Indian women with higher serum concentrations of folate and vitamin B12 are significantly less likely to be infected with carcinogenic or high-risk (HR) types of human papillomaviruses (HPVs)

Chandrika J Piyathilake¹, Suguna Badiga¹, Proma Paul², Vijayaraghavan K³, Haripriya Vedantham³, Mrudula Sudula³, Pavani Sowjanya³, Gayatri Ramakrishna⁴, Keerti V Shah⁵, Edward E Partridge⁶, Patti E Gravitt²

¹Department of Nutrition Sciences, The University of Alabama at Birmingham (UAB), Birmingham, AL, USA; ²Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; ³SHARE INDIA, Mediciti Institute of Medical Sciences, Ghanpur, India; ⁴Center for DNA Fingerprinting and Diagnostics, Hyderabad, India; ⁵Department of Molecular biology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD USA; ⁶UAB Comprehensive Cancer Center, The University of Alabama Birmingham (UAB), Birmingham, AL, USA

Background: Studies conducted in the USA have demonstrated that micronutrients such as folate and vitamin B12 play a significant role in modifying the natural history of high-risk human papillomaviruses (HR-HPVs), the causative agent for developing invasive cervical cancer (CC) and its precursor lesions.

Objective: The purpose of the current study was to investigate whether these micronutrients have similar effects on HR-HPV infections in Indian women.

Methods: The associations between serum concentrations of folate and vitamin B12 and HR-HPV infections were evaluated in 724 women who participated in a CC screening study in the southern state of Andhra Pradesh, India. Serum folate and vitamin B12 concentrations were measured by using a competitive radio-binding assay. Digene hybrid capture 2 (HC2) assay results were used to categorize women into two groups, positive or negative for HR-HPVs. Unconditional logistic regression models specified a binary indicator of HC2 (positive/negative) as the dependent variable and serum folate concentrations combined with serum vitamin B12 concentrations as the independent predictor of primary interest. Models were fitted, adjusting for age, education, marital status, parity, type of fuel used for cooking and smoking status.

Results: Women with higher concentrations of serum folate (>6 ng/mL) and vitamin B12 (>356 pg/mL) were at lower risk of being positive for HR-HPVs compared to those with serum folate ≤6 ng/mL and serum vitamin B12 ≤ 356 pg/mL (odds ratio = 0.26; 95% confidence interval: 0.08–0.89; P = 0.03).

Conclusions: These results demonstrated that improving folate and vitamin B12 status in Indian women may have a beneficial impact on the prevention of CC. Micronutrient based interventions for control of HR-HPV infections may represent feasible alternatives to vaccine based approaches to HPV disease prevention, which are currently unaffordable for use in resource limited areas in rural India.

Keywords: folate, vitamin B12, human papillomavirus, cervical cancer