As
people with HIV live longer thanks to effective
antiretroviral therapy, they have
more time to develop chronic conditions such as cardiovascular
disease and cancer. Several studies have shown that HIV positive people have
a higher risk of cancer than the general HIV negative population, and this is
especially true for malignancies with infectious causes such as HPV.
Anil
Chaturvedi from the National Cancer Institute and colleagues performed an analysis
of HPV-related cancer rates and their association with immune status among people
with AIDS (i.e., HIV positive people with a CD4 cell count < 200 cells/mm3
or with AIDS-defining illnesses or symptoms).
While
considerable research indicates that the risk of HPV-associated cancers of the
anus, cervix, oropharynx (mouth and throat), penis, vagina, and vulva is elevated
among people with AIDS -- invasive cervical cancer is, in fact, considered an
AIDS-defining illness -- the authors noted as background that the etiologic [causal]
role of immunosuppression is unclear, and incidence trends for these cancers over
time -- particularly since the introduction of highly active antiretroviral therapy
(HAART) in 1996 -- are not well described.
The
researchers collected data on 499,230 individuals diagnosed with AIDS between
January 1980 and December 2004 -- that is, spanning nearly the entire course of
the HIV/AIDS epidemic. This information was linked with cancer registries in 15
U.S. regions.
Risk
of in situ (localized) and invasive HPV-associated cancers relative to
that of the general population, was estimated using standardized incidence ratios
(SIRs). The authors evaluated the relationship between immunosuppression and cancer
incidence during the period 4-60 months after AIDS onset according to CD4 cell
counts measured at the time of AIDS onset. HPV-related cancer incidence during
the 4-60 months after AIDS onset was compared across 3 time periods: 1980-1989,
1990-1995, and 1996-2004.
Results
 | People
with AIDS had a significantly elevated risk of all HPV-associated in situ
cancers. |
| SIRs
for in situ cancers ranged from 8.9 (nearly 9 times higher risk) for cervical
cancer to 68.6 (nearly 70 times higher risk) for anal cancer among men. |
| People
with AIDS also had a significantly higher rate for invasive HPV-related cancers. |
| SIRs
for invasive cancers ranged from 1.6 for oropharyngeal cancer to 34.6 for anal
cancer among men. |
| Rates
of cervical cancer were elevated among women with AIDS, but the magnitude of increased
risk was smaller (SIRs 8.9 for in situ, 5.6 for invasive) |
| Like
men, women with AIDS also had a higher risk of anal cancer (SIRs 33.0 for in
situ, 14.5 for invasive). |
| During
1996-2004, low CD4 count was associated with: |
Significantly increased risk of invasive anal cancer among men (relative risk
[RR] 1.34 per decline of 100 cells/mm3; P = 0.006);
Increased risk of in situ vaginal cancer that was not quite statistically
significant (RR 1.52 per 100 cells/mm3; P = 0.055);
Increased risk of invasive cervical cancer that also did not reach statistical
significance (RR 1.32 per 100 cells/mm3; P = 0.077). |
|
|
Among men, incidence of both in situ and invasive anal cancer was significantly
higher during 1996-2004 than during 1990-1995: |
In situ: 61% increase, from 18.3 to 29.5 cases per 100,000 person-years
(RR 1.71; P < 0.001);
Invasive: 104% increase, from 20.7 to 42.3 cases per 100,000 person-years (RR
2.03; P < .001). |
|
| Incidence
of other cancer types was stable over time. |
"Risk
of HPV-associated cancers was elevated among persons with AIDS and increased with
increasing immunosuppression," the researchers concluded. "The increasing
incidence for anal cancer during 1996-2004 indicates that prolonged survival may
be associated with increased risk of certain HPV-associated cancers."
"Given
that individuals currently infected with HIV may obtain little benefit from available
HPV vaccines" -- since so many have already been exposed to the virus --
"our results underscore the need for effective screening for cervical cancer
and anal cancer among persons with HIV infection or AIDS," they recommended
in their discussion of the findings.
"[A]s
the population of HIV-infected patients survives longer through use of HAART and
increasingly enters the older age groups in which HPV-related cancer rates reach
their peak, these tumors will represent an increasing clinical and public health
burden," added Howard Strickler from Albert Einstein College of Medicine
in an accompanying editorial.
Regular
Pap smears for cervical cancer screening are recommended for both HIV positive
and HIV negative women, though many women with HIV do
not receive them in a timely manner. Pap screening is credited with keeping
the rate of invasive cervical cancer and related death relatively low, since it
allows pre-cancerous cell changes to be detected and treated at an early stage.
Anal
Pap smears to screen for anal cancer are currently not part of the standard of
care, though many experts believe they should be, especially for men who have
sex with men, who are at higher risk.
Infections
and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National
Cancer Institute, National Institutes of Health, Rockville, MD; Program in Epidemiology,
Fred Hutchinson Cancer Research Center, Seattle, WA; State Serum Institute, Copenhagen,
Denmark.
8/11/09
References
AK
Chaturvedi, MM Madeleine, RJ Biggar, and EA Engels. Risk of Human Papillomavirus-Associated
Cancers Among Persons With AIDS. Journal of the National Cancer Institute.
July 31, 2009 (Epub ahead of print). (Abstract).
HD
Strickler. Does HIV/AIDS Have a Biological Impact on the Risk of Human Papillomavirus-Related
Cancers? (Editorial). Journal of the National Cancer Institute. July 31,
2009 (Epub ahead of print).
