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Salivary Gland Tumors Diagnosis and Treatment / Head and Neck Cancer Studies · Journal article
Scientific Reports · September 9, 2026
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This retrospective single-center study of 86 recurrent HNSCC patients identified distinct genomic alterations (TP53, CDKN2A, TERT, FGF4, PIK3CA) associated with survival and treatment response using Cox proportional hazards models. The authors explicitly state these findings are exploratory and hypothesis-generating, requiring prospective validation in larger independent cohorts before clinical application.
Retrospective cohort study with targeted DNA sequencing. 86 patients with recurrent head and neck squamous cell carcinoma treated at the University of Maryland Medical Center.. Intervention: Targeted DNA sequencing of recurrent tumor samples to characterize genomic alterations. Compared with: Primary HNSCC genomic profiles from The Cancer Genome Atlas (TCGA). n = 86. University of Maryland Medical Center (single center).
TP53 mutations present in 55% of tumors, associated with worse OS (HR: 1.77, p = 0.033) and poor treatment response (p = 0.0067) CDKN2A mutations (29%) showed better PFS (HR: 0.57, p = 0.045), occurring more frequently in recurrent versus primary TCGA tumors TERT mutations (26%) associated with poorer PFS (HR: 1.66, p = 0.045) and reduced response to immune therapy (p = 0.0854, not statistically significant)
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These exploratory findings identify genomic markers potentially associated with prognosis and treatment response in recurrent HNSCC, but should not yet inform clinical decision-making. Prospective validation in larger independent cohorts is explicitly required before any clinical application.
Single-center retrospective analysis of 86 patients with exploratory, hypothesis-generating associations between genomic alterations and clinical outcomes; the authors explicitly state prospective validation in larger cohorts is necessary before clinical application.
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These exploratory findings identify genomic markers potentially associated with prognosis and treatment response in recurrent HNSCC, but should not yet inform clinical decision-making. Prospective validation in larger independent cohorts is explicitly required before any clinical application.
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Abstract While the genetic landscape of treatment-naïve head and neck squamous cell carcinoma (HNSCC) is well characterized, the molecular features of recurrent disease remain less defined. We investigated the genetic alterations in recurrent HNSCC and their associations with overall survival (OS), progression-free survival (PFS), and treatment response. We performed a retrospective analysis of 86 patients with recurrent HNSCC treated at the University of Maryland Medical Center. Clinical data were extracted from electronic health records, and targeted DNA sequencing of tumor samples was performed by Tempus. Genomic profiles were compared with primary HNSCC profiles from The Cancer Genome Atlas (TCGA). Associations between mutations and clinical outcomes were evaluated using Cox proportional hazards models. TP53 mutations were most prevalent (55%) and significantly correlated with worse OS (HR: 1.77, p = 0.033) and poor treatment response ( p = 0.0067). CDKN2A (29%) and TERT (26%) mutations occurred more frequently in recurrent tumors compared to primary TCGA tumors. While CDKN2A mutations showed better PFS (HR: 0.57, p = 0.045), TERT mutations showed association with poorer PFS (HR: 1.66, p = 0.045) and reduced response to immune therapy ( p = 0.0854), although the latter did not reach statistical significance. Notably, although in small number, FGF4 (9%) mutations were associated with significantly poor survival (HR: 2.16, p = 0.049) and poorer outcomes following surgery and/or radiotherapy ( p = 0.0124). However, contradictory to other mutated genes, PIK3CA mutations (14%) correlated with better OS (HR: 0.37, p = 0.032). Recurrent HNSCC exhibit distinct genomic alterations associated with survival and therapeutic response. These findings are exploratory and hypothesis-generating. Prospective validation in larger, independent cohorts is necessary before these associations can inform treatment decisions.
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