Impact of infection and microbial exposures on pediatric cancer

The etiology of pediatric cancer is likely multifactorial including a combination of genetic alterations and environmental exposures. Infection and antigenic exposures have been identified as contributors to the development of pediatric cancers particularly acute lymphoblastic leukemia (ALL), the most common pediatric malignancy. Viral infections such as Epstein-Barr virus (EBV) and human papilloma virus (HPV) have a well-established association with Hodgkin lymphoma (EBV), Burkitt lymphoma (EBV), and head and neck cancers (HPV). More recent evidence suggests CMV is associated with glioblastoma multiforme and ALL. The incidence of pediatric cancer is much lower than the incidence of these viral infections, indicating that there are likely other factors at play. Aside from these specific viral infections, antigenic exposures in general have been associated with pediatric cancers as well. Early life antigenic exposures are known to impact the gut microbiome which is a crucial component to developing a competent immune system. Higher microbial exposure in early life, such as vaginal delivery (versus cesarean delivery), daycare attendance, and breastfeeding have been associated with lower incidence of pediatric ALL, and this effect is hypothesized to be mediated by the gut microbiome. In this review, we highlight the association between infection, antigenic exposures, and pediatric cancer and potential underlying mechanisms that facilitate this association.