Abstract
DNA hypermethylation is an important epigenetic mechanism for gene expression inactivation in head and neck cancer (HNC). Saliva has emerged as a novel liquid biopsy representing a potential source of biomarkers. We performed a comprehensive meta-analysis to evaluate the overall diagnostic accuracy of salivary DNA methylation for detecting HNC. PubMed EMBASE, Web of Science, LILACS, and the Cochrane Library were searched. Study quality was assessed by the Quality Assessment for Studies of Diagnostic Accuracy-2, and sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (dOR), and their corresponding 95% confidence intervals (CIs) were calculated using a bivariate random-effect meta-analysis model. Meta-regression and subgroup analyses were performed to assess heterogeneity. Eighty-four study units from 18 articles with 8368 subjects were included. The pooled sensitivity and specificity of salivary DNA methylation were 0.39 and 0.87, respectively, while PLR and NLR were 3.68 and 0.63, respectively. The overall area under the curve (AUC) was 0.81 and the dOR was 8.34. The combination of methylated genes showed higher diagnostic accuracy (AUC, 0.92 and dOR, 36.97) than individual gene analysis (AUC, 0.77 and dOR, 6.02). These findings provide evidence regarding the potential clinical application of salivary DNA methylation for HNC diagnosis.
Highlights
Head and neck cancer (HNC) comprises a heterogenous group of epithelial malignancies arising from mucosal linings of the oral cavity, oropharynx, larynx, and hypopharynx
HNC arises through multistep carcinogenic pathways as a result of cumulative genetic and epigenetic aberrations resulting from risk factors including alcohol and tobacco consumption, human papillomavirus infection, chronic inflammation, and genetic predisposition, and leading to reduced tumor suppressor gene function as well as oncogene activation [2,4]
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Summary
Head and neck cancer (HNC) comprises a heterogenous group of epithelial malignancies arising from mucosal linings of the oral cavity, oropharynx, larynx, and hypopharynx. Dysregulation of DNA methylation has been found to be involved in several diseases, representing an early epigenetic event in carcinogenesis These alterations of normal DNA methylation patterns in cancer have been characterized as global hypomethylation and gene-specific hypermethylation. In addition to global hypomethylation, aberrant promoter hypermethylation can drive the inactivation of key tumor suppressor genes, which are unmethylated in non-malignant tissues [15]. In this sense, silencing by DNA hypermethylation of some genes is common in many types of tumors, the methylation profile of gene promoters is different for each human cancer, allowing the identification of cancer-specific hypermethylation patterns [16].
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