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ItemCharacterisation of the remnant foreskin: implications for HIV transmission in circumcised menHallamore, Sandra Leigh ( 2010)Human Immunodeficiency Virus (HIV) prevention remains one of the world’s top public health and development priorities, and male circumcision is the only biomedical intervention that has achieved level 1 scientific evidence for effectiveness in HIV prevention. Three randomised controlled trials have provided strong evidence that adult male circumcision confers significant protection against HIV infection, with a reduction in the relative risk of at least fifty percent. During surgical circumcision, a sleeve of preputial skin is removed and a cuff of skin around the base of the glans penis remains, forming the remnant foreskin. It is thought that the protective affect of circumcision can be attributable to the surgical removal of the inner foreskin epithelium, the main entry site of HIV into the penis. Current accepted wisdom is that the inner foreskin epithelium is abundantly supplied with HIV-1 target cells, is poorly keratinised, at risk of microscopic tears, exposed to vaginal secretions during intercourse, has a higher degree of susceptibility to HIV infection when compared to the outer foreskin, and provides a moist environment that might sustain the viability of pathogens. The aim of this study was to characterise the remnant foreskin (R), in comparison to the penile shaft skin (S) and the inner foreskin (I), and determine its role in the transmission of HIV. Tissue biopsies were obtained from the remnant foreskin and penile shaft skin of 10 circumcised men undergoing elective vasectomy and from the inner foreskin of 10 uncircumcised men undergoing elective circumcision. Biopsies were stained for Langerhans’ cells and keratin, and the number of Langerhans’ cells/mm2 and the thickness of the epithelium and stratum corneum was measured at each site. This study has shown that what was previously accepted wisdom regarding the keratin thickness of the inner foreskin is incorrect. Instead, our results revealed no significant difference in epithelial (RvS: p=0.38; IvS: p=0.53; RvI: p=0.82) or keratin (RvS: p=0.32; IvS: p=0.15; RvI: p=0.66) thickness between the three sites. In keeping with current evidence, we found that the inner foreskin has a high density of Langerhans’ cells. We found that the remnant foreskin has a significantly smaller amount of Langerhans’ cell within its epithelial, in comparison to both the penile shaft skin and the inner foreskin. In fact, relative to the inner foreskin, there is an astonishing scarcity of Langerhans’ cells in the remnant foreskin. There was significantly fewer Langerhans’ cells in the remnant foreskin compared to the inner foreskin (p=0.00001) and penile shaft skin (p<0.01), and significantly more Langerhans’ cells in the inner foreskin than the penile shaft skin (p<0.02). We believe that the reduced transmission of HIV seen in circumcised men is not because of a difference in keratin thickness between the inner foreskin and other penile skin, as has been previously accepted wisdom, but could be due to the surgical removal of HIV-1 target cells (Langerhans’ cells) in the inner foreskin and the subsequent development of the remnant foreskin, a tissue with a remarkable scarcity of Langerhans’ cells.