This review sought to determine the range and nature of prospective-sampling and blinding methods for validating nonviral biofluid markers diagnostic of head and neck carcinomas. Electronic database searching was conducted to identify studies published in English from January 1, 2009 to August 1, 2020. Sixteen studies from 17 articles published between 2011 and 2020 were included in this review. We found that about 3 out of 100 studies utilized at least one of the mock testing approaches for biomarker validation. Protein, mRNA, and metabolomic markers also represented the only groups whose validation has been attempted using these methods. Furthermore, studies that utilized both methods were found to have lower bias concerns on the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. Overall, there is a need to include these protocols in research endeavours verifying diagnostic biomarkers for head and neck carcinomas following the preliminary establishment of their classification accuracy.
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