Human cytomegalovirus (HCMV) infects more than 80% of the global population. While mostly asymptomatic, HCMV infection can be serious among the immunocompromised, and it is implicated in chronic disease pathophysiology in adulthood. Large-scale minimally invasive HCMV screening could advance research and public health efforts to monitor infection prevalence and prevent or mitigate downstream risks associated with infection. We examine the utility of measuring HCMV immunoglobulin-G (IgG) levels in saliva as an index of serum levels. Matched serum and saliva samples from healthy adults (N = 98; 44% female; 51% white) were assayed for HCMV IgG, total salivary protein, and salivary markers related to oral inflammation, blood, and tissue integrity. We examine the serum-saliva association for HCMV IgG and assess the influence of participant characteristics and factors specific to the oral compartment (e.g., oral inflammation) on HCMV IgG levels and cross-specimen relations. We found a robust serum-saliva association for HCMV IgG with serum antibody levels accounting for >60% of the variance in salivary levels. This relation remained after adjusting for key demographic and oral immune-related variables. Compared to the serum test, the salivary HCMV IgG test had 51% sensitivity and 97% specificity. With improvements in assay performance and sample optimization, HCMV antibody levels in oral fluids may be a useful proxy for serum levels
