New study examines role of vitamin D in high-risk HPV infection

By Naveed Saleh, MD, MS
Published December 8, 2020

Key Takeaways

As many as 10% of women aged 30 years and older harbor persistent human papillomavirus (HPV) infections, with high-risk HPV (hrHPV) playing a major role in the development of cervical cancer. In a recent study published in The Journal of Infectious Diseases, researchers identified various vitamin D biomarkers that were related to short-term hrHPV persistence of 14 clinically relevant strains.

“While HPV infection characteristics such as genotype and viral load are established risk factors for persistence, other cofactors are less well defined,” the authors wrote. “Better understanding of modifiable risk factors that contribute to persistent detection of hrHPV may inform efforts to prevent carcinogenic progression.” 

Vitamin D deficiency

Vitamin D deficiency affects 40% of adults in the United States. Sufficient levels of vitamin D are related to better health outcomes, lower incidence of some cancers, and lower risk of respiratory infections like influenza. With respect to immunity, lower serum 25(OH)D concentrations decrease innate immune function and heighten susceptibility to infection. Vitamin D deficiency may also hinder the production of antimicrobial peptides, which are products of endothelial cells that may help ward off hrHPV in the vagina and cervix. Of note, hrHPV is adept at dodging adaptive immune responses, thus any strategy that focuses on innate immunity could be particularly useful in a clinical sense.

In the current study, researchers assessed stored serum specimens from 72 women aged between 30 and 50 years for five vitamin D biomarkers along the micronutrient’s metabolic pathway, with levels of 25(OH)D being the primary outcome. The researchers assessed persistent vs sporadic/transient detection patterns for hrHPV detection patterns via cervicovaginal swabs obtained monthly for 6 months, looking for correlations between vitamin D and persistence of short-term, type-specific hrHPV persistence. Results were adjusted for covariates including age, body mass index (BMI), calcium/phosphate levels, contraceptives, education, race, season, and smoking.

Although previous research has focused on relationships between serum vitamin D levels and hrHPV using a cross-sectional design, the current study leveraged longitudinal data (which was later analyzed in a cross-sectional fashion). Based on monthly evaluation for 6 months, the team found that serum concentrations of 25(OH)D at a cut-off of 30 ng/mL were positively correlated with a short-term pattern of persistently detected hrHPV. Importantly, associations were significant only after discounting covariates, results that the authors possibly attributed to small sample size and low power. 

The researchers conflated sporadic and transient detection patterns. From an operational perspective, combining these two factors increased the power to detect differences from persistent infection. Moreover, during the study period, observed sporadic and transient patterns were nearly indistinguishable, according to the researchers. Nevertheless, future studies with longer follow-up should parse the differences between sporadic and transient phenotypes, with sporadic infections possibly indicating viral load hovering at or near detectable levels and an inability to clear infection. 

Unexpected results

The researchers also expounded on intriguing results that they uncovered on cross-sectional analysis of the data. “Unexpected findings among women with the highest vitamin D concentrations in our cross-sectional analyses of this data prompted the question of whether higher concentrations of vitamin D preceded infection with hrHPV or whether the opposite occurred.”

They added, “It is possible women who were classified as likely using supplements were previously diagnosed as deficient, and an association between hrHPV status and 25(OH)D level prior to supplementation might better reflect a relationship between vitamin D status and detection of hrHPV. Future studies evaluating incident detection of hrHPV should consider capturing data on vitamin D.” 

The bottom line

Looking forward, the author recommended that research on the topic assess the link between vitamin D and hrHPV in those at higher risk of death due to cervical cancer, including White women, women with higher BMIs indicative of obesity, and women who smoke cigarettes. Additionally, because the current study depended on parent data where vitamin D was not the primary impetus, future work could examine dietary sources of the vitamin D, as well as supplementation of this nutrient.

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