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

Br J Cancer. 2019 Oct;121(8):690-698. doi: 10.1038/s41416-019-0575-6. Epub 2019 Sep 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • DNA, Viral / blood*
  • Early Detection of Cancer
  • Endemic Diseases
  • Epstein-Barr Virus Infections / blood*
  • Epstein-Barr Virus Infections / diagnosis
  • Epstein-Barr Virus Infections / epidemiology
  • Female
  • Herpesvirus 4, Human / genetics
  • Hong Kong / epidemiology
  • Humans
  • Liquid Biopsy
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma / blood*
  • Nasopharyngeal Carcinoma / diagnosis
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Carcinoma / virology
  • Nasopharyngeal Neoplasms / blood*
  • Nasopharyngeal Neoplasms / diagnosis
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / virology
  • Neoplasm Staging
  • Prognosis
  • RNA, Viral / blood*
  • Survival Rate
  • Tumor Burden
  • Young Adult

Substances

  • DNA, Viral
  • RNA, Viral

Associated data

  • ClinicalTrials.gov/NCT02476669