The No-Brainer Syndrome : the HPV Vaccine and Male Circumcision Recommendations as the Latest Weapons in the Fight Against HPV, HIV and AIDS

Dr. Paul Offit, director of the Vaccine Education Center at The Children’s Hospital of Philadelphia, called the new HPV vaccine, Gardasil, approved last year by the Center for Disease Control (CDC), “a no-brainer.”  Many advocates in the blogosphere use the same phrase, “no-brainer”, to describe the World Health Organization (WHO) 2006 recommendation for male circumcision as an HIV/AIDS prevention strategy, at least in sub-Saharan Africa. Most health professionals agreed, even if they didn’t use the exact phrase.

Nonetheless, I wondered if they were right – mainly because in my experience the words “no-brainer” usually indicates more about the state of the grey cells of the person uttering the phrase than about the state of the choice that is faced.

Then I noticed the coincidence that Gardasil and male circumcision were each targeted to a single sex: Gardasil to females, and circumcision to males (a second HPV vaccine Cervarix was approved in Europe for both sexes). Was each recommendation the result of some murky sexist plot or was it just a sexist coincidence? And what did it matter?

I also noticed that there were no lines around the block for either medical service. A mere 10% of girls have been vaccinated so far with Gardasil and few if any men have had “the snip”. Within the past weeks the Virginia Legislature has taken steps to repeal its mandate for the HPV vaccine for schoolgirls, and the Health Minister of South Africa has refused to endorse male circumcision as part of its national AIDS program.

So, after all the fanfare, what is going on here, and can we learn any public health lessons?

The Two Epidemics

The HPV- Cervical Cancer Epidemic – Cancer of the cervix is the second most common cancer of women worldwide, with 555,000 new cases and 260,000 deaths annually. Most cases (80%) of cervical cancer occur in the developing world.

Almost all (99%) of cervical cancer cases are linked to HPV, the human papillomavirus. There are over 100 different types of HPV (over 30 of which are transmitted sexually) that can infect women and men. Two types (HPV 16 and 18) cause 70% of cervical cancer, and two other types, HPV 6 and HPV 11, cause 90% of genital warts. Merck’s Gardasil targets these four strains, while GlaxoSmithKline’s Cervarix (approved in Europe and elsewhere but not yet approved by the FDA) mainly targets HPV 16 and 18.

About 3 in 4 men and women will develop HPV in the United States during their lifetimes, but fortunately about 90% of those infected will clear their HPV infection within two years without medical intervention. Currently, 27% of women ages 14-59 have HPV. Every year, about 11,000 women in the U.S. are diagnosed with cervical cancer, and about 3,700 women die of the disease – a high a number but, compared to the number of women with HPV, a tribute to the healing powers of nature and the U.S. Pap smear screening program, even though for some populations of women the program is as porous as a cotton condom.

In the developed world, about half of women have been screened for HPV/cervical cancer within the last five years, but only about 5% in the developing world have. As a result, the death rate from cervical cancer in the developed world has plunged in the last half century but has not in the developing world.

There have been recent studies linking HPV to a rise in oral cancer in men. See http://content.nejm.org/cgi/content/full/356/19/1944?ijkey=qVEw4puuEh6zQ&keytype=ref&siteid=nejm

Men (73%) are far more likely than women to have oral cancer, which hits 35,000 people a year in the U.S. and kills 8,000. The rate for males has increased since 1973, even though there has been over a decrease in tobacco use during that time, which should have resulted in, but didn’t, a reduction in the incidence of oral cancer. That leaves the rise in oral sex as the culprit. Currently, oral sex causes as many cases of oral cancer in men as smoking does. In contrast, the rate of HPV-related upper throat cancer among women has fallen since 1973. Studies do not reveal any reduction in oral sex performed by females during that time, in fact quite the opposite. So what is happening? Are women requiring condoms on their male partners before performing oral sex? No.  As you might imagine, governments are not champing at the bit to fund studies on oral sex, but the few that there are say that condom use during oral sex occurs only slightly more frequently than a lunar eclipse. One British study from 2003-2005 found that 80% of 16-21 year old university students did not use condoms during oral sex, whereas most did during vaginal sex. In the U.S. a 1996 study found that 86% of high school student never used a condom during oral sex and 8% used one sporadically. One suspects that the self-reporting nature of these scientific studies exaggerated the frequency of condom use.

