Folic Acid Clinical Trial for the Prevention of Cervical Cancer
Folic Acid Clinical Trial for the Prevention of Cervical Cancer
RATIONALE: Supplements, such as folic acid, may stop or delay the development of cervical
 cancer in women infected with human papillomavirus.

 PURPOSE: This phase II trial is studying how well folic acid supplements work in preventing
 cancer in women infected with human papillomavirus.
OBJECTIVES:

 Primary

 -  Evaluate the effects of folic acid supplementation on clearance of human papilloma virus
 (HPV) 16 and other specific types of HR-HPV and on prevention of the progression of ≤
 cervical intraepithelial neoplasia (CIN) 1 lesions (not true preneoplastic lesions) to
 CIN ≥ 2 (true neoplastic lesions) by conducting a 12-month double-blind randomized
 placebo-controlled trial with 5 mg of folic acid/day.

 Secondary

 -  Evaluate whether the clearance of HPV 16 and other specific HR-HPV types and the
 progression of cervical lesions (≤ CIN 1 to CIN ≥ 2) is modified by lower levels of
 circulating and/or cervical cell folate, presence of micronuclei or global DNA
 hypomethylation in cervical cells, presence of integrated vs episomal HPV 16, or a high
 HPV 16 viral load in cervical cells at the enrollment.

 OUTLINE: This is a single center study. Patients are stratified according to multivitamin use
 (yes vs no) and smoking status (smoker vs nonsmoker). Patients are randomized to 1 of 2
 treatment arms.

 -  Arm I: Patients receive oral folic acid pill once daily for 12 months in the absence of
 unacceptable toxicity or any other adverse effects.

 -  Arm II: Patients receive oral placebo once daily for 12 months in the absence of
 unacceptable toxicity or any other adverse effects.

 All patients complete a diet, physical activity, and a risk factor questionnaire at the
 enrollment visit (0-month) and at 4, 8, and 12 month visits (a total of 4 visits). Fasting
 blood samples for assessing circulating concentrations of micronutrients (folate, vitamins
 B12, A, E, C, and total carotenes) and exfoliated cervical cell samples for assessing HPV are
 collected at all 4 visits. Anthropometric measures are taken at all study visits. A
 colposcopically directed biopsy is taken at the 0-month visit and at the 12-month visit to
 assess the histological diagnoses of cervical lesions.
DISEASE CHARACTERISTICS:

 -  Received care at the Health Departments in Alabama and with an abnormal pap result,
 including any of the following:

 -  Atypical squamous cells of undetermined significance (ASCUS)

 -  ASCUS, cannot exclude high-grade lesion (ASCUS-H)

 -  Low-grade squamous intraepithelial lesion

 -  High-grade squamous intraepithelial lesion

 -  Referred to University of Alabama at Birmingham (UAB) Highlands Clinic for further
 colposcopic examination by Ob/Gyn physicians

 -  Tested positive for human papilloma virus (HPV) 16 and diagnosed with ≤ cervical
 intraepithelial neoplasia (CIN) 1 lesions at the 0-month visit

 -  With or without concurrent infections with other HR (High Risk) HPV types (HPV
 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68)

 -  Not diagnosed with true preneoplastic lesions of the cervix based on a colposcopically
 directed biopsy

 PATIENT CHARACTERISTICS:

 -  Not pregnant

 -  Willing to take study pills, keep scheduled follow-up study visits, or communicate
 with study personnel about changes in contact information during the study period

 -  No prior diagnosis or treatment for colon polyps or breast lumps

 PRIOR CONCURRENT THERAPY:

 -  No prior treatment for cervical cancer or precancerous condition

 -  No prior surgeries involving the cervix

 -  No concurrent antifolate medications such as methotrexate, sulfasalazine or phenytoin

 -  No concurrent or planned consumption of 400 μg or more of a folic acid supplement on a
 regular basis

 -  Not involved in any other clinical trial