Abstract 5901: Circulating tumor DNA in non-viral head and neck squamous cell carcinoma: A systematic review and meta-analysis
Authors: Vanessa Helou, Nana-Hawwa Abdul-Rahman, Suet Kee Loo, Shou-Jiang Gao, Jose P. Zevallos, Dan Zandberg, Matthew E. Spector, Heath D. Skinner, Robert L. Ferris, Kevin J. Contrera
Journal: Cancer Research (2025)

Abstract Purpose: Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker offering insights into tumor biology, treatment response, and disease monitoring, particularly for less accessible tumors. Although ctDNA in viral-mediated head and neck squamous cell carcinoma (HNSCC) is widely studied, research into the role ctDNA for non-viral HNSCC is limited. This systematic review and meta-analysis consolidates evidence on ctDNA in non-viral HNSCC and examines its implications for diagnosis, prognosis, and management. Experimental Design: A comprehensive literature search was conducted in September 2024 across Medline, PubMed, Embase, and the Cochrane Library. Following PRISMA guidelines, two reviewers independently screened titles, abstracts, and full texts. Clinical outcomes were extracted in duplicate into a standardized pilot-tested form. Pooled hazard ratios (HR) were calculated using a fixed-effect model. Results: Out of 1915 screened studies, 47 studies involving 3, 574 patients were included. The median publication year was 2022, with 64% of studies being prospective. The most common ctDNA assays were next-generation sequencing (n=28, 60%) and PCR-based techniques (n=21, 45%). Median assay sensitivity was 80% (range 38-100%), and specificity was 99% (range 60-100%), with twelve studies reporting specificity exceeding 91%. Pre-treatment ctDNA detection rates ranged from 50% to 100%, with a median of 83%, while post-treatment rates ranged from 28% to 100%, with a median of 48%. ctDNA identified recurrence or progression in 80% of patients (range 40-100%) prior to clinical diagnosis, with five studies reporting 100% detection of recurrence or progression. The median lead time between ctDNA detection and clinically or radiologically confirmed disease progression was 4.6 months (range 1-27 months). On survival analyses, ctDNA detection, SEPT9 methylated ctDNA, and mutated ctDNA were associated with worse overall survival, with pooled HRs of 10.26 (95% CI: 3.58-29.40; P &amp;lt; .0001), 1.15 (95% CI: 1.08-1.23; P &amp;lt; .0001), and 1.96 (95% CI: 1.28-3.00; P = 0.002), respectively. ctDNA correlated with worse progression-free survival (HR 7.32, 95% CI: 4.17-12.86; P &amp;lt; .00001) and recurrence-free survival (HR 7.33, 95% CI: 2.75-19.58; P &amp;lt; .0001). Conclusions: ctDNA shows promise for enhancing diagnostic accuracy, monitoring progression and recurrence in non-viral HNSCC. While additional research is necessary, our findings could inform the development of evidence-based clinical guidelines for the personalized management of non-viral HNSCC. Citation Format: Vanessa Helou, Nana-Hawwa Abdul-Rahman, Suet Kee Loo, Shou-Jiang Gao, Jose P. Zevallos, Dan Zandberg, Matthew E. Spector, Heath D. Skinner, Robert L. Ferris, Kevin J. Contrera. Circulating tumor DNA in non-viral head and neck squamous cell carcinoma: A systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5901.