This article is based on a literature-search and a histological inspection of foreskins taken from the corpses of old men. The big problem with literature searches is that articles making a claim are more likely to be published than ones that show a null result. Added emphasis and comments are in red.
BMJ 2000;320:1592-1594 ( 10 June )
Education and debate
How does male circumcision protect against HIV infection?
Robert Szabo a Faculty of
Medicine, Monash University, Wellington Road, Melbourne 3168, Australia, b Department of
Obstetrics and Gynaecology, University of Melbourne, Royal Women's
Hospital, 132 Grattan Street, Melbourne 3053, Australia
Correspondence to: R V Short
a Faculty of Medicine, Monash University, Wellington Road, Melbourne 3168, Australia, b Department of Obstetrics and Gynaecology, University of Melbourne, Royal Women's Hospital, 132 Grattan Street, Melbourne 3053, Australia
Correspondence to: R V Short
In his otherwise excellent review of the AIDS epidemic in the 21st century, Fauci presented no new strategies for preventing the spread of the disease.1 He made no mention of male [or female] circumcision, yet there is now compelling epidemiological evidence from over 40 studies which shows that male circumcision provides significant protection against HIV infection; circumcised males are two to eight times less likely to become infected with HIV.2
[The evidence is far from "compelling". Each of the studies has its own flaws. See the relevant page of this site. The extraordinary history of circumcision as a panacea, and before that as a rite, strongly suggest that latter-day claims of prophylaxis should be regarded with a sceptical, if not jaundiced, eye. Few if any men can be truly neutral about circumcision. The temptation to justify what was done to oneself seems almost irresistible.]
Furthermore, circumcision also protects against other sexually
transmitted infections, such as syphilis and
[This is contradicted by Laumann]
and since people who have a sexually
transmitted infection are two to five times more likely to become
infected with HIV,5 circumcision may be even more
protective. The most dramatic evidence of the protective effect of
circumcision comes from a new study of couples in Uganda who had
discordant HIV status; in this study the woman was HIV positive and her
male partner was not.6 No new infections occurred among
any of the 50 circumcised men over 30 months, whereas 40 of 137 uncircumcised men became infected during this time. [But as Peiperl points out, over one-third (29 out of 79) of the circumcised men in this study were HIV-positive before the study began.] Both groups had
been given free access to HIV testing, intensive instruction about
preventing infection, and free condoms (which were continuously
available), but 89% of the men never used condoms, and condom use did
not seem to influence the rate of transmission of HIV. [Why not? What's going on? Did circumcision status influence the rate of usage of condoms?] These findings should focus the spotlight of scientific attention onto the foreskin. [No, on the condoms or their use] Why does its removal reduce a man's susceptibility to HIV infection? [This is the fallacy of post hoc ergo propter hoc, after this therefore because of this. Circumcision does not take place in a social vacuum. What is associated with circumcision and intactness in Ugandan society? It very commonly goes with religion, for example, and religion in turn influences sexual practice in a variety of ways:
To compile the information for this review a Medline search was
done using the terms circumcision, HIV, Langerhans' cells, penis,
foreskin, and prepuce, and extensive email correspondence with other
researchers was also undertaken. Histological observations were carried
out on samples of penile tissue obtained from 13 perfusion fixed
cadavers of men aged 60-96 years, seven of whom had been circumcised. [The advanced age of the men from whom the samples were taken, in considering a process that is age-related, throws suspicion on this work.]
Between 75% and 85% of cases of HIV infection worldwide have probably occurred during sexual activity.7 Most cases of primary HIV infection are thought to involve HIV binding initially to the CD4 and CCR5 receptors found on antigen presenting cells - which include macrophages, Langerhans' cells, and dendritic cells - in the genital and rectal mucosa.
The most widely accepted model for the sexual transmission of HIV is based on infection of the genital tract of rhesus macaques with simian immunodeficiency virus. 8 9 After female macaques are inoculated intravaginally with simian immunodeficiency virus, the virus targets the Langerhans' cells located in the vaginal mucosa. [And do Short and Szabo consider advocating the amputation of vaginal mucosa? The fatal sexism of a policy that protects men but not women, compared with one that protects both, such as condom use, is not considered.] Once infected, these cells fuse with adjacent CD4 lymphocytes and migrate to deeper tissues. Within two days of infection, the virus can be detected in the internal iliac lymph nodes and shortly thereafter in systemic lymph nodes. This ultimately leads to a fatal infection.
Similarly, infection in male macaques occurs when simian immunodeficiency virus is inoculated into the penile urethra or onto the foreskin; the same sequence of cellular events involving the infection of Langerhans' cells is then likely to occur.9 Infected Langerhans' cells have also been detected in the penile mucosa of male rhesus macaques that have chronic simian immunodeficiency virus infection.9 In humans, histological studies have identified antigen presenting cells in the mucosa of the inner foreskin and urethra.10 Therefore it seems likely that antigen presenting cells at these mucosal sites are the primary target for HIV in men.
In vitro studies have shown that the CD4 receptor is generally necessary, although insufficient on its own, to permit HIV-1 to enter host cells.11 The entry of HIV-1 into cells requires an additional chemokine receptor, usually CCR5, although CXCR4 is used by cells that become infected during the later stages of the disease.12 After primary infection occurs, the virus mutates, which allows it to utilise other chemokine receptors, such as CXCR4, and thus spread to a variety of cell types. However, more than 99% of HIV-1 isolates from acutely infected patients are homologous, indicating that one specific variant is likely to be responsible for most cases of primary HIV infection.13 HIV variants that are transmitted to other individuals almost invariably use CCR5 as a coreceptor and are therefore named R5 viruses, to reflect their specific requirement for a coreceptor.14
About 70% of men infected with HIV have acquired the virus through vaginal sex, and a smaller number have acquired it from insertive anal intercourse.7 Thus, on a global scale most men who are HIV positive have acquired the virus via the penis. This raises questions of how HIV enters the penis and why men who are uncircumcised are potentially more susceptible to becoming infected with HIV.
