HIV increases risk of nine non-AIDS-defining cancers, largest-ever observational study finds

Edwin J. Bernard
Published: 22 May 2008

Nine non-AIDS-defining cancers are more likely to be seen in HIV-positive individuals compared with the general population, according to the largest analysis ever undertaken of cancer incidence trends among HIV-positive individuals in the United States.

Notably, the study, published this week in the Annals of Internal Medicine (available online here) found that anal cancer is almost 60 times more common in HIV-positive individuals compared with the general population, and, say the investigators “incidence rates are expected to increase as HIV-infected persons live longer.”

Although recent studies have found that the incidence of the three AIDS-defining cancers – Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer – is declining and the incidence of non-AIDS-defining cancers is increasing in HIV-positive individuals following the advent of potent antiretroviral therapy, there are few data comparing the incidence of these cancers in HIV-positive individuals with the general population.

Consequently, investigators from two large prospective cohort studies in the United States – the Adult and Adolescent Spectrum of HIV Disease (ASD) Project and the HIV Outpatient Study (HOPS) – analysed the incidence of cancer in HIV-positive individuals between 1992 and 2003 and compared cancer incidence rates for the same period in the general population, with data derived from the Surveillance, Epidemiology, and End Results (SEER) programme of the National Cancer Institute.

A total of 54,780 HIV-positive individuals (47,832 from the ASD Project and 6948 from HOPS) contributed 157,819 person-years of observation. The median follow-up time was 2.0 years in the ASD Project and 2.6 years in HOPS.

There were 3550 cases of cancer identified, of which 2842 (80%) were considered to be AIDS-defining cancers and 708 (20%) non–AIDS-defining cancers.

The investigators had previously published an initial analysis of their data as a poster at the Fourth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Sydney in 2007, which was reported here.

Their initial analysis found that that seven non-AIDS-defining cancers were significantly more likely to be diagnosed in HIV-positive individuals than in the general population. The incidence of each was calculated as a standardised incidence rate per 100,000 prospective person-years of follow-up, and excluded cases that were alreday diagnosed at the time of HIV or AIDS diagnosis, or at the time that follow-up began.

These cancers were: anal cancer (standardised incidence rate [SIR]: 42.9); Hodgkin’s lymphoma (SIR: 14.7); liver cancer (SIR: 7.7); lung cancer (SIR: 3.3); melanoma (SIR: 2.6); oropharyngeal [mouth and throat] cancer (SIR: 2.6); and, colorectal cancer (SIR: 2.3).

The latest paper adds two more cancers to the list: leukaemia (SIR: 2.5) and renal [kidney] cancer (SIR: 1.8).

They also found that the incidence of prostate cancer was significantly lower (SIR: 0.6) in HIV-positive individuals compared with the general population. There were no significant differences seen between HIV-positive individuals and the general population in the rates of other types of cancer examined.

In this latest paper, the investigators also examined the relative incidence rates of the three AIDS-defining and nine non-AIDS-defining cancers in HIV-positive individuals compared with the general population.

They found that although the relative incidence of Kaposi sarcoma and non-Hodgkin lymphoma in HIV-positive individuals had decreased over time compared with the general population, even in the most recent time period (2000-2003) people with HIV were 112 times and 17 times more likely to be diagnosed with these AIDS-defining cancers, respectively, compared with the general population. By contract, in the pre-HAART era (1992-1995), HIV-positive individuals were 197 and 80 times more likely be diagnosed with Kaposi sarcoma and non-Hodgkin lymphoma, respectively, than the general population.

Most strikingly, however, the overall relative incidence of anal cancer in the HIV-positive individuals increased dramatically over time. The adjusted rate ratio almost doubled from the pre-HAART era (1992-1995) to the most recent time period (2000-2003), from 31.4 and 59.4. This means that anal cancer is almost sixty-times more likely to be seen in HIV-positive individuals (with a SIR of 78.2 per 100,000 person-years in 2000-3) compared with the general population (with SIR of 1.3 per 100,000 person-years in 2000-3.)

The 2000-3 relative incidence of the other cancers affecting HIV-positive individuals compared with the general population were: Hodgkin lymphoma (17.9); cervical cancer (10.1); liver cancer (7.0); lung cancer (3.6); melanoma (3.0); oropharyngeal cancer (3.0); colorectal cancer (2.4); breast cancer (1.1); and prostate cancer (0.7).

The investigators then examined risk factors associated with each type of cancer among HIV-positive individuals, using multivariable analysis adjusting for linear trend, age, race, gender, HIV risk group, nadir CD4 count, antiretroviral use, and hepatitis B or C infection (the latter two for liver cancer only).

They found that men who had acquired HIV through sex with another man were at an increased risk for Kaposi sarcoma (relative risk, 2.88; p<0.001) and non-Hodgkin lymphoma (1.53; p< 0.001).

In addition, they found that antiretroviral therapy was independently associated with a decreased risk for Kaposi sarcoma (relative risk, 0.61; p < 0.001), non-Hodgkin lymphoma (0.68; p < 0.001), cervical cancer (0.48; p = 0.019), breast cancer (0.35; p = 0.013), colorectal cancer (0.50; p = 0.027), and lung cancer (0.52; p < 0.003).

A low nadir CD4 count was found to be associated with an increased risk for Kaposi sarcoma (relative risk, 8.34; p< 0.001), non-Hodgkin lymphoma (6.03; p < 0.001), cervical cancer (3.70; p = 0.010), anal cancer (5.82; p = 0.017), colorectal cancer (6.27; p = 0.013), and lung cancer (2.42; p = 0.017).

Unsurprisingly, co-infection with hepatitis B or C was found to be associated with an increased risk for liver cancer (relative risk, 3.63; p < 0.001).

Although this is the largest analysis ever undertaken of cancer incidence trends among HIV-positive individuals in the United States, the investigators note that there are some limitations to their study. Notably, they did not have information on tobacco use or cancer screening practices. In addition, since they estimate that around 1% of individuals in the SEER database may have been HIV-positive, this would have led to an underestimate of the differences seen between the HIV cohorts and the general population.

They conclude by noting that despite the advent of HAART, “incidence rates increased significantly for melanoma; Hodgkin lymphoma; and colorectal, anal, and prostate cancer,” and that “immune dysfunction; concomitant infection with oncogenic [cancer-causing] viruses; and lifestyle factors, such as smoking, may account for the higher cancer incidence among HIV-infected persons.

“In addition to encouraging tobacco cessation,” they write, “HIV care providers should be aware of these elevated risks and screen for preventable diseases, such as cervical and colorectal cancer. Screening programs for early detection and treatment of precancerous anal lesions should be evaluated and will probably become more important as the HIV-infected population ages and lives longer.”

“Furthermore,” they conclude, “primary prevention strategies to reduce HPV infection and HPV-associated diseases, such as vaccination and circumcision, warrant further evaluation.”

Reference

Patel P et al. Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992–2003. Annals of Internal Medicine 148 (10); 728-736, 2008.

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