Table 2.
Somatic gene mutations detected in liquid biopsies from head and neck cancer patients.
| Author | Cohort | Location | Stage | HPV | Type of samples (N) | Technique | % mutated cases/ (total cases) | Genes Analyzed | Main objective |
|---|---|---|---|---|---|---|---|---|---|
| Wang et al. 2015 | 93 HNSCC | 46 OC 34 OP 10 L 3 HP |
20 (I-II) 73 (III-IV) | 30 (+) 63 (–) |
Saliva | ddPCR and Safe-SeqS | 76%/(93) | TP53, PIK3CA, CDKN2A, FBXW7, HRAS, NRAS | To detect somatic mutations and HPV in plasma and saliva from HNSCC patients |
| Plasma | 87%/(47) | ||||||||
| Braig et al. 2016 | 46 HNSCC | 17 OP 12 OC 8 HP 4 L 2 PNS 2 OP/HP 1 HP/L |
3 (II) 42 (III-IV) 1 (UNK) |
5 (+) 41 (-) |
Plasma | Targeted sequencing | 46%/(20) | EGFR (exon 12), KRAS/NRAS (exons 2/3/4), HRAS (exons 2/3) | To identify acquired RAS mutations which could correlated with resistance to cetuximab in plasma samples from HNSCC patients during and after therapy |
| Mazurek et al. 2016 | 200 HNSCC | 72 OP 85 L 20 HP 15 NP 8 UNK |
83 (I-III) 114 (IV) |
28 (+) 172 (-) |
Plasma | PCR | 0/(200) |
KRAS G12C (c .34 G>T) EGFR (p.E746-A750del) |
To analyze the most frequent mutations of KRAS and EGFR in plasma for identifying HNSCC patients for treatment with anti-EGFR monoclonal antibodies and EGFR inhibitors |
| Perdomo et al. 2017 | 36 HNSCC (ARCAGE study) | n.a. | 14 (I-II) 22 (III-IV) |
36 (-) | Plasma | Targeted sequencing | 42%/ (36) | TP53, NOTCH1, CDKN2A, CASP8, PTEN | To evaluate the presence of DNA alterations in plasma ctDNA and oral rinses |
| 37 HNSCC (LA study) | n.a. | 37 (III-IV) | UNK | Plasma | 8.10%/(37) | TP53 | |||
| Oral rinse | 37.84%/(37) | ||||||||
| van Ginkel et al. 2017 | 6 HNSCC | 5 OC 1 OP |
1 (II) 5 (IV) |
6 (-) | Plasma | ddPCR | 100%/(6) | TP53 | To investigate whether low levels of ctDNA in plasma of HNSCC patients can be detected using ddPCR |
| Egyud et al.2018 | 8 HNSCC | n.a. | 1 (I) 7 (IV) |
4 (+) 4 (-) |
Plasma | Targeted sequencing (SiMSen-Seq) | n.a./(8) | TP53, ARID1B, ATM, CDK8, FANCA, RASA1, CSM2D, SIN3A, KRAS, NSD1, SMARCA4, XRCC2, BCL10, RPTOR | To examine the potential role of ctDNA in treatment monitoring and recurrence detection in HNSCC patients based on patient’s tumor specific mutations |
| Schmidt et al. 2018 | 29 HNSCC | 15 OP 10 OC 1 HP 1 L 2 UNK |
29 (III-IV) | 14 (+) 15 (-) |
Plasma | Allele-specific Plex-PCR™ technology | 31.03%/(29) | PIK3CA (p.E545K) | To determine whether Plex-PCR™ technology could be used to detect PIK3CA p.E545K mutation in HNSCC plasma samples |
| Galot et al. 2020 | 39-HNSCC (20 metastatic disease and 19 with recurrent disease) | 22 OP 8 OC 6 HP 6 L 1 UNK |
20 (IV) | OP 5 (+) OP 17 (-) |
Plasma | Targeted sequencing | 51%/(39) | Custom panel of 604 genes | To investigate the feasibility of detecting ctDNA in a prospective cohort of recurrent and/or metastatic HNSCC patients using a tissue-agnostic approach and evaluate the concordance of the mutational landscape between ctDNA and matched tumor |
| Mes et al. 2020 | 40 HNSCC | 5 OC 18 OP 10 HP 5 L 2 UNK |
2 (I) 4(II) 6 (III) 28 (IV) |
10 (+) 9 (-) 1 UNK 20 n.a. |
Plasma | Targeted sequencing | 67%/(27) | Custom panel of 12 genes (AJUBA, CASP8, CDKN2A, FAT1, FBXW7, HRAS, KMT2D, NOTCH1, NSD1, PIK3CA, PTEN, TP53) | To detect somatic mutations in tumor and corresponding plasma and to identify ctDNA without prior knowledge of tumor DNA aberrations |
| Khandelwal et al. 2020 | 22 OPSCC | 22 OP | n.a. | 11 (+) 11 (-) |
Plasma | Targeting sequencing | 50%/(22) | Accel-Amplicon 56 G Oncology Panel v2 (Swift Biosciences) | To explore the potential of ctDNA for detecting tumor somatic mutations and predicting recurrence or persistence disease |
| Burgener et al. 2021 | 30 HNSCC | 1 PNS 23 OC 3 L 3 HP |
4 (I) 2 (II) 5 (III) 19 (IV) |
9 (-) 21 n.a. |
