Anal Cancer, HIV and Gay/Bisexual Men

In the general population, anal cancer is a rare disease. Few people knew about it before Farrah Fawcett made public her struggle with the illness. Among men who have sex with men (MSM), the incidence of anal cancer is significantly more prevalent and increasing annually1. However, the majority of MSM's know little about the disease, have ever been tested for it, nor know that screening tests exit. Health care professionals, too, remain divided on how and whether to screen for it. In fact, a standardized screening protocol for anal cancer does not yet exist.

Each year anal cancer is diagnosed in about 2 people out of every 100,000 people in the general population. Current estimates are that HIV negative MSMs are 20 times more likely to be diagnosed with anal cancer. Their rate is about 40 cases per 100,000. HIV-positive MSMs are up to 40 times more likely to diagnosed with the disease, resulting in a rate of 80 anal cancer cases per 100,000 people.

Anal cancer is caused by the same strains of Human Papillomavirus (HPV) that cause cervical cancer in women. HPV is the most common sexually transmitted infection2. There are over 100 different types of HPV, although only several strains are believed to increase the risk of cancer. Approximately 75% of all sexually active adults acquire HPV, often within the course of early adulthood, and often in the first two years of becoming sexually active and often without any symptoms3. In MSMs, it is transmitted through both protected and unprotected anal intercourse and skin-to-skin contact. Among heterosexual women, the vast majority of infections are cleared naturally by the body within a few years, usually by age 30, but this appears to be less true for MSM, where the infections are often still present in later adulthood2. Again, not all HPV infections lead to cancer.

Anal HPV is present in approximately 65% of HIV negative MSMs and 95% of MSMs who are HIV positive. Although HAART (highly active antiretroviral therapy) has decreased overall mortality from HIV, it has not reduced the incidence of anal squamous cell carcinoma4. And, since it is spread through sexual skin-to-skin contact, condom use only partially reduces the risk of transmission. Other factors that increase the risk of anal cancer include a high number of sex partners, alcohol, drugs and tobacco use. Although many men have no obvious symptoms, one of the most common manifestations of HPV infection is genital warts which can affect the anus, the penis and/or the peritoneum. Other possible symptoms are abnormal discharge from the anus, bleeding from the rectum and anus, itching of the anus, pain or pressure around the anus, and a sore or sores around the anus that do not heal5.

Cancer of the anus, like the cervix, develops slowly, beginning with minor cell changes. For women, a simple pap smear is used to detect these cell changes in the cervix in their early stages. With regular screening and proper treatment, cervical cancer can be prevented. In fact, since cervical pap smears have become a routine part of women's health care, cervical cancer rates have dropped dramatically, from rates that resemble HIV+ MSM's anal cancer rates (80 per 100,000) to the current rate of approximately 2 per 100,000.

The anus and the cervix are biologically similar and both are target chambers for HPV infection1,2. The same screening methodology (pap smear) can be used to test the anus for cancer and pre-cancerous cell changes. A growing number of gay physicians and health activists now believe that routine screening, using an anal pap smear, could reduce the incidence of anal cancer as dramatically as it has cervical cancer in women. They recommend that all MSMs, especially those who are HIV+, be tested every 1-3 years depending on their immunological well-being and CD4 count. They suggest that HIV negative individuals be tested every 3 years. Still, there are some clinicians who are not convinced that routine screening of all MSMs is warranted. They cite the small number of positive cases, the shortage of facilities for follow-up procedures and the fear, cost and pain involved in pursuing small cell changes, called dysplasias. In addition, most health insurance policies do not cover anal pap smears.

These vastly different opinions and approaches to anal pap smears were replicated in a recent, informal survey of New York City-based physicians whose patient panels are predominately MSMs. There seems to be little consensus on the practicality of offering anal pap smears to all clients, despite the fact that the AIDS Institute of New York recommends that HIV positive gay men "and others with history of HPV disease" should be tested annually.

Recently, the relationship between HPV, anal cancer and HIV has received more research and media attention. The direct link between cervical cancer and HPV has been known for some time and gynecologists typically perform a simple HPV test along with the cervical pap smear. That test is not able to categorize the exact strain of HPV the woman carry. The FDA recently approved a new DNA test that identifies the two HPV strains (types 16, 18) responsible for most cervical cancers. At the moment, the new DNA test, called Cervista HPV 16/18, is not available in doctors' offices, but should start arriving within the next few months. In MSMs, a clear relationship has not yet been determined between a high DNA HPV load and the cell changes that lead to anal cancer, but if confirmed, this test will become more widely used in the future. Then, only those with dangerous strains of HPV would require regular follow up screening with an anal pap smear.

Current research from the Fred Hutchison Cancer Research Center in Seattle, WA6 has found that, not only does HIV infection increase the risk of HPV infection, but that the converse is also true; HPV enhances susceptibility to HIV infection. This occurs because anal HPV lesions make the surface tissue of the anus thinner and more vulnerable to entry of the HIV virus. In addition, the immune cells activated by HPV infection are precisely the ones more vulnerable to HIV infection. This data increases the value of HPV screening for all MSM's.

