People with AIDS Develop Cancer Earlier or More Often?
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.
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.
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.
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).
A total of 3209 people with AIDS died due to any cause during
of these individuals (about 80%) were men, half were injection
drug users and the median age at the time of death was 42
of these deaths had non-AIDS cancer as the underlying cause.
overall risk of non-AIDS cancer death for people with AIDS
was 6.6-fold higher than that of the general population.
most common malignancies leading to death in the AIDS group
cancer (58 cases, 24.6%);
cancer (28 cases, 11.9% of deaths);
lymphoma (28 cases, 11.9% of deaths);
and neck cancers (18 cases).
with AIDS had elevated mortality rates for several non-AIDS
cancer: SMR 270, or 270 times higher likelihood of death;
lymphoma: SMR 174;
cancer: SMR 11.1;
and central nervous system cancer: SMR 10.0.
and neck cancers: SMR 8.2;
cancer: SMR 5.9;
and leukaemia: SMR 5.9;
cancer: SMR 3.1.
with AIDS over age 45 and women had greater excess non-AIDS
cancer mortality than younger individuals and men, respectively.
with a history of injection drug use also had a more elevated
risk of non-AIDS cancer death, especially due to liver cancer.
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
"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."
added that these findings may not extend to HIV positive people
who have better-preserved immune function and never developed
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
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
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.
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.
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.
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.
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.