Plasma | Targeted sequencing | 67%/(30) | CAncer Personalized Profiling by deep Sequencing (CAPP-seq) using 42 frequently recurrent genomic alterations in HNSCC from TCGA | To conduct multimodal profiling of mutations and methylation in ctDNA of HNSCC patients |
| Hilke et al. 2020 | 20 HNSCC | 14 OP 4 HP 2 OC |
n.a. | 5 (+) 14 (-) 1 n.a. |
Plasma | Targeted sequencing | 83%/(60) | 127 driver tumor mutations | To explore the capacity of ctDNA to monitor the treatment response during radio-chemotherapy and detect the molecular residual disease post-treatment |
| Porter et al. 2020 | 60 R/M HNSCC* * | 21 OP 12 OC 8 SG 6 L 4 HP 4 T 3 NP 2 UNK |
n.a. | 15 (+) 9 (-) 36 (UNK) | Blood | Targeted sequencing | 76%/(76) | Custom panel of 1021 genes | To characterize the ctDNA mutational profile of advanced HNC and identify actionable mutations |
| Wilson et al. 2020 | 75 HNSCC | 28 OC 22 OP 14 L 7 HP 3 PNS 1 NP |
28 (I-III) 47 (IVA-C) |
20 (+) 33 (-) 22 (UNK) |
Plasma | Targeted sequencing | 76% /(75) | Guardant360™ platform (73 genes) |
Characterization of genomic landscape in ctDNA and tumor DNA of HNSCC patients and assessment the prognostic impact |
| Wu et al. 2021 | 27 HNSCC | 11 L 10 HP 5 OC 1 OP |
19 (I-II) 18 (III-IV) |
27 (-) | Plasma | Targeted sequencing | 70.04%/(27) | Custom panel of 1021 genes | To profile the mutational features of different HNSCC samples including tumour tissues, tumor-adjacent tissue, pre- and post-surgical ctDNA and salivary ctDNA |
| Saliva | 63%/(27) | ||||||||
| Shanmugam et al. 2021 | 121 OSCC | 121 OC | 58 (I-II) 63 (III-IV) |
UNK | Saliva | Targeted sequencing | 95,87%/(121) | CASP8, PIK3CA, FAT1, CDKN2A, NOTCH1, HRAS, TP53 | To detect tumor-specific mutations in saliva of patients with OSCC |
| Cui et at. 2021 | 11 OSCC | 11 OC | 4 (II) 7 (III-IV) |
UNK | Plasma | Targeted sequencing | 27%/(11) | Custom panel of 71 genes | To examine the feasibility of using serial liquid biopsies in detecting minimal residual disease in oral cancer patients |
| Saliva | 91%/(11) | ||||||||
| Flach et al. 2022 (a) | 8 HNSCC | 3 OC 3 OP 1 L 1 HP |
1 (I-II) 7 (III-IV) | 8 (-) | Plasma | Targeted sequencing | 87.5%/(8) | Oncomine™ Comprehensive Assay v3Panel (161 genes) | Characterization of the mutational landscape in tumor, histopathologically negative resection margins and plasma cfDNA |
| Kogo et al. 2022 | 26 HNSCC | 5 OC 3 OP 7 L 3 HP 6 EAC |
6 (I-II) 20 (III-IV) |
22 (-) 4 (+) |
Plasma | Targeted sequencing | n.a./(18) | TP53, PIK3CA, KMT2D, FAT1, FBXW8, NOTCH3, CREBBP | To detect ctDNA candidate genes and performed ctDNA monitoring using ddPCR |
| Flach et al. 2022 (b) | 17 HNSCC | 5 OC 2 OP 7 L 4 HP 1 SPT |
17 (III-IV) | 17 (-) | Plasma | Multiplex PCR and targeted NGS | 100%/(17) | RaDaR™ patient-specific assay/ Personalised RaDaR™ panels (from 34 to 52 variants) | To determine whether post-operative ctDNA detection can act as a biomarker for surgical tumour clearance and to evaluate the potential of personalised ctDNA analysis for early detection of relapse |
| Rapado-González et al. 2022 | 3 HNSCC | 2 OC 1 HP |
3 (IV) | 3 (-) | Plasma | Targeted NGS | 110%/(3) | TruSight Tumor 170 panel (170 genes) | To detect somatic mutations in tumor and cfDNA from locoregional recurrent and/or metastatic HNSCC patients |
| Lin et al. 2022 | 107 OSCC | 107 OC | 21 (I-II) 86 (III-IV) |
n.a. | Plasma | ddPCR | 56.5%/(23) | TP53 | To evaluate the five most frequent coding TP53 mutations by using cancerous tissue and cfDNA in OSCC patients |
Abbreviations: HNSCC, head and neck squamous cell carcinoma; cfDNA, cell-free DNA; ctDNA, circulating tumor DNA; OC, oral cavity; OP, oropharynx; L, larynx; HP, hypopharynx; T, thyroid; SG, salivary gland; PNS, paranasal sinus; UNK, unknown; EAC, external auditory canal; NP, nasopharynx; SPT, secondary primary tumor; PCR, polymerase chain reaction; ddPCR, droplet digital-PCR; HPV, human papilloma virus; n.a., not available.