan L.Y., Huang D.P., et al. Improved accuracy of detection of nasopharyngeal carcinoma by combined application of circulating Epstein-Barr virus DNA and anti-pstein-Barr viral capsid antigen IgA antibody. Clin. Chem. 2004; 50(2): 339-45. Doi: https://doi.org/10.1373/clinchem.2003.022426
  34. Zhao F.P., Liu X., Zhong Z.M., Lu J., Yu B.L., Zeng F.Y., et al. 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. 2014; 2: 88-93. Doi: https://doi.org/10.1016/j.bbacli.2014.10.003
  35. Yu X., Ji M., Cheng W., Wu B., Du Y., Cao S. Assessment of the Long-term Diagnostic Performance of a New Serological Screening Scheme in Large-scale Nasopharyngeal Carcinoma Screening. J. Cancer. 2018; 9(12): 2093-7. Doi: https://doi.org/10.7150/jca.23755

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Copyright (c) 2019 Senyuta N.B., Smirnova K.V., Kondratova V.N., Ignatova A.V., Mudunov A.M., Dushenkina T.E., Liechtenstein A.V., Gurtsevich V.E.

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