Circulating microRNAs in Head and Neck Cancer: A scoping review of methods

Circulating microRNAs have been described as head and neck cancer biomarkers in multiple anatomical subsites including the oral cavity, nasopharynx, larynx, salivary glands and the skin. While there is an expanding volume of published literature showing the significance of individual or panels of microRNAs, the clinical validation of candidate biomarkers is lacking. The various methods used to collect, store, process and interpret these microRNAs are likely introducing bias and contributing to the inconsistent results. A systematic scoping review was conducted using PRISMA standards to identify published English literature between 2007 and 2018. Pubmed and EMBASE databases were searched using specific keyword combinations related to head and neck cancer, circulating samples (whole blood, plasma or serum) and microRNA. Following the title and abstract review, two primary authors appraised the articles for their suitability to include in the review based on the detail of methodological descriptions. Thirty suitable articles were identified relating to nasopharyngeal carcinoma, oral cavity, oropharyngeal and laryngeal squamous cell carcinoma as well as primary salivary gland malignancies. Comprehensive methodological analysis identified poor reporting of detailed methodology, variations in collection, storage, pre-processing, RNA isolation and relative quantification including normalisation method. We recommend standardising the pre-processing, RNA isolation, normalisation and relative quantitation steps at biomarker discovery phase. Such standardisation would allow for bias minimisation and effective progression into clinical validation phases.