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Episomal and integrated human papillomavirus type 16 loads and anal intraepithelial neoplasia in HIV-seropositive men

Alvarez, Jennifera,b; Pokomandy, Alexandra DEc,d; Rouleau, Daniellea,b; Ghattas, Georged,e; Vézina, Sylvief; Coté, Pierreg; Allaire, Guya; Hadjeres, Rachida; Franco, Eduardo Lc; Coutlée, Françoisa,b,c; for the HIPVIRG Study Group

doi: 10.1097/QAD.0b013e32833db9ea
Clinical Science

Objectives: 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).

Study design: 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.

Conclusion: High episomal HPV-16 load but not HPV-16 integration load measured by real-time PCR was associated with AIN-2,3.

aDépartements de Microbiologie et Infectiologie, Pathologie, et Laboratoire de Virologie Moléculaire, Centre Hospitalier de l'Université de Montréal, Canada

bDépartements de Microbiologie et Immunologie, Université de Montréal, Canada

cDivision of Cancer Epidemiology, McGill University, Canada

dDepartment of Medicine and Immunodeficiency Clinic, McGill University Health Center, Canada

eDepartment of Medicine, McGill University, Canada

fClinique Médicale l'Actuel, Canada

gClinique Médicale du Quartier Latin, Montreal, Quebec, Canada.

*Members of the HIPVIRG Study group are listed in the Acknowledgements.

Received 30 April, 2010

Revised 20 June, 2010

Accepted 29 June, 2010

Correspondence to François Coutlée, Hôpital Notre-Dame du Centre Hospitalier de l'Université de Montréal, 1560 Sherbrooke est, Montreal, QC H2L 4M1, Canada. Tel: +1 514 890 8000/25162; fax: +1 514 412 7512; e-mail:

© 2010 Lippincott Williams & Wilkins, Inc.