To the Editor - We read with interest the opinion piece by Szabo and
Short.[1]
While a number of studies suggest an association between the foreskin and
HIV infection, a simple tallying of studies is both unscientific and
misleading.[2,3] Systematic review using meta-analysis has demonstrated a
significant degree of between-study heterogeneity, which calls into
question the validity of the summary results. Analysis suggests that men
who engage in high-risk behaviors may be placed at further risk by having
a foreskin, but in the general population circumcision status is not a
significant risk factor.[4,5] Based on the number of factors that
influence sexual behavior and the susceptibility to HIV, it is
irresponsible to focus blame on normal anatomy.
The authors report finding Langerhans cells in the preputial mucosa. This
is nothing new: all mucosal tissues have Langerhans cells. The authors
failed to report the concentration of these cells in comparison to other
mucosal tissues, their concentration in the glans, the foreskin
remnant and circumcision scar in circumcised men, the presence of
associated T-cell infiltration, and how their findings in elderly cadavers
correlate to sexually active 20- to 30-year-old men in Africa. The authors
presumptively state "the inner surface of the foreskin ... and the
frenulum ... must be regarded as the most probable sites for viral entry
of primary HIV infections in men;" however, without quantitative
comparative data their statements are
pure speculation.
To date, the only reports of preputial Langerhans cells have been in
specimens from neonates[6,7] and elderly cadavers. If normal genital
mucosa is at risk, the concentration of
Langerhans cells in these tissues is essential information in determining
which normal genital tissue needs to be removed. We need to know the
concentration in healthy men, men with multiple sexual partners, men with
genital infections, men with HIV, and men of differing races and ages
before any recommendations can be made. Because the infectivity of
Langerhans cells may be linked to inflammatory T-cells,[8] their presence
also needs to be documented.
Finally, citing a pro-circumcision tract, the authors dismiss the
complications of circumcision as having a "low incidence." In contrast,
the rate of immediate complications in the United States is between
3.1%[9] and 9%,[10] and another 5% can later expect to develop meatal
stenosis,[11] a common cause of obstructive renal failure.[12] Although it
has never been directly measured, a higher rate of complications is
believed to follow circumcisions performed
in the developing world, where circumcision has been linked to
tuberculosis,[13] tetanus,[14] penile amputation,[15] and death.[16]
HIV transmission is heavily dependent on certain sexual behaviors, not
anatomy. The authors have not provided any new information to alter this
fact, but have taken the discussion off on a needless tangent. Although
medicalized ritualistic circumcision appears to be an easy answer,
as popularized by some Western researchers, this surgery is unproven and
does not address the core behavioral issues that have fueled this
pandemic. As a result, it will not alter the course of AIDS in Africa.
Robert S. Van Howe, MD
Minocqua, Wisconsin USA
Christopher J. Cold, MD
Marshfield, Wisconsin USA
Michelle R. Storms, MD
Hazelhurst, Wisconsin USA
1. Szabo R, Short RV. How does male circumcision protect against HIV
infection? BMJ 2000; 320:
1592-4.
2. Greenland S. Quantitative methods in the review of epidemiological
literature. Epidemiol Rev 1987; 9: 1-30.
3. Hedge LV, Olkin I. Vote-counting methods in research synthesis.
Psychol Bull 1980; 88: 359-69.
4. Van Howe RS. Circumcision and HIV infection: review of the
literature and meta-analysis. Int J STD AIDS 1999; 10: 8-16.
5. O'Farrell N, Egger M. Circumcision in men and the prevention of
HIV infection: a "meta-analysis" revisited. Int J STD AIDS 2000; 11: 137-
42.
6. Hussain LA, Lehner T. Comparative investigation of Langerhans'
cells and potential receptors for HIV in oral, genitourinary and rectal
epithelia. Immunol 1995; 85: 475-84.
7. Weiss GN, Sanders M, Westbrook KC. The distribution and density of
Langerhans cells in the human prepuce: site of a diminished immune
response? Isr J Med Sci 1993; 29: 42-3.
8. Pope M, Frankel SS, Mascola JR, Trkola A, Isdell F, Birx DL, Burke
DS, Ho DD, Moore JP. Human immunodeficiency virus type 1 strains of
subtypes B and E replicate in cutaneous
dendritic cell-T-cell mixtures without displaying subtype-specific
tropism. J Virol 1997; 71: 8001-7.
9. O'Brien TR, Calle EE, Poole WK. Incidence of neonatal circumcision
in Atlanta, 1985-1986. South Med J 1995; 88: 411-5.
10. Sutherland JM, Glueck HI, Gleser G. Hemorrhagic disease of the
newborn: breast feeding as a necessary factor in the pathogenesis. Am J
Dis Child 1967; 113: 524-33.
11. Van Howe RS. Variability in penile appearance and penile
findings: a prospective study. Br J Urol 1997; 80: 776-82.
12. Eke FU, Eke NN. Renal disorders in children: a Nigerian study.
Pediatr Nephrol 1994; 8: 383-6.
13. Annobil SH, Al-Hilfi A, Kazi T. Primary tuberculosis of the penis
in an infant. Tubercle 1990; 71: 229-30.
14. Bennett J, Schooley M, Traverso H, Agha SB, Boring J. Bundling, a
newly identified risk factor for neonatal tetanus: implications for global
control. Int J Epidemiol 1996; 25: 879-84.
15. Özdemir E. Significantly increased complication risks with mass
circumcisions. Br J Urol 1997; 80: 136-9.
16. Phillips K, Ruttman T, Viljoen J. Flying doctors, saving costs. S
Afr Med J 1996; 86: 1557-8.
