Elevated tumor mutation burden in patients with cancer with underlying HIV infection: data from the Oncology Research Information Exchange Network (ORIEN).

Abstract

Background: People living with HIV (PWH) have improved life expectancy due to effective 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 sequencing of tumors from 229 patients with cancer enrolled into ORIEN to classify: total tumor mutation burden (TMB), major histocompatibility complex (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 to 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% CI: 1.26-2.43). We further observed an association between HIV and higher 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 & neck (p<0.01) and thyroid (p=0.01) cancers, and sarcoma (p=0.04).

Conclusion: 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 cancer treatment modalities such as immune checkpoint inhibitors.