See http://www.guttmacher.org/pubs/psrh/full/3800606.pdf

The HIV/AIDS Pandemic – At the end of 2007 there were about 33 million people living with AIDS (about equally divided by gender), with 2.5 million persons newly infected in 2007 and 2.1 million deaths. The majority of HIV infections worldwide are transmitted by heterosexual sex.

There has been a gradual reduction over the past few years in new HIV cases globally, reflecting the natural trend of the epidemic and behavioral changes in at-risk populations. There has also been a reduction in the number of deaths annually, due mainly to greater access to more effective treatments.

The Magic Bullets

Both epidemics, HPV and HIV, have certain similarities: both are viruses, both are transmitted sexually, both have a high death toll and both flourish because of the molasses-like pace of change, or lack thereof, in the human sexual behavior needed to thwart them. The ABC (Abstinence, Be faithful, Condoms) approach has been effective in some countries, mainly resulting in more condom use, in Africa and elsewhere, but alas, condom use is not universal for many reasons – cultural, sexual, economic and otherwise, including the prosaic fact that the worldwide condom supply is both erratic and insufficient. Alas, even when condoms are available and used, they are not universally effective against HPV/genital warts. Thus HPV and HIV march on.

So why the public health establishment embrace of techno-fixes, seeming magic bullets in the fight against HIV and HPV? Why not devote the money to manufacturing and distributing more condoms along with educational messages?

A combination of factors are at work, including impatience and frustration on the part of health officials with the lack of headway against the diseases. One researcher stated, “It has been claimed that primary prevention based on an educational, social and rights-based response has failed, and what is needed is a more thoroughgoing engagement with the principles of ‘traditional’ public health medicine.”

There is pressure to find a solution, any solution, especially one that will attract funding. This has led to an increased emphasis on “biomedical prevention”, i.e. vaccines and surgery, which involve as little human behavioral cooperation as possible, like fluoride in the water supply. For example, there have been recent suggestions that antiretroviral drugs be rolled out to otherwise healthy populations in Africa. In the past month, it was also proposed that antibiotics be given to all aboriginals in Australia to prevent the further spread of sexually transmitted infections (this was before the Australian government’s apology for its treatment of aboriginals; perhaps a new apology is in order). Meanwhile, multiple teams of scientists with dreams of Nobel Prizes dancing in their heads are hard at work on the holy grails/magic bullets of a female microbicide for HIV prevention and a HIV vaccine. These appear to be far in the future, but hopefully one or both will appear before the next solar eclipse in New York (April 24, 2024). See P. Aggleton, ‘Just a Snip’?: A Social History of Male Circumcision, Reproductive Health Matters 2007: 15 (29): 15-21.

So, for starters, what science has given us are a vaccine and circumcision. Neither are 100% effective. And, just as fluoride does not obviate the need for brushing one’s teeth, the WHO made it clear that the HPV vaccination and male circumcision were not cure-alls and that condoms were still needed.

Perhaps for this reason, the reception by men and women for these “new” technologies was less than clamorous.

The HPV Vaccine-Gardasil

Gardasil is recommended for young females, preferably ages 11-12, who are not yet sexually active and hence not already infected with HPV. The vaccine has been approved by the FDA for all females ages 9-26.  Three doses are required over a six month period, and thus repeat visits to the doctor. The vaccine was approved for girls only, since Merck did not have enough boys in its clinical trials to prove safety and effectiveness for them. Trials for boys are continuing, and reportedly a second application to the FDA is due from Merck in 2008 to have Gardasil approved for males.

