Plasma Epstein-Barr virus DNA for disease surveillance in endemic nasopharyngeal carcinoma: Analysis of a real-world database

Abstract

Aim

Plasma Epstein-Barr virus (EBV) DNA is an archetypal biomarker for endemic nasopharyngeal carcinoma (NPC) employed for disease surveillance and early detection of recurrences. However, its accuracy is unknown. We utilised a single institution dataset with homogeneous surveillance procedures and routine EBV DNA testing using a harmonised assay to investigate its accuracy for recurrence detection.

Methods

We utilised a cohort of patients with histologically-confirmed, non-metastatic NPC treated from February, 2017 to July, 2023. All patients had ≥ 1 EBV DNA test using the harmonised BamHI-W polymerase chain reaction-based assay within 3 years post-radiotherapy (RT). We analysed the negative (NPV) and positive predictive values (PPV) for recurrence over a 1-year window (at 3-monthly intervals – windows 1–4) for each test performed. Recurrence was ascertained by radiological imaging and/or histopathological confirmation.

Results

Of 1746 EBV DNA readings from 393 patients diagnosed between January, 2017 to May, 2023, 1385 (79.3 %), 294 (16.8 %), and 67 (3.9 %) were recorded as negative, low (< 500 copies/mL), and high EBV DNA (≥ 500 copies/mL), respectively. NPVs of the assay were high (range: 97.6–99.3 %). PPVs were modest, highest at window 1 (range: 26.3–34.3 %) compared with the other 3 windows (range: 2.6–10.5 %). Sensitivity analyses revealed that PPVs were threshold-dependent; 71.4–100 % at window 1 for ≥ 500 copies/mL versus 16.9–23.1 % for < 500 copies/mL, which corresponded to median time of recurrence onset (0.8 vs 4.8 months, respectively).

Conclusions

Negative EBV DNA test results have high NPVs, suggesting that patients may be routinely surveyed, while a positive result of ≥ 500 copies/mL indicates high recurrence risk.