Lack of keratin overlaying inner foreskin may explain lower HIV infection rates in circumcised men

McCoombe and colleagues from University of Melbourne presented results of a study designed to determine where HIV enters the penis, hoping to understand the reported lower incidence of circumcised men in many African countries.

They studied the distribution of target cells in the glans penis, frenulum, foreskin and urethral meatus from five uncircumcised penises obtained at autopsy and measured the thickness of the overlying layer of keratin. Keratin potentially prevents HIV gaining access to these penile receptors.

Langerhans cells, dendritic cells, macrophages and T-cells and keratin thickness were studied using histochemical staining techniques and microscopy.

HIV target cells expressing CD4 and CCR5 were found in the inner and outer foreskin, frenulum and glans penis, but at lower levels in the urethral meatus and penile urethra. Dendritic cells, macrophages and T cells expressing these receptors were observed in high densities in the dermis of all regions of the penis except the urethra. HIV susceptible Langerhans cells in the inner foreskin and frenulum were closer to the epithelial surface, but less frequent than in the outer foreskin and glans.

There was little if any protective covering of keratin overlying the inner foreskin and frenulum (Langerhans cells were within 4.5um of the epithelial surface), in contrast to the glans penis and outer foreskin which were heavily keratinized and (rarely coming with 20um of the epithelial surface), thus protecting them from viral entry.

The study concluded that HIV is likely to enter the penis of uncircumcised men via superficial Langerhans cells on the inner aspect of the foreskin and frenulum since these sites are not keratinised. These two area are also highly vascular and most prone to trauma. The major protective effect of male circumcision can best be explained by the removal of most HIV receptor sites in the foreskin and frenulum.

McCoombe SG, Cameron PU, Short RV – How HIV enters the human penis. XV Intl AIDS Conference, Bangkok. Abstract MoPeA3048.