Diagnostic value of cell-free DNA in thyroid cancer: A systematic review and meta-analysis

Abstract

Objective: An increasing number of studies have shown the potential diagnostic value of cell-free DNA (cfDNA) as a new biomarker in the management of thyroid cancer (TC); however, the accuracy of research results is inconsistent. This meta-analysis is the first to synthesize published results and evaluate the application value of circulating cfDNA in the diagnosis of TC.Methods: A search strategy was developed according to PICO (P: Patient; I: Intervention; C: Comparison; O: Outcome) principles. We searched 5 databases until October 2022. Original studies that examined cfDNA for the diagnosis of TC and used pathology as the gold standard were included in this meta-analysis. A random-effects model was used to pool the data extracted from individual studies, including the number of patients and the numbers of true positives, false positives, true negatives, and false negatives.Results: A total of 622 patients with TC, 547 patients with benign thyroid nodules, and 98 healthy individuals were included in 20 studies reported in 14 articles. The types of cfDNA included in the research include specific mutations of cfDNA, methylation of cfDNA, the content of cfDNA, and cfDNA index. After rigorous statistical analysis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve were 0.76 (95% confidence interval [CI] 0.62-0.85), 0.87 (95% CI 0.78-0.93), 5.08 (95% CI 3.3-10.3), 0.28 (95% CI 0.17-0.46), 21 (95% CI 9-49), and 0.89 (95% CI 0.86-0.91), respectively. The meta-regression results showed that the number of cfDNAs, cfDNA methylation status, and sample size were the sources of heterogeneity in the specificity of the study. A subgroup analysis showed that the quantitative analysis group (cfDNA level) had a higher diagnostic accuracy than that of the qualitative analysis group (cfDNA methylation, mutation, or integrity index), with a sensitivity of 0.84, specificity of 0.89, and area under the curve of 0.91. Conclusions:The results of this meta-analysis suggest that cfDNA has value as an adjunct for the diagnosis of TC. Quantitative detection of cfDNA can achieve relatively high diagnostic accuracy. However, due to heterogeneity, the test results based on cfDNA for TC should be interpreted with caution.Abbreviations: AUC = area under the curve, BTN = benign thyroid nodule, cfDNA = cell-free DNA, CI = confidence interval, CNKI = China National Knowledge Infrastructure, ctDNA = circulating tumor DNA, DOR = diagnostic odds ratio, HCC = hepatocellular carcinoma, NLR = negative likelihood ratio, PLR = positive likelihood ratio, qPCR = quantitative real-time polymerase chain reaction, SROC = summary receiver operating characteristic, TC = thyroid cancer, Tg = thyroglobulin.

It is time to improve the diagnostic workup of oropharyngeal cancer with circulating tumor HPV DNA: Systematic review and meta‐analysis

“…Previous meta‐analyses on the diagnostic accuracy of quantitative cfDNA testing demonstrated that this technology is better than conventional biomarkers for several cancer diagnoses including gastric cancer, 42 lung cancer, 43 thyroid cancer, 44 HN cancer, 45 and colon cancer 46 …”

“…Included studies fulfilled the items "patient selection," "index test," "reference standard," and "flow and timing" of the risk of the bias section and all three items of the applicability concerns section ("patient selection," "index test," and "reference standard"). Previous meta-analyses on the diagnostic accuracy of quantitative cfDNA testing demonstrated that this technology is better than conventional biomarkers for several cancer diagnoses including gastric cancer, 42 lung cancer, 43 thyroid cancer, 44 HN cancer, 45 and colon cancer. 46 To the best our knowledge, this is the first metaanalysis exploring the accuracy of ctHPVDNA by ddPCR in patients at diagnosis of HPV + OPSCC.…”

Molecular testing in indeterminate thyroid nodules: an additional tool for clinical decision-making

“…On the other hand, there are non-specific biomarkers evaluated for refining the diagnosis of indeterminate thyroid nodule such as the quantification of cfDNA or cfDNA fragmentation index 85 , 86 . In the recent meta-analysis by Hou 87 and colleagues all these biomarkers were debated. They found that a combination of multiple cfDNA biomarkers may be more accurate than single biomarker testing.…”