Human papillomavirus clearance among males is associated with HIV acquisition and increased dendritic cell density in the foreskin. J Infect Dis 2013 Jun 01;207(11):1713-22
Date
01/25/2013Pubmed ID
23345339Pubmed Central ID
PMC3636782DOI
10.1093/infdis/jit035Scopus ID
2-s2.0-84877303672 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
BACKGROUND: The association between human papillomavirus (HPV) infection and the risk of human immunodeficiency virus (HIV) seroconversion is unclear, and the genital cellular immunology has not been evaluated.
METHODS: A case-control analysis nested within a male circumcision trial was conducted. Cases consisted of 44 male HIV seroconverters, and controls were 787 males who were persistently negative for HIV. The Roche HPV Linear Array Genotype Test detected high-risk HPV (HR-HPV) and low-risk HPV (LR-HPV) genotypes. Generalized estimating equations logistic regression was used to estimate adjusted odds ratios (aORs) of HIV seroconversion. In addition, densities of CD1a(+) dendritic cells, CD4(+) T cells, and CD8(+) T cells were measured using immunohistochemistry analysis in foreskins of 79 males randomly selected from participants in the circumcision trial.
RESULTS: HR-HPV or LR-HPV acquisition was not significantly associated with HIV seroconversion, after adjustment for sexual behaviors. However, HR-HPV and LR-HPV clearance was significantly associated with HIV seroconversion (aOR, 3.25 [95% confidence interval {CI}, 1.11-9.55] and 3.18 [95% CI, 1.14-8.90], respectively). The odds of HIV seroconversion increased with increasing number of HPV genotypes cleared (P < .001, by the test for trend). The median CD1a(+) dendritic cell density in the foreskin epidermis was significantly higher among males who cleared HPV (72.0 cells/mm(2) [interquartile range {IQR}, 29.4-138.3 cells/mm(2)]), compared with males who were persistently negative for HPV (32.1 cells/mm(2) [IQR, 3.1-96.2 cells/mm(2)]; P = .047), and increased progressively with the number of HPV genotypes cleared (P = .05).
CONCLUSIONS: HPV clearance was associated with subsequent HIV seroconversion and also with increased epidermal dendritic cell density, which potentially mediates HIV seroconversion.
Author List
Tobian AA, Grabowski MK, Kigozi G, Redd AD, Eaton KP, Serwadda D, Cornish TC, Nalugoda F, Watya S, Buwembo D, Nkale J, Wawer MJ, Quinn TC, Gray RHAuthor
Toby Charles Cornish MD, PhD Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Case-Control Studies
Dendritic Cells
Female
Foreskin
HIV Infections
HIV Seropositivity
Humans
Immunohistochemistry
Male
Middle Aged
Papillomaviridae
Papillomavirus Infections
Young Adult
