Background: Adolescent/young adult (AYA) Hodgkin lymphoma (HL) risk is increasingly linked to a deficit of microbial exposure in early life, especially from fecal-oral transmission.

Methods: In this cross-sectional study, we examined past exposure to 15 infections in serum samples from 291 AYA HL cases and 194 of their unaffected family members. We measured antibodies to HSV1, HSV2, VZV, EBV, HHV7, HCMV, HHV6, KSHV, S. gallolyticus, F. nucleatum, T. gondii, H. pylori, Rubella virus, and Parvovirus B19 using a multiplex serology bead array (Luminex). A positive history was determined by a titer threshold specific for each infection. A logistic regression model was used to calculate the odds ratio (OR) of AYA HL risk for each infection separately adjusted for sex and age at sampling. We then applied the same logistic regression model, adding an adjustment for family.

Results: Evidence of past HHV6 infection was associated with an increased risk of AYA HL (OR= 1.80; 95% CI= 1.06-3.07). Having antibodies to H. pylori was associated with a decreased risk (OR= 0.49; 95% CI= 0.25-0.98). An increasing number of fecal-oral infections (H. pylori, T. gondii) was associated with a decreasing risk of AYA HL (ptrend<0.001), while an increasing number of respiratory-transmitted infections (Rubella virus, Parvovirus) was not significantly associated (ptrend=0.062). After adjusting for family, infection with Parvovirus was the only significant risk factor for AYA HL (OR=3.8,1.06-13.6).

Conclusions: We show preliminary evidence for an inverse association between fecal-oral transmitted agents and risk of AYA HL, supporting the hypothesis that a deficit of early life fecal-oral transmitted microbes may be associated with increased risk. HHV6 and Parvovirus were associated with an increased risk, possibly due to a subclinical immune deficiency or an unknown mechanism. In the final presentation, we will add data from 40 additional unaffected family members currently missing age, and results by histology and EBV status.

Citation Format: Maryam Saleh, Amie Hwang, Julia Simon, Thomas M. Mack, Tim Waterboer, Wendy Cozen. Past infection and risk of adolescent/young adult HL [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-44.