Elsevier

The Lancet HIV

Volume 4, Issue 11, November 2017, Pages e495-e504
The Lancet HIV

Articles
Cancer risk in HIV-infected people in the USA from 1996 to 2012: a population-based, registry-linkage study

https://doi.org/10.1016/S2352-3018(17)30125-XGet rights and content

Summary

Background

Monitoring cancer risk among HIV-infected people in the modern antiretroviral therapy (ART) era is essential given their elevated risk for many cancers and prolonged survival with immunosuppression, ART exposure, and ageing. We aimed to examine cancer risk in HIV-infected people in the USA as compared with that in the general population.

Methods

We did a registry-linkage study with data from population-based HIV and cancer registries in the USA (the HIV/AIDS Cancer Match Study). We assessed a cohort of HIV-infected people identified in HIV registries in Colorado, Connecticut, Georgia, Maryland, Michigan, New Jersey, New York, Puerto Rico, and Texas from 1996 to 2012. Follow-up started 3 months after either the latest of the beginning of systematic name-based state HIV registration, HIV report date (or AIDS diagnosis, if this was earlier), start of cancer registration, or Jan 1, 1996, and ended at the earliest of either death, end of cancer-registry coverage, or Dec 31, 2012. We identified diagnoses of cancer in this population through linkage with corresponding cancer registries and calculated standardised incidence ratios (SIRs) to measure cancer risk in people with HIV compared with the USA general population, by dividing the observed number of cases in people with HIV by the expected number (estimated by applying general population cancer-incidence rates to person-time in the HIV population based on sex, age, race or ethnic group, calendar year, and registry). We tested SIR differences by AIDS status and over time using Poisson regression.

Findings

Among 448 258 people with HIV (who contributed 3 093 033 person-years), 21 294 incident cancers were diagnosed during 1996–2012. In these people, compared with the general population, risk was elevated (p<0·0001 for all) for cancer overall (SIR 1·69, 95% CI 1·67–1·72), AIDS-defining cancers (Kaposi's sarcoma [498·11, 477·82–519·03], non-Hodgkin lymphoma [11·51, 11·14–11·89], and cervix [3·24, 2·94–3·56]), most other virus-related cancers (eg, anus [19·06, 18·13–20·03], liver [3·21, 3·02–3·41], and Hodgkin's lymphoma [7·70, 7·20–8·23]), and some virus-unrelated cancers (eg, lung [1·97, 1·89–2·05]), but not for other common cancers. Risk for several cancers was higher after AIDS onset and declined across calendar periods. After multivariable adjustment, SIRs decreased significantly across 1996–2012 for Kaposi's sarcoma, two subtypes of non-Hodgkin lymphoma, and cancer of the anus, liver, and lung, but remained elevated. SIRs did not increase over time for any cancer.

Interpretation

For several virus-related cancers and lung cancer, declining risks over time in HIV-infected people probably reflect the expansion of ART since 1996. Additional efforts aimed at cancer prevention and screening in people with HIV are warranted.

Funding

National Cancer Institute.

Introduction

HIV-infected people have a higher risk for many cancers than do healthy people, largely as a result of HIV-related immunosuppression, which impairs control of oncogenic viral infections.1, 2, 3 A high prevalence of these infections and other cancer-risk factors (eg, smoking and alcohol use) contribute to the elevated risk.1, 2, 3, 4 Kaposi's sarcoma, some subtypes of non-Hodgkin lymphoma, and cervical cancer are caused by viruses (Kaposi sarcoma-associated herpesvirus, Epstein-Barr virus, and human papillomavirus, respectively) and are among conditions that can mark the onset of AIDS.3 HIV-infected people have elevated risks for these AIDS-defining cancers and other virus-related non-AIDS-defining cancers, but not for most virus-unrelated non-AIDS-defining cancers.1, 2, 3

After the introduction of effective antiretroviral therapy (ART) in 1996, the risks for AIDS and death decreased strikingly in HIV-infected people.3 The incidences of Kaposi's sarcoma and non-Hodgkin lymphomas have also decreased, but remain higher in HIV-infected people than in the general population; trends for other cancers are less clear.3, 5, 6, 7, 8, 9, 10, 11, 12 Few recent comprehensive population-based data exist about cancer risks for HIV-infected people.6, 8, 9, 10, 12

