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BYLINE: Vivien Marx, Graham Lawton.

Vivien Marx is a writer based in New York

SECTION: FEATURES; Feature; Pg. 40-43

LENGTH: 2625 words

IMAGINE a quick and simple surgical procedure that trials have shown could give your newborn child lifelong protection against HIV and may ward off sexually transmitted diseases and cancer too. It involves a little pain and bleeding, and occasionally goes wrong, but the risk of serious adverse effects is tiny. Would you have it done? Chances are you would. But what if you found out that other trials have called the procedure's benefits into question, and that it involves cutting off part of your child's penis. Now how do you feel about it?

This, in a nutshell, is the dilemma facing the parents of newborn baby boys. According to the increasingly vocal advocates of male circumcision, slicing off the foreskin is one of the most effective public-health measures ever invented and should be done routinely, like vaccination. Not so fast, say opponents. They insist that circumcision has no medical benefits and damages a man's sex life. The debate has rumbled on for decades, but recent findings about the role circumcision can play in preventing transmission of HIV have placed the foreskin - or its absence - firmly back on the public-health agenda.

Globally, approximately 30 per cent of men have been circumcised, making it probably the world's most common surgical procedure, says epidemiologist Helen Weiss of the London School of Hygiene & Tropical Medicine. Most circumcisions are carried out for cultural or religious reasons, but there have long been those who advocate the procedure on medical grounds, to improve hygiene and prevent infections.

The latest disease claimed by the circumcision lobby is HIV. Back in the mid-1980s, an American urologist called Aaron Fink noted that a large proportion of the men in Africa who had AIDS were uncircumcised (The New England Journal of Medicine , vol 315, p 1167). Over the next few years, stacks of observational evidence came in suggesting that circumcised men were less likely to be HIV-positive, and by 2000 the idea was widely accepted (AIDS , vol 14, p 2361).

What was still needed, however, was proof from a large, randomised clinical trial that circumcision could protect men against the virus. The first study of this kind to report results began in July 2002 at Orange Farm, a large township near Johannesburg in South Africa. It was supposed to run for three years but was halted early when a halfway analysis showed that circumcision was lowering HIV infection rates by 60 per cent - a result that had trial leader Bertran Auvert of the French National Institute of Health and Medical Research (INSERM) in Saint-Maurice comparing circumcision to "a vaccine of high efficacy" (PLoS Medicine , vol 2, p e298).

Two more big trials, one in Kisumu, Kenya, and the other in Rakai, Uganda, were also stopped early on the strength of overwhelmingly positive results. When these two studies were published in The Lancet (vol 369, p 643, and p 657) an accompanying editorial declared "a new era for HIV prevention" (The Lancet , vol 369, p 615). Auvert calculated that circumcision could avert up to 3.8 million infections and half a million deaths in sub-Saharan Africa between 2006 and 2016, and up to 5.8 million deaths by 2026 (PLoS Medicine , vol 3, p e262).

Circumcision primarily protects men during heterosexual intercourse, but it also appeared to benefit women. Anthony Fauci of the US National Institute of Allergy and Infectious Diseases - which helped to fund the Kisumu and Rakai trials - greeted the results with the comment: "While the initial benefit will be fewer HIV infections in men, ultimately circumcision could lead to fewer infections in women in those areas of the world where HIV is spread primarily through heterosexual intercourse."

So how does circumcision protect against HIV? As Brian Morris, a molecular biologist at the University of Sydney in Australia and a leading supporter of circumcision, explains, it is the inner lining of the foreskin that is the weak point. While the virus does not easily pass through the keratinised skin of the foreskin's outer surface and the penis shaft, the inner surface of the foreskin lacks keratin and is packed with immune cells such as Langerhans cells that HIV uses as an entry point. This makes it "very, very vulnerable", says Morris. "HIV goes straight in."

The African trials have encouraged the World Health Organization and Joint United Nations Programme on HIV/AIDS (UNAIDS) to set up programmes to help African countries establish or scale up circumcision services for adult men - though they emphasise that circumcision does not make men immune, and that couples should still practise safe sex. "This is a huge opportunity for prevention, particularly in areas of Africa with high HIV prevalence," says Daniel Halperin, an epidemiologist at Harvard School of Public Health and former global HIV adviser at USAID, the US Agency for International Development. "To me, this is the greatest medical advance in 20 years," adds Jeffrey Klausner, who directs sexually transmitted disease prevention and control services for San Francisco's Department of Health.

