Diversity model for HPV progression with mediation analysis.

Panel A shows the results of the mediation analysis that focus on V1 Gardnerella and V2 Shannon diversity. Top row shows Average Causal Mediation Effect (ACME) which is the full mediation effect of V2 Shannon diversity after adjusting for the direct effect of V1 Gardnerella on case status. The second row shows Average Direct Effect (ADE) which is the direct effect of Gardnerella on the clearance/progression outcome after accounting for the mediation effect of V2 Shannon diversity. The third row shows the Total Effect which is the direct, unadjusted effect, of Gardnerella on case outcome. The last row shows the Proportion (Prop.) Mediated, which is the proportion of the model that is mediated by V2 Shannon diversity. Based on GLM modeling, we propose the above model (Panel B) in which V1 Gardnerella causes an expansion of bacterial diversity at V2, which acts as a risk factor for the progression of a HR_HPV infection into a CIN2+ lesion.