It is not known whether it was Merck’s decision to concentrate on girls in its initial trials, whether there was true difficulty recruiting boys for the trials, or whether the vaccine is simply not as effective in boys as girls. There is a public health argument that since cervical cancer is the ultimate target of the vaccine that it should be targeted to girls. And, assuming that there are limits to public funds for HPV vaccination, one argument to be made against the vaccination of boys is that the cost thereof would be better spent reaching all girls ages 11-12, thereby providing, eventually, what is called “herd immunity,” which occurs in a population when at least 70% of its females are vaccinated. Thus, the decision to concentrate on females has grounding in public health theory.

Alternatively of course, all funding could have been directed at immunizing males and allowing their herd immunity to protect females. The New York Times recently speculated that there would have been few takers for this among boys and their parents. See http://www.nytimes.com/2008/02/24/fashion/24virus.html?scp=1&sq=herd+immunity&st=nyt

As with any vaccination, there are side effects. The injections are painful. The CDC reports that there have been other reported side effects, including fever, nausea and dizziness, but that these and others are “relatively very rare, in the context of 7 million doses distributed across the U.S.” Both Europe and the U.S. are investigating a few deaths following the administration of the vaccine, which are, at the moment, not believed to be directly related to the vaccine, but coincidental.

Effectiveness.   In clinical trials for the 16-26 year old age group, Gardasil was virtually 100% effective against the four strains of HPV that it targets.  Merck reported that the effectiveness lasted five years.

There are, however, certain unknowns. The effectiveness beyond five years, and thus the need for, and the effectiveness of, boosters is unknown. Also, since relatively few girls between 11 and 15 were in the clinical trials, the safety and effectiveness for that target age group is unproven. The effectiveness for women who already have been exposed to HPV is also unknown, but is believed to be nonexistent. Finally, there is concern that while the vaccine does protect against HPV-16 and HPV-18, by so doing the vaccine may be unleashing other HPV strains which can infect the woman. Thus, the ultimate efficacy of the vaccine against all HPV infections and, ultimately, against cervical cancer may be less than the initial studies indicated (Merck did not test, and the FDA did not require them to, the vaccine as a preventative against cervical cancer, just HPV infection).

Public Reception.  To date, after over a year of availability in the U.S., only about 10% of women ages 18 to 26 have received at least one dose of the HPV vaccine.

Why the low numbers? Public awareness is low about HPV in general, about its connection to cervical cancer and about the HPV vaccine in particular. This lack of public awareness about vaccines is not confined to HPV. There is similar low awareness about the new shingles vaccine, and an even lower vaccination rate (2%).

Cost is another deterrent. The three doses cost $360, plus doctor’s fees. However, most insurers cover the vaccine, but there are varying co-pays. Many, if not most, uninsured will be covered though various public vaccine programs. Availability of the vaccine may not be universal since the initial cost for the clinic or doctor’s office is high. Cost and availability are not the only deterrents. In Ontario, where the vaccine is free and widely available, only half of girls have been vaccinated – five times the U.S. rate but not universal.

Faced with public resistance and in order to maximize its revenues, Merck embarked on an extensive lobbying campaign to have the HPV vaccine required for admission to school, like other childhood vaccines, such as measles and whooping cough. Texas, by executive order, and Virginia and the District of Columbia by legislative action responded to Merck’s lobbying and made HPV vaccination mandatory for girls entering the sixth grade (though the District’s law still needs Congressional approval to take effect).

Then a backlash set in. The Texas legislature recently overturned the Governor’s order, and one house of the Virginia legislature passed a bill delaying the implementation of its legislation. Most other state legislatures have either rejected a mandate or are taking a wait-and-see approach, even though one chamber of the Kentucky Legislature last week passed a mandate. At least four provinces in Canada have free but voluntary HPV vaccination programs in schools for 7^th and 8^th graders.

The backlash against mandates was fueled by a combination of factors.

