Table 1.
Diagnostic biomarkers investigated for head and neck squamous cell carcinoma (Source: Konings et al., 2020; Front. Oncol.) (138).
| ANATOMICAL TUMOR | POTENTIAL BIOMARKER | TYPE OF SAMPLE | EXPRESSION | TEST RESULTS |
|---|---|---|---|---|
| GENOMICS | ||||
| (PROMOTOR) HYPERMETHYLATION | ||||
| Oral SCC | A promotor hypermethylation panel (HOXA9 and NID2) | Tissue biopsies | Downregulation | Sensitivity - 94% Specificity - 75% |
| Oral SCC, Oropharyngeal SCC |
Methylation of cg01009664 of the thyrotropin-releasing hormone gene | Oral rinse, and oral swab | Downregulation | Sensitivity - 91.3% (swab) and 86.15% (rinse) Specificity - 84.85% (swab) and 89.66% (rinse) |
| Oral SCC | Promotor hypermethylation panel (PTEN and p16) | Tissue biopsy | Downregulation | Not specified |
| EBV-RELATED MARKERS | ||||
| NPC | IgA VCA + EBV DNA load | Blood sample | Upregulation | Sensitivity - 99% Specificity - 96-98% |
| HPV-RELATED MARKERS | ||||
| Oropharyngeal carcinoma, HNSCC |
HPV-16 E16 antibodies | Blood sample | Seropositive | Sensitivity - 96% Specificity - 98% Accuracy - 97% |
| miRNA | ||||
| Oral cancer | Combination of miR-196a and miR-196b | Blood sample | Upregulation | Sensitivity - 88% Specificity - 93% |
| Oral leukoplakia, Oral SCC | Three-plasma miRNA panel (miR-222-3p, miR-150-5p, and miR-423-5p) | Blood sample | Upregulation | Not specified |
| Larynx carcinoma | Combination of hsa-miR-657 and hsa-miR-1287 | Tissue biopsy | Downregulation/ Upregulation |
Sensitivity - 86.21% Specificity - 100% |
| Laryngeal SCC | miR-155 | Tissue biopsy, blood sample | Upregulation | Sensitivity- 58.4% Specificity - 69.5% |
| INTERFERONS | ||||
| Oral SCC | Interferon inducible transmembrane protein 1 and ISG15 | Tissue biopsy | Upregulation | Not specified |
| OTHERS | ||||
| Oral SCC | 5-hydroxylmethylcytosine | Tissue Biopsy | Downregulation | Not specified |
| HNSCC, especially oropharyngeal SCC |
Total cfDNA from plasma | Blood sample | Upregulation | Not specified |
| PROTEOMICS | ||||
| CYTOKINES | ||||
| Oral leukoplakia with dysplasia tongue SCC | IL-6 | Saliva | Upregulation | Not specified |
| OTHERS | ||||
| Oral SCC | RACK1 | Tissue biopsy | Upregulation | Not specified |
| Oral SCC and oral epithelial dysplasia lesions |
Phosphorylation of
ribosomal protein s6 (p-RPS6) |
Tissue biopsy | Upregulation | Not specified |
| HNSCC | Midkine | Blood sample | Upregulation | Sensitivity - 57.3% Specificity - 85.3% |
| HNSCC | Salivary total protein + soluble CD44 levels | Salivary rinse | Upregulation | Sensitivity - 62-79% Specificity - 88-100% |
| GLYCOMICS | ||||
| Oropharyngeal carcinoma and oral cancer | Total sialic acid/total protein ratios and α-l-fucosidase | Blood sample, saliva | Upregulation | Sensitivity - 88.2% (serum) and 61.2% (saliva) Specificity - 57.2% (serum) and 44.3% (saliva) |
| Oral SCC | Sialic acid, total protein, total sugar | Saliva | Upregulation | Not specified |
| METABOLOMICS | ||||
| Oral SCC | Altered energy metabolism | Blood sample | Upregulation/ Downregulation |
Not specified |
| Oral SCC | A panel of 4 metabolites: choline, betaine, pipecolinic acid, L-carnitine | Saliva | Upregulation/ Downregulation |
Sensitivity - 100% Specificity - 96.7% Accuracy - 99.7% |
| Oral SCC | Salivary glycine and proline | Saliva | Downregulation | Not defined |
| RADIOMICS | ||||
| HNSCC | MRI | Not applicable | Not applicable | Sensitivity - 84% Specificity - 70% Accuracy - 79% |
cfDNA, cell free DNA; EBV, Epstein-Barr virus; HNSCC, head and neck squamous cell carcinoma; IL, interlukin; miRNA, microRNA; MRI, magnetic resonance imaging; NPC, nasopharyngeal carcinoma; SCC, squamous cell carcinoma.