Pioglitazone Hydrochloride in Preventing Head and Neck Cancer in Patients With Oral Leukoplakia

Criteria: * ECOG 0-2 * Diagnosis of oral cavity or oropharyngeal leukoplakia meeting 1 of the following criteria: * Biopsy-proven hyperplasia in high-risk anatomic areas (e.g., floor of the mouth, mobile tongue, oropharynx, or in any erythroplakia lesion) * Mild, moderate, or severe dysplasia at any site of the oral cavity or oropharynx within the lesion * Measurable lesion that is clinically characterized by leukoplakia, erythroplakia, or erythroleukoplakia * Able to be assessed by bi-directional measurements * Life expectancy: More than 3 months * Hemoglobin \>= lower limit of normal for males and post-menopausal females OR * Hemoglobin \>= 11 g/dL for premenopausal females * WBC \> 3,000/mm\^3 * Hepatic: Bilirubin \< 1.5 times upper limit of normal (ULN); AST and ALT \< 1.5 times ULN * Renal: BUN \< 1.5 times ULN; Creatinine \< 1.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception * No contraindication to thiazolidinediones * No allergy to pioglitazone or other thiazolidinediones * No serious oral infection * No invasive carcinoma within the past 60 months except nonmelanoma skin cancer or carcinoma in situ of the cervix * No concurrent malignancy * More than 3 months since prior biologic or immunologic therapy * No concurrent insulin for diabetes * No prior radiotherapy to the oral cavity * More than 3 months since prior chemopreventative agents * More than 3 months since prior experimental therapy * More than 3 months since prior megadose vitamins or alternative therapy * No prior thiazolidinediones * No prior participation in this study * No concurrent pharmacologic treatment for diabetes * Concurrent chronic use of non-steroidal anti-inflammatory drugs allowed * Platelet count \> 125,000/mm\^3 * Index lesion must be located in an anatomic site accessible by punch biopsy