Somatic genetics

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There is some variation in the genetic profile of oral and oropharyngeal SCC that reflects the site-specific impact of various casual agents and differences in clinical presentation. The carcinogens in tobacco smoke, for example, increase the prevalence and spectrum of TP53 mutations {268}. Compared to carcinomas that arise in patients who smoke, carcinomas in patients who have never smoked harbour fewer p53 mutations, disproportionately involve women, typically arise from the oral tongue, and affect very young or very old patients {1351,2258}. For carcinomas of the oropharynx, oncogenic human papillomavirus (HPV), particularly the HPV-16 subtype, is an important causative agent: More than 50% of oropharyngeal carcinomas harbour integrated HPV DNA {60,888,1999}. The E6 and E7 viral oncoproteins bind and inactivate the TP53 and retinoblastoma gene products respectively, disengaging two of the more critical pathways involved in cell cycle regulation {2788}. These HPV-positive oropharyngeal tumours compose a distinct pathological entity with its own clinical spectrum and basaloid morphology {888,1012,2072}, illustrating the emerging role of genetic characterization as a potential means of determining prognosis and influencing management {1691}.

Genetic evidence has clarified the vague concept of "field cancerization". Most, if not all, multiple primary carcinomas of the upper aerodigestive tract derive from a common clonal progenitor cell that undergoes a common early genetic alterations {187,2271}. Genetic evidence has helped account for the perplexing problem of local tumour recurrence following seemingly complete tumour resection. In many instances, local tumour recurrence reflects extension of genetically damaged cells beyond the clinical and microscopic boundaries of carcinoma to the margins of surgical resection {268,1626, 1983,2777}.

Microsatellite analysis of exfoliated cells swabbed or rinsed from the oral cavity of patients with head and neck squamous carcinomas consistently harbour genetic changes that are identical to those in the primary tumours, suggesting a non-invasive test for specific DNA-sequence variants in saliva as a means of identifying patients with pre-invasive or invasive neoplasms {2430}. Clonal genetic changes identical to those found in primary head and neck SCC have been identified in circulating plasma or serum, suggesting a mechanism for early cancer detection and tumour surveillance {1853}. The use of highly sensitive genetic assays for detecting rare cancer cells at the margin of tumour resection shows promise for predicting the likelihood of tumour recurrence {268,1983}.

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