DNA methylation biomarkers in peripheral blood of patients with head and neck squamous cell carcinomas. A systematic review

• Published in: PloS one 2020-12, Vol.15 (12), p.e0244101-e0244101
• Main Authors: Danstrup, Christian Sander, Marcussen, Mette, Pedersen, Inge Søkilde, Jacobsen, Henrik, Dybkær, Karen, Gaihede, Michael
• Format: Article
• Language: English
• Subjects: Audiology; Bias; Biological markers; Biological properties; Biology and life sciences; Biomarkers; Biomarkers, Tumor - blood; Blood; Blood plasma; Cancer; Clinical medicine; Colorectal cancer; Deoxyribonucleic acid; Diagnosis; Diagnostic software; Diagnostic systems; DNA; DNA Methylation; DNA, Neoplasm - blood; Epigenesis, Genetic; Epigenetics; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Head & neck cancer; Head and neck; Head and neck cancer; Head and neck carcinoma; Head and Neck Neoplasms - blood; Health aspects; Hepatocellular carcinoma; Hospitals; Human papillomavirus; Humans; Literature reviews; Medical libraries; Medical prognosis; Medical research; Medical screening; Medicine and Health Sciences; Methylation; Molecular diagnostic techniques; Otolaryngology; Peripheral blood; Physical Sciences; Plasma; Research and Analysis Methods; Septin; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - blood; Surgery; Systematic review; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0244101

Head and neck squamous cell carcinomas (HNSCC) are often diagnosed in advanced stages. In search of new diagnostic tools, focus has shifted towards the biological properties of the HNSCC, and the number of different biomarkers under investigation is rapidly growing. The objective was to review the current literature regarding aberrantly methylated DNA found in peripheral blood plasma or serum in patients with HNSCC and to evaluate the diagnostic accuracy of these changes. The inclusion criteria were clinical studies involving patients with verified HNSCC that reported findings of aberrantly methylated DNA in peripheral blood serum or plasma. We systematically searched PubMed, OVID Embase and Cochrane Library. In addition to the search, we performed forward and backward chaining in references and Web of Science. The protocol was registered in PROSPERO: CRD42019135406. Two authors independently extracted data. The quality and the risk of bias of the included studies were assessed by the QUADAS-2 tool. A total of 1,743 studies were found eligible for screening, while ultimately seven studies were included. All studies were found to have methodological weaknesses, mainly concerning patient selection bias. The best individual marker of HNSCC was Septin 9 in plasma with a sensitivity of 57% and a specificity of 95%. None of the aberrantly methylated genes found in the retrieved studies are applicable as single diagnostic markers for HNSCC and the best gene-panels still lack diagnostic accuracy. Future studies may benefit from newer sequencing techniques but validation studies with well-designed cohorts are also needed in the process of developing epigenetic based diagnostic tests for HNSCC.