Detection of Epstein–Barr virus DNA methylation as tumor markers of nasopharyngeal carcinoma patients in saliva, oropharyngeal swab, oral swab, and mouthwash

Xiao-Hui Zheng , Xi-Zhao Li , Cao-Li Tang , Yu-Meng Zhang , Ting Zhou , Xiao-Jing Yang , Ying Liao , Yong-Qiao He , Tong-Min Wang , Wen-Qiong Xue , Wei-Hua Jia

MedComm ›› 2024, Vol. 5 ›› Issue (9) : e673

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MedComm ›› 2024, Vol. 5 ›› Issue (9) : e673 DOI: 10.1002/mco2.673
ORIGINAL ARTICLE

Detection of Epstein–Barr virus DNA methylation as tumor markers of nasopharyngeal carcinoma patients in saliva, oropharyngeal swab, oral swab, and mouthwash

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Abstract

Saliva biopsy of nasopharyngeal carcinoma (NPC) has been developed in our latest study, indicating the application of oral sampling in NPC detection. Further exploration of the potential for self-sampling from the oral cavity is necessary. A total of 907 various samples from oral cavity, including saliva (n = 262), oropharyngeal swabs (n = 250), oral swabs (n = 210), and mouthwash (n = 185), were collected. Epstein–Barr virus (EBV) DNA methylation at the 12,420 bp CpG site in EBV genome from the repeat-copy W promoter (Wp) region and at the 11,029 bp CpG site in the single-copy C promoter (Cp) region were simultaneously detected in these samples. A significant increase in EBV methylation, no matter at Wp or Cp region, was found in all types of samples from NPC patients. However, EBV DNA methylation in saliva and oropharyngeal swab showed a better diagnostic performance in detecting NPC. The combination of these two sample types and two markers could help to improve the detection of NPC. Our study further explored the optimal self-sampling methods and detection target in the detection of NPC and may facilitate the application of EBV DNA methylation detection in a home-based large-scale screening of NPC.

Keywords

Epstein–Barr virus DNA methylation / nasopharyngeal carcinoma / oral swab / oropharyngeal swab / saliva

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Xiao-Hui Zheng, Xi-Zhao Li, Cao-Li Tang, Yu-Meng Zhang, Ting Zhou, Xiao-Jing Yang, Ying Liao, Yong-Qiao He, Tong-Min Wang, Wen-Qiong Xue, Wei-Hua Jia. Detection of Epstein–Barr virus DNA methylation as tumor markers of nasopharyngeal carcinoma patients in saliva, oropharyngeal swab, oral swab, and mouthwash. MedComm, 2024, 5(9): e673 DOI:10.1002/mco2.673

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References

[1]

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6): 394-424.

[2]

Lee AWM, Ng WT, Chan LLK, et al. Evolution of treatment for nasopharyngeal cancer—success and setback in the intensity-modulated radiotherapy era. Radiother Oncol. 2014; 110(3): 377-384.

[3]

Woellmer A, Hammerschmidt W. Epstein–Barr virus and host cell methylation: regulation of latency, replication and virus reactivation. Curr Opin Virol. 2013; 3(3): 260-265.

[4]

Zhang L, Wang R, Xie Z. The roles of DNA methylation on the promotor of the Epstein–Barr virus (EBV) gene and the genome in patients with EBV-associated diseases. Appl Microbiol Biotechnol. 2022; 106(12): 4413-4426.

[5]

Mutirangura A, Pornthanakasem W, Theamboonlers A, et al. Epstein–Barr viral DNA in serum of patients with nasopharyngeal carcinoma. Clin Cancer Res. 1998; 4(3): 665-669.

[6]

Lo YM, Chan LY, Lo KW, et al. Quantitative analysis of cell-free Epstein–Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Res. 1999; 59(6): 1188-1191.

[7]

Tune CE, Liavaag PG, Freeman JL, et al. Nasopharyngeal brush biopsies and detection of nasopharyngeal cancer in a high-risk population. J Natl Cancer Inst. 1999; 91(9): 796-800.

[8]

Chien YC, Chen JY, Liu MY, et al. Serologic markers of Epstein–Barr virus infection and nasopharyngeal carcinoma in Taiwanese men. N Engl J Med. 2001; 345(26): 1877-1882.

[9]

Chan KC, Lo YM. Circulating EBV DNA as a tumor marker for nasopharyngeal carcinoma. Semin Cancer Biol. 2002; 12(6): 489-496.

[10]

Tong JHM, Tsang RKY, Lo KW, et al. Quantitative Epstein–Barr virus DNA analysis and detection of gene promoter hypermethylation in nasopharyngeal (NP) brushing samples from patients with NP carcinoma. Clin Cancer Res. 2002; 8(8): 2612-2619.

[11]

Hao SP, Tsang NM, Chang KP. Screening nasopharyngeal carcinoma by detection of the latent membrane protein 1 (LMP-1) gene with nasopharyngeal swabs. Cancer. 2003; 97(8): 1909-1913.

