Comparing cell‐free circulating tumor DNA mutational profiles of disease‐free and nonresponders patients with oropharyngeal squamous cell carcinoma

• Published in: Laryngoscope investigative otolaryngology 2020-10, Vol.5 (5), p.868-878
• Main Authors: Khandelwal, Alok R., Greer, Adam H., Hamiter, Mickie, Fermin, Janmaris Marin, McMullen, Thomas, Moore‐Medlin, Tara, Mills, Glenn, Flores, Jose M., Yin, Hong, Nathan, Cherie‐Ann O.
• Format: Article
• Language: English
• Subjects: Cancer; cfDNA; Deoxyribonucleic acid; DNA; Epigenetics; Genes; Genetic testing; Genomes; Head and Neck, and Tumor Biology; Human papillomavirus; Medical prognosis; Mortality; Mutation; Oncology; Original Research; oropharynx; Patients; Plasma; recurrence; Squamous cell carcinoma; Throat cancer; TP53
• ISSN: 2378-8038; 2378-8038
• DOI: 10.1002/lio2.447

Objective The purpose of this study was to investigate whether somatic nonsynonymous variants in tumor tissue can potentially be identified in circulating cell‐free DNA (cfDNA) of head and neck oropharyngeal squamous cell carcinoma (OPSCC) patients using next‐generation sequencing and can predict recurrence or persistence disease. Methods A total of 22 OPSCC patients with tumor tissue and respective plasma samples were included in this study. Matching cfDNA and tumor tissues were processed, and DNA sequencing was conducted using the MiSeq platform. Variants were identified using Biomedical Genomic Workbench and Genialis's online data analysis platform for Swift Biosciences' Accel‐amplicon panels. Results Among 11 nonresponders, 6 matched mutations were detected in 5 patients suggesting a predictive factor for patients with likelihood of recurrence. The matched variants and their allele frequencies identified in the nonresponder group were (tumor DNA/cfDNA in %): TP53 G325fs (27/0.62), TP53 R282W (48/1.74), TP53 R273C (39/2.17), FBXW7 R505G (30/0.6), FBXW7 R505L (31/0.65), and TP53 Q331H (56.5/0.52). Interestingly, the matched somatic mutations were only detected in patients who did not respond to therapy or had persistent disease. Conclusions Somatic nonsynonymous variants in tumor tissue can potentially be identified in cfDNA of OPSCC patients using NGS. The likelihood of variant detection in cfDNA is greater in nonresponders, especially in human papillomavirus‐negative nonresponders, rendering it beneficial as a less invasive detection method for disease persistence/recurrence and prognosis. Level of evidence Cohort study. Somatic nonsynonymous variants in tumor tissue can potentially be identified in cell‐free DNA (cfDNA) of head and neck oropharyngeal squamous cell carcinoma patients using next‐generation sequencing (NGS). The likelihood of variant detection in cfDNA is greater in nonresponders, especially in human papillomavirus‐negative nonresponders, rendering it beneficial as a less invasive detection method for disease persistence/recurrence and prognosis.