The risk of infection-related malignancies and tumor mutational burden in immunocompromised hosts: A systematic review and meta-analysis

Background Immunocompromised individuals exhibit an increased risk of malignancies attributable to impaired immune surveillance and increased susceptibility to oncogenic infections, resulting in distinct responses to immunotherapy. The intricacies of infection-related cancer risks and the feasibility and efficacy of immunotherapy in these patients remain inadequately understood.

Methods A comprehensive search of PubMed, Web of Science, EMBASE, Medline, and Cochrane Library was conducted up to Nov 10, 2024. A random-effects model was pre-specified as the primary analytical method to account for anticipated clinical and methodological heterogeneity among the included studies. Heterogeneity was quantified using the I² statistic. Tumor mutational burdens (TMBs) were assessed for Spearman correlation with standardized incidence ratios (SIRs).

Results This systematic review included 151 studies, comprising 74 in solid organ transplant (SOT), 15 in hematopoietic stem cell transplant (HSCT), and 62 in people living with HIV (PLHIV). The analysis encompassed 2,418,274 SOT recipients, 117,264 HSCT recipients, and 5,762,641 PLHIV, covering 17 infection-related cancers. Excluding nasopharyngeal cancer, 16 cancers showed higher SIRs in SOT recipients and PLHIV compared to the general population. A statistically significant correlation was observed between TMBs and SIRs in SOT recipients (Spearman’s ρ = 0.85, P = 0.002), with consistent findings across key subgroups (kidney [Spearman’s ρ = 0.92, P < 0.001], liver [Spearman’s ρ = 0.91 (P < 0.001)], heart and/or lung [Spearman’s ρ = 0.74, P = 0.023]), and PLHIV (Spearman’s ρ = 0.89, P = 0.002), whereas no significant association was detected in HSCT recipients (Spearman’s ρ = 0.15, P = 0.805).

Conclusion These findings suggest that TMBs from infections or immunosuppression may contribute to cancer risk, emphasizing the potential of immune checkpoint inhibitors despite rejection risks. Personalized cancer surveillance and tailored therapies are essential for immunosuppressed populations.