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People with HIV Are at Higher Risk for Cancers Linked to Smoking, Viruses

People with HIV appeared to have a higher overall rate of cancer in a large Danish study, but the difference was only significant for malignancies caused by smoking or other viruses, including lung cancer, anal cancer, and liver cancer. A related U.S. study found the rate of prostate cancer was actually lower among HIV positive men.

Since the advent of effective combination antiretroviral therapy (ART) in the mid-1990s, rates of AIDS-defining cancer -- Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer -- have fallen. Although results have been mixed, most studies have found that people with HIV remain at higher risk for certain malignancies compared to HIV negative populations. Thanks to effective HIV treatment, in fact, more people with HIV are staying alive long enough to develop cancer.

Smoking and Viral Cancers

As described in the June 19 edition of AIDS, Marie Helleberg from Copenhagen University Hospital and colleagues looked at rates of different cancers among HIV positive and negative people and estimated "population-attributable fractions" (PAFs), or the proportion of cancers associated with having HIV, immune deficiency (as indicated by CD4 T-cell count), and smoking. They specifically looked at cancers related to smoking (like lung and mouth cancer) and those caused by viruses including human papillomavirus (HPV; anal and cervical cancer), hepatitis B or C (liver cancer), and Epstein-Barr (some types of lymphoma).

This nationwide population-based cohort study compared cancer incidence (new cases) between 3503 people with HIV and 12 ,979 matched HIV negative population controls. Among people with HIV, the average baseline CD4 count was 450 cells/mm³ -- indicating relative well-preserved immune function -- and most were on antiretroviral therapy.

Results

• There were 157 cancer diagnoses during the study period among HIV positive people, compared with 255 among the much larger HIV negative population.
• People with HIV had nearly twice the risk of developing cancer overall compared with HIV negative people (84 vs 45 per 10,000 people, respectively; incidence rate ratio [IRR] 2.0).
• Virus-related cancers accounted for 43% of malignancies in the HIV positive population during the study period.
• Smoking-related cancers accounted for 23% of all cancers among people with HIV.
• HIV positive people had a higher likelihood of developing these cancers than HIV negative people:

o   Virus-related cancers: IRR 11.5, or more than 11-fold higher risk;

o   Smoking-related cancers: IRR 2.8, or nearly 3 times higher risk.

• In contrast, incidence rates for other types of cancer did not differ significantly between HIV positive and negative people (IRR 1.0).
• Among non-smokers, people with HIV did not have an increased risk of non-viral cancers compared to HIV negative controls (IRR 1.2).
• The population-attributablefraction of cancerassociated with having HIV was 49%.
• The population-attributable fraction associated with smoking was 27%.
• However, for cancers not strongly related to either smoking or viral infection, the fractions associated with having HIV and with immune deficiency were both 0%.
• Among people with HIV, a nadir (lowest-ever) CD4 count below 200 cells/mm³ was associated with a nearly 4-fold higher risk of lung cancer (IRR = 3.54) -- in fact, no one with a nadir above this level developed smoking-related cancers.

"The risk of cancer is increased in HIV patients compared to the background population," according to the study authors. "In absence of smoking, the increase in risk is confined to cancers related to viral infections, whereas the risk of other cancers is not elevated and does not seem to be associated with immune deficiency."

Prostate Cancer

A second study, published in the May 12 advance edition of Journal of Acquired Immune Deficiency Syndromes, looked at prostate cancer risk among men with HIV. This cancer is not known to have a viral cause and its association with smoking is unclear.

Julia Marcus from Kaiser Permanente Northern California and colleagues aimed to determine whether previously reported lower prostate cancer incidence rates among HIV positive men is attributable to confounding factors, reduced screening, or some other reasons.

This cohort study included 17,424 HIV positive and 182,799 HIV negative participants in Kaiser Permanente's managed health organization in Northern and Southern California. Fewer than half were on ART at study entry, rising to 76% by the end, but the mean CD4 count was relatively high at 466 cells/mm³. HIV positive men were more likely than negative men to smoke (39% vs 23%) and to have testosterone deficiency (13% vs 1%).

Participants were followed from their first Kaiser Permanente enrollment (after January 1996 in Northern California and after January 2000 in Southern California) until prostate cancer diagnosis, loss to follow-up, or December 2007. The mean duration of follow-up was nearly 5 years.

The researchers compared cancer rates by HIV status, adjusting for age, race, smoking, alcohol or drug use, being overweight or obese, and diabetes. For the Northern subset, they also looked at testosterone deficiency and prostate-specific antigen (PSA) tests as a proxy for cancer screening.

Results

• There were 74 prostate cancer cases among HIV positive men, for an incidence rate of 102 per 100,000 person-years.
• There were 1195 cases among HIV negative men, or 131 per 100,000 person-years -- a significant difference (p=0.008).
• The adjusted relative risk was 0.73, indicating a 27% lower risk for the HIV negative men.
• HIV positive men were less likely to be diagnosed with late-stage cancer (5% vs 11%) and more likely to have only local involvement (93% vs 83%).
• In the Northern California subset, HIV positive participants were significantly more likely than HIV negative men to have received a PSA test by age 55 (91% vs 86%, respectively).
• However, when looking only at those who received PSA tests, and after adjusting for testosterone deficiency, HIV positive men still remained at lower risk for prostate cancer compared with HIV negative men (RR 0.55, or about half as likely).

"Prostate cancer incidence rates are lower in HIV positive compared with HIV negative men, which is not explained by screening differences or the risk factors evaluated," the researchers concluded.

Taken together, the findings from these 2 studies indicate that people with HIV are at higher risk of some -- but by no means all -- cancers. Preventive measures can help reduce the likelihood of some of these disproportionate cancers, including regular screening, smoking cessation, and receiving hepatitis B and possibly HPV vaccines.

6/11/14

References

M Helleberg, J Gerstoft, S Afzal, et al. Risk of cancer among HIV-infected individuals compared to the background population: impact of smoking and HIV. AIDS 28(10):1499-1508. June 19, 2014.

JL Marcus, CR Chao, WA Leyden, et al. Prostate cancer incidence and prostate-specific antigen testing among HIV-positive and HIV-negative men.Journal of Acquired Immune Deficiency Syndromes. May 12, 2014 (Epub).