1. There were parental concerns about the long-term safety and efficacy of the vaccine, especially for the 11-15 year old age group. Merck is currently conducting more trials to study this population.
2. Budgetary concerns. Gardasil is expensive. Funds to pay for it as part of the Medicaid program or some other government program will have to come from somewhere, leading to a reduction in health prevention or treatment of some other disease. There is an argument that whatever millions are spent might be better spent on a more comprehensive STI prevention program, including condom use and more extensive Pap screening. It has not gone unnoticed that Gardasil protects against only 70% of HPV-causing strains, while condoms protect against all of them, plus other STI’s.
3. There is also a growing concern with the safety of all vaccines in general, and especially with childhood vaccines, with parents demanding the right to opt their children out of any mandated vaccine (all state vaccine mandates have an opt-out provision). This deferral to parental rights did not satisfy some conservative groups, which, while they didn’t openly oppose the FDA approval of Gardasil and stated publicly that they welcomed vaccines against HPV, did oppose any state mandate that all girls be vaccinated, even with a parental opt-out.
4. Finally, there’s sex. Girl sex in particular. Conservative groups argued that HPV vaccination would inevitably lead to adolescents engaging in more and earlier sex, thereby causing more transmission of HPV and other sexually transmitted infections. They argued that vaccinated, and unvaccinated, adolescents will have a reduced fear of HPV, even though Gardasil does not prevent all HPV strains, and will thus engage in more and riskier sex. This is known in the public health world as “risk compensation”, and occurs when there is a perceived change (i.e. reduction) in the risk of acquiring a disease or being involved in an accident, for instance with drivers with seat belts and air bags driving faster. The conservative argument is identical to their argument against birth control – that a reduced fear of pregnancy leads to more sex and thus more pregnancy. The fact that there is still a multiplicity of sexually transmitted infections out there that Gardasil does not prevent, and thus that there should be no false sense of immunity, has not dissuade these conservative groups from their campaign.

I suspect that it is the realization that their daughters may be sexual beings is too much for some parents to take. Their response is to bury their heads in the sand and refuse to vaccinate their daughters. This raises the question whether the HPV vaccine would have had an easier road to acceptability if it had been targeted to boys first and their epidemic of genital warts. I wonder if fewer parents would have blanched at being confronted with their sons being sexual beings and thus would not have objected as vociferously to the vaccine, which could then slowly have been rolled out for girls. Even if never rolled out for girls,  the male herd effect protecting girls would have occurred after 70% of males were vaccinated. See The New York Times story referred to above.

That said, I can only imagine the screaming if Merck had filed for males first. The company clearly saw an easier path to riches by treating girls first, even though there may have been a less antagonistic conservative response if sons were called upon to be vaccinated before daughters.

Now that millions of doses have been administered in the U.S. and Europe, Gardasil will get its real world clinical trial. Preventive medicine is supposed to save lives and money in the long run. We will see if it does.

There will not be mandates, at least in the short run, in the U.S.  Europe will probably lead us in that regard. It is likely, therefore, that a familiar health care pattern will repeat itself: wealthy, well-educated, more prosperous American girls who get advised to by their private physicians will get vaccinated at greater rates than lower-income and minority girls who won’t. This will repeat the same disparity that currently exists with cervical cancer itself. Pap screening programs do not reach those marginalized in our society. The incidence of cervical cancer is 1.5 time higher for African American and Latina women in the U.S. than white women. Cervical cancer is highest along the Mexican border, in Appalachia, among Native Americans and in rural areas, exactly where the public health system is weakest. That is why mandates in a way make sense, especially since school drop-out rates for lower income and minority girls begin earlier than for more affluent, white girls.

Male Circumcision

In 2007 the World Health Organization announced that it was recommending male circumcision “as an efficacious intervention for HIV prevention.” The CDC has yet to make a recommendation for the United States.