Yet as with most things circumcision-related, all is not necessarily as it first seems - starting with the trials themselves. Numerous criticisms levelled at their design and execution have cast doubt on whether circumcision will be anywhere near as effective in the real world as the results suggest (Future HIV Therapy , vol 2, p 193). It is widely recognised, for example, that clinical trials which are stopped early because the results are good generally exaggerate the beneficial effect (The Lancet , vol 368, p 1236). Many researchers argue that if the trials had continued for the full three years and beyond, many more circumcised men would have caught the virus.

According to Michel Garenne of the Pasteur Institute in Paris, France, factors like this make the vaccine analogy highly misleading. A 60 per cent reduction in infection rate over 18 months is not the same as the near-complete protection offered by a vaccine, and may not do very much to protect men over a lifetime of sexual activity (PLoS Medicine , vol 3, p e78). He also warns against generalising from the studies which found that circumcised men tend to have lower rates of HIV, pointing out that in some countries - notably Cameroon, Lesotho and Malawi - the opposite is true (African Journal of AIDS Research , vol 7, p 1).

Then there is the issue of whether circumcision protects women. At a major AIDS conference earlier this year, a team from Johns Hopkins University in Baltimore, Maryland, reported that men who are circumcised when they are already HIV-positive are more likely to infect their partners. The reason, according to team leader Maria Wawer, is that some couples resume sex too early, before the circumcision wound heals, thus exposing the woman to virus-infected blood.

Of course, circumcision cannot protect men who are already HIV-positive, but the fear is that if circumcision becomes the norm such men will have the procedure done - either because they don't know they are infected or because uncircumcised penises come to be seen as a marker of being HIV-positive.

Another fear is that circumcision could encourage risky sexual behaviour by lulling men into a false sense of security, or even making them believe they are immune and so can stop using condoms. Auvert's team has estimated that this effect would reduce the effectiveness of circumcision from 60 per cent to 50 per cent (PLoS Medicine , vol 3, p e517). Another model found that if 40 per cent of circumcised men significantly increased their risky behaviour, the benefits of circumcision would be completely eliminated (International Journal of Epidemiology , DOI: 10.1093/ije/dyn038). However, a real-world Kenyan study found no increase in risky sex acts such as failure to use a condom among recently circumcised men (Journal of Acquired Immune Deficiency Syndromes , vol 44, p 66).

As the controversy over circumcision in Africa continues, it has spilled over into a secondary debate in the western world. If circumcision is an effective weapon against AIDS in Africa, does that mean it should be promoted elsewhere?

Convincing evidence one way or the other is thin on the ground. Huge regional differences in the nature of the epidemic mean that applying the African findings to other parts of the world is not straightforward, Halperin says.

In sub-Saharan Africa, for example, the main mode of HIV transmission is heterosexual sex, whereas in the developed world it is sex between men, prostitution and injected drugs. That calls into question the public-health benefits of a procedure established only as a way of protecting men during sex with women. What's more, HIV is much less prevalent in the west than in Africa, and the predominant subtype is HIV B, rather than A, C and D - factors which have unknown consequences for the effectiveness of circumcision. And while a handful of observational studies have looked at HIV and circumcision in the west, the results have been inconclusive (PLoS Medicine , vol 4, p e223).

Last year, the US Centers for Disease Control and Prevention (CDC) assessed evidence relating to HIV and concluded that there was no compelling reason to advocate widespread circumcision in the US, though there may be a case for certain high-risk men choosing to undergo the procedure. New York City's health authorities have also considered whether to start promoting circumcision .

But HIV is not the only reason advocates still claim that boys should be routinely circumcised. They point to a large and growing body of evidence - though much of it is disputed and none of it is yet from randomised controlled trials - that circumcision can prevent numerous other health problems, from mild urinary tract infections to cancer.

Some studies have shown, for example, that circumcised baby boys have a lower rate of urinary tract and kidney infections. Others find that uncircumcised men have a higher risk of catching sexually transmitted diseases, including chlamydia, genital warts, herpes, gonorrhea, syphilis and chancroid. Circumcision also prevents a problem called phimosis, where the foreskin is overly tight making erections and urination painful; phimosis is a strong predisposing factor for penile cancer. Circumcision also offers protection against human papilloma virus (HPV), another cause of penile cancer. One recent review concluded that uncircumcised men are more than 20 times as likely to get penile cancer (Journal of the American Academy of Dermatology , vol 54, p 369). Some studies even show that uncircumcised men have a higher incidence of sexual dysfunction.

