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Title inconsistent with study results

Posted by vanhowe on 04 Dec 2007 at 20:11 GMT

To the Editor:

I read with interest the study by Mor et al. with the provocative title, “Declining Rates in Male Circumcision admist Increasing Evidence of its Public Health Benefit.”[1] Based on the title I expected to find evidence that the rates of male circumcision were declining and evidence of circumcision’s public health benefit. The article only delivered on half of its promise.

This study confirms what other studies have hinted at for the past couple decades, namely that Blacks as an ethnic group have highest rate of circumcision in the United States.[2,3] The authors fail to acknowledge that in the United States the ethnic group with the highest circumcision rate also has the highest rate of heterosexually transmitted HIV. If circumcision was truly protective against HIV infection, why has it failed in the Black population?

The study results put the brakes on the whole concept of “increasing evidence” of public health benefit from circumcision. This large study failed to find a significant association between circumcision status and HIV infection in heterosexual men (OR=0.93, 95%CI=0.83-1.05). Given the narrow confidence levels, this is robust finding. This non-significant 7% reduction is a far cry from the 50% reduction seen in Africa.[4-6] Does this mean that results of the randomized clinical trials in Africa do not apply to the United States?

The trend toward a reduction in syphilis infections must be tempered by the low rate of syphilis in the population studied. In heterosexual men the absolute risk reduction was 0.33%, which translates into number needed to treat of 303. Given that attendees of a sexually transmitted disease clinic would be at greater risk for sexually transmitted diseases, one would expect the number needed to treat to be greater for the general population. For gay/bisexual men, the absolute risk reduction was 0.05% with a number needed to treat of 2000.
The authors fail to explore why genitally intact men were significantly less likely to be gay/bisexual (OR=0.89, 95%CI=0.88-0.93). Does this mean that infant circumcision influences subsequent sexual preference?

There are a couple of things the authors inaccurately reported. When stating that circumcision was a “cost-effective procedure,” the authors cite a study that extrapolated the results of one of the randomized clinical trial in Africa to the rest of Africa.[4,7] These results do not apply to the United States and may not apply outside of a research setting in Africa.

The second study cited, is a cost-analysis, not a cost-effectiveness study, that found that circumcision, overall, was more costly than forgoing the procedure.[8] Other analyses have failed to find circumcision cost-effective in the United States.[9-12] Likewise, the authors cite a case-series to support the contention that circumcision lowers the risk of penile cancer,[13] while two recent case-controlled studies have found that when controlled for phimosis, circumcision status has not significantly associated with the risk for penile cancer.[14,15]
Finally, the authors state, as though it were fact, that the “foreskin, after exposure during erection, provides a warm, most and supportive environment for infectious agents possibly prolonging those pathogens’ survival.” This statement should be properly identified as unsubstantiated speculation since there is no scientific evidence to support it. Instead the authors cite a study that did not address this issue, but rather found that circumcised men in Botswana were at great risk for genital discharge syndrome.[16]
What is most troubling is that the submission made it through the review process without it being noticed that the results of the study contradict the conclusion in the abstract and the title of the article. This begs the question, why would the authors call for a reconsideration of national male circumcision policy when their large study failed to find any benefit from the procedure?

Robert S. Van Howe, MD, MS, FAAP
Department of Pediatrics
Michigan State University College of Human Medicine
Marquette, Michigan USA

References:
1. Mor Z, Kent CK, Kohn RP, Klausner JD (2007) Declining rates in male circumcision amidst increasing evidence of its public health benefit. PLoS ONE 2(9): e861.
2. Mansfield CJ, Hueston WJ, Rudy M (1995) Neonatal circumcision: associated factors and length of hospital stay. J Fam Pract 41: 370-376.
3. O'Brien TR, Calle EE, Poole WK (1995) Incidence of neonatal circumcision in Atlanta, 1985-1986. South Med J 88: 411-415.
4. Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A (2005) Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: The ANRS 1265 Trial. PLoS Med 2(11): e298.
5. Bailey RC, Moses S, Parker CB, Agot K, Krieger JN, Williams CFM, Campbell RT, Ndinya-Achola JO (2007) Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet 369: 643-656.
6. Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S, Nalugoda F, Kiwanuka N, Moulton LH, Chaudhary MA, Chen MZ, Sewankambo NK, Wabwire-Mangen F, Bacon MC, Williams CFM, Opendi P, Reynolds SJ, Laeyendecker O, Quinn TC, Wawer MJ (2007) Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet 369: 657-666.
7. Kahn JG, Marseille E, Auvert B (2006) Cost-effectiveness of male circumcision for HIV prevention in a South African setting. PLoS Med 3(12); e517.
8. Schoen EJ, Colby CJ, To TT (2006) Cost analysis of neonatal circumcision a large health maintenance organization. J Urol 175: 1111-1115.
9. Ganiats TG, Humphrey JB, Taras HL, Kaplan RM (1991) Routine neonatal circumcision: a cost-utility analysis. Med Decis Making 11: 282-293.
10. Lawler FH, Bisonni RS, Holtgrave DR (1991) Circumcision: a decision analysis of its medical value. Fam Med 23: 587-593.
11. Chessare JB (199) Circumcision: is the risk of urinary tract infection really the pivotal issue? Clin Pediatr Phila 31: 100-104.
12. Van Howe RS (2004) A cost-utility analysis of neonatal circumcision. Med Decis Making 24: 584-601.
13. Schoen EJ, Oehrli M, Colby CJ, Machin G (2000) The highly protective effect of newborn circumcision against invasive penile cancer. Pediatrics 105(3): e36.
14. Tseng HF, Morgenstern H, Mack T, Peters RK (2001) Risk factors for penile cancer: results of a population-based case-control study in Los Angeles County (United States). Cancer Causes Control 12: 267-277.
15. Daling JR, Madeleine MM, Johnson LG, Schwartz SM, Shera KA, Wurscher MA, Carter JJ, Porter PL, Galloway DA, McDougall JK, Krieger JN (2005) Penile cancer: Importance of circumcision, human papillomavirus and smoking in in situ and invasive disease. Int J Cancer 116: 606-616.
16. Langeni T (2005) Male circumcision and sexually transmitted infections in Botswana. J Biosoc Sci 37: 75-88.

