TABLE 1.
Epigenetic mechanisms related in HNSCC.
| Methylation status | ||||||
| Author | Tissue | Samples | HPV-related | Hypermethylation | Hypomethylation | Results |
| DNA methylation | ||||||
| Liyanage et al. (2019) | Saliva | OC/OPC/Controls | Yes | p16INK4a, RASSF1A, TIMP3, PCQAP/MED15 | – | Discrimination and early detection of OC/OPC |
| Wen et al. (2018) | Oral rinse/Tissue/Blood | OSCC/Controls | No | PASSF1A, RARb, CDH1 (meta-analysis) | – | Association with the oral cancer risk |
| Ovchinnikov et al. (2012) | Saliva | HNSCC/Controls | No | RASSF1A, DAPK1, p16INK4a | – | Prediction of incidence risk in HNSCC |
| Sailer et al. (2017) | Tissue | HNSCC/Controls | Yes | PITX2 | – | Prognostic biomarker in HNSCC |
| Sailer et al. (2019) | Tissue, Cell lines | HNSCC/Controls | Yes | IDO1 | – | Potential biomarker for prediction of response to IDO1 immune checkpoint inhibitors |
| Misawa et al. (2017) | Tissue | HNSCC/Controls | Yes | SALL3 | – | Potential biomarker in HNSCC |
| Imai et al. (2019) | Tissue | HNSCC/Controls | Yes | SALL2 | – | Important clinical risk assessment |
| Misawa et al. (2018) | Tissue, Cell lines | HNSCC/Controls | Yes | TET1,TET2,TET3 | – | TET3 methylation independently associated with aggressive tumor |
| Cheng et al. (2016) | Oral scrapings | OPMD/OSCC/Controls | No | ZNF582, PAX1 | – | Detection of oral dysplasia and oral cancer and prediction of oral cancer recurrence |
| Huang et al. (2017) | Tissue (tumor/paracancerous) | ESCC/Controls | No | ZNF582, PAX1 | – | Distinguishing ESCC tumor tissues from non-tumor tissues |
| Tang et al. (2019) | Tissue | ESCC/Controls | No | PAX1, SOX1, ZNF582 | – | Promising biomarker for ESCC screening and diagnosis |
| Giuliano et al. (2020) | Oral gargles | OPC/Controls | Yes | EPB41L3 | – | Possible utility in identifying OPC early |
| Esposti et al. (2017) | Tissue | HNSCC | Yes | CDH18, CTNND2 (methylome analyses) | NCAN, NRXN1, COL19A1, SYCP2, RPA2, SMC1B (methylome analyses) | Novel epigenetic signature of HPV infection in HNSCCs independent of the anatomic site |
| Das et al. (2019) | Tissue | OSCC-GB/Controls | No | TET1 (methylome analyses) | CD274, CD80, DNMT3B (methylome analyses) | Indication of novel therapeutic targets, including immunotherapeutic, for treatment of OSCC-GB |
| Ren et al. (2018) | Tissue | OPSCC/Controls | Yes | OR6S1, KCNA3,EMBP1, CCDC181, DPP4,ITGA4,BEND4, ELMO1,SFMBT2,C1QL3, MIR129–2,NID2, HOXB4,ZNF439,ZNF93, VSTM2B, ZNF137P, ZNF773 (methylome analyses) | – | 20 highly specific DMRs in HPV- related OPSCC, with potential application to molecular-based detection tests |
| Gašperov et al. (2020) | Tissue | Oral lesions/HNSCC/Controls | Yes | RAD51B, BARX2, SLC5A10/FAM83G, NINL NSMCE2, PGAP2, INO80C, IL34, ZNF516, GFOD2, PARD3, MCEE, POLM, ASPG, TBC1D2 (Promoters in HNSCC Tissue Compared to Oral lesions-methylome analyses) | ART4, EPB41L3, ESRRG, ENPP1, GNG7, PAPSS2, NGEF, HIPK4, GPR158, GSG1L, SMPD3, GDF2, RERE, CDH13, HS3ST4 (Promoters in HNSCC Tissue Compared to Oral lesions-methylome analyses) | Potential biomarkers for early diagnostics of HNSCC and premalignant oral lesions |
| miRNAs | ||||||
| Gao et al. (2019) | Tissue | HNSCC/LSCC/Controls | No | miR-145-5p | Promoter hypermethylation | miR-145-5p and FSCN1 are important potential prognostic markers and therapeutic targets for LSCC |
| Lajer et al. (2012) | Tissue | HNSCC/TSCC/OSCC/PSCC/Control | Yes | miR-15a/miR-16/miR195/miR-497 family, miR-143/miR-145 and the miR-106-363 cluster | – | New knowledge to known pathogenic pathways of HPV and substantiates the oncogenic role of HPV in subsets of HNSCCs |
| Tu et al. (2015) | Tissue/Cell lines | OSCC/Control | No | miR-372, miR-373 | – | Overexpression of miR-372 and miR-373 indicates worse survival in OSCC |
| Zhang et al. (2019) | Tissue/Cell lines | OSCC/Control | No | miR-373 | – | MiR-373/SPOP potential therapeutic target for OSCC |
| Wang L. et al. (2019) | Tissue/Cell lines | ESCC/Control | No | miR-371a-5p, miR- 371b-5p, miR-372-3p, miR-373-3p | miR-373-3p promoter hypomethylation | DNA epigenetic modification in the miR-373-3p promoter region and the Hippo and p53 signaling pathways play important roles during the miR-373-3p mediating ESCC development process |
| Wu et al. (2016) | Tissue | LSCC/Control | No | lncRNA H19/miR-148a-3p/DNMT1 | Promoter hypomethylation | lncRNA H19 promoted LSCC progression via miR-148a-3p and DNMT1 |
| Wang Y. et al. (2019) | Tissue/Cell lines | ESCC/Control | No | miR-148a-3p | – | miR-148a-3p, by targeting DNMT1, likely regulates cell proliferation and invasion in esophageal cancer. Might also be used prognostically in esophageal cancer and serve as a therapeutic target in the future |
| Liu et al. (2019) | Tissue | HNSCC/Control | Yes | 128 miRNAs as significantly differentially expressed in HNSCC tissue compared with the normal samples | – | hsa-miR-383, hsa-miR-615, and hsa-miR-877 may serve as an excellent diagnostic biomarker for HNSCC, and potential prognostic significance for HNSCC patients |
| Hess et al. (2019) | Tissue | HNSCC/DKTK-ROG/LMU-KKG (radiochemotherapy received) | Yes (negative) | hsa- let-7g-3p, hsa-miR-6508-5p, hsa-miR-210-5p, hsa-miR-4306, and hsa-miR-7161-3p | – | The five-miRNA signature is a strong and independent prognostic factor for disease recurrence and survival of patients with HPV-negative HNSCC |
DKTK-ROG, German Consortium for Translational Cancer Research-Radiation Oncology Group; ESCC, esophageal squamous cell carcinoma; HNSCC, head and neck squamous cell carcinoma; LMU-KKG, Ludwig- Maximilians-University of Munich-Clinical Cooperation Group; LSCC, laryngeal squamous cell carcinoma; OC, oral cancer; OPC, oropharyngeal cancer; OPMD, oral potentially malignant disorders; OSCC, oral squamous cell carcinoma; OSCC-GB, Gingivo-buccal oral squamous cell carcinoma; PSCC, pharyngeal squamous cell carcinoma; TSCC, tonsillar squamous cell carcinoma.