Trial Information

HPV Clearance by Folic Acid Supplementation (FACT for HPV)

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.