See http://www.cdc.gov/hiv/resources/factsheets/circumcision.htm

Male circumcision is a different medical animal than a HPV vaccination. It is surgery. It is more expensive – in the U.S. the cost is in the thousands of dollars with insurance coverage variable and no government programs to cover the uninsured (some states, including recently Florida, have dropped infant circumcision from Medicaid coverage). Medical benefits, if any, and side effects are hotly debated. The side effects include pain, shock, hemorrhage, infection, and accidental disfiguration. There is also the hotly debated issue of loss of sexual sensitivity and increased friction and pain during intercourse, not to mention other psychological complications.

Circumcision has a long and often contested history – socially, culturally, medically and religiously. It is not “just a snip,” as some advocates put it. It is virtually universal among Jews and Muslims, and less so among Christians and rare among other religions. Circumcision, or the lack thereof, is a literal marker of identity, of coming of age and of maturity, of being a member of a group, tribe, nation or religion. It may have originated, some anthropologists argue, as an intra-sexual control mechanism, designed to reduce male and female sexual sensitivity, so as to better control adolescents and to confine their sexual activity to within culturally-approved bounds. Circumcision is thus nothing less than a cultural and sexual minefield. Getting acceptance for an HPV vaccine will be a walk in the park compared to getting acceptance for circumcision in some societies.

Effectiveness.  In 2007 two studies, one in Kenya and one in Uganda, were halted early by medical authorities, when the preliminary results showed a 53% and 51% reduction in risk respectively in acquiring HIV infection by circumcised males as opposed to uncircumcised males. The case was so clear that it appeared to be a “no-brainer”. Another earlier clinical trial in South Africa showed a 60% reduction in risk. These studies confirmed, or appeared to, earlier observational studies that circumcised males had a lower incidence of HIV. The WHO called the evidence compelling and the case proved beyond a reasonable doubt.

Interestingly, there is no agreement on how circumcision might actually work as an HIV preventative. There are a variety of theories including the keratinisation of the penis that occurs after circumcision serving as a retardant to HIV transmission. Another is that there is a susceptibility to HIV in the Langerhans cells in the inner foreskin, although one researcher published a paper a few weeks before the WHO recommendation came out arguing that langerin produced by Langerhans cells blocked HIV transmission. See http://www.nature.com/nm/journal/v13/n3/abs/nm1541.html;jsessionid=B7086F8AE0A92211B2E59C3669A60A66

Langerhans cells also appear in other parts of the male and female genitals, including the clitoris. There was no suggestion by WHO that these cells, or the surrounding skin on the organs that contain them, be excised. The WHO circumcision recipe for the goose is not one for the gander.

The WHO emphasized that circumcision was not 100% effective, and that, in fact, the HIV infection rate in circumcised males in the African clinical trials was still unacceptably high. There was no evidence that male circumcision protects female partners, or the partners of men who have sex with men. Both these sad facts have been born out by subsequent trials. In a recent study, the CDC announced that circumcision offers no protective benefit to U.S. black and Latino gay and bi-sexual men. See http://www.msnbc.msn.com/id/22096758/

The WHO took pains to point out that circumcision did not replace other HIV prevention strategies, including delay of sex, abstinence, reduction of partners, condom use and HIV testing and counseling services and treatment.

The WHO recommended that the target population be men in countries with high HIV prevalence and low circumcision rates, i.e. sub-Saharan Africa, with an emphasis on men ages 12-30 and older men with a high risk of acquiring HIV.

Public Reception. There as been no stampede for circumcision. As with the HPV vaccine, cost is a factor, as well as the lack of public education on the benefits of male circumcision. Some public health officials argued that a more effective use of funds was the current armament of HIV prevention strategies, such as ABC, especially the “C”.

To date, no U.S. state has announced a circumcision campaign, much less proposed a mandate.  Recently, Rwanda and a few other African countries announced campaigns to promote male circumcision, while Brazil has stated that it will not. At the moment the campaign in Rwanda is voluntary, though it has been reported that men in the army will be required to be circumcised in order to be promoted.

