Do People with AIDS Develop Cancer Earlier or More Often?

		SUMMARY: People with a history of AIDS diagnosis have a higher likelihood of developing -- and dying from -- several types of non-AIDS-defining cancer compared with the general population, and individuals who survived several years after an AIDS diagnosis had persistent excess risk for both AIDS-defining and certain non-AIDS malignancies, according to 2 recently published reports. Another study, however, found that people with AIDS did not develop most types of cancer at an earlier age on average.

By Liz Highleyman

It is well established that AIDS-defining malignancies -- Kaposi's sarcoma (KS), non-Hodgkin lymphoma (NHL), and invasive cervical cancer -- have declined since the advent of effective combination antiretroviral therapy (ART). Studies of non-AIDS cancers in people with HIV and AIDS, however, have produced conflicting results.

Italian Study

As described in the November 1, 2010 issue of Clinical Infectious Diseases, Antonella Zucchetto and colleagues compared rates of non-AIDS malignancies among 10,392 HIV positive Italian citizens age 15 or older who were diagnosed with AIDS between 1999 and 2006, and members of the general population matched for age and sex.

The median duration of follow-up was 37 months, yielding 35,224 person?years worth of data. Risk of death during this period was estimated using standard mortality ratios (SMRs).

Results

	A total of 3209 people with AIDS died due to any cause during follow-up.
	Most of these individuals (about 80%) were men, half were injection drug users and the median age at the time of death was 42 years.
	7.4% of these deaths had non-AIDS cancer as the underlying cause.
	The overall risk of non-AIDS cancer death for people with AIDS was 6.6-fold higher than that of the general population.
	The most common malignancies leading to death in the AIDS group were:
	Lung cancer (58 cases, 24.6%); Liver cancer (28 cases, 11.9% of deaths); Hodgkin's lymphoma (28 cases, 11.9% of deaths); Head and neck cancers (18 cases).
	People with AIDS had elevated mortality rates for several non-AIDS cancers:
	Anal cancer: SMR 270, or 270 times higher likelihood of death; Hodgkin lymphoma: SMR 174; Liver cancer: SMR 11.1; Brain and central nervous system cancer: SMR 10.0. Head and neck cancers: SMR 8.2; Lung cancer: SMR 5.9; Myeloma and leukaemia: SMR 5.9; Stomach cancer: SMR 3.1.
	People with AIDS over age 45 and women had greater excess non-AIDS cancer mortality than younger individuals and men, respectively.
	Those with a history of injection drug use also had a more elevated risk of non-AIDS cancer death, especially due to liver cancer.

"In this analysis of the risk of death for non-AIDS-defining cancers among Italian people with AIDS in the [ART] era, we found a nearly 7 fold excess, compared with the general population of the same sex and age," the investigators concluded.

People with a history of AIDS had especially elevated risk of death due to cancers with infectious viral causes, including liver cancer, associated with chronic hepatitis B and C, and anal cancer, which is considered non-AIDS-defining even though it is caused by the same types of human papillomavirus (HPV) as AIDS-defining cervical cancer.

"Our findings of an excess mortality for non-AIDS-defining cancers cannot be totally explained by the well?known excess incidence of non-AIDS-defining cancers among people with AIDS," they explained in their discussion. "Some very high SMRs detected in our study should be considered as the joint result of increased incidence of such tumors and of their worse prognosis among people with AIDS versus the general population."

They added that these findings may not extend to HIV positive people who have better-preserved immune function and never developed AIDS.

U.S. Studies

Researchers at the U.S. National Cancer Institute (NCI) recently published 2 related studies of cancer in people with AIDS.

In the first analysis, described in the August 9, 2010 Archives of Internal Medicine, Edgar Simard and colleagues assessed long-term cancer risk among people diagnosed with AIDS relative to the general population, and the impact of ART on cancer incidence.

