Pembrolizumab in Treating Patients With High Risk Oral Intraepithelial Neoplasia

Inclusion Criteria: * Histological evidence of oral intra-epithelial neoplasia within 12 months prior to enrollment; subjects with a history or clinical diagnosis suggestive of oral intra-epithelial neoplasia, or patients with a history of invasive oral cancer are eligible, but must have a confirmed histological diagnosis of oral intra-epithelial neoplasia before randomization; histological evidence of oral intraepithelial neoplasia on an invasive oral cancer resection specimen is acceptable; a visible, measurable, clinical lesion (such as leukoplakia and/or erythroplakia) is not required; only individuals with high risk profiles will be considered eligible for randomization; high risk profiles are defined as patients without a prior oral cancer and have loss of heterozygosity (LOH) at 3p14 and/or 9p21 plus at least at one additional chromosomal site (4q,8p,11p,13q, or 17p) or patients with a prior oral cancer history and have LOH at 3p14 and/or 9p21; all high risk patients must also meet the additional eligibility criteria * Be willing and able to provide written informed consent * Be greater than or equal to 18 years of age on day of signing informed consent for the trial * Be willing to provide tissue from a newly obtained oral biopsy * Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance scale * Absolute neutrophil count \>= 1,500/mcL * Platelets \>= 75,000/mcL * Serum total bilirubin =\< 1.5 X upper limit of normal (ULN) or direc…