All in all, says Morris, 1 in 3 uncircumcised men will eventually require medical attention for a condition that could have been prevented by circumcision. "There are benefits at all ages," he says. "There is a huge public-health problem if you're not circumcising" (BioEssays , vol 29, p 1147). There are also claimed health benefits for women. The female sexual partners of uncircumcised men have a moderately increased risk of cervical cancer, probably due to HPV, along with an elevated incidence of herpes and chlamydia.

Despite this, medical authorities are loath to promote circumcision. The American Academy of Pediatrics is looking into the issue in the light of the HIV data but its current position is that the potential medical benefits are not sufficient to recommend routine circumcision. The British Medical Association, meanwhile, describes the medical evidence as "equivocal". These positions are echoed by authorities across the developed world.

One reason for this caution is the risk of complications arising from the procedure. These are largely minor, such as bleeding, pain and the side effects of anaesthesia. But very occasionally they can be more serious: a few cases of severe infection or injury and even death have been recorded. Figures for the incidence of complications are inconsistent, however, not least because the conditions under which circumcision is performed vary so widely. The CDC says that somewhere between 0.2 and 2 per cent of circumcisions in the US result in complications, almost all of them minor.

This uncertainty makes the relative costs and benefits of circumcision hard to calculate. For example, Morris reckons that circumcising just 1000 boys will prevent one case of penile cancer, but other analyses argue that the number is closer to 300,000.

As the pro-circumcision message has gained momentum, anti-circumcision groups have proliferated, arguing that the supposed benefits are overblown and are outweighed by the risks. Some argue that circumcising a child without consent is a violation of his human rights. "Circumcision is the harmful removal of a very important part of a man's body," says George Denniston of Doctors Opposing Circumcision in Seattle, Washington.

Circumcision proponents say the objections are based on anecdotes rather than science. "I don't think there is any evidence other than emotion that drives people to say we cause harm," says Irwin Goldstein, director of sexual medicine at the University of California, San Diego.

The debate is at its most raucous and scientifically murky when it comes to sex. According to supporters, circumcision has no effect on a man's sex life and can improve that of his partner's. Opponents say the exact opposite, claiming that the foreskin is a highly sensitive part of the penis that is necessary for normal sexual function and enjoyment. Here too, the science is equivocal. Some studies have shown that circumcised men have reduced sensation to fine touch (BJU International , vol 99, p 864). Many more, however, including one by William Masters and Virginia Johnson in their classic 1966 book Human Sexual Response , find no difference in penile sensitivity. A recent example is reported in The Journal of Sexual Medicine , vol 4, p 667.

Outside the laboratory the results are equally contradictory. Most of the information comes from non-scientific surveys that tend to confirm the prejudices of the people carrying them out. In 1988, for example, circumcision advocate James Badger found that men who had experienced sex both uncircumcised and then after being circumcised said it was better circumcised, while women found circumcised penises more attractive. However, a similar survey by circumcision critic Kristen O'Hara found that women overwhelmingly preferred "natural" intercourse (BJU International, vol 83, p s79).

The most recent contribution to the sex debate comes from the circumcision trial in Uganda. A team led by Ronald Gray of Johns Hopkins University compared two groups of more than 2000 men: the members of one group underwent circumcision at the start of the two-year study, while those in the other group remained uncircumcised throughout. When they asked the men about their sexual desire, functioning and satisfaction, the researchers found no significant difference (BJU International , vol 101, p 65).

"I think we need quite a bit more data on the direct effects of circumcision on penile sensation," says Erik Janssen, a sex researcher at the Kinsey Institute in Bloomington, Indiana. "Is it leading to additional types of stimulation that are more pleasurable? I don't know of really good research on this topic; if there was funding for it, I would study it."

For now, the debate over circumcision continues to arouse passion, prejudice and confusion on both sides. What is urgently needed is rock-solid data from randomised, controlled trials. "Scientists keep an open mind," Morris advises. "Ten years down the track, if there is evidence circumcision is not necessary, I will just back off."

Vivien Marx is a writer based in New York.

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