BACKGROUND Epidemiologic studies have indicated that environmental and personal habits, particularly tobacco use and alcohol abuse, are major etiologic factors in the induction and progression of head and neck squamous cell carcinomas (HNSCC). Molecular studies have focused on HNSCC related to smoking but not those associated with smokeless tobacco. METHODS The authors studied immunohistochemical evidence of alterations of p53, cyclin D1, and Rb in 34 human oral carcinomas related to tobacco use. They also examined p53 and H‐ras using single strand conformation polymorphism (SSCP) and sequencing analysis. RESULTS Overexpression of cyclin D1 was found in 41% of cases, and accumulation of p53 was found in 59%. Only 9% of the samples did not show Rb staining. In SSCP and sequencing analysis, 17 cases showed mutations in the conserved region of the p53 gene. No mutations were detected in codons 12, 13, or 61 of the H‐ras gene. CONCLUSIONS Overexpression of cyclin D1 and p53 mutations are common alterations in HNSCC. In contrast, the loss of Rb function seems to occur infrequently, and mutations in the H‐ras gene apparently do not play a role in this cancer. HNSCC associated with smokeless tobacco contained the same alterations as those related to smoking. Cancer 1998;83:204‐212. © 1998 American Cancer Society.

p53 protein accumulation is frequently observed in these tumors suggesting possible mutations of this gene in VC. Overexpression of cyclin D1 but no alterations of Rb staining were also observed in this low grade tumor suggesting that Rb may be functionally inactivated by overexpression of cyclin D1 or HPV infection.

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