Chapter 57.1

## Abstract

Abstract

1. Oral and pharyngeal cancer is the sixth most common malignancy reported worldwide. About 62 percent arise in developing countries. Oral neoplasms are uncommon in Western countries, but in the past decade rising trends have been reported among young males. Malignancies of this site are a serious public health problem in Asia.

2. Major risk factors, tobacco and excess alcohol consumption, are well established. The primary cause of high incidence in Asians is the widespread habit of chewing betel quid. Antioxidant micronutrients such as b carotene and vitamin C are protective. Some viruses, such as HPV (types 16 & 18), are also implicated.

3. Most mouth cancers are asymptomatic at early stages. Many present at a late stage, approximately 70 percent with nodal metastases. There is also a high incidence of second primary tumors in the upper aerodigestive tract following an oral or pharyngeal, squamous cell carcinomous (SCC). In most Western countries, the reported 5-year survival is around 50 percent.

4. Several potentially malignant lesions and conditions that arise on the oral mucosa are known. This makes oral cancer a candidate site for screening. Knowledge of molecular markers may assist in the detection of high-risk individuals.

5. Multiple chromosome losses and gains are described with substantial variations in loss of heterozygosity in individual tumors. Clustering of fragile sites is demonstrated in 3p and 9p, and by gene amplification at 11q13.

6. While ras mutations are rare in white caucosoid populations, they are frequently seen in tobacco/areca-chewing Asian subjects with oral SCC. When mutated or amplified, ras may cooperate with cyclin D1 in altering G0/G1 transition.

7. p53 mutations and overexpression of the protein may be demonstrated in at least half of oral SCC. Mutations are predominant in exon 8, but may occur in exon 5 as well. Codons 176, 245-8, 273, and 296-8 appear to harbor a high proportion of the mutations described so far. The profiles of these results, so far, are discordant against other tobacco-induced cancers. p53 mutations are uncommon in the preinvasive stage but appear to occur in the transition from preinvasive to the invasive stage. p53 therefore does not serve as a potential biomarker to detect which precancers may progress with time. p53 overexpression is an independent prognostic marker in advanced tumors.

8. Other cell-cycle regulatory proteins, namely, p21, p27, and pRb, have been investigated. Some tumors appear to have independent pathways of expression, or inactivation of these molecules that is unrelated to p53 status. P16 inactivation may occur in nearly half of oral cancers causing dysregulation of growth arrest.

9. p53 and CYFRA 21-1 may serve as tumor markers but are not universally present. Immunogenicity of p53 needs further study. Saliva may also serve as a useful biological fluid in tumor marker assessments.

10. Although multiple genetic hits are observed in individual tumors, their temporal sequence is yet to be elucidated.

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