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Background: Evidence regarding the characteristics of second primary cancer (SPC) in people living with HIV (PLWHIV) is limited., Setting: We performed a national population-based data linkage study to determine the incidence and risk factors of SPC in PLWHIV in Australia between 1982 and 2012., Methods: We conducted a probabilistic data linkage study to compare the incidence of SPC over time, defined using HIV treatment eras, for SPCs related to oncogenic viral infection in comparison with non-infection-related SPCs. Risk factors considered included age at diagnosis of cancer, sex, HIV exposure modality, and CD4 + count., Results: Of 29,383 individuals diagnosed with HIV, 3123 individuals who developed a first primary cancer were included in the analysis. Among them, 229 cases of SPC were identified across 27,398 person-years of follow-up. The most common SPCs were non-Hodgkin lymphomas (n = 71, 31%). The incidence of SPC overall did not change over time; however, there was an increase in individuals diagnosed with HIV in later eras ( P trend =0.001). The incidence of non-infection-related SPC increased over time and was associated with older age ( P trend = 0.005) and the acquisition of HIV in later eras ( P trend <0.001). Conversely, the incidence of infection-related SPC decreased ( P trend <0.001), but this was no longer significant after adjustment for age ( P trend = 0.14)., Conclusions: The risk of SPC in PLWHIV in Australia remains high, with a temporal increase observed in non-infection-related cancer, likely due to aging of the population. Optimal screening and prevention strategies for SPC in PLWHIV are increasingly important., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Only a few types of cancer are recognised as being directly related to immune deficiency in people with HIV/AIDS. Large population-based studies in transplant recipients have shown that a wider range of cancers could be associated with immune deficiency. Our aim was to compare cancer incidence in population-based cohort studies of people with HIV/AIDS and people immunosuppressed after solid organ transplantation., Methods: Two investigators independently identified eligible studies through searches of PubMed and reference lists. Random-effects meta-analyses of log standardised incidence ratios (SIRs) were calculated by type of cancer for both immune deficient populations., Findings: Seven studies of people with HIV/AIDS (n=444,172) and five of transplant recipients (n=31 977) were included. For 20 of the 28 types of cancer examined, there was a significantly increased incidence in both populations. Most of these were cancers with a known infectious cause, including all three types of AIDS-defining cancer, all HPV-related cancers, as well as Hodgkin's lymphoma (HIV/AIDS meta-analysis SIR 11.03, 95% CI 8.43-14.4; transplant 3.89, 2.42-6.26), liver cancer (HIV/AIDS 5.22, 3.32-8.20; transplant 2.13, 1.16-3.91), and stomach cancer (HIV/AIDS 1.90, 1.53-2.36; transplant 2.04, 1.49-2.79). Most common epithelial cancers did not occur at increased rates., Interpretation: The similarity of the pattern of increased risk of cancer in the two populations suggests that it is immune deficiency, rather than other risk factors for cancer, that is responsible for the increased risk. Infection-related cancer will probably become an increasingly important complication of long-term HIV infection.