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Having AIDS Raises Risk of HPV-related Malignancies, including Cervical and Anal Cancer

Having AIDS increases the likelihood of developing malignancies caused by human papillomavirus (HPV), which include cervical cancer, anal cancer, genital cancers, and some oral cancers, according to a study published in the July 31, 2009 online edition of the Journal of the National Cancer Institute.

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.


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.



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).





























































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