Topical oestrogen induces keratinisation of human inner foreskin whilst Langerhans cell distribution remains unaffected – implications for HIV prevention. Introduction Human Immunodeficiency Virus is a leading cause of mortality worldwide. Male Circumcision (MC) has been shown to reduce HIV incidence by 50-60% and is equivalent to a high efficacy vaccine 1,2,3. Current knowledge suggest that Langerhans’ cells (LC) are the first cells to come into contact with HIV via CD1a, an HIV-coreceptor involved in the displaying of antigens for T cell responses. It is thought that the increased risk of HIV transmission in uncircumcised men is attributable to an inner foreskin that is rich in HIV target cells, has a thinner, unkeratinised inner preputial mucosa, is at risk of microtears, especially at the frenulum, and is more susceptible to Genital Ulcer Disease and STIs 4,5,6. Post-menopausal women are at a four to eightfold increased chance of HIV infection, secondary to vaginal atrophy. Experiments in ovariectomised Rhesus monkeys found that intravaginal topical oestrogen increased keratinisation of the mucosa, and prevented SIV infection through the vaginal epithelium 7. Conclusions The reduced transmission of HIV seen in circumcised men 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. Topical oestrogen to the inner foreskin does not affect the distribution of Langerhans cells but does increase the keratin layer, which has been previously shown to effectively reduce the risk of HIV infection through the mucosa. Further studies are currently being conducted to aid in the assessment of the efficacy of this novel approach to reducing HIV infection in men. Results A HISTOLOGY IMMUNOHISTOCHEMISTRY Remnant foreskin Penile shaft Inner foreskin Anti-CD1a antibody staining immature LC Results B There was no significant difference in epithelial or keratin thickness between the inner foreskin, remnant foreskin or shaft skin in the men. There were significantly fewer Langerhans cells in the remnant foreskin compared to the inner foreskin and penile shaft skin, and significantly more Langerhans cells in the inner foreskin than the penile shaft skin. We found that topical oestrogen causes a highly significant increase in keratin thickness, however it does not significantly change the number or distribution of Langerhans cells. Aim This research aims to determine epithelial thickness and Langerhans cell distribution of the inner foreskin (I), in comparison to the remnant foreskin (R) and penile shaft skin (P), and evaluate the potential of topical oestrogen to reduce the risk of HIV infection in males through increased keratinisation of the inner foreskin. References 1. Auvert et al 2005; 2. Bailey et al 2007; 3. Gray et al 2007; 4. Donoval et al 2006; 5. McCoombe et al 2006; 6. Patterson et al 2002; 7. Smith et al Sandra Elmer 1, Melissa Low 1,2, Cheryl Bell 3, Anthony Johnson 3,4, Eugene Yeboah 3, David Webb 1, Roger Short 2, Andrew Pask 2,3, Damien Bolton 1 1Department of Urology, Austin Health, Victoria, Australia; 2Department of Zoology, University of Melbourne, Victoria, Australia; 3Department of Molecular and Cell Biology, Genetics and Genomics, University of Connecticut, Storrs, CT; 4Department of Biology, Wiley College, Marshall, TX No. 085 Posters Proudly Supported by: Methods 50 men were recruited from the urological elective surgery waiting list at the Austin Hospital, Heidelberg, Victoria, Australia. A: 10 patients were planned for elective vasectomy (previously circumcised in childhood) and biopsies of their remnant foreskin and penile shaft skin were taken at the time of surgery. B: 40 patients were planned for elective circumcision. Of these, 30 men applied oestrogen cream or placebo to their inner foreskin for a period of two weeks prior to circumcision, whilst 10 men received no treatment. Foreskin epithelial biopsies were collected both before and after treatment. The thickness of the epithelium and keratin was measured, and the number of Langerhans cells/mm2. Oestrogen Receptor Distribution