Folate Is Associated with the Natural History of High-Risk Human Papillomaviruses

Abstract

Several micronutrients have been implicated in cervical carcinogenesis. However, their mode of action is still a matter of speculation. In particular, it is unclear whether certain nutrients reduce the probability of acquiring high-risk human papillomavirus (HPV) or whether they facilitate the clearance of high-risk HPV. We conducted a 24-month prospective follow-up study to test the hypothesis that systemic concentrations of folate are associated with the occurrence and duration of high-risk HPV infections after controlling for other micronutrients (vitamins B 12 , A, E, and C, total carotene) and known risk factors for high-risk HPV infections and cervical cancer. Circulating concentrations of these micronutrients and risk factors for cervical cancer were determined in a cohort of 345 women who were at risk of developing cervical intraepithelial neoplasia. Using the hybrid capture 2 (HC-2) assay, high-risk HPV status was evaluated at 6-month intervals up to 24 months. All women had at least three consecutive visit high-risk HPV test results. Higher folate status was inversely associated with becoming HC-2 test-positive [odds ratio (OR): 0.27; 95% confidence interval (CI), 0.08 -0.91; P ‫؍‬ 0.04]. Women with higher folate status were significantly less likely to be repeatedly HC-2 test-positive (OR: 0.33; 95% CI, 0.13-0.86; P ‫؍‬ 0.02) and more likely to become test-negative during the study (OR: 2.50; 95% CI, 1.18 -5.30; P ‫؍‬ 0.02). To our knowledge, this is the first long-term prospective follow-up study reporting an independent protective role of higher folate status on several aspects of the natural history of high-risk HPV after controlling for known risk factors and other micronutrients. Improving folate status in subjects at risk of getting infected or already infected with high-risk HPV may have a beneficial impact in the prevention of cervical cancer.

Selective Suppression of NF-kBp65 in Hepatitis Virus-Infected Pregnant Women Manifesting Severe Liver Damage and High Mortality

“…Therefore pregnancy appears to be a potential risk factor for enhanced viral replication/ expression and along with this extremely low immunity in Indian/Asian pregnant women, a vast majority of whom suffer from malnutrition and folate deficiency (43), which also contribute to liver injury, low immunity, and disease severity, leading to death (see Figure 8). Highly reduced immunocompetence is known to be associated with folate deficiency (43)(44)(45), which increases the multiple viral infection and/or increased viral load (43), including multifactorial disorders, in the Asian population (46,47).…”

“…Therefore pregnancy appears to be a potential risk factor for enhanced viral replication/ expression and along with this extremely low immunity in Indian/Asian pregnant women, a vast majority of whom suffer from malnutrition and folate deficiency (43), which also contribute to liver injury, low immunity, and disease severity, leading to death (see Figure 8). Highly reduced immunocompetence is known to be associated with folate deficiency (43)(44)(45), which increases the multiple viral infection and/or increased viral load (43), including multifactorial disorders, in the Asian population (46,47). A selective high susceptibility of Asian pregnant women to viral hepatitis leading to liver failure could also be due to ethnicity-associated host genetic susceptibility, particularly associated with the genes of the major histocompatibility complex (MHC), which has a strong effect on immune response to viral antigens (48,49).…”

Protective association of MTHFR polymorphism on cervical intraepithelial neoplasia is modified by riboflavin status

“…Detailed descriptions of sample collection and methodologies used to assess MTHFR polymorphism and folate, vitamins B-12, A, E, C and total carotene are published elsewhere (10,15). RBC samples frozen at −80°C within two hours of collection were used to determine riboflavin status using the erythrocyte glutathione reductase activity coefficient (EGRAC), a preferred method for evaluating riboflavin status (16).…”

Increase in the prevalence of the MTHFR 677 TT polymorphism in women born since 1959: potential implications for folate requirements

“…Nutritional status and food consumption may be important HPV cofactors that increase risk of persistence and progression to cervical intraepithelial neoplasia (CIN; Garcia-Closas et al, 2005). Previous research has shown that high folate status significantly influences the natural history of infections with high-risk HPV (Piyathilake et al, 2004) and lower likelihood of developing high-risk HPV-associated CIN grades higher than 2 (CIN 2 þ ; Piyathilake et al, 2007Piyathilake et al, , 2009). The apparent role of folate in cervical carcinogenesis has lead to the interest in folate metabolism enzymes that may be the cofactors linking folate deficiency and cervical carcinogenesis.…”