Вопросы вирусологии. 2019; 64: 229-237
Диагностика рака носоглотки с помощью серологических и молекулярных маркёров вируса Эпштейна-Барр (Herpesviridae, Lymphocryptovirus, HHV-4) в случаях невыявленного первичного очага опухоли
Сенюта Н. Б., Смирнова К. В., Кондратова В. Н., Игнатова А. В., Мудунов А. М., Душенькина Т. Е., Лихтенштейн А. В., Гурцевич В. Э.
https://doi.org/10.36233/0507-4088-2019-64-5-229-237Аннотация
Введение. Причинами поздней диагностики рака носоглотки (РНГ) являются длительное бессимптомное течение патологического процесса, анатомическое строение носоглотки, часто маленькое, визуально и эндоскопически не обнаруживаемое новообразование и другие факторы. При этом доказано, что этиологическим агентом при наиболее часто встречающемся недифференцированном неороговевающем гистологическом типе РНГ (нРНГ) является вирус Эпштейна–Барр (ВЭБ).
Целью работы стала оценка значимости диагностических маркёров ВЭБ (титров гуморальных антител к вирусу и концентрации вирусной ДНК в плазме) для диагностики нНРГ в группе больных с метастатическим поражением лимфатических узлов шеи без выявленного первичного очага опухоли.
Материал и методы. Материалом для исследования служила плазма крови 83 больных с метастатическим поражением шейных лимфатических узлов и не установленной локализацией первичной опухоли. Плазму от указанных больных тестировали на содержание и титры IgG- и IgA-антител к вирусному капсидному антигену ВЭБ и концентрацию вирусной ДНК.
Результаты и обсуждение. Полученные данные свидетельствуют о том, что совместное тестирование плазмы крови на ВЭБ-специфические антитела и вирусную нагрузку является полезным инструментом для предварительного скрининга больных на нРНГ, что подтверждается данными последующих морфологических и инструментальных исследований, устанавливающих окончательный диагноз. На нескольких примерах показано, что концентрация вирусной ДНК в плазме крови больных нРНГ отражает эффект проведённой терапии и прогноз болезни: ремиссию, стабилизацию опухолевого процесса, рецидив или метастазирование.
Заключение. Несмотря на то, что титры вирус-специфических антител менее точно, чем концентрация вирусной ДНК в плазме, отражают клинические проявления болезни, серологические маркёры чрезвычайно важны для предварительной диагностики нРНГ в случаях невыявленного первичного очага опухоли. Они также могут использоваться для первичного скрининга этого новообразования среди лиц из группы риска.
Список литературы
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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
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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
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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
Problems of Virology. 2019; 64: 229-237
Diagnostics of nasopharyngeal carcinoma with Epstein-Barr virus (Herpesviridae, Lymphocryptovirus, HHV-4) serological and molecular markers in cases of undetected primary tumor location
Senyuta N. B., Smirnova K. V., Kondratova V. N., Ignatova A. V., Mudunov A. M., Dushenkina T. E., Liechtenstein A. V., Gurtsevich V. E.
https://doi.org/10.36233/0507-4088-2019-64-5-229-237Abstract
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.
References
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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
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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
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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
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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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