This randomized phase I/II trial studies the side effects and best way to give lyophilized black raspberries in preventing oral cancer in high-risk patients previously diagnosed with stage I-IV or in situ head and neck cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of lyophilized black raspberries may prevent oral cancer. Studying samples of oral cavity scrapings, blood, urine, and saliva in the laboratory from patients receiving lyophilized black raspberries may help doctors learn more about changes that occur in DNA and the effect of lyophilized back raspberries on biomarkers.

PRIMARY OBJECTIVES: I. Determine the adherence of post-surgical head and neck (HN) cancer patients to clinical trial design expectations and define tolerability and potential adverse effects of long-term black raspberry administration in this patient cohort. II. Determine the effects of dose and delivery vehicle on the degree of uptake of black raspberry components in target oral tissues of post-surgical HN cancer patients over time and determine the relationships between adherence/exposure data and uptake. III. Determine the ability of black raspberries to modulate patterns of gene expression within key regulatory pathways in "at-risk normal" oral mucosa of post-surgical HN cancer patients that would favor the inhibition, delay or reversal of oral carcinogenesis. IV. Determine the persistence of modulation of "berry-responsive genes" for 2 years following commencement of black raspberry treatment and preliminarily define rate of recurrence and second primary oral cancers in a former oral cancer patient sub-cohort. OUTLINE: Patients are randomized to 1 of 4 treatment arms. ARM I: Patients receive lozenge placebo orally (PO) four times daily (QID). ARM II: Patients receive lyophilized black raspberries lozenge PO QID. ARM III: Patients receive Saliva Substitute placebo PO QID. ARM IV: Patients receive lyophilized black raspberries Saliva Substitute PO QID. In all arms, treatment continues for 6 months. Oral cavity scrapings, blood, urine, and saliva samples are collected periodically for laboratory analyses. After completion of study treatment, some patients are followed up at weeks 1-5 and then at 2, 6, 12, and 18 months.