Influence of blood EBV-DNA level on survival of patients with nasopharyngeal cancer on immune checkpoint inhibitors: A meta-analysis

Pretreatment plasma Epstein–Barr virus (EBV) DNA is a promising biomarker in nasopharyngeal cancer (NPC). However, its prognostic significance in patients receiving immune checkpoint inhibitors (ICIs) remains unclear. This meta-analysis evaluated the association between pretreatment EBV-DNA levels and survival outcomes in NPC patients treated with ICIs. PubMed, Embase, and Web of Science were searched up to June 29, 2025. Eligible longitudinal studies included adult NPC patients treated with ICIs, with pretreatment EBV-DNA assessed by quantitative PCR and survival outcomes reported as hazard ratios (HRs). Pooled analyses used random-effects models accounting for the potential influence of heterogeneity. Thirteen cohorts from 12 studies, comprising 1507 patients, were included. Most cohorts were prospective; two were retrospective. Overall, high pretreatment EBV-DNA was significantly associated with poorer progression-free survival (PFS; HR = 1.72, 95 % CI: 1.46 to 2.03, p < 0.001; I 2 = 0 %) and overall survival (OS; HR = 2.03, 95 % CI: 1.50 to 2.77, p < 0.001; I 2 = 18 %). Sensitivity analyses by excluding one study at a time showed similar results. Subgroup analyses for the outcome of PFS showed consistent associations across study design (prospective vs. retrospective), treatment line (first vs. later), concurrent therapy, cutoff thresholds (< 7800 vs. ≥ 7800 copies/mL), follow-up duration, analytic model, and study quality (all p for subgroup differences >0.05). High pretreatment EBV-DNA levels predict significantly worse PFS and OS in NPC patients receiving ICIs. Pretreatment EBV-DNA may serve as a practical biomarker for risk stratification and treatment decision-making in this population.