Infections and smoking increase risk of non-AIDS cancers for people with HIV

A meta-analysis has found that, compared to the general population, HIV-positive individuals have an increased risk of several non-AIDS-defining cancers. The research, which is published in the online edition of the Journal of Acquired Immune Deficiency Syndromes, showed that HIV-positive individuals had an increased risk of several infection-related cancers, as well as malignancies that are related to smoking.

However, the authors were unable to say if HIV per se increased the risk of such cancers, or if “confounding by unadjusted cancer risk factors may be responsible for the apparent elevated incidence”.

Cervical cancer, Kaposi’s sarcoma and non-Hodgkin’s lymphoma are all AIDS-defining cancers. Research suggests that people with HIV may also have an increased risk of developing several other cancers. A previous meta-analysis of seven studies showed that these cancers were often related to viral infections.

US investigators have now conducted a further meta-analysis including six additional studies. The investigators stratified their results to see if gender, a previous AIDS diagnosis and antiretroviral exposure affected the risk of non-AIDS-defining cancers.

Over one million person years of follow-up were available for analysis. The standardised incidence ratio (SIR) for 34 separate cancers was compared between individuals with HIV and HIV-negative individuals.

A total of 4797 non-AIDS-defining cancers were diagnosed in the studies, which were conducted between 1981 and 2007.

The most frequently observed non-AIDS-defining cancers were lung cancer (847 cases), Hodgkin’s lymphoma (643 cases) and anal cancer (254 cases).

All but two non-AIDS-defining cancers (breast cancer and prostate cancer) were more common amongst individuals with HIV than HIV-negative individuals.

This was especially the case with cancers linked to infections such as anal cancers (SIR = 28), liver cancer (SIR = 5.6), and Hodgkin's lymphoma (SIR = 11).

The incidence of some cancers associated with cigarette smoking was also elevated amongst people with HIV, including lung cancer (SIR = 2.6), kidney cancer (SIR = 1.7) and laryngeal cancer (SIR = 1.5).

Overall, people with HIV were twice as likely to develop a non-AIDS-defining cancer (SIR = 2) than the general population.

HIV-positive men had a greater risk of non-AIDS-defining cancers than HIV-positive women (SIR = 1.59). However, the risk varied by cancer type with women having an increased risk of several cancers including those of the kidney and larynx, as well as leukaemia and multiple myeloma.

The risk of non-AIDS-defining cancers was higher for patients with an AIDS diagnosis than those who had not progressed to AIDS (all non-AIDS malignancies, SIR = 3.17).

There was a modest fall in the incidence of non-AIDS-related cancers in the period after effective HIV treatment was introduced.

“HIV-infected individuals had twice the risk of a non-AIDS cancer than the general population”, write the investigators.

They note that many of the cancers were related to viral infections. These include human papillomavirus and anal cancer, hepatitis B and C and liver cancer, and Epstein Barr virus and Hodgkin’s lymphoma.

“Decreased immune function paired with increased incidence of these infections may be responsible for the increased rates of virally associated cancers among people with HIV”, comment the authors.

Cigarette smoking also appears to have been the underlying cause of many of the cancers, especially for women.

Reduced hormone levels due to HIV could, the investigators suggest, explain why rates of breast and prostate cancer were lower amongst people with HIV than in the general population. But they also caution “the decreased incidence of these cancers among HIV-infected individuals may also be due to differential screening by HIV status.”

The investigators conclude, “this study found an increased SIR for many types of non-AIDS cancers.” However, “it remains unclear whether HIV-infected individuals are truly at a greater risk of non-AIDS-defining cancers, or if confounding by unadjusted cancer risk factors may be responsible for the apparent elevated increase.”