REVIEW article
Front. Oncol.
Sec. Head and Neck Cancer
This article is part of the Research TopicReviews in Head and Neck CancersView all 9 articles
EGFRvIII expression in head and neck squamous cell carcinoma: clinical significance and sources of frequency variation across studies
Provisionally accepted
Sherin James1
Benjamin Kasten1
Jackie Shi1Akhilesh Mohan Wodeyar1Julian Barnhill2Ivan Reap1Carissa M Thomas3
Anthony Morlandt4Eben Rosenthal5Jason M Warram1*- 1The University of Alabama at Birmingham, Birmingham, United States
- 2The University of Alabama System, Tuscaloosa, United States
- 3University of Colorado Anschutz Medical Campus, Aurora, United States
- 4The University of Alabama at Birmingham School of Dentistry, Birmingham, United States
- 5Vanderbilt-Ingram Cancer Center, Nashville, United States
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EGFRvIII is a tumor-specific, gain-of-function mutation of the EGFR gene that was first detected in 1990 in glioblastoma. For the past two decades, its significance in head and neck cancer has been intensely debated, both in terms of its clinical implications and its mere presence in the disease. This review aims to synthesize evidence on the prevalence, frequency, detection methods, and clinical significance of EGFRvIII in head and neck cancer studies. Our search included major databases such as PubMed, Embase, and Web of Science with keywords such as EGFRvIII, EGFR variants, and head and neck cancer, and stratified the results using Boolean logic to enhance relevance and specificity. Data extraction involved classifying studies by detection method, anatomic subsite, etiology, geography, and population size. The results revealed a frequency of EGFRvIII expression ranging from 0 to 75% across studies, with the major factors influencing this variation being technical sensitivity and specificity issues, primer set variability, sample type and quality heterogeneity, low prevalence and statistical power, and the lack of validation standards. There appears to be an association with a poorer clinical prognosis, though the association with survival remains inconsistent across studies. For future research, it is preferable to be informed about methodological rigor and orthogonal diagnostic assays with extensive prospective validation. Understanding EGFRvIII's genuine frequency and prognostic utility in HNSCC will help guide biomarker development and targeted therapies.
Keywords: biomarker, Clinical significance, Detection methods, EGFRvIII, Frequency variation, Head and neck squamous cell carcinoma, Therapeutic target
Received: 17 Jan 2026; Accepted: 10 Feb 2026.
Copyright: © 2026 James, Kasten, Shi, Wodeyar, Barnhill, Reap, Thomas, Morlandt, Rosenthal and Warram. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jason M Warram
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