Circulating Biomarkers of Iron Storage and Clearance of Incident Human Papillomavirus Infection

Background: Iron is an essential mineral for both cellular and pathogen survival and is essential for viral replication. In turn, iron metabolism has been shown to be altered by several viral infections. However, little is known about the association between iron status and human papillomavirus (HPV) natural history. We hypothesize iron to be an HPV cofactor that is associated with longer duration of infection.

Methods: Ferritin and soluble transferrin receptor (sTfR) were measured in baseline serum samples from 327 women enrolled in the Ludwig-McGill cohort. Incident HPV clearance rates (any-type, oncogenic HPV, nononcogenic HPV, and HPV-16) over a 3 year time period were estimated from Cox proportional hazard models accounting for correlations between multiple infections.

Results: Women with ferritin levels above the median were less likely to clear incident oncogenic HPV [adjusted hazard ratio (AHR), 0.73; 95% confidence interval (CI), 0.55-0.96] and HPV-16 infections (AHR, 0.29; 95% CI, 0.11-0.73). Using physiologic cutoff points, women with enriched iron stores (>120 μg/L) were less likely to clear incident oncogenic HPV infections than those with low levels of iron (<20 μg/L; AHR, 0.34; 95% CI, 0.15-0.81).

Conclusion: This study observed that women with the highest ferritin levels were less likely to clear incident oncogenic and HPV-16 infections than women with low ferritin. Rising iron stores may decrease probability of clearing new HPV infection, possibly by promoting viral activity and contributing to oxidative DNA damage.

Impact: This novel study suggests that elevated iron stores may put women at risk for persistent HPV infection, an early event in cervical carcinogenesis. Further examination of the association between iron status and HPV natural history is warranted.