The WHO estimate of the efficacy of male circumcision was immediately challenged by scientists who raised the specter of risk compensation, i.e. an increase in risky sexual behavior by those circumcised, including reduced condom use and more sexual partners. Shades of Gardasil! Risk compensation is likely, some scientists believe, because of the widespread male dissatisfaction with condom use and because males, and females, they argue, have an innate desire for more than one sexual partner. In fact, the distaste for condoms, combined with a desire, in parts of Africa at least, for a large number of children, might be the chief motivators for males to seek circumcision in the first place.

While, as the WHO carefully pointed out, circumcision does not obviate the need for condoms, it is hard to imagine an effective public health campaign that urged circumcision and continued condom use – why should a man go through circumcision if he still has to wear a condom? That said, in the birth control arena there have been campaigns for dual protection, i.e., both the male and the female using contraception, though with mixed results.

There are two other major dangers for women here. It was recently reported that females do not get HIV protection from male circumcision. Circumcised men who are HIV positive transmit the virus to their partners at the same rate as uncircumcised men. In fact, there was an observed increase in infection in the partners of circumcised men who commenced sexual intercourse before their circumcision wounds had healed, despite extensive counseling of the couples to abstain until they got a go-ahead from a nurse. However, there was an observed decrease in other sexually transmitted infections in the males, but not in their partners.

See http://www.medpagetoday.com/MeetingCoverage/CROIMeeting/tb/8221

This study, which the researchers were careful to point out did not reach statistical significance, shows the intractable nature of human nature and risk compensation in action. The couples had been warned about not commencing intercourse before the wound healed and had been given condoms, and yet…. So, here we have a medical strategy designed to reduce HIV transmission, which, in fact, in this study increased it. Has the recommendation for circumcision been revisited, revised or withdrawn? No. Will it, if a larger study confirms these results?

A second danger for women is that there might be a conflation of male circumcision with female genital mutilation, especially if the theory of the Langerhans cells is proven. The conflation in some parts of the world of male and female circumcision as a cultural marker or initiation rite is already problematic. It would be horrific if the call for more males to be circumcised in cultures where it is not practiced led to more female genital mutilation. This would be compounded if Langerhans cells are seen as the culprit, since there might be a call for the removal of the clitoris which, like the foreskin, contains these cells.

As a disease preventative, circumcision has, so far, fallen short of expectations. There is some evidence in the U.S. or U.K. associating circumcision with reduced rates of sexually transmitted infections. See http://www.cdc.gov/hiv/resources/factsheets/circumcision.htm.  Studies in Africa are reportedly not rigorous enough to have a firm conclusion.

The real world experiment of the United States, which has the highest rates of circumcision in the developed world (65%) and also high rates of STIs and of heterosexually-transmitted HIV infection, should give one pause. The adult HIV prevalence rate in the U.S. is 0.6%, compared with 5% in sub-Saharan Africa. In the Middle East and North Africa, where circumcision is virtually universal, the HIV adult prevalence rate is 0.6%, though reliable statistics are hard to come by.

Circumcision, Biology and Human Evolution

There is already a concern among scientists that Gardasil, which only protects against four strains of HPV, may be unleashing the other strains to infect women. This is an example of evolutionary biology in action. Viruses will do their utmost to survive. We may be breeding new strains of HPV that will need new medicines and vaccinations. We are marching into the biological unknown with HPV vaccination, as perhaps we are with any vaccination.

Circumcision also involves unanswered biological questions. Unmentioned in almost all the debates pro and con circumcision is the question of the biological function of the foreskin in the first place. Have we evolved out of whatever purpose it once had, like a protective effect in the days of yore when humans didn’t wear clothes? Is the foreskin therefore some vestigial piece of the anatomy like an appendix? If we have evolved out of its original function, why hasn’t the foreskin disappeared? Parenthetically, scientists are beginning to discover biological functions for the appendix, and now believe that it is not vestigial at all, but related to the functioning of the immune system.

