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Determinants of high-grade anal intraepithelial lesions in HIV-positive MSM

Clifford, Gary M.a; Siproudhis, Laurentb; Piroth, Lionelc,d; Poizot-Martin, Isabellee,f; Radenne, Sylvieg; Reynes, Jacquesh; Lesage, Annei; Heard, Isabellej,k; Henno, Sébastienl; Fléjou, Jean-Françoism,n; Marchand, Lucieo; Combes, Jean-Damiena; Etienney, Isabellei for the ANRS EP57 APACHES Study group

doi: 10.1097/QAD.0000000000001947
Epidemiology and Social

Objective: To assess determinants for histologically proven high-grade anal intraepithelial lesions (hHSIL) in HIV-positive men who have sex with men (MSM), a population at high-risk of HPV-related anal cancer.

Design: APACHES is a prospective study of anal HPV and related-lesions in 513 HIV-positive MSM aged at least 35 years in six centres across France.

Methods: At baseline, participants underwent high-resolution anoscopy (HRA) with biopsy of suspicious lesions, preceded by anal swabs for liquid-based cytology, p16/Ki67 immunostaining, and HPV DNA. hHSIL diagnosis was established by histopathological review panel consensus, and determinants assessed by logistic regression.

Results: Baseline hHSIL prevalence was 10.4% and did not differ significantly by age, sexual behaviour or HIV/immunodeficiency markers. hHSIL prevalence was significantly elevated in participants who smoked (ORadj = 2.6, 95% CI 1.3–5.5) or who, in concurrent anal swabs, had ASCUS/LSIL (3.6, 95% CI 1.4–9.3) or ASC-H/HSIL (22.2, 95% CI 6.8–72.6) cytologic abnormalities, p16/Ki67 dual positivity (3.4, 95% CI 1.5–7.5), or non-HPV16 HR (13.0, 95% CI 1.7–102), but most notably, HPV16 (46.3, 95% CI 6.1–355) infection. Previous diagnosis of low-grade (2.3, 95% CI 1.0–5.4) or high-grade (3.8, 95% CI 1.5–9.9) anal lesion also conveyed higher hHSIL risk. After controlling for patient-specific determinants, there remained significant centre-specific effects, most clearly in higher risk groups (HPV16-positive participants: 31.3% hHSIL in centres A–D versus 5.1% in centres E and F, P < 0.01).

Conclusion: Anal cytology and HPV16 infection are potentially useful determinants of hHSIL risk in HIV-positive MSM, but HIV/immunodeficiency-related variables appear not to be. Controlling for patient-specific hHSIL determinants highlights variability in HRA practice across diverse clinical settings and the need for better standardization of this difficult procedure.

aInternational Agency for Research on Cancer, Lyon

bService de Gastro-Entérologie et groupe InPhy CIC 1414, CHU Rennes, Rennes

cDépartement d’Infectiologie, CHU de Dijon

dINSERM CIC 1432, Université de Bourgogne, Dijon

eAix Marseille University, APHM Sainte-Marguerite, service d’Immuno-Hématologie Clinique

fInserm U912 (SESSTIM), Marseille

gService d’Hépatologie, Hôpital de la Croix Rousse, Unité INSERM 1052, CHU Lyon, Lyon

hDépartement des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire Montpellier, Montpellier

iService de Proctologie Médico-Interventionnelle, Groupe Hospitalier Diaconesses Croix-Saint-Simon

jCentre National de Référence des HPV, Institut Pasteur

kHôpital Tenon, AP-HP, Paris

lService d’Anatomie et Cytologie Pathologiques, CHU Pontchaillou, Rennes

mService d’Anatomie et Cytologie Pathologiques, Hôpital Saint-Antoine, GH HUEP, AP-HP

nFaculté de Médecine Sorbonne Université

oClinical and Therapeutic Research on HIV/AIDS, ANRS (France Recherche Nord et Sud Sida-HIV et Hépatites), Paris, France.

Correspondence to Dr Gary M. Clifford, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France. Tel: +33 472738425; fax: +33 472738345; e-mail:

Received 23 April, 2018

Revised 15 June, 2018

Accepted 18 June, 2018

Copyright © 2018 Wolters Kluwer Health, Inc.