Mutated <i>TP53</i> 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
Affiliations
Liyona Kampel
The Head and Neck Cancer Research Laboratory, The Sackler School of Medicine, Tel-Aviv University, 6 Weizman St., Tel-Aviv 6423906, Israel
Sara Feldstein
The Cancer Research and Pathology Institute, Tel Aviv Sourasky Medical Center, The Sackler School of Medicine, Tel-Aviv University, 6 Weizman St., Tel-Aviv 6423906, Israel
Shlomo Tsuriel
The Cancer Research and Pathology Institute, Tel Aviv Sourasky Medical Center, The Sackler School of Medicine, Tel-Aviv University, 6 Weizman St., Tel-Aviv 6423906, Israel
Victoria Hannes
The Cancer Research and Pathology Institute, Tel Aviv Sourasky Medical Center, The Sackler School of Medicine, Tel-Aviv University, 6 Weizman St., Tel-Aviv 6423906, Israel
Narin N. Carmel Neiderman
The Head and Neck Cancer Research Laboratory, The Sackler School of Medicine, Tel-Aviv University, 6 Weizman St., Tel-Aviv 6423906, Israel
Gilad Horowitz
The Department of Otolaryngology, Head and Neck Surgery and Maxillofacial Surgery, The Sackler School of Medicine, Tel-Aviv University, 6 Weizman St., Tel-Aviv 6423906, Israel
Anton Warshavsky
The Department of Otolaryngology, Head and Neck Surgery and Maxillofacial Surgery, The Sackler School of Medicine, Tel-Aviv University, 6 Weizman St., Tel-Aviv 6423906, Israel
Leonor Leider-Trejo
The Cancer Research and Pathology Institute, Tel Aviv Sourasky Medical Center, The Sackler School of Medicine, Tel-Aviv University, 6 Weizman St., Tel-Aviv 6423906, Israel
Dov Hershkovitz
The Cancer Research and Pathology Institute, Tel Aviv Sourasky Medical Center, The Sackler School of Medicine, Tel-Aviv University, 6 Weizman St., Tel-Aviv 6423906, Israel
Nidal Muhanna
The Head and Neck Cancer Research Laboratory, The Sackler School of Medicine, Tel-Aviv University, 6 Weizman St., Tel-Aviv 6423906, Israel
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.