Multiple primary tumors may be present at initial diagnosis but more often are detected later, at an estimated rate of 3% to 7% per year; patients who survive 5 years after diagnosis of the initial tumor have up to a 35% chance of developing at least one new primary tumor within that interval. The development of these secondary tumors can be particularly devastating for individuals whose initial lesions were small. Therefore, surveillance and early detection of new premalignant lesions are critical for the longterm survival of patients with oral squamous cell carcinoma.
The elevated risk for development of additional primary tumors in these patients has led to the concept of “field cancerization.” This hypothesis suggests that multiple primary tumors develop independently as a result of years of chronic mucosal exposure to carcinogens such as alcohol or tobacco (described next).
Fig. 15.3 Leukoplakia.(A)Grossappearanceofleukoplakiaishighlyvariable.Inthisexample,thelesionissmoothwithwell-demarcatedbordersandminimalelevation.(B)Histologicappearanceofleukoplakiashowingdysplasia,characterizedbynuclearandcellularpleomorphismandlossofnormalmaturation.
Squamous cancers of the oropharynx arise through two distinct pathogenic pathways, one involving exposure to carcinogens, and the other related to infection with high risk variants of human papilloma virus (HPV). Carcinogen exposure mainly stems from chronic alcohol and tobacco (both smoked and chewed) use. In India and Southeast Asia, chewing of betel quid and paan are important predisposing factors. Betel quid is a “witch’s brew” containing araca nut, slaked lime, and tobacco, all wrapped in betel nut leaf. It is likely that these tumors arise by a pathway similar to that characterized for tobacco use– associated tumors in the West. Deep sequencing of these cancers has revealed frequent mutations that bear a molecular signature consistent with exposure to carcinogens in tobacco. These mutations frequently involve TP53 and genes that regulate cell proliferation, such as RAS. The HPV-related tumors tend to occur in the tonsillar crypts or the base of the tongue and harbor oncogenic “high-risk” subtypes, particularly HPV-16. These tumors carry far fewer mutations than those associated with tobacco exposure and often overexpress p16, a cyclin-dependent kinase inhibitor.
http://ebooksmedicine.net
Fig. 15.4 Oralsquamouscellcarcinoma.(A)Grossappearancedemonstratingulcerationandindurationoftheoralmucosa.(B)Histologicappearancedemonstratingnumerousnestsandislandsofmalignantkeratinocytesinvadingtheunderlyingconnectivetissuestroma.
It is conservatively predicted that the incidence of HPV-associated oropharyngeal squamous cell carcinoma will surpass that of cervical cancer by 2020, in part because the anatomic sites of origin—tonsillar crypts, base of tongue, and oropharynx—are not readily accessible or amenable to cytologic screening (unlike the cervix). The prognosis for patients with HPV-positive tumors is better than for those with HPV-negative tumors. The HPV vaccine, which is protective against cervical cancer, offers hope to limit the increasing frequency of HPV-associated oropharyngeal squamous cell carcinoma.
The incidence of oral cavity squamous cell carcinoma (particularly in the tongue) has been on the rise in individuals younger than 40 years of age who have no known risk factors. The pathogenesis in this group of patients, who are nonsmokers and are not infected with HPV, is unknown
MORPHOLOGYSquamouscellcarcinomamayariseanywhereintheoralcavity.However,themostcommonlocationsaretheventralsurfaceofthetongue,floorofthemouth,lowerlip,softpalate,andgingiva(