Investigacion

CHAPTER 32

Oral Cancer: Classification, Staging, and Diagnosis
G. E. Ghali, DDS, MD M. Scott Connor, DDS, MD

Estimates indicate that more than 1.3 million new cancers will be diagnosed in the United States this year, and 27,700 will be located in the mouth and oropharynx.1 This number represents approximately 3% of all cancers and is the eighth most common cancer affecting males in theUnited States. Globally, more than 360,000 new cases of oral cancer will be diagnosed this year.2 Mortality rates remain high despite some advances in locoregional control. There will be approximately 200,000 deaths worldwide, of which 7,200 will occur in the United States. Most patients will present for diagnosis with either regional or distant disease. Data have shown a trend for African Americansto have more advanced disease compared with white Americans (68% vs 52%) at the time of diagnosis. Even more alarming is the fact that, when compared with equal stages at the time of diagnosis, African Americans have a poorer 5-year relative survival rate compared with other races. A review of trends in 5-year relative survival rates over the past three decades has shown a statistical differencebetween the time periods of 1974 to 1976 and 1992 to 1996 (54% vs 59%); the improvement in sur-

vival again fails to hold true for the African American population.1 Approximately 85 to 95% of all oral cancer is squamous cell carcinoma (SCC).3,4 However, multiple other malignant lesions can be found in the oral cavity such as sarcoma, minor salivary gland tumors, mucosal melanoma, lymphoma, ormetastatic disease from nearly any site in the body.

Risk Factors for SCC of the Oral Cavity
The etiology of SCC of the oral cavity has been studied extensively. Numerous risk factors have been suggested as etiologic agents for the development of these malignancies. While no single causative agent can be attributed to the development of all oral cancers, several carcinogens have been identified,and of those tobacco and alcohol appear to have the greatest impact on malignancy development. Both extrinsic and intrinsic factors likely play a role in the development of SCC of the oral cavity. The risk of oral cancer associated with tobacco use is noted to be 2 to 12 times higher than in the nonsmoking population, and 90% of individuals with oral cancer will have a smoking history.5–9 Thecombination of various carcinogens within tobacco, combined with the heat, may lead to a variable number of genetic mutations in the epithelium of the upper aerodigestive tract. At some point these continued mutations, coupled with the patients’ own inherent genetic susceptibility, expressed in the hetero- or homogeneity of certain tumor suppressor genes or oncogenes (TP53, c-myc), may lead to thedevelopment of a cell line capable of unregulated growth. Alcohol in itself is not a recognized initiator in the development of oral SCC. However, the role of alcohol as a promoter in the development of oral cancer when coupled with the use of smoking tobacco has been shown.10 This may be related to the effects of contaminants in alcohol and its ability to solubilize carcinogens and enhance theirpenetration into oral mucosa.5,11 A possible viral etiology has been demonstrated in oral cancers, especially by the human papilloma virus (HPV). The HPV subtypes 16 and 18, similar to those causing cervical cancer, have been implicated. Smith and colleagues showed that when individuals in his study had other risk factors adjusted, such as smoking, alcohol, and

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Part 5: MaxillofacialPathology

age, the presence of HPV in the oral cavity was associated with a 3.7 times greater chance of cancer development than in the noninfected individual.12 Other authors have noted a unique subset of characteristics in individuals that may develop SCC as a result of HPV infection, showing less association with tobacco or alcohol abuse, frequently involving the tonsils, and having an...