Diagnosing Burkitt Lymphoma in Sub-Saharan Africa by Sequencing of Circulating Tumor DNA: A Comparative Microcosting Study

Abstract

Objectives: Determining the cost of diagnosis of Burkitt lymphoma by DNA sequencing from a blood sample, compared with current histopathology. Estimating future sequencing costs at increased scale and exploring the effect of positivity rate on per-case cost.

Methods: We conducted a microcosting of both diagnostics. Resource use information was derived from standard operating procedures and interviews with staff. Unit cost data were from salary scales, purchase records, and publicly available prices. Costs were collected during 2021 and 2022, in the currency of purchase, and converted to common year (2024) and currency (US dollar [$]), with a discount rate of 5%. For increased scale, we assumed simple scaling up of current sample preparation and higher-capacity sequencing machines running at least once a week to maintain turnaround times.

Results: We estimated a cost of $185.01 per patient for histopathology, with the main cost drivers being staining ($87.20, largely immunohistochemistry consumables, including $34.52 for antibodies) and the biopsy procedure ($72.29). The cost of the sequencing-based diagnostic was $710.15 at current throughput, with the largest contribution from the sequencing step because of the cost of sequencing reagents ($175.48 per sample). Costs are sensitive to throughput, reagent costs, and efficiency of utilization of equipment. At the current prevalence, cost per positive case is 2-fold higher at a positivity rate of 25% compared with 75%.

Conclusions: With the current technology and throughput, sequencing is likely to increase the cost of diagnosis compared with current pathology. Costs will reduce with increased scale, which requires establishing local reagent supply and maintenance capability.

Keywords: Burkitt lymphoma; circulating tumor DNA; diagnosis; microcosting; sub-Saharan Africa.

Figure 1

Costing of histopathology. Biopsy: collection of tumor tissue sample from patient; tissue preparation: grossing, fixing in formalin; morphology: sectioning, hematoxylin and eosin staining, interpretation and review; immunostaining: sectioning, preparing control sections, staining with antibodies, interpretation, and review. Morphology and immunohistochemistry costs both include tissue sectioning, staining, interpretation, and reporting—shown in detail for the immunohistochemistry.

Figure 2

Costing of liquid biopsy. Plasma: blood collection and preparation of plasma from blood; cfDNA: isolation of cell-free DNA; library: amplification of DNA and hybridization capture of relevant sequences; sequencing: sequencing, analysis, and reporting; QC: checking of DNA concentration and the size of DNA fragments throughout the process. QC indicates quality control.

Figure 3

Cost per sample at increasing throughput. Cost in $ for the sequencing components (machine, reagents, and maintenance) for each machine at increasing throughput.

Figure 4

Cost per positive case detected. Cost ($) per case detected at varying levels of number of cases detected per year. Cost estimates are taken from the scale-up scenarios and use the cost estimate for the lowest-cost machine for the relevant number of samples (MiSeq up to 18 samples per week, NextSeq using a P1 flowcell thereafter).