Rates of anal cancer among people with HIV have progressively increased as patients live longer with effective antiretroviral therapy (ART) and have more time to develop chronic disease, according to research presented at the 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009) last month in Cape Town, South Africa.

By Liz Highleyman

Due to increased survival of people with HIV, non-AIDS-related conditions, including malignancies, have become an important cause of illness and death. Anal cancer is not classified as an AIDS-defining malignancy -- in contrast with invasive cervical cancer -- even though it is caused by the same high-risk human papillomavirus (HPV) types.

Nancy Crum-Cianflone and colleagues with the U.S. veterans' health service evaluated the incidence of and risk factors for anal squamous cell carcinoma using longitudinal data from a prospective Natural History Study started in 1985. In particular, they compared cancer rates before and after the advent of effective combination therapy, or HAART, in the mid-1990s.

Anal Cancer (Squamous Cell Carcinoma of the Anus)

Results

	Among 4901 HIV positive individuals (> 90% men) contributing a total of 40,951 person-years (PY) of follow-up data, the anal cancer incidence rate increased 5-fold from the pre-HAART to the HAART era, from 11 to 55 cases per 100,000 PY.
	Rates continued to increase in the HAART era, reaching 51 cases per 100,000 PY during 2001-2005 and 128 per 100,000 PY during 2006-2008.
	This compares with an anal cancer rate of 1 to 1.5 cases per 100,000 PY among the general population.
	Looking at the 20 patients who developed anal cancer, all but 1 were men and 55% were white (the researchers did not ask about sexual practices due to the military's "Don't Ask, Don't Tell" policy).
	The median age at the time of anal cancer diagnosis was 42 years (although 40% developed cancer in their 20s or 30s).
	75% of case patients were on HAART, about 40% had an HIV viral load < 400 copies/mL, 40% had a prior AIDS-defining event, and 65% had other sexually transmitted infections.
	Case patients had a median CD4 count of 375 cells/mm3, but the nadir (lowest-ever) level was considerably lower.
	Patients who developed anal cancer had a lower CD4 count (HR 0.9 per 50 cells/mm3; P = 0.10) and were more likely to have had a prior AIDS-defining event (hazard ratio [HR] 3.5; P = 0.01); they also had more sexually transmitted infections, but this did not reach statistical significance.
	Receiving HAART was not protective against developing anal cancer, and in fact was associated with a higher rate (HR 2.8; P = 0.19).

"The rates of anal cancer have progressively increased over the HIV epidemic," the investigators concluded. "As HIV patients are living longer, it may allow for sufficient time for anal cancer development, hence rates may continue to increase."

Discussing these findings, Crum-Cianflone speculated that "low-level chronic immunosuppression, which is not completely corrected by HAART, is what's driving these cancers."

Although this study did not collect data about anal cancer treatment, recent research suggests that HIV positive should be treated the same as HIV negative people, and outcomes are the same, especially if patients have a relatively high CD4 count. "We should treat them the same, and they'll likely do as well," Crum-Cianflone said.

The researchers also stated that since ART was not protective, "[p]reventive strategies for anal cancer among HIV-infected persons are needed."

One potential strategy is regular anal Pap smears to detect precancerous cell changes at an early, treatable stage. The widespread use of cervical Pap smears has dramatically lowered the rate of death due to cervical cancer in women. Regular anal Pap smears are not currently part of the standard of care for people with HIV -- as cervical smears are for HIV positive women -- but some experts believe they should be.

Another approach is HPV vaccination. Effective vaccines are available for the most common high-risk (cancer-causing) HPV strains, but are currently only approved for young women. The vaccine is only effective if administered before HPV infection occurs, so vaccination is recommended before people become sexually active. The vaccine has shown promising results in HIV negative boys and men, and is being tested in HIV positive men.

Naval Medical Center San Diego, San Diego, CA; Infectious Disease Clinical Research Program, Bethesda, MD; University of Minnesota, Minneapolis, MN.

8/21/09

Reference
N Crum-Cianflone, K Huppler Hullsiek, A Weintrob, and others. Anal cancers among HIV-infected persons: HAART is not slowing rising incidence. 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape Town, South Africa.
Abstract WEAB101. (Abstract).

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