Topical Fluorouracil and Imiquimod in Treating Patients With High-Grade Cervical Intraepithelial Neoplasia

Inclusion Criteria:

* Women with biopsy confirmed high grade cervical squamous intraepithelial lesions (i.e., cervical squamous intraepithelial neoplasia 3 \[CIN3\] lesions, and cervical squamous epithelial neoplasia 2 \[CIN2\] lesions with diagnosis confirmed by positive p16 immunohistochemistry staining) within 12 weeks of baseline visit
* Karnofsky \>= 70%
* Leukocytes \>= 3,000/microliter
* Absolute neutrophil count \>= 1,500/microliter
* Platelets \>= 100,000/microliter
* Serum creatinine =\< the upper institutional limits
* Participants must have a negative human immunodeficiency virus (HIV) antibody/antigen test and negative Chlamydia (C.) trachomatis/Neisseria (N.) gonorrhea nucleic acid amplification test (NAAT)
* Agree to use an effective form of contraception; the effects of intravaginal 5-fluorocuracil and imiquimod on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because 5- fluorouracil is known to be teratogenic, women of child-bearing potential must agree to use adequate dual methods of contraception (hormonal method of birth control, intrauterine device, or tubal ligation - plus condoms) or abstinence prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Women treated previously with 5-fluorouracil or imiquimod or other medications for high-grade squamous intraepithelial lesions will be excluded from the study
* Concurrent vaginal, vulvar, anal lesions or symptomatic infections
* Pregnant or planning pregnancy within the next 6 months, or breastfeeding; pregnant women are excluded from this study because 5-fluorouracil is an antimetabolite with the potential for teratogenic effects; because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with 5-fluorouracil, breastfeeding should be discontinued if the mother is treated with 5-fluorouracil
* Inability to speak or read English or Spanish
* Prior hysterectomy
* Use of anticoagulant medications
* Subjects who have a known immunocompromised condition (HIV positive \[+\], use of immunosuppressive medications or systemic steroids, organ transplant recipients) or autoimmune conditions (e.g. psoriasis, rheumatoid arthritis or other known autoimmune conditions)
* Evidence of invasive anal, vulva, vaginal, or cervical carcinoma; prior loop electrosurgical excision procedure (LEEP) or ablative treatment within 6 months prior to study entry; other invasive malignancies, with the exception of non-melanoma skin cancer, within the last 5 years
* Pathologic findings consistent with

  * Atypical endometrial cells or serious glandular-cell atypia (atypical glandular cells, favor neoplasia cytology diagnosis)
  * Evidence of cervical carcinoma on Pap smear or biopsy
  * More than two cervical quadrants of CIN 3 as visualized by colposcopy
  * Nonvisual squamous columnar junction on colposcopy with no concurrent endocervical sampling performed
* Use of other investigational agents within 6 months prior to enrollment
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to 5-fluorouracil or imiquimod
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (other than human papilloma virus \[HPV\]), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Subjects with known partial or complete dihydropyrimidine dehydrogenase (DPD) enzyme deficiency