The uncircumcised penis consists of the penile shaft, glans, urethral meatus, inner and outer surface of the foreskin, and the frenulum, the thin band connecting the inner foreskin to the ventral aspect of the glans. A keratinised, stratified squamous epithelium covers the penile shaft and outer surface of the foreskin. This provides a protective barrier against HIV infection. [There is no evidence for this claim.] In contrast, the inner mucosal surface of the foreskin is not keratinised15 and is rich in Langerhans' cells,10 making it particularly susceptible to the virus. [Again, this is conjecture.] This is particularly important because during heterosexual intercourse the foreskin is pulled back down the shaft of the penis, and the whole inner surface of the foreskin is exposed to vaginal secretions, providing a large area where HIV transmission could take place. [In that case, why are women, with the much greater area of their vaginal surfaces, not vastly more susceptible to HIV infection from men?]
There is controversy about whether the epithelium of the glans in uncircumcised men is keratinised; some authors claim that it is not,15 but we have examined the glans of seven circumcised and six uncircumcised men [...aged 60 to 96...], and found the epithelia to be equally keratinised. In circumcised males only the distal penile urethra is lined with a mucosal epithelium. However, this is unlikely to be a common site of infection because it contains comparatively few Langerhans' cells.10 [This is an example of begging the question, assuming what you have to prove.]
Ulcerative or inflammatory lesions of the penile urethra, foreskin,
frenulum, or glans that are caused by other sexually transmitted infections may provide additional potential routes for HIV
transmission. In uncircumcised males, the highly vascular frenulum is
particularly susceptible to trauma during intercourse, [It is equally so in circumcised males - if it has not been ablated - and in addition traumas and tearing of the scarred ring are only possible in circumcised men] and lesions
produced by other sexually transmitted infections commonly occur there. Thus, male circumcision further reduces the risk of infection by
reducing the synergy that normally exists between HIV and other sexually transmitted infections.5
Of the estimated 50 million people infected with HIV worldwide, about half are men, most of whom have become infected through their penises [... and a vast number of whom were circumcised]. The inner surface of the foreskin, which is rich in HIV receptors, and the frenulum, a common site for trauma and other sexually transmitted infections, must be regarded as the most probable sites for viral entry in primary HIV infection in men. ["Must"? Yet a vast number of them don't have one.] Although condoms must remain the first choice for preventing the sexual transmission of HIV, they are often not used consistently or correctly, they may break during use, and there may be strong cultural and aesthetic objections to using them. Cultural and religious attitudes towards male circumcision are even more deeply held, [and the perfectly rational view that it reduces sexual pleasure, and the human rights issue of consent] but in the light of the evidence presented here circumcising males seems highly desirable, ["Desirable"? A strange choice of word, suggesting a sexual rather than rational motivation] especially in countries with a high prevalence of HIV infection. [Yet Ethiopia and the US already have high prevalences of both HIV infection and circumcision.] Although neonatal circumcision is easy to perform, and has a low incidence of complications,16 [Other references cite much higher rates] it would be 15-20 years before a programme of circumcision had any effect on HIV transmission rates. Circumcision at puberty, as practised by many Muslim communities, would be the most immediately effective intervention for reducing HIV transmission since it would be done before young men are likely to become sexually active [... and knew what they had been deprived of].
It may also be time to re-think the definition of "safe sex." Since the penis is the probable site of viral entry, neither infected semen nor vaginal secretions should be allowed to come in contact with the penis, particularly in uncircumcised males. Thus, mutual male masturbation during which a penis is exposed to the potentially infected semen of another male should be regarded as risky sexual behaviour. [Szabo and Short present no evidence for this claim. They have reasoned backward from their analysis of the literature of heterosexual transmission.]
New preventive strategies are needed that could be used by men or women
before the onset of intercourse. The disadvantage of topical virucides,
such as nonoxinol 9, is that they may cause local irritation and thus
increase susceptibility to HIV infection. The development of topically
active agents that could block HIV binding sites, such as CCR5, and
which could be applied to the penis or vagina to create a "chemical
condom," might be more effective and acceptable than any mechanical
barrier or surgical intervention.
We thank Professor John Mills for helpful comments on an early draft of the manuscript and Professor Daine Alcorn and the staff of the Department of Anatomy, University of Melbourne, for supplying and processing the specimens from human cadavers.
Contributors: RS reviewed all the relevant literature, carried out the histological examination of the specimens, and wrote the first draft of the manuscript. RVS initiated the study and participated in redrafting of the paper. Both authors will act as guarantors.
Competing interests: None declared.
(Accepted 11 May 2000)
© BMJ 2000
from a Commentary by Laurence Peiperl, MD on The Rakai Study: Risk Factors for Heterosexual Transmission:
Caution must be exercised in applying the results of this study to individual risk-reduction strategies. For example, the result that no circumcised men seroconverted during the course of the study might be casually interpreted to mean that a circumcised man cannot be infected with HIV through heterosexual sex. This conclusion is illogical, as the relatively small sample size (50 circumcised seronegative men) and short duration of follow-up (median less than 2 years) allow for a significant possibility that infection of circumcised men would be observed in a larger population or over a longer period of time. The fact that over one-third (29/79) of the circumcised men in this study were HIV-positive on entry demonstrates that transmission to circumcised men occurs in this population, and it seems extremely unlikely that heterosexual transmission did not contribute.
HIV InSite Journal Club, April 14, 2000
Back to the Intactivism index page.