'Straight cuts' and HIV prevention: translational research on conceptual, methodological and scientific challenges in Papua New Guinea

This thesis presents data on four separate areas related to male circumcision (MC) and preventing human immunodeficiency virus (HIV) in Papua New Guinea (PNG). First, this thesis examines the literature related to MC, with a specific focus on its protective mechanisms. This systematic review of MC's different proposed protective mechanisms indicated that several mechanisms are involved in explaining the total of 60% protection against HIV demonstrated by MC, as indicated by three large randomised clinical trials. Second, this thesis measures the proportion of surface area of the foreskin on an erect status penis, and compares this with the total exposed surface area of the penis encountering sexual fluids during sexual intercourse. The results demonstrate that the exposed surface area of the foreskin represents only 48.4% (± 9.5) of the total exposed areas of the erect penis encountering sexual secretions. These results indicate the importance of factors other than loss of surface area of the foreskin in terms of the protection offered by MC. This provides room for theories on the potential protection provided by the 'straight cut' foreskin cuttings prevalent in PNG. Third, this thesis assesses the reliability of self-reporting MC status among men in PNG. This is measured by comparing men's self-reported MC status and investigators' classification of MC status of the participants' genital photographs. Using a three-category classification, there was 90.6% (201/222) agreement between the self-reported MC status and investigator classification (κ value: 0.805). Given the great variety of foreskin cutting practices and appearances, feasible explanations could be suggested for the two-thirds (13/21) of the discordant results. Thus, this study demonstrates a high level of agreement between self-reporting and investigator assessment of MC status in PNG, which suggests that self-reporting of MC status is highly reliable among men in PNG. Finally, Phase 1 of the study—titled '"Straight Cuts" and HIV Prevention: The Immunohistological Correlates of Dorsal Slit Foreskin Cuttings'—was completed at Pacific Adventist University of Papua New Guinea. Phase 1 focused on the feasibility of conducting a complex immunohistological study in resource-limited PNG. During this study, the conceptual, methodological and scientific challenges (and opportunities) of conducting such a study were successfully assessed. In addition to generating valuable data on changes in three histological features (the keratin layer, rete pegs and supra-papillary ridges) of dorsal slit (or 'straight cut') foreskins, this study proved that conducting such a study in PNG is feasible and effective. The scientific findings of Phase 1 of the study, while not conclusive, indicated a positive relationship between 'straight cuts' and HIV prevention. The results for keratin thickness demonstrated that the outer foreskin is thicker than the inner foreskin, which aligns with the findings of other prominent studies. For the two other histological features—the rete peg length and supra-papillary length, which were tested for the first time ever for human foreskins during this study—the results revealed that supra-papillary ridges could be an important predictor in determining the level of protection provided by dorsal slit foreskins against HIV infection. However, rete peg length needs to be measured with an improved methodology during future studies because the measurements taken during this study did not reflect the accurate effect of the rete pegs in terms of a physical barrier against HIV invasion. In conclusion, this thesis fills gaps in knowledge in three areas related to PNG's efforts to prevent heterosexual HIV transmission using MC. Epidemiological evidence is emerging to indicate a positive correlation between 'straight cuts' and HIV prevention. The findings of this study, alongside the results of Phase 2 of the study, will provide scientific evidence to determine the importance of dorsal slit foreskin cuttings in preventing heterosexual transmission of HIV to men