RE: Title inconsistent with study results

Hugh_Young replied to vanhowe on 11 Dec 2007 at 00:48 GMT

Mor et al.[1] say “There was a trend towards a protective effect of circumcision for syphilis infection in heterosexual HIV-uninfected men and in a lesser extent in HIV-infected men.”

In fact, Mor et al.’s data shows no such trend. The ratios of the prevalence of circumcision (syphilis : no syphilis) are in all cases less than or equal to 1:1 -
Heterosexual: HIV- 0.92:1 HIV+ 0.85:1
Gay/Bisexual HIV- 0.98:1 HIV+ 1.00:1
None of the ratios is statistically significant.
Likewise for HIV, Mor et al.’s data shows prevalence of circumcision ratios (HIV+ : HIV-) in all but one case, more than 1:1 -
Heterosexual Syphilis 0.94:1 No Syphilis 1.02:1
Gay/Bisexual Syphilis 1.04:1 No Syphilis 1.01:1
In no class does the difference reach statistical significance. (And in the first class - because only six of the heterosexual men with HIV were non-circumcised - if one more HIV+ man had been circumcised, that ratio would also have been greater than 1:1.)

The discussion of any proposed mechanism for a greater susceptibility of uncircumcised men to HIV or syphilis is therefore irrelevant when no such greater susceptibility is evident. (If this paper is intended rather to be a review of the evidence concerning circumcision and HIV, it should cite and discuss some of the other papers that show no such connection. [2] [3][4][5][6]])

The paper does have some findings of interest. Why should gay and bisexual men be more likely to be circumcised than heterosexual men? The relationship is unlikely to be causal in either direction. Why did circumcised men pay more clinic visits than non-circumcised men? Did their STDs give them more trouble? There are also problems with the figures. According to its Table 1 there were 15,515 non-circumcised men, while according to its Table 2 non-circumcised men paid only 14,409 visits to the clinic.

The conclusion “a reconsideration of national male circumcision policy is needed to respond to current trends” may have a meaning its authors did not intend. Perhaps the time has come for bodies such as the AAP to recommend that neonatal circumcision should not be performed.


Hugh Young
Independent researcher.

References:

1. Mor Z, Kent CK, Kohn RP, Klausner JD (2007) Declining Rates in Male Circumcision amidst Increasing Evidence of its Public Health Benefit. PLoS ONE 2(9): e861. doi:10.1371/journal.pone.0000861

2. Thomas A G, Bakhireva L N, Brodine S K, Shaffer R A Prevalence of male circumcision and its association with HIV and sexually transmitted infections in a U.S. navy population Int Conf AIDS. 2004 Jul 11-16; 15: abstract no. TuPeC4861.

3. Grulich A E, Hendry O, Clark E, Kippax S, Kaldor J M Circumcision and male-to-male sexual transmission of HIV. AIDS 2001 Jun 15;15(9):1188-1189.

4. Auvert B, Ballard R, Campbell C, Caraël M, Carton M, Fehler G, Gouws E, MacPhail C, Taljaard D, Van Dam J, Williams B, HIV infection among youth in a South African mining town is associated with herpes simplex virus-2 seropositivity and sexual behaviour. AIDS. 2001 May 4;15(7):931-4.

5. HIV and circumcision in South Africa
C.A. Connolly, O. Shisana, L. Simbayi, M. Colvin.
Poster at the XV AIDS Conference in Bangkok [MoPeC3491]