Fig. 2
Longitudinal EBV BALF2 genotyping and modeled variant-informed NPC screening strategies in 12 high-risk endemic populations. A A subset of 16 patients with serial EBV-positive plasma specimens were subject to BALF2 genotyping by qPCR and NGS to assess temporal haplotype stability. Variant allele fraction (VAF) is plotted against time from first specimen collection for the three qPCR targets (V700L, I613V, V317M). The sample’s viral load in log10 EBNA-1 IU/mL is plotted below the allele frequencies. Two patients had one specimen each with temporally-discordant haplotypes. Patient #2 was a lung/liver transplant recipient with I613V detected in only the third of seven plasma specimens collected over 8.7 months. Patient #10 was a kidney transplant recipient with large-cell lymphoma who had V700 detected only in the first of five specimens collected over 7.8 months, whereas the subsequent four specimens harbored V700L, possibly indicating mutagenesis. B Map of east/southeast Asia with 12 included high-risk populations. Shading represents the national NPC incidence rate. Each bubble indicates a single population with size proportional to incidence rate. Bubble color indicates the cost-effectiveness of variant-informed screening at variable willingness-to-pay thresholds. C Modeled survival in a hypothetical cohort of 50-year-old patients in southern China. Survival differs with no screening (black line), seven variant-agnostic screening strategies (red solid lines), and seven variant-informed screening strategies (blue dashed lines) due to weighted stage distributions dictated by effective screening sensitivity. D Cost-effectiveness of variant-agnostic and variant-informed screening strategies across variable screening frequencies. Box plots indicate median with interquartile range. E Resource utilization after initial biomarker screening for variant-agnostic (A0-G0) and variant-informed screening strategies (ABALF2-GBALF2). Bar charts indicate absolute number of screening endoscopies and MRIs per 100,000 screened subjects. Referrals for endoscopy/MRI decrease after triage with BALF2 qPCR. F NPC deaths per 100,000 screened individuals with variable screening frequencies and initial screening ages