Sir: Robert Van Howe published in the December 2007 issue a meta-analysis of data on genital ulcerative disease (GUD) and sexually transmitted urethritis in relation to male circumcision status.¹ We have reservations about this paper, in particular regarding the citing of source data, but as well, poorly defined search terms and inclusion criteria, failure to include appropriate studies and absence of adjustment for confounding factors.

Previous statistical analyses by Van Howe relating to circumcision have been criticized.^2–4 In his latest meta-analysis, there is application of incorrect methodology and the data presented differ from the original published data that appear in the literature he cites (Table 1). The differences are in many cases significant and difficult to explain.

Van Howe’s identification of relevant papers appears insufficient. For example, four studies addressing the association of male circumcision and chancroid identified in an earlier meta-analysis⁵ (references 38 and 40–42 therein) were excluded.

Another error is that Van Howe appears to present crude measures of association between circumcision and sexually transmitted infection (STI), even though adjusted figures are available for many studies, and are more appropriate because they partially control for confounding, such as by religion or sexual behaviour. For example, Diseker et al. (Van Howe’s ref. 151) reported adjusted ORs of 1.3 and 1.6 for the association of gonorrhoea and lack of circumcision in cross-sectional and cohort analyses, respectively, but Van Howe cites the crude ORs of 1.09 and 1.24.

The study population used in each paper also needs careful consideration. Around half of the studies included in Van Howe’s Table 1 took place among STI clinic attenders.¹ STI populations have inherent selection biases,⁵ as Van Howe recognizes. He does not, however, note that the comparison group are likely to be men with another STI, which might itself be associated with circumcision status. This would result in an under-estimation of any true protective effect of circumcision. Similarly, Van Howe’s adjustment of raw data from two studies (his refs 32 and 361) would have introduced selection bias for the same reason. For example, in Wilson’s study (Van Howe’s ref 36), lack of circumcision was associated with increased risk for every STI that was included. Van Howe rejected Wilson’s original control group and instead chose to compare men with a particular STI with all men in the STI population.

Van Howe uses the keyword ‘circumcision’, which will fail to identify those papers that examined circumcision as one of the many potential risk factors for STI, but that did not include ‘circumcision’ as a keyword, or in the title or abstract. Further, this search strategy could introduce ascertainment bias, since the keyword ‘circumcision’ is more likely to be used for studies that find associations.

Finally, Van Howe’s definition of GUD is not fully clear. Did the analyses of GUD include studies with specific aetiologies of GUD (e.g. chancroid, syphilis and genital herpes)? If so, why are the studies of chancroid not included with GUD? We are left to conclude that by ‘GUD’ he actually means GUD of unknown aetiology, which is a relatively weak definition.

To illustrate the effect of Van Howe’s errors, we consider non-specific urethritis (NSU). Table 2 shows all 10 NSU studies used by Van Howe and lists the source data alongside his cited data. We then provide the outcome of performing a meta-analysis on the correct source data (Table 2). Our analysis thereby shows that NSU is not associated with circumcision status in these data, contrary to Van Howe’s assertion.

In conclusion, we find Van Howe’s meta-analysis to be based on incorrect data and to be flawed methodologically. We show as an example that at least one of his results is incorrect as a result.

J H Waskett*, B J Morris† and H A Weiss‡
*Circumcision Independent Reference and Commentary Service, 157 Stand Lane, Radcliffe, Manchester M26 1JR, UK;
†School of Medical Sciences, University of Sydney, Sydney, NSW 2006, Australia;
‡Infectious Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
Correspondence to: J H Waskett
Email: jake@waskett.org
DOI: 10.1258/ijsa.2009.008126

References

1. Van Howe RS. Genital ulcerative disease and sexually transmitted urethritis and circumcision: a meta-analysis. Int J STD AIDS 2007;18:799–809
2. Moses S, Nagelkerke NJD, Blanchard JF. Commentary: analysis of the scientific literature on male circumcision and risk for HIV infection. Int J STD AIDS 1999;10:626–8
3. O’Farrell N, Egger M. Commentary: Circumcision in men and the prevention of HIV infection: a ‘meta-analysis’ revisited. Int J STD AIDS 2000;11:137–42
4. Castellsague X, Albero G, Cleries R, Bosch FX. HPV and circumcision: a biased, inaccurate and misleading meta-analysis. J Infect 2007;55:91–3
5. Weiss HA, Thomas SL, Munabi SK, Hayes RJ. Male circumcision and risk of syphilis, chancroid, and genital herpes: a systematic review and meta-analysis. Sex Transm Infect 2006;82:101–9