Simple SummaryThere is a correlation between quality of life (QoL) scores and treatment outcomes in patients receiving head and neck cancer (HNC) treatment. Higher QoL scores have been associated with improved survival yet there are considerable differences in the assessment of QoL in clinical trials. The aim of this systematic scoping review is to evaluate the variability of QoL reporting in clinical trials investigating anti-EGFR treatment. Our study confirms no standard method for reporting QoL data in clinical trials for HNC patients. QoL benchmarks are assessed and reported differently between studies. Therefore, these metrics are difficult to evaluate on a larger scale, preventing quantitative analysis. This review identifies the need to standardize the method for QoL assessment.AbstractIn patients receiving treatment for head and neck cancer (HNC), there is a correlation between quality of life (QoL) scores and treatment outcomes. Higher QoL scores have been associated with improved survival. Despite this, the assessment of QoL in clinical trials varies considerably. Three databases (Scopus, PubMed, and Cinahl) were queried for articles published in English between 2006 and 2022. Two reviewers (SRS and ANT) performed study screening, data extraction, and risk of bias assessment. The authors identified 21 articles that met the inclusion criteria. A total of 5961 patients were evaluated. QoL was reported as average scores for specific variables across five different surveys in 12 included articles. Supplemental QoL data were available in 10 included studies. Critical appraisal of studies indicated a high risk of bias due to the inclusion of trials. There is no standard method for reporting QoL data in clinical trials for HNC patients undergoing treatment with anti-EGFR inhibitors. Future clinical trials should standardize their method for assessing and reporting quality-of-life data to increase patient-centered care and refine treatment choices to optimize survival.