In their response to our study, Gray et al. question our conclusion that there is no significant difference between the keratin thickness of the inner and outer foreskin keratin layer [1,2]. However, their arguments are not supported by any quantitative published data or scientific references. Male circumcision has the potential to play an important role in HIV prevention and understanding its mechanism is critical. Great interest in this topic has unfortunately also led to a large amount of erroneous information. Dr Morris, one of the ‘letter to the editor’ authors, states on his circumcision website that the inner foreskin ‘resembles other mucosal epithelia such as constitute the cervix, nasal passages and rectum’ . This statement is incorrect: the inner foreskin is composed of stratified squamous epithelium, not the simple columnar epithelium observed in the cervix and rectum [4–6]. This type of misinformation and assumption must be replaced by evidence and data such as what we have provided in our detailed analysis of the foreskin keratin layers.
Gray et al. argue that our use of adult foreskins from men undergoing elective circumcision may be problematic because of preexisting medical conditions. The published work of others argues against this view: a report by Qin et al.  using foreskins from a cohort of 30 prepubescent boys and 20 young adult men with no history of sexually transmitted infections found that the outer foreskin was only 3 μm thinner than the inner foreskin. This similar result in an independent study suggests that our findings were not marred by previous inflammatory conditions. In fact, Dr Bailey himself authored a qualitative report of foreskin keratinization that used specimens obtained from donors with ‘phimosis, with or without balanitis, adhesions …’ . If such donated tissue is adequate for his work, then it must also be appropriate for ours.
Their second point is also invalid. We sampled more than ‘one histological section … per participant.’ This was necessary because of considerable intra-individual heterogeneity; multiple measurements were taken on three separate sections each of inner and outer donor foreskin. In addition, to compare different fixing and staining techniques, we randomly selected samples from which six separate sections of inner and outer foreskin were measured. This demonstrates that our sampling method was quite extensive.
Finally, the authors of the reply suggest that ‘naked eye examination’ of the foreskin reveals ‘a qualitative difference in the appearance of the inner surface mucosa’. We do not think that it is possible to determine the thickness of a keratin layer by ‘naked eye examination’. On the contrary, our quantitative analyses with high-resolution epifluorescent microscopy showed that the measured keratin thickness of the inner and outer foreskin was very similar.
We agree that this is an important subject and that further investigation is needed. Drs Gray and Bailey have access to many of the samples that they describe as ideal (‘from men receiving circumcision for personal choice’) and they have ample opportunity to analyze the keratin thickness in various aspects of the inner foreskin as they recommend. However, these studies have not yet been undertaken. For the field to move forward, this issue must be resolved. We would be delighted to assist in the analysis of healthy donor samples using our quantitative methods. We emphasize that these studies should be done in a double-blinded fashion to ensure that no bias influences the outcome of the study.
We appreciate the desire to advance this previously under-studied matter and welcome further suggestions to improve the science in this field.
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