Mutated TP53 in Circulating Tumor DNA as a Risk Level Biomarker in Head and Neck Squamous Cell Carcinoma Patients

Liyona Kampel, Sara Feldstein, Shlomo Tsuriel, Victoria Hannes, Narin N. Carmel Neiderman, Gilad Horowitz, Anton Warshavsky, Leonor Leider-Trejo, Dov Hershkovitz, Nidal Muhanna*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Circulating tumor DNA (ctDNA) has been suggested as a surrogate biomarker for early detection of cancer recurrence. We aimed to explore the utility of ctDNA as a noninvasive prognostic biomarker in newly diagnosed head and neck squamous cell carcinoma (HNSCC) patients. Seventy HNSCC specimens were analysed for the detection of TP53 genetic alterations utilizing next-generation sequencing (NGS). TP53 mutations were revealed in 55 (79%). Upon detection of a significant TP53 mutation, circulating cell-free DNA was scrutinized for the presence of the tumor-specific mutation. ctDNA was identified at a minimal allele frequency of 0.08% in 21 out of 30 processed plasma samples. Detectable ctDNA correlated with regional spread (N stage ≥ 1, p = 0.011) and poorer 5-year progression-free survival (20%, 95% CI 10.9 to 28.9, p = 0.034). The high-risk worst pattern of invasion (WPOI grade 4–5) and deep invasion were frequently found in patients whose ctDNA was detected (p = 0.087 and p = 0.072, respectively). Detecting mutated TP53 ctDNA was associated with poor progression-free survival and regional metastases, indicating its potential role as a prognostic biomarker. However, ctDNA detectability in early-stage disease and the mechanisms modulating its release into the bloodstream must be further elucidated.

Original languageEnglish
Article number1418
JournalBiomolecules
Volume13
Issue number9
DOIs
StatePublished - Sep 2023

Keywords

  • TP53
  • adjuvant therapy
  • circulating tumor DNA
  • head and neck squamous cell carcinoma
  • next-generation sequencing

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