Infection-Related Cancers Elevated Among the Immunodeficient

SYDNEY, Australia, July 6 -- A greater variety of infection-related malignancies than previously suspected may be brought on by immunodeficiencies, according to a meta-analysis.
Twenty of the 28 types of malignancies examined -- most with a known infectious cause -- had a significantly increased incidence among patients with HIV or AIDS and those with solid organ transplants, reported Andrew E. Grulich, Ph.D., of the University of New South Wales, and colleagues, in the July 7 issue of The Lancet.
In an accompanying editorial, Gary Clifford, M.D., and Silvia Franceschi, M.D., both of the International Agency for Research on Cancer in Lyon, France, said that "the likeliest explanation for the similarity in cancer patterns in HIV patients and transplant recipients is chronic immune suppression, because the two groups differ greatly in all other respects, notably lifestyle."
Historically, only Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer have represented AIDS-defining illnesses.
Increased incidence of other cancers has been reported, but this was judged to be the result of lifestyle and other risk factors rather than immunodeficiency by investigators in the largest study to look at the issue, the AIDS-Cancer Match Registry Study published in the Journal of the American Medical Association in 2001.
With publication of two large cohort studies reporting increased rates of a range of cancers in immunosuppressed renal transplant recipients, Dr. Grulich and colleagues decided to revisit the issue.
Their literature search turned up for inclusion in the meta-analysis seven cohort studies of those with HIV/AIDS and five cohort studies of patients who received solid organ transplants.
Studies had to include mainly adults and collect data on incident cancer using cancer registries in developed countries. For studies with more than one report per cancer site only the most recent was included to prevent overlapping data.
The meta-analysis encompassed 444,172 patients with HIV/AIDS in the United States, Europe, and Australia and 31,977 organ-transplant recipients in Europe, Australia, and Canada (97% renal graft).
The investigators calculated standardized incidence ratios (SIRs) for each cancer type by dividing the number of observed cases by the number expected.
For cancers related to infection with Epstein-Barr virus, incidence was elevated in both study populations, but particularly so for HIV/AIDS patients. The standardized incidence ratio findings were:
11.03 for Hodgkin's lymphoma among HIV/AIDS patients (95% confidence interval 8.43 to 14.4).
3.89 for Hodgkin's lymphoma among transplant patients (95% CI 2.42 to 6.26).
76.67 for non-Hodgkin's lymphoma among HIV/AIDS patients (95% CI 39.4 to 149).
8.07 for non-Hodgkin's lymphoma among transplant patients (95% CI 6.40 to 10.2).
As expected, Kaposi's sarcoma-linked to human herpesvirus 8-incidence was far more common among HIV/AIDS patients than the general population (SIR 3,640.0, 95% CI 3,326 to 3,976). It was also much more common among transplant patients (SIR 208.0, 95% CI 114 to 349).
Liver cancer incidence -- related to hepatitis viruses B and C (HBV and HCV) -- was 5.22-fold higher among HIV/AIDS patients (95% CI 3.32 to 8.20) and 2.13-fold higher among transplant patients (95% CI 1.16 to 3.91) than expected from the general population.
Stomach cancer incidence -- related to Helicobacter pylori -- was more common in both groups as well (SIR 1.90, 95% CI 1.53 to 2.36, and 2.04, 95% CI 1.49 to 2.79, respectively).
Findings for cancers related to, human papillomavirus infection, or possibly related to it, included (SIRs all significant):
Cervix uteri 5.82 for HIV/AIDS patients and 2.13 for transplant patients.
Vulva and vagina 6.45 for HIV/AIDS patients and 22.76 for transplant patients.
Penis 4.42 for HIV/AIDS patients and 15.79 for transplant patients.
Oral cavity and pharynx 2.32 for HIV/AIDS and 3.23 for transplant patients.
Non-melanoma skin 4.11 for HIV/AIDS patients and 28.62 for transplant patients.
Lip 2.80 for HIV/AIDS patients and 30.00 for transplant patients.
Esophagus 1.62 for HIV/AIDS patients and 3.05 for transplant patients.
Larynx 2.72 for HIV/AIDS patients and 1.99 for transplant patients.
Eye 1.98 for HIV/AIDS patients and 6.94 for transplant patients.
However, most common epithelial cancers, including breast, prostate, and ovarian cancers, were not significantly elevated in either group.
Colorectal cancer, though, was somewhat elevated among transplant patients (SIR 1.69, 95% CI 1.34 to 2.13) but not among HIV/AIDS patients. And, lung cancer incidence was more than twice as high in both groups as in the general population (SIR 2.72 and 2.18, respectively).
Also, both groups had higher incidences of kidney cancer, multiple myeloma, leukemia, and melanoma. Bladder and thyroid cancers were elevated among transplant recipients only; brain cancer and testicular cancer were elevated among HIV/AIDS patients only.
Overall, "the range of infection-related cancers associated with immune deficiency is much wider than previously appreciated and that a range of infectious organisms seems to be implicated," Dr. Grulich and colleagues concluded.
Another possible explanation for the elevated cancer incidence for the two groups is heightened medical surveillance for cancer, but the lack of increased risk for breast and prostate cancer, which are typically diagnosed by screening "argues against this bias," they said.
Shared lifestyle and other cancer risk factors could be another explanation, such as higher exposure to sexually transmitted viruses linked to cancer, they noted.
They cautioned that the study was limited by the uniformity of the transplant recipients (nearly all renal transplants) and that most of the HIV/AIDS studies followed people only after AIDS onset.
The editorialists warned against comparing relative risks between the two groups quantitatively because of other characteristics that differ between them.
They noted that HIV patients tend to be younger than transplant recipients, which "can lead to higher relative risks in individuals with HIV simply because of the normally low cancer incidence in their age-group" whereas older patients would be more likely to show "excess risk for epithelial cancers with a long latent period."
Dr. Grulich's center was funded by the Australian Government Department of Health and Aging and other researchers reported funding from the National Health and Medical Research Council or the Cancer Institute, though the study received no direct funding.
Dr. Grulich reported being on the advisory board for the Gardasil human papillomavirus vaccine for Commonwealth Serum Laboratories and receiving a travel grant from the company. The editorialists reported no conflicts of interest.Primary source: The LancetSource reference: Grulich AE, et al "Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis" Lancet 2007; 370: 59-67. Additional source: The LancetSource reference: Clifford G, Franceschi S "Immunity, infection, and cancer" Lancet 2007; 370: 6-7.