"It was striking that the trials were in very different settings, but yielded consistent results," says Ronald Gray, study leader for the Uganda trial and epidemiologist at Johns Hopkins Bloomberg School of Public Health in Baltimore. "This was the largest protective effect ever seen next to condom use," adds Sten Vermund, director of the Institute for Global Health at Vanderbilt University School of Medicine in Nashville, Tenn. But the question remained: Why?
Microscopic examination of the foreskin yielded important clues for unraveling the benefits of circumcision. Normally, the skin provides a thick protective barrier stemming from
keratin—a tough structural protein also found in hair and fingernails. But on the inner surface of the foreskin, the keratin layer is much thinner, resembling the inner lining of the mouth or eyelid more than the palm of the hand.
In uncircumcised men Langerhans cells—immune cells that are primary targets for HIV transmission—"are more richly concentrated near the surface of the foreskin," says
Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases in Bethesda, Md. Without the keratin barrier, HIV can easily access these cells in the foreskin. Following infection, Langerhans cells not only serve as reservoirs for replicating virus, but also transport the virus to nearby
lymph nodes where HIV spreads to other immune cells.
In fact, the foreskin's anatomical function actually amplifies the risks. In uncircumcised men the foreskin covers and protects the tip of the penis, paradoxically making the skin there more delicate and prone to microscopic abrasions. These tiny injuries promote inflammation, Fauci says, allowing the virus to come into closer contact with target
immune cells. The moist environment that forms under the foreskin also enhances the growth of microbes on the penis's tip,
Fauci adds, further stimulating immune responses near the skin's surface.
That's what science is about. Seek the truth through empirical testing and analyze the conditions to understand why particular results appeared.