Men living with HIV have an approximately 25% lower risk of prostate cancer, says meta-analysis

Rates of prostate cancer are approximately 25% lower among men living with HIV compared to men in the general population, a research team led by Dr Dianqin Sun of the National Cancer Center, Beijing report in Prostate Cancer and Prostatic Diseases

Analysis of the results of 27 separate studies involving approximately 600,000 HIV-positive men showed that the incidence of prostate cancer was 24% lower among men with HIV compared to men in the general population. This finding was little changed when the researchers undertook a series of secondary, or ‘sensitivity’ analyses.

“Overall, the standardized incidence ratio was 0.76 and remained steady in a range of sensitivity analyzes, indicating an approximately a quarter lower prostate cancer incidence in men with HIV/AIDS compared with the general population.”

Glossary

meta-analysis

When the statistical data from all studies which relate to a particular research question and conform to a pre-determined selection criteria are pooled and analysed together.

sensitivity

When using a diagnostic test, the probability that a person who does have a medical condition will receive the correct test result (i.e. positive). 

middle income countries

The World Bank classifies countries according to their income: low, lower-middle, upper-middle and high. There are around 50 lower-middle income countries (mostly in Africa and Asia) and around 60 upper-middle income countries (in Africa, Eastern Europe, Asia, Latin America and the Caribbean).

heterogeneous or heterogeneity

Diverse in character or content. For example, the ‘heterogeneity’ of clinical trials means that they, and their results, are so diverse that comparisons or firm conclusions are difficult.

sensitivity analysis

An additional analysis of data, also known as a “what–if” analysis, which indicates how robust the study’s results are. Specific assumptions or variables may be changed, to estimate the outcome in a range of scenarios.

But there was considerable heterogeneity, or diversity, between the studies included in the review and there continues to be uncertainty about the reasons why men living with HIV have a reduced risk of prostate cancer. Therefore, the investigators believe their findings should be treated with some caution and urge more research into this area.

Diseases of ageing, including several cancers, are an important cause of illnesses and death among people living with HIV. The early detection and treatment of these diseases and malignancies is now a priority in routine HIV care.

It is well known that people with HIV are at greater risk of some cancers which can be caused by viral infections, probably due both to higher rates of those infections and to HIV’s impact on the immune system. These include lymphomas, Kaposi’s sarcoma, liver cancer, cervical cancer and anal cancer. Rates of lung cancer are also elevated. 

However, there is ongoing debate about the association between HIV infection and the risk of prostate cancer. Two meta-analyses published in 2007 and 2009 suggested HIV-positive men had lower incidence of prostate cancer compared to men in the general population. However, several studies have been published since then, some with findings that conflict with the meta-analyses.

Dr Sun and colleagues wanted to get a clearer understanding of this question. They therefore conducted a systematic review and meta-analysis of published studies comparing incidence of prostate cancer between men with HIV and men in the general population.

The results of the studies were pooled and the investigators compared overall incidence observed in men with HIV to that observed in the overall male population.

Cohort studies (prospective and retrospective) published before March 2020 were included in the review. A search of databases identified 27 eligible studies. The date range for data collection was 1981 to 2013, but most were published after 2000. The pooled studies included approximately 600,000 men with HIV. The number of men with HIV in each cohort ranged from 1730 to 57,500. The studies were conducted in eleven separate countries, the majority high-income.

There were 2780 cases of prostate cancer in HIV-positive men. The number of cases per study ranged from zero to over 1000. Pooled results showed that the incidence of prostate cancer was 24% lower in men with HIV compared to men in the general population (standardised incidence ratio (SIR) = 0.76; 95% CI, 0.64-0.91, p < 0.001).

This headline finding remained largely unchanged in a series of sensitivity analyses. These included adjustment according to individual characteristics such as age, race and CD4 count.

Most of the studies (n = 23) were conducted in high-income countries and their results showed an overall reduction in prostate cancer incidence of 29% (SIR = 0.71; 95% CI, 0.59-0.86, p < 0.001). The five studies carried out in low- and middle-income countries had less clear results. 

"Given that living with HIV is associated with an increased risk of several other cancers, how can the reduced incidence of prostate cancer be explained?"

The researchers excluded one study at a time from their analysis to test the robustness of their overall finding of a 24% reduction in prostate cancer risk. This did not have any significant impact on incidence calculations, with HIV infection associated with a reduction in prostate cancer risk of between 21% and 29%.

Given that living with HIV is associated with an increased risk of several other cancers, how can the reduced incidence of prostate cancer be explained? The investigators discuss a range of reasons, such as less frequent screening, reduced testosterone production and the impact of some anti-HIV drugs on the mechanisms associated with the development of prostate cancer. But they do not believe that any of these explanations is satisfactory.

They also highlight the considerable heterogeneity in the studies included in the meta-analysis – they were rarely comparing studies with the same methodology or of the same rigour. This means that some caution is needed when interpreting the results of the meta-analysis. They are not definitive.

“Our meta-analysis shows that men with HIV/AIDS have a lower prostate cancer incidence compared with the general population,” conclude the Beijing researchers. “Our findings support the need for further studies to address the epidemiological or biological pathways that affect the incidence of prostate cancer in men with HIV/AIDS.”

References

Sun D et al. Risk of prostrate cancer in men with HIV/AIDS: a systematic review and meta-analysis. Prostrate Cancer and Prostatic Diseases, published online ahead of print, 14 August 2020.

doi.org/10.1038/s41391-020-00268-2