Abstract
Background: 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. Methods: 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. Results: The high level of the oral EBV DNA load (>2,100 copies/mL) was independently associated with worse OS (HR = 1.45, 95% CI: 1.20–1.74, p < 0.001), PFS (HR = 1.38, 95% CI: 1.16–1.65, p < 0.001), DMFS (HR = 1.66, 95% CI: 1.25–2.21, p = 0.001), and LRFS (HR = 1.43, 95% CI: 1.05–1.96, p = 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%, p < 0.001) and the median load of oral EBV DNA (13,368 vs. 382 copies/mL, p < 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. Conclusion: Oral EBV DNA load was an alternative non-invasive predictor of prognosis and may facilitate risk stratification for the LA-NPC patients.
Highlights
Nasopharyngeal carcinoma (NPC) is characterized by its distinguished geographical distribution, with more than 70% of all worldwide cases located in south China and southeast Asia (Tang et al, 2016a; Bray et al, 2018)
Similar and robust associations between oral Epstein–Barr virus (EBV) DNA load and prognosis were observed for patients in both the pretreatment and mid-treatment stages
Our study included 1,194 eligible patients from the GARTP cohort according to the following criteria: 1) histologyconfirmed NPC of WHO type II or III; 2) locoregionally advanced NPC (TxN2-3M0 or T2-4N0-3M0 according to the 6th AJCC/UICC TNM staging systems); 3) no other EBVassociated diseases, such as T-cell lymphoma, natural killer cell leukemia/lymphoma, Hodgkin’s disease, pyothorax-associated B-cell lymphoma, gastric carcinoma, and human immunodeficiency virus (HIV) infection; 4) received radiotherapy with or without chemotherapy; 5) available mouthwashes collected before the completion of radiotherapy; 6) available necessary clinical information; and 7) no loss to follow-up within 2 y
Summary
Nasopharyngeal carcinoma (NPC) is characterized by its distinguished geographical distribution, with more than 70% of all worldwide cases located in south China and southeast Asia (Tang et al, 2016a; Bray et al, 2018). Early-stage NPC is relatively asymptomatic; nearly 80% of patients present locally advanced disease with poor prognosis (Pan et al, 2016; Lee et al, 2017). Due to tumor heterogeneity, traditional anatomy–based TNM staging is inadequate for accurately predicting the prognosis or therapeutic benefits of patients with locoregionally advanced NPC (Leung et al, 2006). This highlights the importance of identifying feasible biomarkers to help risk stratification and risk-adapted therapeutic strategy modification for the long-term follow-up of NPC survivors. Plasma Epstein–Barr virus (EBV) DNA load has been widely used for nasopharyngeal carcinoma (NPC) prognostic risk stratification. 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
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