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. 2021 Nov 11;13(22):5630. doi: 10.3390/cancers13225630

Table 1.

Epigenetic biomarkers in head and neck squamous cell carcinoma.

Gene/Genomic Element HNSCC Site Sample Type Genomic Region Molecular Alteration Ref.
Risk factor exposure: TOBACCO
p16INK4a and MYOD1 HNSCC Tissue Promoter Hypermethylation [61]
SFRP4 HNSCC Tissue Promoter Hypermethylation [62]
CYP1A1 HNSCC Tissue Promoter Hypermethylation [63]
RBSP3, LIMD1 and CDC25A HNSCC Tissue Promoter Hypermethylation [64]
miR-200 family OSCC Tissue N.A. Downregulation [65]
miR-155 OSCC Tissue N.A. Upregulation [66]
miR-29c LSCC Tissue N.A. Downregulation [67]
miR-202-3p LSCC Tissue N.A. Upregulation [68]
miR- 4768-3p, miR-548aa and miR-3713 LSCC Tissue N.A. Downregulation [68]
miR-34 family HNSCC Tissue N.A. Upregulation [69]
mir-133a-3p OPSCC Tissue N.A. Downregulation [70]
Risk factor exposure: ALCOHOL
p15INK4b HNSCC Oral rinse Promoter Hypermethylation [71]
FUSSEL18 and SEPT9 HNSCC Tissue Promoter Hypermethylation [72]
DAPK HNSCC Tissue Promoter Hypermethylation [73]
SFRP1 HNSCC Tissue Promoter Hypermethylation [62]
p16INK4a, RASSF1A and FANCF HNSCC Tissue Promoter Hypermethylation [61,74]
MGMT and CHRNA3 HNSCC Tissue Promoter Hypomethylation [61]
MLH1 LSCC Tissue Promoter Hypomethylation [75]
miR-30a, miR-934, miR-3178, miR-675, miR-101, miR-126, miR-3164 and miR-3690 HNSCC Tissue N.A. Upregulation [48]
miR-375 HNSCC Tissue N.A. Upregulation [76]
Risk factor exposure: HPV
p16INK4a OSCC, OPSCC and HNSCC Tissue and Saliva Promoter Hypermethylation [77,78]
Hypomethylation [79,80]
RASSF1A, TIMP3 and PCQAP/MED15 HNSCC Saliva Promoter Hypomethylation [79]
RXRG, CTNNA2, GHSR and ITGA4 OPSCC Tissue Promoter Hypermethylation [80]
Global methylation/Repetitive Element HNSCC and OPSCC Tissue LINE1 Hypermethylation [20]
miR-99a-3p and miR-4746-5p HNSCC Tissue N.A. Upregulation [81]
miR-411-5p HNSCC Tissue N.A. Downregulation [81]
miR-320a, miR-222-3p, and miR-93-5p OPSCC Tissue N.A. Upregulation [82]
miR-199a-3p//miR-199b-3p, miR-143, miR-145, and miR-126a OPSCC Tissue N.A. Downregulation [82]
Cancerization field biomarkers—alterations in premalignant lesions
SOCS-3 HNSCC and dysplasias Tissue Promoter Hypermethylation [83]
p16INK4a and MGMT OSCC and individuals at risk Oral rinse and Blood Promoter Hypermethylation [84,85]
RARB OSCC precursor lesions Tissue Promoter Hypermethylation [86]
ZNF582 and PAX1 OSCC cavity Tissue Promoter Hypermethylation [87]
ZAP70 and GP1BB Oral squamous intraepithelial lesions Oral brushing Exon 3/Exon 1 Hypermethylation/Hypomethylation [88]
miR-204, miR-31, miR-31*, miR-133a, miR-7, miR-206, and miR-1293 OSCC precursor lesions Tissue N.A. Upregulation [89]
Diagnostic biomarkers
ABO OSCC Tissue Promoter Hypermethylation [90]
APC OSCC Tissue Promoter Hypermethylation [91]
C/EBPα HNSCC Tissue Promoter Hypermethylation [92]
CDH1 OSCC Tissue Promoter Hypermethylation [91,93,94,95,96]
HNSCC Tissue Promoter Hypermethylation [97]
LSCC Tissue Promoter Hypermethylation [98]
Hypopharynx Tissue Promoter Hypermethylation [98]
CDKN2A OSCC Tissue Promoter Hypermethylation [91,93,94,95,96,99,100,101,102]
HNSCC Tissue Promoter Hypermethylation [97,103]
HNSCC Saliva Promoter Hypermethylation [102,104]
LSCC Tissue Promoter Hypermethylation [75,98,105]
Hypopharynx Tissue Promoter Hypermethylation [98]
CHD5 LSCC Tissue Promoter Hypermethylation [106]
CYGB OSCC Tissue Promoter Hypermethylation [100]
CYCA1 OSCC Tissue Promoter Hypermethylation [93,96]
DAPK OSCC Tissue Promoter Hypermethylation [73,91,94,99,101,107]
OSCC Blood Promoter Hypermethylation [107]
HNSCC Tissue Promoter Hypermethylation [73,97,102]
HNSCC Saliva Promoter Hypermethylation [102,104]
LSCC Tissue Promoter Hypermethylation [75,98,108]
Hypopharynx Tissue Promoter Hypermethylation [98]