The risk for some types of cancers might continue to decline as ART regimens improve, treatment is initiated at earlier stages of HIV disease, and access to ART increases.13 However, treatment might not fully reverse the effect of early immune suppression, and immune dysfunction and chronic inflammation can persist among people receiving ART.2 HIV-infected people, including those who have not developed AIDS, might therefore still have an elevated risk of cancer. Furthermore, many cancer types have latency periods of decades, and the modern ART era is only 20 years old; elevated risks for some cancers might, therefore, emerge over time. Finally, with prolonged survival the HIV population is ageing, and the effect of HIV-related immunosuppression in an ageing population is unclear.10, 14 For these reasons, continued monitoring of cancer risks in this population is vital. In this study, we describe the range of cancer risks among HIV-infected people in the USA during the modern ART era by use of linked data from several population-based HIV and cancer registries.

Research in context

Evidence before this study

We searched PubMed for citations published in English during Jan 1, 2000, to Dec 31, 2016, with MeSH terms “cancer”, “incidence”, and “HIV infections”, reviewed personal collections of study reports and reviews, and examined reference lists of reviewed publications to identify publications about cancer risk in people with HIV, compared with the general population or uninfected groups. Specifically, we examined publications that reported risk estimates overall and by AIDS onset, and recent trends covering the era of effective antiretroviral therapy (ART) beginning in 1996. Evidence indicates that HIV-infected people, especially those with AIDS, have an elevated risk for many cancers, especially those from viral causes. Additionally, after the introduction of ART in 1996, the incidence of two AIDS-defining cancers, Kaposi's sarcoma and non-Hodgkin lymphoma, decreased. However, trends for other cancers are less clear, and there is a shortage of recent and comprehensive population-based data about cancer risks for people with HIV.

Added value of this study

The HIV/AIDS Cancer Match (HACM) Study is the largest population-based study of cancer in HIV-infected people. We used data from the study to assess the risk of cancers in a sample of 448 258 people with HIV in the USA during 1996–2012. We found that, compared with the general population, HIV-infected people (including those without AIDS) had a greater risk for various cancers, including AIDS-defining cancers, many other virus-related cancers, and lung cancer. Although the risk for Kaposi's sarcoma, non-Hodgkin lymphoma, and some non-AIDS-defining cancers (anus, liver, and lung) decreased over time, risks generally have remained high.

Implications of all the available evidence

The decreases in cancer risk in people with HIV over time probably reflect the sustained and widened use of ART. Despite these decreases, however, cancer risks in HIV-infected people have remained elevated during the modern treatment era, indicating that continued cancer control efforts are warranted with additional efforts aimed at cancer prevention and screening.

Section snippets

Study design, participants, and data sources

We used data from the HIV/AIDS Cancer Match (HACM) Study, which examines linked data collected by USA HIV and cancer registries.15 The study was approved by institutional review boards at participating registries as required, and received exemption from review at the USA National Institutes of Health. Because the study used data collected for public health surveillance, consent of participants was not required.

For this analysis we assessed a cohort of HIV-infected people from HACM identified in

Results

448 258 HIV-infected people contributed 3 090 033 person-years of follow-up (table 1). Across calendar periods during 1996–2012, the contribution by women and older age groups increased, while the contribution from non-Hispanic whites and injection drug users decreased. The proportion of follow-up time of at least 10 years after an HIV report or AIDS diagnosis increased from <1% (1996–99) to 24% (2009–12).

21 294 cases of cancer were diagnosed during 1996–2012 (incidence: 689 per 100 000

Discussion

During 1996–2012, HIV-infected people in the USA, including those who had not developed AIDS, had elevated risks for many cancer types, especially those with viral causes. There was a decrease in risk during this period for several virus-related cancers and lung cancer, presumably resulting, at least partly, from improved efficacy, earlier use, and wider access to ART over time.12, 13 Although risk remained elevated for several cancers even in the most recent years of the analysis (2009–12), we

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