Although HIV-positive patients with severe immune suppression had a vastly increased risk of developing the AIDS-defining cancers Kaposi’s sarcoma (KS) and non-Hodgkin lymphoma (NHL), they did not have a significantly increased risk of developing other cancers in the pre-HAART era, according to a large US study published in the April 15th edition of the Journal of Acquired Immune Deficiency Syndromes.
The incidence of non-AIDS defining cancers in HIV-positive patients is the subject of debate, and the findings of this study stand in contrast to a large retrospective study conducted amongst AIDS patients in New York which found a substantially increased risk of malignancies (see link below). It also contradicts other studies which have suggested that HIV-positive patients have an increased incidence of cancers of the lip, lung, anus, penis and Hodgkin disease.
To establish if there is a link between severe immune suppression and the risk of developing non-AIDS defining cancers, investigators from the US National Cancer Institute looked at the incidence of cancer in an AIDS-Cancer Match Registry. The study involved 94,901 patients aged 15 or older with an AIDS diagnosis from eleven US regions from 1990 to 1996, and therefore did not include patients treated with HAART. Investigators developed a standard incidence ratio for each cancer from cancer registry information on HIV-negative individuals and calculated if AIDS patients were at an increased risk of developing the cancers.
Patients were divided into four categories according to CD4 count. Just under a third of patients had a CD4 count below 50 cells mm3; 17% had a CD4 cell count between 50 and 99 cells/mm3; 38% had a cell count between 100 and 199 cells/mm3 and 13% had a CD4 cell count greater than 200 cells/mm3.
Patients were followed up for between four and 27 months. Patients with lower CD4 cell counts, unsurprisingly were found to have a higher risk of dying.
As expected, the AIDS-defining cancers KS and NHL occurred much more frequently amongst the study population than would be expected in healthy people. Furthermore, the risk of developing both KS and NHL increased as CD4 cell count fell.
Cervical cancer is also an AIDS-defining condition. Investigators identified 26 cases of invasive and 77 cases of in situ cervical cancer, but its incidence did not vary with CD4 cell count.
When investigators looked at non-AIDS-defining cancers, they found that the risk of developing some cancers increased modestly amongst their study population. Lung cancer, anal cancer and Hodgkin disease occurred with greatest frequency, but the rate at which these cancers occurred across the CD4 cell categories established by the investigators was not consistent.
Investigators also found some surprising results. Although the overall risk of developing oral cancer increased slightly amongst AIDS patients, the risk appeared to fall as CD4 cell count fell. And fewer cases than expected were seen of prostate and breast cancer, although the decrease in risk was not statistically significant.
”Our study is the largest to use CD4 counts to assess the relationship between immune status and cancer risk”, note the investigators. Commenting on the vastly increased incidence of KS and NHL, they observe that the risk of developing these cancers increased by 40% to 50% with each CD4 cell count fall of 100 cells/mm3 in patients with AIDS.
However, “risks of cervical cancer...and non-AIDS-defining cancers were unrelated to CD4 counts.”
The slightly increased incidence of some non-AIDS-defining cancers could, the investigators suggest, be partly explained by lifestyle factors, noting that “exposures such as smoking, alcohol consumption and sexually transmitted diseases are common among people with AIDS.”
A study which monitored a large population of HIV-positive patients from the moment of diagnosis would help determine the cancer risk for all HIV-positive patients, suggest the investigators. They also note that some cancers in the patients included in their study have have been missed by doctors as patients who are severely ill from other conditions may not be evaluated for cancer.
The investigators conclude that an association between immunosuppression and KS and some types of NHL was found. “Nevertheless, the incidence of other cancers, including cervical cancer, did not show a trend with decline in CD4 cell count”.
Further information on this website
Cancers - overview
Non-AIDS cancers also more common in advacned HIV - news story
Lung cancer more common in HIV-positive patients since HAART - news story
Mbulaiteye SM et al. Immune deficiency and risk of malignancy among people with AIDS JAIDS 32: 527 - 533, 2003.