Folic Acid Clinical Trial for the Prevention of Cervical Cancer

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