Viral suppression reduces cancer risk but does not affect common cancers

People with HIV whose viral load has been fully suppressed for at least two years have a significantly lower risk of developing any form of cancer than other people with HIV, but still retain a higher risk of developing cancer than HIV-negative people of a similar age, a study of US military veterans published in Annals of Internal Medicine shows.

Researchers from the Veterans Aging Cohort say that although long-term suppression of viral load lowers the risk of non-AIDS cancers, HIV infection raises the risk of non-AIDS cancers for all people with HIV, possibly due to the long-term impact of inflammation caused by the virus.

Cancers in people with HIV may be associated with severe immunosuppression (the AIDS-defining cancers Kaposi’s sarcoma, non-Hodgkin lymphoma and invasive cervical cancer).

People with HIV may also have a higher prevalence of risk factors for some cancers, including smoking, human papillomavirus (HPV) infection or viral hepatitis.

HIV itself may promote the development of some cancers through inflammation or over-activation of the immune system.

Of course, people with HIV are also vulnerable to the same cancers that affect everyone else. For example, a recent study projects that by 2030, prostate cancer will be the most common form of cancer diagnosed in men with HIV in the United States, largely as a consequence of the improved life expectancy of people with HIV.

What has been unclear is the extent to which long-term antiretroviral therapy and viral suppression reduce the risk of developing cancer in people living with HIV.

To answer this question, researchers from the Veterans Aging Cohort Study compared the incidence of cancer between 1999 and 2015 in over 42,000 HIV-positive military veterans with a demographically matched sample of 104,712 veterans without HIV.

The cohort of people with HIV was predominantly male (98%), a majority were black (51%) and 67% had ever smoked. Twenty-two per cent had chronic hepatitis C virus (HCV) infection. At the time follow-up began (either in 1999 or at the point of entering care after 1999), 38% were aged 40-49 years, 26% were aged 50-59 years, 11% were over 60 years of age and 25% were under 40 years of age. The matched HIV-negative control group had very similar demographic characteristics with the exception of a lower frequency of hepatitis C (10%).

Participants with HIV were followed for a median of 7.4 years and the HIV-negative control group for 10.1 years. During the follow-up period, participants spent 22% of the time with unsuppressed viral load, 27% with early viral suppression (defined as a viral load below 500 copies for less than two years) and 37% of the time with long-term suppression (defined as continuous suppression below 500 copies/ml for more than two years). Sixty-two per cent of people with HIV achieved long-term suppression at some point during follow-up.

The researchers compared the risk of developing any form of cancer according to viral load suppression.

During the follow-up period, 4169 cancers were diagnosed in 3821 people with HIV. Of these, 616 were AIDS-defining cancers. Overall, after controlling for cancer risk factors and demographics, people with fully suppressed viral load were 52% more likely to develop any form of cancer than people without HIV (relative risk 1.52, 95% CI 1.44-1.61). People with early suppressed viral load were twice as likely to develop any form of cancer (RR 1.99, 95% CI 1.87-2.12) and people with an unsuppressed viral load just under two-and-a-half times more likely to develop any form of cancer than people without HIV (RR 2.35, 95% CI 2.19-2.51).

Considering these risks in numerical terms:

• In those without HIV, an average of seven cancers were diagnosed each year for every thousand people followed.

• Eleven cancers were diagnosed each year in every thousand people with long-term viral suppression followed for a full year.

• Among people with early viral suppression, 14 cancers were diagnosed each year in every thousand people followed for a full year.

• 17 cancers were diagnosed each year in every thousand people without viral suppression followed for a full year.

The reduction in the risk of cancer in virally suppressed people was largely explained by the reduction in the incidence of AIDS-defining cancers. The incidence of virus-related non-AIDS cancers such as oropharyngeal and anal cancers caused by HPV, liver cancer caused by hepatitis B or C and Hodgkin lymphoma caused by Epstein-Barr virus declined less sharply. The incidence of these cancers was 23% lower in people with long-term viral suppression compared with those with a detectable viral load.

People with long-term viral suppression had no increase in their risks of larynx cancer, melanoma of the skin and leukaemia compared to people without HIV but did have a slightly elevated risk of prostate cancer compared both to people with unsuppressed HIV and people without HIV. The researchers suggest that a lower rate of screening in men with HIV in the past may explain this finding.

The researchers conclude that more research is needed to determine whether having a viral load below 50 copies/ml rather than 500 copies/ml makes any difference to the risk of developing non-AIDS cancers and whether longer-term viral suppression beyond two years further reduces cancer risk.

Further research is also needed to determine if cancer risk differs between men and women; the researchers acknowledge that their cohort of US military veterans did not record enough reproductive tract or breast cancer cases to assess the impact of viral suppression on these cancers.