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. 2022 Jun 16;14(12):2968. doi: 10.3390/cancers14122968

Table 2.

Key studies examining EBV ctDNA as a biomarker for EBV-associated NPC.

Reference Study Design Sample Size Findings/Strengths Limitations
[50] Prospective 1363
  • -

    EBV ctDNA detectable group had a 10-fold higher incidence for NPC than undetectable group

  • -

    Large sample size
  • -

    Did not retest or monitor EBV DNA fluctuation

  • -

    Endemic population
[57] Prospective 523
  • -

    EBV cfDNA load levels had poorer performance in screening for NPC than EBV IgA titers
  • -

    Endemic population

  • -

    Only first-degree family members of NPC patients
[58] Prospective 773
  • -

    Detectable EBV ctDNA levels had lower sensitivity for screening for early stage NPC than advanced stage

  • -

    Large study population
  • -

    Endemic population

  • -

    Not all high-risk patients underwent diagnostics
[59] Prospective 20,174
  • -

    EBV ctDNA detection in plasma samples had a sensitivity and specificity of 97.1% and 98.6% in screening for NPC

  • -

    Large sample size

  • -

    2 different measurements to confirm EBV ctDNA
  • -

    Endemic population

  • -

    Male only

  • -

    Short 2-year follow-up interval
[63] Retrospective 480
  • -

    Undetectable EBV ctDNA levels before treatment was associated with earlier T and N classification NPC
  • -

    Retrospective design

  • -

    Single-institutional study
[64] Retrospective 278
  • -

    After induction chemotherapy, detectable EBV ctDNA levels were associated with worse 3-year OS, DMFS, and DFS than undetectable levels
  • -

    Endemic population

  • -

    Single-institutional study
[65] Retrospective 637
  • -

    Pre-treatment EBV ctDNA loads >1500 copies/mL and post-treatment detectable EBV ctDNA were both associated with higher risk for recurrence and mortality
  • -

    Endemic population

  • -

    Retrospective

  • -

    Limited follow-up
[66] Retrospective 4469
  • -

    Patients with large EBV ctDNA load had higher tendency for distant metastases

  • -

    Large sample size
  • -

    Only pre-treatment EBV DNA measured
[67] Retrospective 1124
  • -

    EBV ctDNA load > 4000 copies/mL during chemotherapy and IMRT treatment was an independent risk factor for OS

  • -

    Large sample size
  • -

    Single-institutional study

  • -

    Patients with heart, liver, renal, and/or hematologic comorbidities were excluded
[68] Prospective 260
  • -

    Undetectable EBC ctDNA at 8 weeks and 6 months post-IMRT was associated with longer 3-year survival endpoints
  • -

    Endemic Population

OS = Overall survival; DMFS = Distant metastasis-free survival; DFS = Disease-free survival; IMRT = Intensity-modulate radiation therapy.