Since the advent of effective combination antiretroviral therapy that has dramatically extended the lives of people with HIV, studies have produced conflicting data about the occurrence of cancer in this population.

A meta-analysis published in The Lancet last July, for example, found that while malignancies associated with infectious pathogens -- including anal and cervical cancer related to human papillomavirus (HPV) and liver cancer related to chronic hepatitis B or C -- were more common among people with HIV, several other types (including breast and prostate cancer) occurred with similar frequency in HIV positive and HIV negative individuals.

More recently, as reported in the May 20, 2008 Annals of Internal Medicine, Pragna Patel from the Centers for Disease Control and Prevention (CDC) and colleagues studied cancer rates in 2 U.S. large cohorts of people with HIV/AIDS.

This prospective observational analysis included 47,832 HIV positive participants in the Adult and Adolescent Spectrum of Disease Project (AASD) and 6948 in the HIV Outpatient Study (HOPS), who collectively contributed 157,819 person-years of follow-up between 1992 and 2003. The researchers also looked at nearly 335,000,000 records from 13 general population cancer registries in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program.

Standardized rate ratios (SRRs) were calculated to compare cancer incidence in the HIV positive cohorts with standardized cancer incidence in the general (i.e., predominantly HIV negative) population. The investigators also looked at changes in cancer incidence in the pre-HAART (1992-1995), early HAART (1996-1999), and more recent HAART (2000-2003) periods.

Results

• Over a median follow-up period of 2.0 (AASD) to 2.6 (HOPS) years, 3550 total new cases of cancer were reported:

• • 2842 (80%) AIDS-defining cancers;

• 708 (20%) non-AIDS-defining cancers.

• The incidence of the following types of non-AIDS-defining cancer was significantly higher in the HIV positive cohorts compared with the general population:

• Anal cancer: 59 times more common (SRR 42.9);

• Vaginal cancer: more than 20 times more common (SRR 21.0);

• Hodgkin lymphoma: 18 times more common (SRR 14.7);

• Liver cancer: about 7 times more common (SRR 7.7);

• Lung cancer: nearly 4 times more common (SRR 3.3);

• Melanoma (a form of skin cancer): about 3 times more common (SRR 2.6);

• Oropharyngeal (mouth and throat) cancer: about 3 times more common (SRR 2.6);

• Leukemia: more than twice as common (SRR 2.5);

• Colorectal cancer: more than twice as common (SRR 2.3);

• Renal (kidney) cancer: nearly twice as common (SRR 1.8).

• Conversely, the incidence of prostate cancer was significantly lower among HIV positive individuals compared with the general population (SRR 0.6).

• No significant differences were seen for any other types of cancer.

• While rates of AIDS-defining Kaposi's sarcoma (KS) fell dramatically from 1993 to 2003, the incidence rate remained significantly higher among HIV positive people compared with the general population (112 times more common in 2000-2003).

• Rates of AIDS-defining non-Hodgkin's lymphoma (NHL) also fell, but again remained higher in the HIV positive cohorts than in the general population (17 times more common in 2000-2003).

• Incidence rates of Hodgkin lymphoma, melanoma, and anal, colorectal, and prostate cancer increased significantly over time.

• Only anal cancer increased in both incidence among HIV positive individuals and relative incidence compared with the general population over time.

Conclusion

Based on these findings, the study authors concluded, "The incidence of many types of non-AIDS-defining cancer was higher among HIV-infected persons than among the general population from 1992 to 2003."

The investigators suggested that higher malignancy rates in HIV positive people may be due to a higher rate of coinfection with cancer-causing viruses such as HPV and hepatitis B or C virus, weakened immune systems that are unable to maintain adequate surveillance against cancerous cells, and perhaps a higher likelihood of high-risk lifestyle factors such as smoking.

As a limitation to their study, the researchers noted that it may have underestimated cancer rate disparities between the HIV positive and negative groups, since a small proportion of the general population likely would have been HIV positive. In addition, the study was not able to evaluate the influence of tobacco use or the effect of changes in cancer screening practices over time.

Several prior studies have also observed elevated rates of lymphoma and anal cancer among people with HIV. While NHL is considered an AIDS-defining cancer, Hodgkin lymphoma is not. Anal cancer is also not considered AIDS-defining, though invasive cervical cancer - caused by the same high-risk HPV types - does fall into this category.

While incidence rates of the AIDS-defining cancers KS, NHL, and cervical cancer remain higher in HIV positive compared with HIV negative people, they have fallen since the advent of HAART.

Conversely, rates of several non-AIDS-defining malignancies have risen in the HAART era, reflecting the fact that HIV positive people are surviving longer and therefore have more time to develop cancer. For example, prostate cancer - though it was the only malignancy found to occur at a lower rate in people with HIV - is nevertheless becoming more common as HIV positive men reach the 60 and older age group.

Recent studies, including the large ongoing D:A:D cohort study and the SMART treatment interruption trial, have shown that the risk of both AIDS-defining and non-AIDS-defining cancers rises as CD4 cell count declines - even before it falls below the current antiretroviral therapy threshold of 350 cells/mm3 - adding to the growing body of evidence that earlier HAART may be beneficial.

The authors of the present study recommended screening programs for early cancer detection and treatment (for example, Pap tests for pre-cancerous anal lesions), as well as risk-reduction measures such as smoking cessation.

5/30/08

Reference
P Patel, DL Hanson, PS Sullivan, and others (Adult and Adolescent Spectrum of Disease Project and HIV Outpatient Study). 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. May 20, 2008.