It should be considered in the studies that the pathological changes at the early stages of the relationship between DM and oral cancer may be related to p16 expression; however, it may also be linked with p16-related aging process.
Both pRB/p16(INK4A) and p53 are dysfunctional in many cancers, including the most common type of oral cancer, squamous cell carcinoma (OSCC) and other evidence is accumulating in support of the idea that senescence acts as a barrier to tumour development and/or progression.
The detection of CCND1 and p16 aberrations using a simple and sensitive method would be valuable for the development of effective treatment modalities for oral cancer.
Frequent promoter hypermethylation of RASSF1A and p16INK4a and infrequent allelic loss other than 9p21 in betel-associated oral carcinoma in a Vietnamese non-smoking/non-drinking female population.
We can conclude that high-risk HPV types are associated with p16 overexpression, and p16 may serve as a biomarker in oral cancer related to high-risk HPV infection.
Our previous work showed that acquisition of immortality at the dysplasia stage of oral cancer progression was consistently associated with four changes: loss of retinoic acid receptor (RAR)-beta and p16INK4A expression, p53 mutations and activation of telomerase.
In an attempt to model oral cancer in a human cell-based system, we analyzed normal oral epithelial keratinocytes with the pRB pathway dysregulated by loss of expression of the cyclin-dependent kinase (cdk) 4/cdk6 inhibitor p16(INK4A) and/or ectopic expression of cdk4 or expression of the human papillomavirus (HPV) type 16 E7 oncoprotein.
These data support that INK4a/ARF locus alterations are frequent events preceding the development of oral cancer and that p16(INK4a) inactivation occurs to a greater extent in oral dysplasia than does p14(ARF) inactivation.
We reported previously that acquisition of the immortal phenotype is an early event in oral cancer development (F. McGregor et al., Cancer Res., 57: 3886-3889, 1997); our current data indicate that about half of oral dysplasia cultures are immortal, and this is associated with loss of expression of retinoic acid receptor (RAR)-beta and the cell cycle inhibitor p16(ink4a) (p16), p53 mutations, and increased levels of telomerase/human telomerase reverse transcriptase mRNA.
Not only do Li Fraumeni patients develop second primary malignancies, but defects of the p53 pathway (p53 mutation, MDM2 over-expression, CDKN2A deletion) appear to be a ubiquitous feature of sporadic oral cancer as it occurs in the West.