Patient description: A Pap smear in a 54-year-old woman revealed abnormal cervical squamous intraepithelial/glandular lesion. She tested positive for HPV 16. She is sexually active with her husband and has 4 children. She is menopausal and uses no contraception. She smokes and drinks alcohol frequently. She is otherwise healthy. She was offered conization.

Clinical trial eligibility criteria: eligible ages (years): 18.0-45.0,  Cervical Intraepithelial Neoplasia Grade 2/3 Cervical Squamous Cell Carcinoma In Situ Cervical Squamous Intraepithelial Neoplasia 2 High Grade Cervical Intraepithelial Neoplasia 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  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)