Suppressor Gene p53. The p53 is a tumor suppressor gene, which has a length of 16-29 kb DNA, it is localized on the short arm of chromosome 17 (17p13.1) and codes phosphoprotein, which controls the transfer from the G1 to the S phase of the cell cycle; p53 is considered as a key prognostic marker with clinical significance. Mutations in p53 have been found in about 60% of human tumors, in­cluding tumors of the HNSCC. These mutations are char­acteristic of low differentiated tumors [18]. Research showing connection between the p53 gene and the out­come of the disease has proved that the overexpression of p53 is associated with recurrence and death. These studies present that histological negative margins are not necessar­ily genetically negative and that genetically positive mar­gins are more likely to recur [4]. It is supposed that the presence of a p53 mutation correlates with a shorter sur­vival and nodal metastases, while correlation with the grade of tumor development has not been found. Co-ex­pression of p53 and erbB‑1 and erbB‑2 has also been de­termined [19]. Replacing a mutated p53 gene with a wild-type p53 gene using an adenoviral vector is a potential approach to HNSCC treatment [4].

Suppressor Gene Rb. The Rb tumor suppressor gene (13q14) also takes part in the control of the cell cycle. Hypophosphorylated Rb connects and inactivates the tran­scription factor responsible for cell progression, E2f. Mu­tations in the Rb gene, or lack of its activity, lead to a malfunction in the cell cycle. Loss of heterozygosity has been detected in 14 to 59% of HNSCC. It is speculated that the lack of expression of this protein correlates with a worse survival rate. A simultaneous loss of heterozy­gosity of Rb and p53 is associated with shorter survival.

The CDKN2-Coding Protein p16 Gene. There is also analysis concerning gene CDKN2-coding protein p16 (cyclin-dependent kinase inhibitor), located at the 9p21 region, which regulates the cell cycle through inhibiting the process of phosphorylating of the Rb product. Loss of heterozygosity was found in 57% of the tumors [4]. The use of markers proved that deletions do not always involve the CDKN2 gene. Thus, the conclusion is that this is an­other tumor suppressor gene, most probably located in proximity to 9p21, which also plays a crucial role in the development of HNSCC [20]. The abnormal p16 protein is associated with a worse survival rate, increased recur­rence, tumor progression and nodal metastases.

The p21/p27 Genes. The p21 and p27 genes (located at 6p21 and 14q32) encode products that are activated by p53 and inhibit cell cycle arrest. Malfunctions of those genes have also been demonstrated in HNSCC. There is no correlation between the expression of p21 and clinical parameters. The presence of p27 is clearly connected with improved survival [4]. The tumor suppressor genes Rb, p16, p21 are frequently mutated in HNSCC. Their investi­gation is of great interest because they could be used as potential gene therapy targets [4]. It has been established in preclinical testing that, the cyclin-dependent kinase inhibitors flavopiridol and CCI-779 repress the transcrip­tion of cyclin D and induce p53-mediated apoptosis [21].