DKK3 OSCC Tissue Promoter Hypermethylation [109]
Global methylation/Repetitive Element OSCC Blood LRE1/LINE1 Hypomethylation [110]
OSCC Oral rinse Alu Hypomethylation [111]
HOXA9 OSCC Tissue and Saliva Promoter Hypermethylation [112]
MGMT OSCC Tissue Promoter Hypermethylation [91,94,95,96,99,101]
HNSCC Tissue Promoter Hypermethylation [103,113]
HNSCC Saliva Promoter Hypermethylation [102]
LSCC Tissue Promoter Hypermethylation [75,98]
Hypopharynx Tissue Promoter Hypermethylation [98]
MLH1 LSCC Tissue Promoter Hypermethylation [75,95]
OSCC Tissue Promoter Hypermethylation
MINT1 OSCC Tissue Promoter Hypermethylation [114]
NID2 OSCC Tissue and Saliva Promoter Hypermethylation [112]
p14 HNSCC Tissue Promoter Hypermethylation [103,115]
p15 OSCC Tissue Promoter Hypermethylation [95,116]
PCQAP/MED15 OPSCC Saliva Promoter Hypermethylation [117]
OSCC Saliva Promoter Hypermethylation [117]
RARβ OSCC Tissue Promoter Hypermethylation [93,96]
HNSCC Tissue Promoter Hypermethylation [103]
RARβ2 Salivary Gland Carcinomas Tissue Promoter Hypermethylation [118]
RASSF1A OSCC Tissue Promoter Hypermethylation [119]
Salivary Gland Carcinomas Tissue Promoter Hypermethylation [118]
HNSCC Tissue Promoter Hypermethylation [97]
HNSCC Saliva Promoter Hypermethylation [104]
OPSCC Saliva Promoter Hypermethylation [117]
RUNX3 OSCC Tissue Promoter Hypermethylation [94]
SFRP1 OSCC Tissue Promoter Hypomethylation [109]
SFRP2 OSCC Tissue Promoter Hypermethylation [109]
SFRP4 OSCC Tissue Promoter Hypermethylation [109]
SFRP5 OSCC Tissue Promoter Hypermethylation [109]
SOCS-3 HNSCC Tissue Promoter Hypermethylation [83]
SSTR2 LSCC Tissue Promoter Hypermethylation [120]
WIF1 OSCC Tissue Promoter Hypermethylation [109,119]
WRN OSCC Tissue Promoter Hypermethylation [91]
ZNF14 HNSCC Tissue and Saliva Promoter Hypermethylation [121]
ZNF160 HNSCC Tissue and Saliva Promoter Hypermethylation [121]
ZNF420 HNSCC Tissue and Saliva Promoter Hypermethylation [121]
miR-375 LSCC Tissue N.A. Downregulation [122]
miR-21 LSCC Tissue N.A. Upregulation [122]
miR-204 and mir-144 OSCC Tissue and plasma N.A. Upregulation [123]
miR-193b-5p and miR-370-3p OSCC Tissue and plasma N.A. Downregulation [123]
miR-657 LSCC Tissue N.A. Upregulation [124]
miR-1287 LSCC Tissue N.A. Downregulation [124]
Relapse biomarkers
EDNRB and HOXA9 HNSCC surgical margins Tissue Promoter Hypermethylation [125]
DCC, CCNA1 and p16INK4A HNSCC surgical margins Tissue Promoter Hypermethylation [126]
PAX5 HNSCC surgical margins Tissue Promoter Hypermethylation [127]
CDKN2A LSCC Tissue Nonpromoter Hypomethylation [128]
miR-375 OSCC precursor lesions Tissue N.A. Downregulation [129]
Biomarkers of poor prognosis
KL HNSCC Tissue Promoter Hypermethylation [130]
HIN1, RASSF1A and RASSF2 OSCC Tissue Promoter Hypermethylation [131]
DAPK OSCC Tissue Promoter Hypermethylation [119]
MGMT OSCC Tissue Promoter Hypermethylation [95,119,132,133]
MINT31 OSCC Tissue Promoter Hypermethylation [114]
p16INK4A and p14ARF OSCC Tissue Promoter Hypermethylation [134]
PAX5 and PAX1 HNSCC Tissue Promoter Hypermethylation [135]
TIMP3 HNSCC Saliva Promoter Hypermethylation [136]
SEPT9 and SHOX2 HNSCC Plasma Promoter Hypermethylation [137]
EPHX3 OSCC Pre-operative oral brushing Exon 1 Hypomethylation [138]
ITGA4 and MIR193A OSCC Pre-operative oral brushing Exon 2/Promoter Hypermethylation [138]
miR-21 LSCC Tissue N.A. Upregulation [122]
miR-375 LSCC Tissue N.A. Downregulation [122]
miR-186-5p and miR-374b-5p HNSCC Plasma—before treatment N.A. Upregulation [139]
miR-142-3p HNSCC Plasma—after treatment N.A. Upregulation [139]

HNSCC, head and neck squamous cell carcinoma; LSCC, laryngeal squamous cell carcinoma; N.A., not applicable; OPSCC, oropharyngeal squamous cell carcinoma; OSCC, oral squamous cell carcinoma; Ref., references.