Head and neck cancer in nonsmokers: A distinct clinical and molecular entity

Objectives/Hypothesis: Clinical and molecular patterns of head and neck squ amous cell carcinoma (HNSCC) in nonsmokers and smokers may be differ ent, A nalysis of these patterns may improve understanding and management of this disease. Study Design: three hundred five subjects were included (46 nonsmo kers, 29 former smokers, and 230 smokers). Subsets were analyzed for p53 mu tation, human papillomavirus (HPV), and loss of heterozygosity (LOH) at 10 chromosomal loci. Methods: Clinical information was analyzed for common pat terns of disease among the groups. The p53 gene was sequenced, and polymera se chain reaction was used to detect HPV DNA and LOH at two microsatellite markers for each loci. The chi(2) test was used to assess differences in ge netic alterations between groups, logistic regression to examine the indepe ndence of association of tobacco exposure with each alteration, and Kaplan Meier estimates and the log-rank statistic to assess differences in surviva l. Results: Nonsmokers included a disproportionate number of women, oral ca vity (especially tongue) tumors, and very young or old individuals. Smokers had more tumors of the larynx, hypopharynx, and floor of mouth. The rate o f p53 mutation was much greater in smokers; the percentage with HPV was mar ginally lower. The percentage of LOH at 3p, 4q, and 11q13, and the overall average number of chromosomal losses, was significantly lower in nonsmokers ' tumors. Survival did not vary with smoking or age. Conclusions: The clini cal and genetic features of HNSCC are distinct between groups defined by to bacco use, Tumors of nonsmokers contain a lower frequency of common genetic alterations, suggesting that the underlying changes in these tumors may re main undiscovered.