Human papillomavirus clearance among males is associated with HIV acquisition and increased dendritic cell density in the foreskin.
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.
Department of Pathology, Johns Hopkins University, Carnegie 437, 600 N Wolfe St, Baltimore, MD 21287, USA. atobian1@jhmi.edu
Aaron A R
AA
Tobian
Mary K
MK
Grabowski
Godfrey
G
Kigozi
Andrew D
AD
Redd
Kevin P
KP
Eaton
David
D
Serwadda
Toby C
TC
Cornish
Fred
F
Nalugoda
Stephen
S
Watya
Denis
D
Buwembo
James
J
Nkale
Maria J
MJ
Wawer
Thomas C
TC
Quinn
Ronald H
RH
Gray
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D052816:Foreskin / Q000276:immunology* / Q000821:virology*; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000473:pathology; D006679:HIV Seropositivity; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D055815:Young Adult