What do the results of an anal pap tell the medical practitioner? There are six possible outcomes: 1) insufficient cells; 2) a negative result; 3) atypical squamous cells of undetermined significance (ASCUS); 4) low grade squamous intraepithelial lesion (LSIL); 5) high grade squamous intraepithelial lesion (HSIL); and, finally, 6) squamous cell carcinoma (SCC).

If the results show insufficient cells, the procedure should be repeated. For an HIV negative, gay male, the usual recommendation for a negative anal pap result is to repeat the procedure every 3 years. For an HIV positive gay man with a CD4 of over 500, it is recommended to repeat the test every 2 years. For an HIV positive individual with a CD4 of fewer than 500, the recommendation is to repeat the test once a year.

When the results of the pap smear reveal ASCUS, LSIL or HSIL, the provider may decide to investigate further. Treatment for early cell changes and cancer malignancies is performed with high-resolution anoscopy or HRA. The relative scarcity of this equipment and the high cost of its use have been evidence by some clinicians in their argument against widespread use of early screening procedures.

The best form of prevention for anal cancer may be a vaccination against HPV infection. Currently, Gardasil by Merck, has been approved as a prophylaxis against HPV and cervical cancer for girls between the ages of 9 and 26. The FDA is considering its use in boys, ages 9 to 26 also, based on preliminary research showing that it was effective for them as well. The large study included 500 self-identified gay men. While that will prevent boys from developing anal cancer later in their lives, it is unclear how Gardasil may help adult MSMs over 26 years old, HIV+ men and those already infected with HPV. Gardasil and its competitor, Cervarix by the pharmaceutical company, GlaxoSmithKline, are both expensive, between $360 and $500 for the three injections required. It is unclear if they will be covered by health insurance for adults who choose to be vaccinated.

There are some practitioners advocating Gardasil for use in MSMS who have already been infected with HIV and/or HPV. This would be considered an "off label" use. The National Institutes of Health is carrying out a clinical trial to see what benefits Gardasil might have for HIV-infected people. A number of men, both HIV-positive and negative, have opted to get vaccinated despite the fact Gardasil is not yet FDA-approved for use in men. This is considered an "off-label use" of the vaccine7.

Anal cancer is an increasing health threat to MSMs, especially those who are HIV+, and there is no professional consensus about whether to vaccinate against it, screen for cell changes or how to treat positive results on an anal pap smear. More research is needed and both the consumer and provider communities need to be educated. Most health care providers are not offering anal cancer screening to their patients, either because they are unaware of the risk factors for anal cancer, do not inquire about their patients' high risk sexual practices, and/or do not know how to perform an anal pap smear. Some providers are knowledgeable but do not believe that routine screening of this population is warranted.

In order for health care providers to offer anal cancer screening to their patients who warrant it, it is critical that MSMs talk to their medical providers about their sexual orientation, HIV status and sexual practices. This does not happen often enough. The NYC Dept of Health found that nearly 40% of MSMs do not come out to their provider8. Those that are open about their sexual orientation often do not know enough about anal cancer to request a screening. It is critical that the gay community be educated, both HIV negative and HIV positive MSMs, about HPV, anal cancer risk factors and the options available for screening and treatment. Then individuals can make an informed decision about whether to be screened and seek out a provider who is familiar with the options. Some who choose to be screened may ask that their current medical providers shift practice policies to include routine anal HPV and cancer exams. Finally, it is critical and essential that the association between HPV infection and anal cancer receive more research and that there be increased education of both providers and consumers.

This article, by Liz Margolies, LCSW and Bill Goeren, LCSW, first appeared in Treatment Issues, a publication of GMHC, in September '09 and can be read by clicking here

References

  1. Palefsky, Joel, MD. "Update on HPV: Beyond Cervical Cancer", Sexuality, Reproduction and Menopause, webcast, 2009.
  2. Bratcher, Jason, MD and Palefsky, Joel, MD. "Anogenital Human Papillomavirus Coinfection and Associated Neoplasia in HIV-Positive Men and Women" The PRN Notebook, vol. 13, Sept, 2008.
  3. Koutsky L, Galloway D, Holmes K. Epidemiology of Genital Human Papillomavirus. Epidemial Rec. 1988; 10: 122-163.
  4. Goldstone, Stephen, MD, et. al., "Hybrind Capture II Detection of Oncogenic Human Papillomavirus: A Useful Tool When Evaluating Men Who Have Sex with Men with Atypical Squamous Cells of Undetermined Significance on Anal Cytology" The A3
  5. Cichock, Mark, RN, "The Dangers of Anal Cancer - The Silent Killer in Men with HIV" University of Michigan HIV/AIDS Treatment Program, Dec., 2008.
  6. Researchers link infection with anal human papillomavirus with a higher risk of new HIV infection http://fhcrc.org/about/pubs/center_news/online/2009/05/HIV_study.html may 23, 2009
  7. http://www.thebody.com/Forums/AIDS/Fatigue/Archive/Help/Q191583.html June 19, 2009
  8. http://www.nyc.gov/html/doh/html/pr2008/pr052-08.shtml June 21, 2009

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