folic acid clinical trial for the prevention of cervical cancer

Conditions: Cervical Cancer; Precancerous Condition

Summary: 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.

Eligibility criteria:
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

Keywords: cervical cancer human papilloma virus infection low-grade squamous intraepithelial lesion high-grade squamous intraepithelial lesion atypical squamous cells of undetermined significance cervical intraepithelial neoplasia grade 1 cervical intraepithelial neoplasia grade 2 cervical intraepithelial neoplasia grade 3