Abstract 6233: Human cytomegalovirus, tumor characteristics and patient survival in head and neck squamous cell carcinoma

Abstract Human cytomegalovirus (CMV) is a beta-herpes virus that may play a role in head and neck squamous cell carcinoma (HNSCC). CMV is a highly prevalent latent infection among older US adults, and viral reactivation occurs in response to immune suppression and inflammation. Previously, in a study of 184 HNSCC we reported that elevated CMV IgG titers were associated with worse patient survival. Here, we have expanded our evaluation of CMV IgG and patient survival in 983 cases from the CoHANDS study. CMV positive patients had significantly worse HNSCC survival (p<0.003); this association remained after controlling for age, sex and stage (HR=1.30, 95% CI 1.02- 1.74). The association between CMV and outcome was independent of the known association between human papilloma virus infection (HPV) and patient survival. Next, we used nCounter gene expression data to evaluate immune infiltration and inflammation in 34 tumors from HNSCC patients with and without active CMV infection; active infection was defined as having DNAemia, the presence of cell-free CMV DNA in serum. Tumors from patients with active CMV infection were more likely to contain CMV transcript (p<0.06) and have increased T-cell infiltration (p<0.05), however there were no other differences in the immune infiltrate. The Tumor Inflammation Signature (TIS), a gene expression indicator that correlates with response to immune checkpoint inhibitors, was significantly higher in CMV positive patients (p=0.007). CMV positive patients were 12 times more likely to have an elevated TIS score (adjusted OR 12.4, 95% CI 1.2 - 124.2). In summary, HNSCC patients who are CMV IgG positive have poor survival and tumors from patients with active CMV infection have both increased T-cell infiltration and elevated tumor inflammation. These findings may have potential implications for immune therapy in HNSCC. Citation Format: Heather H. Nelson, DeVon Hunter-Schlichting, Rondi Butler, Karl Kelsey. Human cytomegalovirus, tumor characteristics and patient survival in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6233.