Background: In addition to its idely accepted role in cardiovascular disease, aspirin use has been associated ith decreased risk of several malignancies, especially colorectal cancer. The United States Preventive Task Force has recently updated their guidelines and added colorectal cancer prevention as an added benefit to aspirin use. Hoever, the impact of aspirin use on the risk of cancers of the head and neck  HNC  has not been revieed previously. Methods: A systematic search of PubMed and Embase as performed to identify studies hich evaluated the relationship beteen aspirin use and risk of cancers of the head and neck. Case-control studies and cohort studies ere both included in the revie. Random effects model as use to estimate a pooled effect size and the inconsistency index  I2  as used to estimate heterogeneity beteen included studies. We hypothesized that tobacco users are more likely to be prescribed aspirin and also had an increased risk for HNC and thus planned a sensitivity analysis to exclude studies hich did not adjust for tobacco usage. Results: After revieing 879 reports, 8 studies hich described the association beteen aspirin use and HNC risk ere selected, all of hich ere reported from Europe or North America. A total of 206, 865 patients ere included in 6 case-control studies and 2 cohort studies of hom 8,395 patients had HNC. Controls ere matched for age and sex in all case-control studies and for tobacco use in 2 studies. In a meta-analysis, aspirin use reduced the risk of head and neck cancers; hoever, this association as of borderline statistical significance  OR 0.87, 95 percent CI 0.75- 1.02 . Moderate heterogeneity  I2= 50 percent, P = 0.05  as seen in this meta-analysis hich as lost in our sensitivity analysis. On restricting meta-analysis to studies hich adjusted for tobacco use  N = 7 , aspirin use as found to be associated ith a significantly reduced risk of HNCs  OR 0.84; 95 percent CI 0.73- 0.96  ith lo heterogeneity  I2= 35 percent, P = 0.16  Conclusions: Aspirin users appear to be at loer risk for cancers of the head and neck after adjustment for tobacco use. Additional cohort studies are required to evaluate the optimal dose or duration of use of aspirin that may be confer this protective effect.,J Clin Oncol 34, 2016  suppl; abstr 1546 00:00.0,Cancer Prevention, Genetics, and Epidemiology