title: Lower red blood cell folate enhances the HPV-16-associated risk of cervical intraepithelial neoplasia.
abstract: OBJECTIVE
  We previously reported that higher circulating concentrations of folate are independently associated with a lower likelihood of becoming positive for high-risk human papillomaviruses (HR-HPVs) and of having a persistent HR-HPV infection and a greater likelihood of becoming HR-HPV negative (Cancer Res 2004;64:8788-93). In the present study conducted in the same study population, we tested whether circulating folate concentrations modify the risk of cervical intraepithelial neoplasia (CIN) > or =2 associated with specific types of HR-HPV.
  
  
  METHODS
  Multiple logistic regression models were used to assess associations (odds ratio with 95% confidence intervals) across HR-HPV, folate, and rigorously reviewed cervical histology of each subject.
  
  
  RESULTS
  HPV-16-positive women with low red blood cell folate were significantly more likely to be diagnosed with CIN > or =2 than were HPV-16-negative women with higher red blood cell folate (odds ratio 9, 95% confidence interval 3.3-24.8).
  
  
  CONCLUSIONS
  To our knowledge, this is the first study reporting an independent association of folate with risk of having CIN > or =2 in a population tested extensively for HR-HPV and CIN that also adequately controlled for several other micronutrients and known risk factors for CIN. Our findings suggest that improving the folate status in HR-HPV-infected women may reduce the risk of CIN and thus the risk of cervical cancer. Folate supplementation should be tested as a means of reducing the risk of developing CIN > or =2 in women exposed to HR-HPV, especially HPV-16.
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Chandrika J
authors.initials: CJ
authors.lastname: Piyathilake
authors.forename: Maurizio
authors.initials: M
authors.lastname: Macaluso
authors.forename: Ilene
authors.initials: I
authors.lastname: Brill
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Heimburger
authors.forename: Edward E
authors.initials: EE
authors.lastname: Partridge
mesh_terms: D000328:Adult; D016001:Confidence Intervals; D004912:Erythrocytes / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D005492:Folic Acid / Q000032:analysis / Q000378:metabolism*; D052162:Human papillomavirus 16; D006801:Humans; D016015:Logistic Models; D016017:Odds Ratio; D030361:Papillomavirus Infections / Q000097:blood / Q000453:epidemiology*; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000097:blood / Q000453:epidemiology* / Q000473:pathology / Q000821:virology
chemical_list: D005492:Folic Acid