Wednesday, February 11, 2015

Real Deal #7: Why Circumcision is (Probably) a Good Idea

THE INTRODUCTION

New York Times:
“No one is going to tell a parent, ‘You have to circumcise your child.’ That would be foolish,” Dr. Brady said. “The key thing physicians should be doing is providing information on both risks and benefits and allow the parent to make the best decision.”

After years of reviewing the scientific evidence on circumcision with an eye to issuing new policy recommendations, the CDC and the American Academy of Pediatrics recommend circumcision, but not enough to assert that it should be a routine procedure. The American College of Obstetricians and Gynecologists supports the AAP’s recommendation, but also notes that the benefits are only “modest.”

Some 80 percent of American men are circumcised, one of the highest rates in the developed world. Yet even advocates of circumcision acknowledge that an aggressive circumcision drive in the United States would be unlikely to have a drastic impact on HIV rates here, since the procedure does not seem to protect those at greatest risk, men who have sex with men. And while studies in Africa found that circumcision reduced the risk of a man’s becoming infected by an H.I.V.-positive female partner, it is not clear that a circumcised man with H.I.V. would be less likely to infect a woman.

THE EVIDENCE

New York Times:
Circumcision may provide even more protection against AIDS than was realized when two clinical trials in Africa were stopped two months ago because the results were so clear, according to studies being published today.

The trials, in Kenya and Uganda, were stopped early by the National Institutes of Health, which was paying for them, because it was apparent that circumcision reduced a man’s risk of contracting AIDS from heterosexual sex by about half. It would have been unethical to continue without offering circumcision to all 8,000 men in the trials, federal health officials said.

That decision, announced on Dec. 13, made headlines around the world and led the two largest funds for fighting AIDS to say they would consider paying for circumcisions in high-risk countries. But the final data from the trials, to be published today in the British medical journal The Lancet, suggest that circumcision reduces a man’s risk by as much as 65 percent.

The December announcement described only the follow-up on the men as originally divided into two groups: those who agreed to be circumcised and those who agreed not to. But some in the first group never went to the circumcision clinic, and some in the second had private circumcisions before the study ended.

Re-evaluating the data, excluding a few men whose H.I.V. status was misdiagnosed during the trial and combining the results of three trials — those in Uganda and Kenya as well as one in South Africa that was stopped in 2005 when the protective effect became apparent — produces a protection rate of about 65 percent.

Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, which paid for the trials, said he planned to keep saying officially that circumcision cuts a man’s risk by about half, not by 65 percent, because the validity of clinical trials depends on following randomized groups of patients, not selected ones.

“But, yes, the 65 percent makes me feel better,” he conceded.

“Look,” he added. “This is a one-time, permanent intervention that’s safe when done under the appropriate medical conditions. If we had an AIDS vaccine that was performing as well as this, it would be the talk of the town.”

He said President Bush’s $15 billion AIDS initiative and the World Health Organization were considering paying for circumcisions in high-risk countries, but must work out what training and equipment they would require circumcisers to have.

Daniel Halperin, an AIDS expert at the Harvard Center for Population and Development, noted that the world’s highest rates of infection with H.I.V., the virus that causes AIDS, are in southern African countries like Botswana, Swaziland and South Africa, which are relatively wealthy by African standards and the best prepared to offer safe circumcisions in public hospitals.

Acceptance of circumcision is growing among African men, Dr. Halperin said. Muslims in East and West Africa have long practiced it, as have some ethnic groups.

A review of 13 surveys in different African communities published last year in the journal AIDS and Behavior found that 29 percent to 87 percent of uncircumcised men said they would be willing to be circumcised if it protected them against AIDS.

How Stuff Works:
The numbers are pretty shocking, especially considering that AIDS vaccine researchers typically aim for a 30 percent decrease in risk of infection from intercourse with an infected partner. Why might circumcision offer such a high protective effect? It may have to do with the composition of that foreskin that gets removed during circumcision.

­First, the foreskin is delicate and very susceptible to tears during intercourse. This provides an easy entry point for the AIDS virus, which creeps in through the torn blood vessels. But the bigger issue is the high concentration of a type of white blood cell in the foreskin. Langerhans cells are present in the foreskin, and especially in the underside of the foreskin, in very high concentrations. These cells are "sentinel cells" of the immune system. Located in the skin, they are some of the first to detect and pick up an antigen for processing. An antigen is a foreign substance that triggers an immune response when it gets in the body. A virus, such as HIV, contains antigens.

Because there are so many Langerhans cells in the foreskin, and because these particular cells seem to be excellent at binding to HIV antigens, when the foreskin tears during sex with an HIV-infected woman, there is a very good chance that those blood cells are going to contact and bind to the virus. Langerhans cells are supposed to trigger the immune system's antibody response that fights off the virus; but once HIV gets in, the immune system can't seem to fight it effectively. Once the foreskin is removed, the increased risk of blood exposure and the higher concentration of HIV-receptors in that blood disappears.

THE VERDICT

The Lancet:
The pathophysiology of male circumcision to reduce viral and bacterial STIs is probably due both to anatomical and cellular factors. Male circumcision removes a warm, moist subpreputial cavity that is formed by the foreskin, likely reducing the survival of viruses and bacteria. Male circumcision also removes a thinly keratinised, vascular foreskin tissue that is stretched and exposed to vaginal fluids when the penis is erect. The foreskin tissue is also prone to microabrasions that might allow STIs to penetrate. In addition to anatomical factors, the foreskin mucosa contains a high density of CD4+ T cells, CD8+ T cells, and CD1a+ dendritic cells. These cellular and anatomical factors for the protective role of male circumcision are supported by the finding that risk of HIV is highest in men with the largest foreskin surface area.

After the randomised trials showed that male circumcision reduces acquisition of HIV in men, in 2007 WHO–UNAIDS recommended that male circumcision should be promoted and scaled up to curb heterosexual transmission of HIV. After these initial findings were released, the medical benefits of male circumcision have only become stronger with additional protection shown against herpes simplex virus type 2, high-risk human papillomavirus, and now syphilis. These new data should squelch concerns that there are no medical benefits of male circumcision, and should continue to support programmes that encourage neonatal male circumcision and adult male circumcision globally, especially in the 14 priority countries in eastern and southern sub-Saharan Africa with large HIV epidemics. These programmes will not only have a substantial effect by improving the health of men and their female partners, but also by reducing health-care costs associated with the long-term treatment of STIs.

More information:
» N Eng J Med: "Male circumcision reduces the risk of HSV-2 incidence and prevalence of HPV"
» Oxford Journals: "Uncircumcised men have an increased risk of HPV infection, including with oncogenic HPV"
» mBiosphere: Circumcision alters penis microbiome, decreases facultative anaerobes
» The Atlantic: Circumcision Wars - What's a Parent to Do?

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