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CATIE News - Finding and treating anal cancer - a German study

September 17, 2010 - Among HIV-negative people anal cancer is generally rare, affecting mostly middle-aged adults. However, rates of anal cancer seem to be increasing in recent decades, particularly among men who have sex with men (MSM) and especially among HIV-positive MSM.

Despite ART

The widespread use of potent anti-HIV therapy (commonly called ART or HAART) in high-income countries has greatly reduced deaths due to AIDS-related infections. However, not all complications that arise in HIV-positive people are influenced by ART. For instance, the microbe human papillomavirus (HPV) is a common sexually transmitted infection. As a result, many HIV-positive people are co-infected with HPV. This virus can cause anogenital warts and abnormal growths in both women (on the cervix and anus) and men (on the anus). If left untreated, these abnormal growths can transform into precancerous lesions and, in some cases, tumours, causing cervical and anal cancer. The use of ART does not seem to decrease the risk of developing these growths and cancers.

For the past several years, researchers in Germany have been monitoring hundreds of HIV-positive men to understand more about HPV-related abnormal growths in or around the anus. The researchers found that anal pre-cancer and cancer appear to be more common in HIV-positive men. Also, the transformation of precancerous anal cells into tumours seemed to occur relatively quickly in these men. This report also covers details about the treatment of anal cancer.

Study details

Researchers in the following German cities conducted an observational study of anal abnormalities in HIV-positive men:

  • Bochum
  • Cologne
  • Dortmund
  • Düsseldorf

All participants were interviewed and underwent standardized clinical examinations, including the following:

  • digital rectal exam
  • high-resolution anoscopy

When researchers found anal lesions, they were biopsied for analysis. Residual anal lesions, regardless of the degree of abnormality, were treated with an electrical current and/or Aldara (imiquimod).

Swabs of the anal canal were done to capture HPV for subsequent analysis.

The study assessed health information collected from participants between August 2003 and October 2009. The average profile of men when they entered the study was as follows:

  • age - 41 years
  • CD4+ count - 470 cells
  • 67% of participants were taking ART
  • HIV viral load - 53 copies/ml
  • 51% of participants were tobacco smokers

Results-Overall findings

On average, the men were monitored for 21 months. Key findings were as follows:

  • 26% - no anal abnormalities
  • 37% - mildly abnormal anal lesions
  • 35% - highly abnormal anal lesions (precancerous cells)
  • 3% - invasive anal cancer

(Note: Numbers do not total 100 because of rounding.)

Focus on cancer

Researchers diagnosed anal cancer in 11 men. Here is the average profile of these men at the time of anal cancer diagnosis:

  • age - 51 years
  • duration of HIV infection - 14 years
  • length of time on ART - 9 years
  • lowest-ever CD4+ count - 94 cells
  • CD4+ count at cancer diagnosis - 290 cells

In six of these 11 cases, anal cancer tumours were found inside the anal canal. In the five remaining men the tumours were found at the anal margin, where the canal meets the skin.

All cancers had types or strains of HPV that have previously been associated with cancer, including HPV-16. The cancers found at the anal margin were more likely to have additional strains of HPV, such as HPV-33, HPV-59 and HPV-68 (there are more than 100 strains of HPV).

In five of the 11 men diagnosed with anal cancer, precancerous anal lesions had previously been identified. However, for unknown reasons, these men chose to not have the precancerous lesions removed. On average, these precancerous lesions took about nine months to transform into anal cancer.

Aside from the 11 men who were diagnosed with anal cancer, none of the other participants in whom researchers found precancerous anal cells and who were treated for this subsequently developed anal cancer.

Treatment of anal cancer

Doctors removed the tumours of the five men who had anal cancer at the margin. One of these five men also received radiation therapy. No relapse of anal cancer occurred in these men. However, two of them subsequently died, one of a heart attack and another from complications due to cancer of the throat.

Among the six men with cancer of the anal canal, five were treated with a combination of radiation and chemotherapy. The results were as follows:

  • long-term remission - one man
  • recurring cancer - two men
  • death from severe side effects of chemotherapy - two men

The sixth man with cancer of the anal canal refused treatment and committed suicide.

A note about tobacco

Smoke from tobacco contains many cancer-causing chemicals. Some of these chemicals appear to concentrate in the mucus of genital tissues. This may, in part, explain findings from some other studies in which tobacco smoke has been linked to an increased risk for HPV-related cancer.

Furthermore, another study has found that tobacco smokers do not respond well to treatment for anal cancer. In this same study, researchers found that tobacco smokers were more likely to experience a recurrence of anal cancer than non-smokers.

In the present German study, only one participant who had anal cancer and was treated experienced a prolonged remission. The study team noted that he never smoked tobacco.

Thus, the German research team states that "patients should be cautioned about tobacco smoking once anal [cancer] is diagnosed in an attempt to improve their long-term [survival]."

Limitations

The present German study was not a controlled clinical trial. The average length of observation was 20 months. These factors preclude drawing definitive conclusions about the consequences of HPV infection in HIV-positive men.

Despite these limitations, the study made the following important discoveries:

  • precancerous anal lesions can rapidly develop into tumours
  • cancers of the anal canal and anal margin show differences in how they respond to treatment

As evidence increasingly accumulates that screening for anal cancer can help prevent this disease, hopefully funding for such programs will become widespread.

-Sean R. Hosein

REFERENCES:

  1. Kreuter A, Potthoff A, Brockmeyer NH, et al. Anal carcinoma in human immunodeficiency virus-positive men: results of a prospective study from Germany. British Journal of Dermatology . 2010; in press .
  2. Alam S, Conway MJ, Chen HS, et al. The cigarette smoke carcinogen benzo[a]pyrene enhances human papillomavirus synthesis. Journal of Virology . 2008 Jan;82(2):1053-8
  3. Ramamoorthy S, Luo L, Luo E, et al. Tobacco smoking and risk of recurrence for squamous cell cancer of the anus. Cancer Detection and Prevention . 2008;32(2):116-20.

CATIE-News is written by Sean Hosein, with the collaboration of other members of the Canadian AIDS Treatment Information Exchange, in Toronto.

From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information Network at http://www.catie.ca

Source: CATIE: CANADIAN AIDS TREATMENT INFORMATION EXCHANGE


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