A Comparative Study of Epstein-Barr Virus Genomes Detected in Tumor, Nasopharyngeal Swab, and Saliva Samples From Patients With Nasopharyngeal Carcinoma

Abstract

Background

Specific genetic variations of Epstein-Barr virus (EBV) have been linked to nasopharyngeal (NP) carcinoma (NPC). Because EBV is shed through saliva, saliva samples are commonly used for EBV genotyping in studies of EBV-associated diseases. However, it remains uncertain whether infection with the same EBV strains occurs across different tissues within a host and whether EBV detected in saliva accurately represents the strain in diseased tissues.

Methods

We conducted whole-genome sequencing of EBV from paired biopsy tissues, saliva samples, and NP swab samples from 33 patients with newly diagnosed NPC to determine the genetic concordance of EBV strains across different tissue types within the same individual.

Results

Phylogenetic and pairwise genetic distance analysis revealed a high degree of intrahost concordance, indicating infection with the same EBV strains among different samples within the host. Multiple EBV infections were identified in 6% of saliva samples, compared with 3% in tumor tissues. Notably, NPC tumor EBV strains were consistently detected in paired saliva and swab samples. For multiple infections in saliva and NP swab samples, EBV variants of the major strain showed higher genetic concordance with the variants detected in NPC tumors than with variants of the minor strain.

Conclusions

Our study highlight the genetic consistency of EBV across tumor, NP swab, and saliva samples, supporting the use of saliva as a reliable source for EBV sequencing and genotyping in future epidemiological studies.

Epstein-Barr virus, nasopharyngeal carcinoma, virus whole-genome sequencing, intrahost concordance, EBV genetic variation