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. 2012;7(7):e41271.
doi: 10.1371/journal.pone.0041271. Epub 2012 Jul 18.

No Difference in Keratin Thickness Between Inner and Outer Foreskins From Elective Male Circumcisions in Rakai, Uganda

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Free PMC article

No Difference in Keratin Thickness Between Inner and Outer Foreskins From Elective Male Circumcisions in Rakai, Uganda

Minh H Dinh et al. PLoS One. .
Free PMC article

Abstract

It has been hypothesized that increased HIV acquisition in uncircumcised men may relate to a more thinly keratinized inner foreskin. However, published data are contradictory and potentially confounded by medical indications for circumcision. We tested the hypothesis that the inner foreskin was more thinly keratinized than the outer foreskin using tissues from 19 healthy, HIV-uninfected men undergoing routine prophylactic circumcision in Rakai, Uganda. Sections from 3 foreskin anatomic sites (inner, outer, and frenar band) were snap-frozen separately. Two independent laboratories each separately stained, imaged, and measured keratin thicknesses in a blinded fashion. There was no significant difference in keratin thickness between the inner (mean = 14.67±7.48 µm) and outer (mean = 13.30±8.49 µm) foreskin, or between the inner foreskin and the frenar band (mean = 16.91±12.42 µm). While the frenar band showed the greatest intra-individual heterogeneity in keratin thickness, there was substantial inter-individual variation seen in all regions. Measurements made by the two laboratories showed high correlation (r = 0.741, 95% CI, 0.533-0.864). We conclude that, despite inter- and intra-individual variability, keratin thickness was similar in the inner and outer foreskin of healthy Ugandan men, and that reduced keratin thickness is not likely to make the inner foreskin more susceptible to HIV acquisition.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Mean foreskin keratin thicknesses by donor and region.
(A) Representative image of intra-individual variation in keratin thickness (outer foreskin). White ‘⁁⁁⁁’ symbols show areas of thinner keratin and white solid triangles show areas of thicker keratin. Involucrin (green), filaggrin (red), cell nuclei (blue). Inset: magnification of boxed area with only filaggrin staining (red) shown; scale depicts thickness in microns. (B) Illustration of foreskin regions examined: inner (red), frenar band (yellow), and outer (green) foreskin. Whisker and boxplots of individual keratin measurements demonstrating distribution of thicknesses. Median  =  middle line, box = 25–75th percentiles, whiskers = 5–95th percentiles, mean  =  ‘+’ symbols, outliers not shown for ease of viewing. *p<0.05, **p<0.001. (C) Correlation of mean regional measurement per donor. Each symbol represents mean thickness calculated for one donor. Light gray boxes/line = inner: frenar band ratio and dark gray circles/line = inner: outer ratios.
Figure 2
Figure 2. Cumulative foreskin keratin thicknesses by region.
(A) Whisker and boxplots of cumulative keratin thicknesses per region: inner foreskin (white), frenar band (light gray), outer foreskin (dark gray). Median  =  middle line, mean  =  ‘+’ symbol, outliers not shown for ease of viewing. (B) Representative tissue from each region stained for filaggrin (red), involucrin (green), and cell nuclei (blue). White scale bars = 50 µm.
Figure 3
Figure 3. Data obtained from two independent laboratories.
(A) Mean thicknesses recorded by laboratory 1 (black bars) and laboratory 2 (hatched bars) for 11 donors. (B) Spearman rank correlation of two laboratory measurements. Shorter line  =  correlation coefficient calculated excluding donor sample #13.

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