• Be willing and able to provide written informed consent/assent for the trial.

• Subjects must have leukoplakia, erythroleukoplakia or proliferative verrucous leukoplakia (PVL) with lesions measurable in 2 dimensions, not amenable to surgical resection or radiation or who have refused surgery or radiation. Patients must have at least 1 lesion that can be followed on treatment. (Patients who have undergone complete excision of lesions and are clinically without evidence of disease will not be eligible for study.)

• Evidence of moderate or severe dysplasia or carcinoma in situ.

• Baseline biopsy specimen available for biomarker analysis or willingness to undergo fresh baseline biopsy.

• Willingness to consent to photographs of lesions.

• Willingness to undergo biopsy at 6 months.

• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale.

• Absolute neutrophil count (ANC) \>= 1,500 /mcL within 10 days of treatment initiation.

• Platelets \>= 100,000/mcL within 10 days of treatment initiation.

• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment).

• Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN within 10 days of treatment initiation. (Glomerular filtration rate \[GFR\] can also be used in place of creatinine or CrCl).

⁃ Creatinine clearance should be calculated per institutional standard.

• Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN within 10 days of treatment initiation.

• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases within 10 days of treatment initiation.

• Albumin \>= 2.5 mg/dL within 10 days of treatment initiation.

• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants. (Within 10 days of treatment initiation.)

• Activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. (Within 10 days of treatment initiation.)

• Female subject of childbearing potential should have a negative urine or serum pregnancy within 10 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.

• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.