Elevated Tumor Mutation Burden in Cancer Patients with Underlying HIV Infection: Data from the Oncology Research Information Exchange Network (ORIEN).

Background: People living with HIV (PWH) have improved life expectancy because of effective human immunodeficiency virus (HIV) therapy but still experience immune impairment (e.g., altered CD4/CD8 T cells). We hypothesized that tumors diagnosed in PWH would have distinct molecular features.

Methods: We utilized whole-exome sequencing of paired tumor and germline DNA and RNA from 229 patients with cancer enrolled into the Oncology Research Information Exchange Network to classify total tumor mutation burden (TMB), MHC class I neoantigen count, and MHC class II neoantigen count.

Results: Specimens from 229 patients with cancer (110 PWH and 119 without HIV) were evaluated. Average TMB for tumors diagnosed in PWH was 249, compared with 172 for those without HIV. After adjustment for age, sex, race, smoking, and cancer site, the association between HIV and TMB remained statistically significant (OR = 1.72; 95% confidence interval (CI), 1.26-2.43). We further observed an association between HIV and higher putative class I neoantigen count (OR = 1.62; 95% CI, 1.10-2.41) but no association with putative class II neoantigens. When considering cancer sites separately in unadjusted analyses, average TMB was elevated in PWH for thyroid (P < 0.01) and bladder cancers (P = 0.03) and sarcoma (P = 0.04). Similarly, putative class I neoantigen count was elevated in PWH for head and neck (P < 0.01) and thyroid (P = 0.01) cancers, as well as sarcoma (P = 0.04).

Conclusions: Our findings indicate that tumors diagnosed in PWH harbor a higher TMB and a higher number of putative class I neoantigens.

Impact: A higher TMB in PWH may portend a more favorable response to certain cancer treatment modalities such as immune checkpoint inhibitors.