Rapid Response:
A little bit of science wouldn't have gone amiss
To the Editor - We read with interest the opinion piece by Szabo and
Short.[1]
While a number of studies suggest an association between the foreskin and
HIV infection, a simple tallying of studies is both unscientific and
misleading.[2,3] Systematic review using meta-analysis has demonstrated a
significant degree of between-study heterogeneity, which calls into
question the validity of the summary results. Analysis suggests that men
who engage in high-risk behaviors may be placed at further risk by having
a foreskin, but in the general population circumcision status is not a
significant risk factor.[4,5] Based on the number of factors that
influence sexual behavior and the susceptibility to HIV, it is
irresponsible to focus blame on normal anatomy.
The authors report finding Langerhans cells in the preputial mucosa. This
is nothing new: all mucosal tissues have Langerhans cells. The authors
failed to report the concentration of these cells in comparison to other
mucosal tissues, their concentration in the glans, the foreskin
remnant and circumcision scar in circumcised men, the presence of
associated T-cell infiltration, and how their findings in elderly cadavers
correlate to sexually active 20- to 30-year-old men in Africa. The authors
presumptively state "the inner surface of the foreskin ... and the
frenulum ... must be regarded as the most probable sites for viral entry
of primary HIV infections in men;" however, without quantitative
comparative data their statements are
pure speculation.
To date, the only reports of preputial Langerhans cells have been in
specimens from neonates[6,7] and elderly cadavers. If normal genital
mucosa is at risk, the concentration of
Langerhans cells in these tissues is essential information in determining
which normal genital tissue needs to be removed. We need to know the
concentration in healthy men, men with multiple sexual partners, men with
genital infections, men with HIV, and men of differing races and ages
before any recommendations can be made. Because the infectivity of
Langerhans cells may be linked to inflammatory T-cells,[8] their presence
also needs to be documented.
Finally, citing a pro-circumcision tract, the authors dismiss the
complications of circumcision as having a "low incidence." In contrast,
the rate of immediate complications in the United States is between
3.1%[9] and 9%,[10] and another 5% can later expect to develop meatal
stenosis,[11] a common cause of obstructive renal failure.[12] Although it
has never been directly measured, a higher rate of complications is
believed to follow circumcisions performed
in the developing world, where circumcision has been linked to
tuberculosis,[13] tetanus,[14] penile amputation,[15] and death.[16]
HIV transmission is heavily dependent on certain sexual behaviors, not
anatomy. The authors have not provided any new information to alter this
fact, but have taken the discussion off on a needless tangent. Although
medicalized ritualistic circumcision appears to be an easy answer,
as popularized by some Western researchers, this surgery is unproven and
does not address the core behavioral issues that have fueled this
pandemic. As a result, it will not alter the course of AIDS in Africa.
Robert S. Van Howe, MD
Minocqua, Wisconsin USA
Christopher J. Cold, MD
Marshfield, Wisconsin USA
Michelle R. Storms, MD
Hazelhurst, Wisconsin USA
1. Szabo R, Short RV. How does male circumcision protect against HIV
infection? BMJ 2000; 320:
1592-4.
2. Greenland S. Quantitative methods in the review of epidemiological
literature. Epidemiol Rev 1987; 9: 1-30.
3. Hedge LV, Olkin I. Vote-counting methods in research synthesis.
Psychol Bull 1980; 88: 359-69.
4. Van Howe RS. Circumcision and HIV infection: review of the
literature and meta-analysis. Int J STD AIDS 1999; 10: 8-16.
5. O'Farrell N, Egger M. Circumcision in men and the prevention of
HIV infection: a "meta-analysis" revisited. Int J STD AIDS 2000; 11: 137-
42.
6. Hussain LA, Lehner T. Comparative investigation of Langerhans'
cells and potential receptors for HIV in oral, genitourinary and rectal
epithelia. Immunol 1995; 85: 475-84.
7. Weiss GN, Sanders M, Westbrook KC. The distribution and density of
Langerhans cells in the human prepuce: site of a diminished immune
response? Isr J Med Sci 1993; 29: 42-3.
8. Pope M, Frankel SS, Mascola JR, Trkola A, Isdell F, Birx DL, Burke
DS, Ho DD, Moore JP. Human immunodeficiency virus type 1 strains of
subtypes B and E replicate in cutaneous
dendritic cell-T-cell mixtures without displaying subtype-specific
tropism. J Virol 1997; 71: 8001-7.
9. O'Brien TR, Calle EE, Poole WK. Incidence of neonatal circumcision
in Atlanta, 1985-1986. South Med J 1995; 88: 411-5.
10. Sutherland JM, Glueck HI, Gleser G. Hemorrhagic disease of the
newborn: breast feeding as a necessary factor in the pathogenesis. Am J
Dis Child 1967; 113: 524-33.
11. Van Howe RS. Variability in penile appearance and penile
findings: a prospective study. Br J Urol 1997; 80: 776-82.
12. Eke FU, Eke NN. Renal disorders in children: a Nigerian study.
Pediatr Nephrol 1994; 8: 383-6.
13. Annobil SH, Al-Hilfi A, Kazi T. Primary tuberculosis of the penis
in an infant. Tubercle 1990; 71: 229-30.
14. Bennett J, Schooley M, Traverso H, Agha SB, Boring J. Bundling, a
newly identified risk factor for neonatal tetanus: implications for global
control. Int J Epidemiol 1996; 25: 879-84.
15. Özdemir E. Significantly increased complication risks with mass
circumcisions. Br J Urol 1997; 80: 136-9.
16. Phillips K, Ruttman T, Viljoen J. Flying doctors, saving costs. S
Afr Med J 1996; 86: 1557-8.
Competing interests: No competing interests