Table 2.
Summary of quantitative findings of the reviewed studies.
| N | Author/year/ ocation | Cases | Controls | Loci identified | Biological pathway | Methylated cases (%) | Unmethylated cases (%) | Methylated controls (%) | Unmethylated controls (%) |
|---|---|---|---|---|---|---|---|---|---|
| Longitudinal studies | |||||||||
| 1 | Kresty et al. [49] Ohio, USA |
Oral dysplastic lesions | None | p16 | Cell cycle control | 57.7 | 42.3 | NR | NR |
| p14 | Cell cycle control | 3.8 | 96.2 | ||||||
| 2 | Hall et al. 2008[31] UK |
Oral dysplastic lesions transformed into OSCC | Regressed oral dysplastic lesions | p16 | Cell cycle control | 57.0 | 43.0 | 8.0 | 92.0 |
| MGMT | DNA repair | 4.0 | 96.0 | 3.0 | 97.0 | ||||
| 3 | Cao⁎ et al. [30] China |
Oral dysplastic lesions transformed into OSCC | Regressed oral dysplastic lesions | p16 | Cell cycle control | 63.6 | 46.4 | 32.1 | 67.9 |
| Cross sectional studies | |||||||||
| 4 | Takeshima, et al. [43] Sri Lanka |
Oral dysplastic leukoplakia | Healthy oral mucosa | p16 | Cell cycle control | 29.6 | 70.4 | 0.0 | 100.0 |
| p14 | Cell cycle control | 73.4 | 26.6 | 0.0 | 100.0 | ||||
| Non dysplastic OSMF | Healthy oral mucosa | p16 | Cell cycle control | 70.0 | 30.0 | 0.0 | 100.0 | ||
| p14 | Cell cycle control | 80.0 | 20.0 | 0.0 | 100.0 | ||||
| 5 | Liu et al. [33] USA |
Oral dysplastic leukoplakia | None | p16 | Cell cycle control | 41.1 | 58.9 | NR | NR |
| DAPK | Apoptosis | 35.2 | 64.8 | NR | NR | ||||
| MGMT | DNA repair | 38.2 | 61.8 | NR | NR | ||||
| Oral hyperplastic leukoplakia | None | p16 | Cell cycle control | 19.4 | 80.6 | NR | NR | ||
| DAPK | Apoptosis | 18.2 | 81.8 | NR | NR | ||||
| MGMT | DNA repair | 24.6 | 75.4 | NR | NR | ||||
| 6 | Silva et al. [47] Brasil |
Oral dysplastic leukoplakia | Healthy oral mucosa | p16 | Cell cycle control | 87.5 | 12.5 | 8.3 | 91.7 |
| 7 | Liu et al. [46] China |
Oral dysplastic leukoplakia | None | DAPK | Apoptosis | 19.5 | 80.5 | NR | NR |
| 8 | Dang et al. [35] China |
Non dysplastic oral lichen planus | Healthy oral mucosa | p16 | Cell cycle control | 25.0 | 75.0 | 0.0 | 100.0 |
| 9 | Ghosh et al. [48] India |
Oral dysplastic lesions | Normal mucosa adjacent to lesions | p16 | Cell cycle control | 17.5 | 82.5 | NR | NR |
| p14 | Cell cycle control | 20.0 | 80.0 | NR | NR | ||||
| 10 | Bhatia et al. [32] India |
Oral dysplastic leukoplakia | Healthy oral mucosa | p16 | cell cycle control | 36.4 | 63.6 | 14.3 | 85.7 |
| OSMF | Healthy oral mucosa | MGMT | DNA repair | 72.7 | 27.3 | 14.3 | 85.7 | ||
| p16 | Cell cycle control | 61.5 | 38.5 | 14.3 | 85.7 | ||||
| MGMT | DNA repair | 43.1 | 53.9 | 14.3 | 85.7 | ||||
| OLP | Healthy oral mucosa | p16 | cell cycle control | 50.0 | 50.0 | 14.3 | 85.7 | ||
| MGMT | DNA repair | 25.0 | 75.0 | 14.3 | 85.7 | ||||
| 11 | Towle et al [39] Caucasians |
Oral dysplastic lesions | Normal mucosa adjacent to lesions | p16 | Cell cycle control | 50.0 | 50.0 | NR | NR |
| MGMT | DNA repair | 60.0 | 40.0 | NR | NR | ||||
| DAPK | Apoptosis | 70.0 | 30.0 | NR | NR | ||||
| 12 | Asokan et al. [34] India |
Oral leukoplakia | Healthy oral mucosa | p16 | Cell cycle control | 60.0 | 40.0 | 0.0 | 100.0 |
| MGMT | DNA repair | 30.0 | 70.0 | 0.0 | 100.0 | ||||
Epigenome wide methylation study [39] reported a total of 605 hyper-methylated genes and 90 hypo-methylated genes including Wnt and MAP kinase pathway genes and 3 novel sites in TRHDE, ZNF454, KCNAB3.
NR – not reported; OSMF – oral submucous fibrosis; OLP – oral lichen planus.
⁎
Oral dysplastic lesions included leukoplakia, oral lichen planus and discoid lupus erythmatosus.