All primates, indeed virtually all mammals, have a foreskin or prepuce, both males and females. If the foreskin has a “pathogenic burden”, why has it continued through evolutionary time and why has humanity propagated so successfully despite it? The foreskin must confer some reproductive advantage. For instance, the foreskin might contribute to the lubrication of the penis, making it easier, for vaginal intromission (penetration). It may also serve to protect and clean the penis, contributing to penile hygiene.

Not surprisingly, the debates over the usefulness, utility and importance of the foreskin quickly turn into issues of gender and the battle of the sexes. There is one school of biological thought that argues the male penis is not just a sperm delivery device, but also a sperm removal device. It has been reported that some females (one in eight in one study) copulate serially with one or more men within a 24 hour period and that, as a result, there is what is known as “internal sperm competition” to see which man’s sperm gets to fertilize the egg. This battle is literally the survival of the fittest swimmer, or perhaps it is the last sperm standing that wins.

See http://www.springerlink.com/content/8nbw6ldv8r6vgqb0/

Some scientists theorize that the penis of the last man is able to remove some of the sperm of the previous male before depositing his own. A male with a penis that is designed to not only deposit his sperm but remove the sperm of the preceding male would have more offspring and thus his genital characteristics would be transmitted to the next generation. There is an argument that the shape of the male penis with its head larger than its shaft acts as a roto-rooter in evolutionary sperm competition. Perhaps the foreskin contributes to this function, though I have seen no scientific research pro or con this.

Other arguments for the existence of the foreskin involve sexual pleasure – the foreskin adds to it for the male, or so it is alleged. Studies vary on this one, and, as you might imagine, the debate is heated. See for example http://www.newscientist.com/channel/sex/mg19426015.500-does-circumcision-harm-your-sex-life.html

Assuming for the moment that an uncircumcised male has more sexual pleasure, why on earth would any male, or any parent of a male, seek to reduce his sexual pleasure? Well, lots of reasons, and argument.  To the extent the lack of a foreskin retards male orgasm and thereby reduces premature ejaculation, it makes for longer intercourse and more female pleasure. There are numerous arguments and purported “studies” with some arguing there is more, and some less, male and female pleasure in circumcised and uncircumcised. The foreskin perhaps evolved as a result of female sexual choice, if more females found sex more pleasurable with uncircumcised males.

No matter what the biological or evolutionary implications are for circumcision, I suspect that males are going to be most concerned about their own sexual pleasure. They are not going to be thinking about the role of the foreskin in human evolution, alas. Circumcision is a risk. It can not generally be undone. The appendix is generally not removed prophylacticly; it is removed when infected. It is a difficult argument for males to say that any part of their body, much less one that contributes to sexual pleasure, should be surgically removed when it is not diseased. It is like saying that all males are born defective and need surgical fixing. It is a decision akin to that that some women with genetic markers for breast cancer must make in deciding whether or not to have a mastectomy. It is a drastic measure.

HPV Vaccination and Male Circumcision: Case Studies in the Failure of Public Health

So, here we have two new public health recommendations relating to sexually transmitted infections, one for females and one for males.

Even though one is a vaccination and the other surgery, each has certain common characteristics.

Cost—         Each is expensive. This is not only a deterrent but may deflect funds from other prevention measures.

Side Effects— Each has serious potential side effects, though they are rare.

Effectiveness— Each is not 100% effective. This may result in risk compensating behavior and either less protection than envisioned or even more infection.

Culture— Each has cultural/gender sensitivities: each is about sex, the vaccination with the sexuality of girls and circumcision with male sexual prowess, pleasure and identity.

Public Health Impact— Each may not be the best, or most cost-effective, way to target the disease. Cervical cancer can be caught and cured with pap smears, and HIV by a comprehensive ABC program. HIV in Africa is mostly transmitted by female prostitutes. Thailand embarked on a program to require condom use in brothels. Africa has not. The HIV prevalence rate in Thailand is now far lower than in Sub-Saharan Africa. ABC can work. The circumcision recommendation is, I believe, more a comment on the world’s failure to implement ABC than on the benefits of the procedure.

