Longitudinal detection of somatic mutations in saliva and plasma for the surveillance of oral squamous cell carcinomas

Abstract

Purposes Although clinical and radiological examinations can be used to diagnose oral cancer, and surgical pathology remains the gold standard, these conventional methods have limitations. We evaluated the feasibility of longitudinal next-generation sequencing-based liquid biopsy for oral squamous cell carcinoma surveillance. Materials and methods Eleven patients were enrolled, and plasma and saliva were collected before, and 1, 3, and 6 months after surgery. Tumor-specific mutations were selected using paired, whole-exome analyses of tumor tissues and whole blood. Genes frequently mutated in head and neck cancer were identified using the Cancer Genome Atlas (TCGA) and Catalogue of Somatic Mutations in Cancer (COSMIC) databases to design targeted deep sequencing panels. Results In five of the six patients with recurrent cancer, circulating tumor DNA (ctDNA) was detected earlier with liquid biopsy than with conventional monitoring techniques. Moreover, patients without recurrence exhibited decreased ctDNA allele frequency post-treatment. Conclusions Longitudinal liquid biopsy of plasma and saliva may be feasible for detecting somatic mutations associated with oral squamous cell carcinomas. It might be attributable to determine early tumor recurrence through genetic analysis of ctDNA.

Tracking the Molecular Fingerprint of Head and Neck Cancer for Recurrence Detection in Liquid Biopsies

“…EBV ctDNA is another promising biomarker with low cost and high sensitivity for predicting disease recurrence [ 46 ]. For non-viral-driven subtypes of HNSCC, specific mutations, methylation markers, or RNA expression have been explored as biomarkers [ 24 , 26 , 50 , 51 , 52 , 53 , 56 , 57 , 64 , 67 , 68 , 69 , 79 , 80 , 81 , 82 ].…”

“…Recently, Cui and colleagues [ 56 ] improved on a panel of genes implicated in HNSCC. Tumor-specific mutations were identified in a study on oral squamous cell carcinoma (OSCC) using whole-exome sequencing, and frequent somatic mutations were searched for in TCGA and COSMIC to yield a final panel of 71 frequently mutated genes involving oral cancer, optimized for HNSCC.…”

Clinical applications of liquid biopsy in HPV‐negative and HPV‐positive head and neck squamous cell carcinoma: advances and challenges

“…Saliva specimen has been described as a suitable biological tool offering a non-invasive approach for molecular screening and clinical monitoring in HNSCC patients. Cui et al [ 21 ] investigated single nucleotide variants in cfDNA from plasma and saliva samples of 11 patients with oral squamous cell carcinoma (OSCC) by whole-exome sequencing. The index tumors revealed TP53 as the most frequently mutated gene (55%), followed by CASP8 , AJUBA , CDKN2A , and NOTCH1 mutations.…”

Circulating tumor DNA in Hodgkin lymphoma

“…In comparison to the "classic" tumor biopsy, the main advantages of ctDNA analysis are minimal invasivity, reflection of the tumor heterogeneity across all affected tumor sites, and easy repetitive sampling allowing longitudinal assessment in various timepoints. Depending on the stage and location of tumor, ctDNA can be found in a variety of body fluids, including blood plasma, urine, sputum, cerebrospinal fluid, pleural fluid, and saliva [39][40][41][42][43][44], but low levels of ctDNA may represent a substantial issue for its analysis. The amount of required input cfDNA is dependent on the analysis technique and approach.…”