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Human Papillomavirus Persistence and Nutrients Involved in the Methylation Pathway among a Cohort of Young Women¹

Arizona Cancer Center [R. L. S., M. A., R. B. H., D. J. R., S. B., A. R. G.], Arizona College of Public Health [R. B. H., D. J. R., A. R. G.], and Obstetrics and Gynecology [S. B.], University of Arizona, Tucson, Arizona 85724-5024, and Stanley S. Scott Cancer Center, Louisiana State University Health Science Center, New Orleans, Louisiana 70112 [P. I.]

Persistent oncogenic human papillomavirus (HPV) infection is associated with cervical dysplasia. Cofactors, such as nutrient status, may be required for the progression of HPV infection to neoplasia. HPV DNA methylation patterns in vitro have been shown to be associated with viral transcriptional activity. Folate, vitamin B₁₂, vitamin B₆, and methionine may function to prevent cervical cancer through their role in DNA methylation. This study was conducted to examine the relationship of dietary intake of folate, vitamin B₁₂, vitamin B₆, and methionine, as well as circulating levels of folate and vitamin B₁₂ to HPV persistence. Oncogenic HPV status was determined at baseline and at 3 and 9 months postbaseline. Multivariate logistic regression analysis was used to determine the adjusted odds ratios for persistent HPV infection associated with each tertile of individual nutrient among 201 women with a persistent or intermittent HPV infection. Circulating vitamin B₁₂ levels were inversely associated with HPV persistence (P for trend, 0.037) after adjusting for age, age at first intercourse, marital status, cigarette smoking status, race, and body mass index. In addition, women with circulating levels in the highest tertile (>493.2 pg/ml) of vitamin B₁₂ were less likely to have a persistent infection (adjusted odds ratio = 0.4; 95% confidence interval = 0.17–0.96). No significant associations were observed between HPV persistence and dietary intake of folate, vitamin B₁₂, vitamin B₆, or methionine from food alone or from food and supplements combined or from circulating folate. These data suggest a role for circulating vitamin B₁₂ in early cervical carcinogenesis.

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