Incidence and mortality of non-AIDS-defining cancers among people living with HIV: A systematic review and meta-analysis

Abstract

Background: Non-AIDS-defining cancers (NADCs) are now becoming a rising cause of morbidity among people living with HIV (PLHIV) in the highly active antiretroviral therapy (HAART) era. We conducted a systematic review and meta-analysis to estimate the summary risk of incidence and mortality of a wide range of NADCs among PLHIV compared with the general population.

Methods: This systematic review and meta-analysis was registered in the PROSPERO (registration number CRD42020222020). We searched PubMed, EMBASE, Cochrane library, and Web of Science for relevant studies published before Jan 24, 2022. Cohort or registry linkage studies comparing the incidence or mortality of individual NADCs in PLHIV with that in the general population were included. Studies simply reporting outcomes of cancer precursor lesions or combined NADCs were excluded. We calculated pooled standardised incidence (SIRs) and standardised mortality ratios (SMRs) and their 95% confidence intervals (CIs) using random-effects models, and used robust variance estimation to account for non-independence in study-level effect sizes.

Findings: We identified 92 publications arising from 46 independent studies including 7 articles out of 7 studies from developing countries. Among the 40 types of NADCs investigated, all of the 20 infection-related NADCs, cancers related with human papillomavirus infection in particular, and half of the 20 non-infection-related NADCs occurred in excess in PLHIV compared with the general population. This risk pattern was consistent in most WHO regions and in both high-income and low-and middle-income countries. The increased SIRs for various NADCs were more evident among PLHIV with advanced immunodeficiency, and was explored by HIV transmission route, and use of HAART. PLHIV had increased mortality for anal cancer (SMR 124·07, 95% CI 27·31-563·72), Hodgkin lymphoma (41·03, 2·91-577·88), liver cancer (8·36, 3·86-18·11), lung cancer (3·95, 1·52-10·26), and skin melanoma (3·95, 1·28-12·2).

Interpretation: PLHIV had increased incidence and mortality for a wide spectrum of NADCs. Primary prevention and effective treatment for NADCs in this population is urgently needed.

Funding: Natural Science Foundation of China Excellent Young Scientists Fund, Natural Science Foundation of China International/Regional Research Collaboration Project, National Science and Technology Major Project of China, Sanming Project of Medicine in Shenzhen, High Level Project of Medicine in Longhua, Shenzhen, Shenzhen Science and Technology Innovation Commission Basic Research Program, Special Support Plan for High-Level Talents of Guangdong Province, the Guangzhou Basic Research Program on People's Livelihood Science and Technology, the National Natural Science Foundation of China.

Keywords: Cancer; Incidence; Meta-analysis; Mortality; People living with HIV.

Figure 1

Flow chart of selecting studies for inclusion. Abbreviations: PLHIV, people living with HIV; NADCs, non-AIDS-defining cancers; ADCs, AIDS-defining cancers; SIR, standardised incidence ratio; SMR, standardized mortality ratio.

Figure 2

Meta-analysis of standardised incidence ratio for non-AIDS-defining cancers. Abbreviations: SIR, standardised incidence ratio; CI, confidence interval. In all the forest plots, the number of effect sizes refers to the number of single outcome estimates included in the meta-analysis, some of them were non-independent because they derived from one same study cohort or cancer registry. The number of studies refers to the number of independent cohort studies or registry linkage studies.

Figure 3

Subgroup analyses for SIRs by income levels of countries. Abbreviations: SIR, standardised incidence ratio; CI, confidence interval.

Figure 4

Subgroup meta-analysis for SIR by HIV transmission group. Abbreviations: SIR, standardised incidence ratio; CI, confidence interval.

Figure 5

Meta-analysis of standardised mortality ratio for non-AIDS-defining cancers. Abbreviations: SMR, standardised mortality ratio; CI, confidence interval.