Negative plasma Epstein-Barr virus DNA nasopharyngeal carcinoma in an endemic region and its influence on liquid biopsy screening programmes

Abstract

Background Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in endemic regions may have undetectable plasma EBV DNA. Methods We prospectively recruited 518 patients with non-metastatic NPC and measured their pre-treatment plasma EBV DNA. The stage distribution and prognosis between pre-treatment plasma EBV DNA-negative (0–20 copies/ml) and EBV DNA-positive (>20 copies/ml) patients following radical treatment were compared. Results Seventy-eight patients (15.1%) were plasma EBV DNA-negative, and 62 in this subset (12.0%) had 0 copy/ml. Only 23/78 (29.5%) plasma EBV DNA-negative patients with advanced NPC (stage III-IVA) had strong EBV encoded RNA (EBER) positivity (score 3) in their tumours compared to 342/440 (77.7%) EBV DNA-positive patients of the same stages (p < 0.001). Though EBV DNA-negative patients had more early-stage disease (p < 0.001) and smaller volumes of the primary tumour and the positive neck nodes (p < 0.001), they had similar 5-year overall survival and cancer-specific survival to those EBV DNA-positive counterparts by stage. Similar results were also seen when plasma EBV DNA cut-off was set at 0 copy/ml. Conclusions Patients with low-volume NPC may not be identified by plasma/serum tumour markers and caution should be taken in its utility as a screening tool for NPC even in endemic regions. Clinical trial registration Clinicaltrials.gov Identifier: NCT02476669.

Clinicopathological and prognostic features of nasopharyngeal carcinoma in children and adolescents: A retrospective study of 196 cases in South China

“…The results showed that patients with plasma EBV DNA ≥1000 copies/mL, EA‐IgA ≥1:10 (and/or) VCA‐IgA ≥1:40 had significantly shorter periods of OS in comparison with other corresponding groups. Of note, the positive rate (71.6%) of plasma EBV DNA in present cohort was relatively low compared to previous studies (88%‐97%) 41,42 . Plasma EBV DNA levels were measured by quantitative PCR.…”

“…Of note, the positive rate (71.6%) of plasma EBV DNA in present cohort was relatively low compared to previous studies (88%-97%). 41,42 Plasma EBV DNA levels were measured by quantitative PCR. The test results will be affected by the methods of DNA extraction, as well as the experiment instruments used in different labs.…”

Whole-Tumor Histogram and Texture Imaging Features on Magnetic Resonance Imaging Combined With Epstein-Barr Virus Status to Predict Disease Progression in Patients With Nasopharyngeal Carcinoma

“…In this study, T1 cases were excluded because these cases had segmentation and assessment issues. However, a greater number of patients who were tested EBV DNA-negative had early-stage disease compared with patients who were tested EBV DNA-positive ( 15 ). We also found that tumor volume was another reliable choice for the radiologic evaluations of tumor burden because patients with positive pretreatment of EBV DNA plasma had larger tumor sizes.…”

Prognostic and Predictive Value of Circulating Inflammation Signature in Non-Metastatic Nasopharyngeal Carcinoma: Potential Role for Individualized Induction Chemotherapy

“…In endemic regions, 17.2–29.3% of all newly diagnosed NPC patients have undetectable circulating EBV. 41 , 42 Second, large interlaboratory variability in the detection of circulating EBV DNA is also a factor, even when using the same PCR assay and identical procedures without harmonization. 43 Third, although pre-treatment plasma EBV DNA levels reflect the tumor burden and correlate with prognosis, the kinetics of circulating EBV DNA during chemoradiotherapy might add more prognostic value and identify distinct prognostic subtypes.…”