Gene-nutrient interactions and risk of human papillomavirus (HPV) persistence

CJ Piyathilake, PhD, a, OL Henao, MS,b, S Meleth, PhD,c, GL Johanning, PhD a, PE Cornwell, PhD, a, EE Partridge, MD, d,and DC Heimburger, MD, a

The Departments of aNutrition Sciences, bEpidemiology, cBiostatistics and dObstetrics & Gynecology, University of Alabama at Birmingham, Birmingham, Alabama, United States.

Although persistent high-risk (HR) HPV infections are etiologically linked to cervical carcinogenesis, life-style factors that might modify this relation are largely unknown. This prospective follow-up study was conducted to test the hypothesis that plasma concentrations of folate, vitamins B-12 and C, and genetic polymorphisms of methylenetetrahydrofolate reductase, methionine synthase and manganese superoxide dismutase are associated with increased HPV persistence. The status of circulating vitamins, polymorphisms and known risk factors for cervical cancer (oral contraceptive use, smoking, race, age at first intercourse, and number of sexual partners) at base line were determined in a cohort of 720 women who were at risk of developing high-grade squamous intraepithelial lesions (HSIL), a precursor for cervical cancer. HR-HPV status (positive vs. negative) was evaluated at 6-month intervals up to 24 months. 60 and 40 subjects were positive and negative for HR-HPV at all visits respectively. 97 subjects were HPV positive at two consecutive visits. HR-HPV persistence (as determined by all visits and consecutive visits positive) was associated with a significantly increased risk of developing HSIL (OR=58 and 91 respectively, p less than 0.0001). Concentrations of plasma folate were significantly lower in HR-HPV positive subjects compared to HR-HPV negative subjects (p=0.04). In a logistic regression model that included all variables, the number of sexual partners was significantly associated with HPV persistence (OR=2.3, 95% CI=1.3-4.2, p=0.004). Older age (OR=0.15, 95% CI= 0.06-0.39, p=0.0001) and higher concentrations of plasma folate (OR= 0.86, 95% CI= 0.76-0.98, p=0.02) protected against HPV persistence. To our knowledge, this is the first report to suggest a protective role of folate in HR-HPV persistence.

KEY WORDS: Folate, polymorphism, cervical cancer, cervical dysplasia.

For more information, contact PIYATHIC@UAB.EDU

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Dietary Influences.