[12]

Stevens SJ, Verkuijlen SA, Hariwiyanto B, et al. Noninvasive diagnosis of nasopharyngeal carcinoma: nasopharyngeal brushings reveal high Epstein–Barr virus DNA load and carcinoma-specific viral BARF1 mRNA. Int J Cancer. 2006; 119(3): 608-614.

[13]

Cao SM, Liu Z, Jia WH, 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.

[14]

Liu Y, Huang QH, Liu WL, et al. Establishment of VCA and EBNA1 IgA-based combination by enzyme-linked immunosorbent assay as preferred screening method for nasopharyngeal carcinoma: a two-stage design with a preliminary performance study and a mass screening in southern China. Int J Cancer. 2012; 131(2): 406-416.

[15]

Yip TTC, Ngan RKC, Fong AHW, Law SCK. Application of circulating plasma/serum EBV DNA in the clinical management of nasopharyngeal carcinoma. Oral Oncol. 2014; 50(6): 527-538.

[16]

Zheng XH, Lu LX, Li XZ, Jia WH. Quantification of Epstein–Barr virus DNA load in nasopharyngeal brushing samples in the diagnosis of nasopharyngeal carcinoma in southern China. Cancer Sci. 2015; 106(9): 1196-1201.

[17]

Chan KCA, Woo JKS, King A, et al. Analysis of plasma Epstein–Barr virus DNA to screen for nasopharyngeal cancer. N Engl J Med. 2017; 377(6): 513-522.

[18]

Chen GH, Liu ZW, Yu KJ, et al. Utility of Epstein–Barr virus DNA in nasopharynx swabs as a reflex test to triage seropositive individuals in nasopharyngeal carcinoma screening programs. Clin Chem. 2022; 68(7): 953-962.

[19]

Zhang PF, Zheng XH, Li XZ, et al. Nasopharyngeal brushing: a convenient and feasible sampling method for nucleic acid-based nasopharyngeal carcinoma research. Cancer Commun (Lond). 2018; 38(1): 8.

[20]

Zheng XH, Lu LX, Cui C, Chen MY, Li XZ, Jia WH. Epstein–Barr virus mir-bart1-5p detection via nasopharyngeal brush sampling is effective for diagnosing nasopharyngeal carcinoma. Oncotarget. 2016; 7(4): 4972-4980.

[21]

Zheng XH, Wang RZ, Li XZ, et al. Detection of methylation status of Epstein–Barr virus DNA C promoter in the diagnosis of nasopharyngeal carcinoma. Cancer Sci. 2020; 111(2): 592-600.

[22]

Zheng XH, Li XZ, Zhou T, et al. Quantitative detection of Epstein–Barr virus DNA methylation in the diagnosis of nasopharyngeal carcinoma by blind brush sampling. Int J Cancer. 2023; 152(12): 2629-2638.

[23]

Tang CL, Li XZ, Zhou T, et al. EBV DNA methylation profiles and its application in distinguishing nasopharyngeal carcinoma and nasal NK/T-cell lymphoma. Clin Epigenet. 2024; 16(1): 11.

[24]

Jiang CT, Zheng XH, Lin L, et al. CRISPR Cas12a-mediated amplification-free digital DNA assay improves the diagnosis and surveillance of nasopharyngeal carcinoma. Biosens Bioelectron. 2023; 237: 115546.

[25]

Zheng XH, Deng CM, Zhou T, et al. Saliva biopsy: detecting the difference of EBV DNA methylation in the diagnosis of nasopharyngeal carcinoma. Int J Cancer. 2023; 153(4): 882-892.

[26]

Kaczor-Urbanowicz KE, Wei F, Rao SL, et al. Clinical validity of saliva and novel technology for cancer detection. Biochim Biophys Acta Rev Cancer. 2019; 1872(1): 49-59.

[27]

Drobnik A, Judd C, Banach D, Egger J, Konty K, Rude E. Public health implications of rapid hepatitis C screening with an oral swab for community-based organizations serving high-risk populations. Am J Public Health. 2011; 101(11): 2151-2155.

[28]

Hadinoto V, Shapiro M, Sun CC, Thorley-Lawson DA. The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output. PloS Pathog. 2009; 5(7): e1000496.

[29]

Munz C. Latency and lytic replication in Epstein–Barr virus-associated oncogenesis. Nat Rev Microbiol. 2019; 17(11): 691-700.

[30]

Buschle A, Hammerschmidt W. Epigenetic lifestyle of Epstein–Barr virus. Semin Immunopathol. 2020; 42(2): 131-142.

[31]

Faulkner GC, Krajewski AS, Crawford DH. The ins and outs of EBV infection. Trends Microbiol. 2000; 8(4): 185-189.

[32]

He YQ, Liao XY, Xue WQ, et al. Association between environmental factors and oral Epstein–Barr virus DNA loads: a multicenter cross-sectional study in China. J Infect Dis. 2019; 219(3): 400-409.

[33]

Xue WQ, He YQ, Liao XY, et al. Decreased oral Epstein–Barr virus DNA loads in patients with nasopharyngeal carcinoma in Southern China: a case–control and a family-based study. Cancer Med. 2018; 7(7): 3453-3464.

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2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.

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