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

John Malcolm Nicholls, Victor Ho-Fun Lee, Sik-Kwan Chan, Ka-Chun Tsang, Cheuk-Wai Choi, Dora Lai-Wan Kwong, Ka-On Lam, Sum-Yin Chan, Chi-Chung Tong, Tsz-Him So, To-Wai Leung, Mai-Yee Luk, Pek-Lan Khong, Anne Wing-Mui Lee, John Malcolm Nicholls, Victor Ho-Fun Lee, Sik-Kwan Chan, Ka-Chun Tsang, Cheuk-Wai Choi, Dora Lai-Wan Kwong, Ka-On Lam, Sum-Yin Chan, Chi-Chung Tong, Tsz-Him So, To-Wai Leung, Mai-Yee Luk, Pek-Lan Khong, Anne Wing-Mui Lee

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.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study flowchart
Fig. 2
Fig. 2
Progression-free survival of NPC patients in the study population stratified by pre-treatment plasma EBV DNA (0–20 copies/ml vs >20 copies/ml). a Stage I. b Stage II. c Stage III. d Stage IVA
Fig. 3
Fig. 3
Overall survival of NPC patients in the study population stratified by pre-treatment plasma EBV DNA (0–20 copies/ml vs >20 copies/ml). a Stage I. b Stage II. c Stage III. d Stage IVA
Fig. 4
Fig. 4
Cancer-specific survival of NPC patients in the study population stratified by pre-treatment plasma EBV DNA (0–20 copies/ml vs >20 copies/ml). a Stage I. b Stage II. c stage III. d stage IVA

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