High risk of Aids patients dying of cancer

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People diagnosed with Aids have a very high risk of dying of a non-Aids-defining cancer, Italian investigators report.

Overall, people with an Aids diagnosis had a sevenfold increase in their risk of dying from a non-Aids-defining malignancy compared to HIV-negative patients. The risk of death due to certain cancers was remarkably high, including anal cancer. Aids patients with a history of injecting drug use had especially high excess mortality due to non-Aids-related cancers.

“The study documented a statistically higher mortality…for cancers not directly associated with HIV/Aids, with an overall 7.3-fold excess risk for all non-ADCs [Aids-defining cancers] combined,” write the authors. “This latter figure can be interpreted as a combination of the increased incidence of such malignancies and the reduced cancer survival of people with HIV/Aids.”

Patients with HIV should be closely monitored for both virus and lifestyle related cancers, suggest the investigators.

Three cancers are classified as Aids-related: non-Hodgkin lymphoma, Kaposi’s sarcoma and cervical cancer. However, thanks to effective antiretroviral therapy, the incidence of these cancers in patients with HIV is falling.

In contrast, non-Aids-defining cancers are now recognised as an important cause of serious illness and death in people with HIV. However, the increased risk of death that patients with HIV have due to non-Aids-defining cancers compared to age- and sex-matched individuals in the general population is unclear. Italian investigators therefore designed a population-based, retrospective study to quantify the excess risk of cancer-related death among patients with Aids compared to patients in the general population.

Data were collected from death certificates and central registries for patients aged between 15 and 74 years who were diagnosed with or died of Aids between 2006 and 2011. Death records of approximately 952,000 non-Aids patients who died in the same time period were used for comparison purposes. Causes of death for non-Aids patients were scrutinised to ensure that patients with Aids/HIV-related causes of death were excluded.

Excess mortality among Aids patients compared to non-Aids patients was estimated using sex- and age-adjusted standardised mortality ratios (SMRs).

People with Aids were followed for a median of 2.5 years and contributed 14,180 person-years of analysis. During this time, 1229 patients died. Mortality was highest among patients with a history of injecting drug use (IDU) and lowest among gay men (17%).

Aids-defining cancers were reported on 23% of death certificates, with non-Hodgkin lymphoma reported on 18% of certificates, Kaposi’s sarcoma on 5% of certificates and cervical cancer on 2.5% of certificates.

Non-Aids-defining cancers were reported on the death certificates of 10% of Aids patients. The most common were lung cancer (38 deaths, 3%), liver cancer (17 deaths, 1.4%) and Hodgkin lymphoma (twelve deaths, 1%). Non-Aids-defining malignancies were more common among patients aged 50 years and over compared to younger patients (14 vs. 8%, respectively). Cancer was recorded on the death certificates of 47% of non-Aids patients.

When all non-Aids-defining cancers were considered together, patients with Aids had a sevenfold increase of death due to these cancers compared to non-Aids patients. The excess mortality risk was higher for younger (under 50 years) Aids patients compared to older Aids patients (SMR = 14.2 vs. 5.2, respectively).

Remarkably elevated risks of death were detected for anal cancer (SMR = 228) and Hodgkin lymphoma (SMR = 122). A significant risk of excess mortality was identified for several cancers, including non-specified uterine cancers (SMR = 52.5), liver cancer (SMR = 13.2), melanoma (SMR = 11), lung cancer (SMR = 8), head and neck cancers (SMR = 7.8), leukaemia (SMR = 7.6) and cancer of the colon-rectum (SMR = 5.4).

Younger patients had an especially high risk of death due to liver cancer (SMR = 38.8 vs. 7.6 for over 50s) and lung cancer (SMR = 38.8 vs. 57 for over 50s). Patients with a history of injecting drug use had a higher risk of death due to non-Aids cancers (SMR = 20.0) compared to other HIV risk groups. As expected, risk of liver cancer (often due to the blood-borne viruses, HBV and HCV) was especially high (SMR = 74.7) for injecting drug users. However, patients who injected drugs also had a remarkably high risk of death due to anal cancer (SMR = 440) and non-specified uterine cancer (SMR = 157).

For patients infected with HIV sexually, the overall risk of a non-Aids-defining cancer was increased fivefold compared to non-Aids patients. Mortality risk due to anal cancer (SMR = 189.5) and Hodgkin lymphoma (SMR = 116) was especially elevated in this risk group, and they also had excess mortality risk due to leukaemia (SMR = 8.2), lung cancer (SMR =5.1) and colorectal cancer (SMR = 3.5).

“It is worth remembering that our data included only HIV-infected individuals having already had an Aids diagnosis,” comment the authors. “Thus, study results cannot be referred to HIV-infected people at an earlier stage of immunodeficiency.”

They believe their findings show the need for Aids patients to be monitored for cancers related to viruses (anal or liver cancer) and lifestyle related cancers (lung cancer), concluding “our results call for taking primary and secondary preventive actions to reduce both cancer incidence and mortality among people with HIV or Aids.”

Abstract
Background: Non-AIDS defining cancers (non-ADCs) have become the leading non-AIDS-related cause of death among people with HIV/AIDS. We aimed to quantify the excess risk of cancer-related deaths among Italian people with AIDS (PWA), as compared to people without AIDS (non-PWA).
Methods: A nationwide, population-based, retrospective cohort study was carried out among 5285 Italian PWA, aged 15-74 years, diagnosed between 2006 and 2011. Date of death and multiple-cause-of-death (MCoD) data were retrieved up to December 2011. Excess mortality, as compared to non-PWA, was estimated using sex- and age-standardized mortality ratios (SMRs) and corresponding 95% confidence intervals (CIs).
Results: Among 1229 deceased PWA, 10.3% reported non-ADCs in the death certificate, including lung (3.1%) and liver (1.4%) cancers. A 7.3-fold (95% CI: 6.1-8.7) excess mortality was observed for all non-ADCs combined. Statistically significant SMRs emerged for specific non-ADCs, i.e., anus (5 deaths, SMR=227.6, 95% CI: 73.9-531.0), Hodgkin lymphoma (12 deaths, SMR=122.0, 95% CI: 63.0-213.0), unspecified uterus (4 deaths, SMR=52.5, 95% CI: 14.3-135.0, liver (17 deaths, SMR=13.2, 95% CI: 7.7-21.1), skin melanoma (4 deaths, SMR=10.9, 95% CI: 3.0-27.8), lung (38 deaths, SMR=8.0, 95% CI: 5.7-11.0), head and neck (9 deaths, SMR=7.8, 95% CI: 3.6-14.9), leukemia (5 deaths, SMR=7.6, 95% CI: 2.4-17.7), and colon-rectum (10 deaths, SMR=5.4, 95% CI: 2.6-10.0). SMRs for non-ADCs were particularly elevated among PWA infected through injecting drug use.
Conclusion: This population-based study documented extremely elevated risks of
death for non-ADCs among PWA. These findings stress the need of preventive interventions for both virus-related and non virus-related cancers among HIV-infected individuals.

Authors
Zucchetto, Antonella; Virdone, Saverio; Taborelli, Martina; Grande, Enrico; Camoni, Laura; Pappagallo, Marilena; Regine, Vincenza; Grippo, Francesco; Polesel, Jerry; Dal Maso, Luigino; Suligoi, Barbara; Frova, Luisa; Serraino, Diego

Aidsmap material
Journal of Acquired Immune Deficiency Sydromes abstract


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