Episomal and integrated human papillomavirus type 16 loads and anal intraepithelial neoplasia in HIV-seropositive men.
OBJECTIVE
To assess levels of episomal and integrated human papillomavirus type 16 (HPV-16) loads in HIV-seropositive men who have sex with men (MSM) in anal infection and to study the association between episomal and integrated HPV-16 loads and anal intraepithelial neoplasia (AIN).


METHODS
A cohort study of 247 HIV-positive MSM followed each 6 months for 3 years. Overall, 135 (54.7%) men provided 665 HPV-16-positive anal samples.


METHODS
Episomal and integrated HPV-16 loads were measured with quantitative real-time PCR assays. HPV-16 integration was confirmed in samples with a HPV-16 E6/E2 of 1.5 or more with PCR sequencing to demonstrate the presence of viral-cellular junctions.


RESULTS
The HPV-16 DNA forms in anal samples were characterized as episomal only in 627 samples (94.3%), mixed in 22 samples (3.3%) and integrated only in nine samples (1.4%). HPV-16 episomal load [odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.1-2.1], number of HPV types (OR = 1.4, 95% CI 1.1-1.8) and current smoking (OR = 4.8, 95% CI 1.3-18.6) were associated with high-grade AIN (AIN-2,3) after adjusting for age and CD4 cell counts. Integrated HPV-16 load was not associated with AIN-2,3 (OR = 0.7, 95% CI 0.4-1.1). Considering men with AIN-1 at baseline, four (16.7%) of the 24 men who progressed to AIN-2,3 had at least one sample with integrated HPV-16 DNA compared with three (23.1%) of 13 men who did not progress (OR = 0.7, 95% CI 0.2-3.8; P = 0.64). Integration was detected in similar proportions in samples from men without AIN, with AIN-1 or AIN-2,3.


CONCLUSIONS
High episomal HPV-16 load but not HPV-16 integration load measured by real-time PCR was associated with AIN-2,3.
Alvarez
Jennifer
J
Départements de Microbiologie et Infectiologie, Pathologie, et Laboratoire de Virologie Moléculaire, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
de Pokomandy
Alexandra
A
Rouleau
Danielle
D
Ghattas
George
G
Vézina
Sylvie
S
Coté
Pierre
P
Allaire
Guy
G
Hadjeres
Rachid
R
Franco
Eduardo L
EL
Coutlée
François
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D001005:Anus Neoplasms / Q000235:genetics / Q000276:immunology* / Q000821:virology; D018791:CD4 Lymphocyte Count; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015331:Cohort Studies; D004279:DNA, Viral / Q000235:genetics; D006679:HIV Seropositivity / Q000235:genetics / Q000276:immunology* / Q000821:virology; D018451:Homosexuality, Male; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D030361:Papillomavirus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D010957:Plasmids / Q000235:genetics / Q000276:immunology*; D019562:Viral Load; D055815:Young Adult
D004279:DNA, Viral