Unintended Consequences— As a biological matter, there are unintended consequences with each. HPV strains not caught by Gardasil may be proliferating when their sibling strains are vaccinated out, leading to more HPV infection. The solution is ever more vaccines for the HPV strains not currently covered. Risk compensation is a real threat to the real world effectiveness of each intervention, though I believe the problem is vastly more acute with circumcision with the real possibility of reduced condom use by circumcised men.

Just last week the oft-ridiculed South African Health Minister, Manto Tshabalala-Msimang, questioned whether the evidence was strong enough to recommend a government circumcision program as part of HIV prevention. She made the comments in the context of a meeting with traditional healers, many of whom view circumcision, along with other HIV remedies, as a Western attempt to force foreign values on South Africans. She noted that the Xhosa ethnic tribe has a high HIV rate even though almost all Xhosa men are circumcised. She failed to mention that the infection rate is even higher among Zulus, who are not circumcised. Whatever her reasoning, or lack thereof, her opposition to circumcision may be a case of a stopped clock telling the correct time twice a day.

It seems to me that male circumcision is a pretty expensive “fix” when we don’t know how male circumcision works to prevent HIV transmission through the foreskin and penis in the first place. See the CDC article referred to above to the theories. If scientists could figure this out, then perhaps there is a less drastic, more cost effective or direct way to prevent transmission rather than by circumcision.

It is difficult to imagine that the path for human health and wellbeing is the removal of a part of the body (male circumcision) that nature has given us. But, given that there has been a real world experiment with Jews and Muslims for millennia, male circumcision does not appear to cause lasting harm in terms of morbidity or mortality or reproductive success, and, so far as we can tell, the Muslim HIV prevalence rate is relatively lower.

It would seem that we will continue to muddle through with a dual health care system for HPV and HIV prevention. In the developed world, there will be little demand for, or call for, circumcision and only slightly more for HPV vaccination. Preventive efforts will continue on ABC prevention – including behavior change, condom use and smarter decision making. And they will be slow to show results. In the developing world where there is less cancer screening and more sexual partners and less condom use, there will be a greater call for vaccination and circumcision. Since males in Africa, and females too, want more children than in the West, any perceived reduction of the need to wear a condom will most likely meet with favor. I suspect that there will be less than unanimous support for circumcision in general and probably too many violations of the no-sex-until-the-circumcision-wounds-have- healed guidelines.

The real world for HPV vaccine and male circumcision is a lot messier than the studies would indicate. Neither is a “no-brainer.” Science not only has produced incomplete information, it may have produced wrong information for real world use. It would have been preferable in the roll out of each intervention to have it be part of a program directed towards both sexes. In the case of HPV vaccine to have it tested thoroughly on boys and girls ages 11 and up. This would have reduced the imbedded cultural/gender fears of parents about their daughters being sexual beings. Additionally, though scientifically difficult, it would have been preferable to have a HPV vaccine that worked against all HPV strains, not just a few.

In the case of HIV, since the target is Sub-Saharan Africa where prostitution is the main mode of infection, a more extensive campaign, a la Thailand, directed at female prostitutes and brothels requiring condom use would have been salutary. This is hardly easy or in itself a “no-brainer,” but the alternative is waiting until the epidemic exhausts itself. Not a pretty picture.

A citation for the proposition for the potential unleashing of other HPV strains caused by HPV vaccination is as follows: George F. Sawaya, MD and Karen Smith McCune, MD, Ph. D, HPV Vaccination: More Questions More Answers,

http://content.nejm.org/cgi/reprint/356/19/1991.pdf

This editorial states in part:

“In contrast to a plateau in the incidence of disease related to HPV types 16 and 18 among vaccinated women, the overall disease incidence regardless of HPV type continued to increase, raising the possibility that other oncogenic HPV types eventually filled the biological niche left behind after the elimination of HPV types 16 and 18.”