The researchers looked at medical records from 263,254 adults and adolescents with AIDS in 15 U.S. regions, spanning the period 1980 through 2004. These records were matched with cancer registries to capture new cancers occurring 3-5 years and 6-10 years after onset of AIDS.

Standardized incidence ratios (SIRs) -- which estimate likelihood of developing new cancers, while the SMRs used in the previous study estimate cancer deaths -- were used to assess risks relative to the general population. Rate ratios (RRs) were used to compare cancer incidence before and after 1996 to assess the impact of ART.

As expected, people with AIDS had elevated risk for the 2 major AIDS-defining cancers, Kaposi sarcoma (SIR 5321 for years 3-5 after AIDS diagnosis and SIR 1347 for 6-10 years) and non-Hodgkin lymphoma (SIRs 32 and 15, respectively. Incidence of both malignancies declined after the advent of ART.

People with AIDS was had increased risk for all non-AIDS-defining cancers combined (SIRs 1.7 and 1.6, respectively), as well as for several specific non-AIDS cancers including Hodgkin lymphoma, mouth and throat cancers, anal and penis cancer, and lung cancer. Absolute incidence of anal cancer (RR 2.9) and Hodgkin lymphoma (RR 2.0) increased between 1990-1995 and 1996-2006.

"Among people who survived for several years or more after an AIDS diagnosis, we observed high risks of AIDS-defining cancers and increasing incidence of anal cancer and Hodgkin lymphoma," the study authors concluded.

In the second NCI study, published in the October 5, 2010 Annals of Internal Medicine, Meredith Shiels and colleagues compared ages at the time of diagnosis for non-AIDS cancers among people with AIDS and the general populations. They looked at data from 212,055 people with an AIDS diagnosis enrolled in the U.S. HIV/AIDS Cancer Match Study from 1996 through 2007.

The proportion of person-time contributed by older individuals (age 65 or older) was far smaller for the AIDS group (1.5%) than for the general population (12.5%), the researcher explained. Reflecting this difference, the age at diagnosis for most types of cancer was approximately 20 years younger for people with AIDS.

After adjusting for differences in the 2 populations, however, the median ages at diagnosis did not differ significantly between people with AIDS and members of the general populations for most types of cancer including colon, prostate, and breast cancer. But the age at diagnosis was significantly younger in the AIDS group for lung cancer (median 50 vs 54 years) and anal cancer (median 42 vs 45 years), and significantly older for Hodgkin lymphoma (median 42 vs 40 years).

"For most types of cancer, the age at diagnosis is similar in the AIDS and general populations, after adjustment for the ages of the populations at risk," the researchers concluded. "Modest age differences remained for a few types of cancer, which may indicate either acceleration of carcinogenesis by HIV or earlier exposure to cancer risk factors."

Investigator affiliations: Zucchetto study: Unit of Epidemiology and Biostatistics and Scientific Directorate, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico, Aviano, Italy; Dipartimento di Malattie Infettive, Centro Operativo AIDS, Istituto Superiore di Sanità, Roma, Italy; Direzione Centrale per le Statistiche e le Indagini Sulle Istituzioni Sociali, Servizio Sanità e Assistenza, National Institute of Statistics, Rome; Statistica Medica e Biometria, Università degli Studi di Milano, Milan, Italy. Simard and Shiels: National Cancer Institute, National Institutes of Health, Rockville, MD.

11/5/10

References

A Zucchetto, B Suligoi, A De Paoli, and others. Excess mortality for non-AIDS-defining cancers among people with AIDS. Clinical Infectious Diseases 51(9): 1099-1101 (Abstract). November 1, 2010.

EP Simard, RM Pfeiffer, and EA Engels. Spectrum of cancer risk late after AIDS onset in the United States. Archives of Internal Medicine 170(15): 1337-1345 (Abstract). August 9, 2010.

MS Shiels, RM Pfeiffer, and EA Engels. Age at cancer diagnosis among persons with AIDS in the United States. Annals of Internal Medicine 153(7): 452-460 (Abstract). October 5, 2010.