AUTHOR=He Yong-Qiao , Zhou Ting , Yang Da-Wei , Jia Yi-Jing , Yuan Lei-Lei , Zhang Wen-Li , Wang Tong-Min , Liao Ying , Xue Wen-Qiong , Zhang Jiang-Bo , Zheng Xiao-Hui , Li Xi-Zhao , Zhang Pei-Fen , Zhang Shao-Dan , Hu Ye-Zhu , Wang Fang , Cho William C. , Ma Jun , Sun Ying , Jia Wei-Hua 

TITLE=Prognostic Value of Oral Epstein–Barr Virus DNA Load in Locoregionally Advanced Nasopharyngeal Carcinoma

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.757644

DOI=10.3389/fmolb.2021.757644

ISSN=2296-889X

ABSTRACT=<p><bold>Background:</bold> Plasma Epstein–Barr virus (EBV) DNA load has been widely used for nasopharyngeal carcinoma (NPC) prognostic risk stratification. However, oral EBV DNA load, a non-invasive biomarker that reflects the EBV lytic replication activity, has not been evaluated for its prognostic value in NPC yet.</p><p><bold>Methods:</bold> A total number of 1,194 locoregionally advanced NPC (LA-NPC) patients from south China were included from a prospective observational cohort (GARTC) with a median follow-up of 107.3 months. Pretreatment or mid-treatment mouthwashes were collected for EBV DNA detection by quantitative polymerase chain reaction (qPCR). The difference of pre- and mid-treatment oral EBV DNA load was tested by the Wilcoxon signed-rank test. The associations of oral EBV DNA load with overall survival (OS), progression-free survival (PFS), distant metastasis–free survival (DMFS), and locoregional relapse-free survival (LRFS) were assessed using the log-rank test and multivariate Cox regression.</p><p><bold>Results:</bold> The high level of the oral EBV DNA load (&gt;2,100 copies/mL) was independently associated with worse OS (<italic>HR</italic> = 1.45, 95% <italic>CI</italic>: 1.20–1.74, <italic>p</italic> &lt; 0.001), PFS (<italic>HR</italic> = 1.38, 95% <italic>CI</italic>: 1.16–1.65, <italic>p</italic> &lt; 0.001), DMFS (<italic>HR</italic> = 1.66, 95% <italic>CI</italic>: 1.25–2.21, <italic>p</italic> = 0.001), and LRFS (<italic>HR</italic> = 1.43, 95% <italic>CI</italic>: 1.05–1.96, <italic>p</italic> = 0.023). Similar and robust associations between oral EBV DNA load and prognosis were observed for patients in both the pretreatment and mid-treatment stages. The detection rate (71.7 vs. 48.6%, <italic>p</italic> &lt; 0.001) and the median load of oral EBV DNA (13,368 vs. 382 copies/mL, <italic>p</italic> &lt; 0.001) for patients in the pretreatment stage were significantly higher than those in the mid-treatment stage. The combination of the oral EBV DNA load and TNM staging provided a more precise risk stratification for the LA-NPC patients.</p><p><bold>Conclusion:</bold> Oral EBV DNA load was an alternative non-invasive predictor of prognosis and may facilitate risk stratification for the LA-NPC patients.</p>