Gary M Clifford1, Laurent Siproudhis2, Lionel Piroth3,4, Isabelle Poizot-Martin5,6, Sylvie Radenne7, Jacques Reynes8, Anne Lesage9, Isabelle Heard10,11, Sébastien Henno12, Jean-François Fléjou13,14, Lucie Marchand15, Jean-Damien Combes1, Isabelle Etienney9. 1. International Agency for Research on Cancer, Lyon. 2. Service de Gastro-Entérologie et groupe InPhy CIC 1414, CHU Rennes, Rennes. 3. Département d'Infectiologie, CHU de Dijon. 4. INSERM CIC 1432, Université de Bourgogne, Dijon. 5. Aix Marseille University, APHM Sainte-Marguerite, service d'Immuno-Hématologie Clinique. 6. Inserm U912 (SESSTIM), Marseille. 7. Service d'Hépatologie, Hôpital de la Croix Rousse, Unité INSERM 1052, CHU Lyon, Lyon. 8. Département des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire Montpellier, Montpellier. 9. Service de Proctologie Médico-Interventionnelle, Groupe Hospitalier Diaconesses Croix-Saint-Simon. 10. Centre National de Référence des HPV, Institut Pasteur. 11. Hôpital Tenon, AP-HP, Paris. 12. Service d'Anatomie et Cytologie Pathologiques, CHU Pontchaillou, Rennes. 13. Service d'Anatomie et Cytologie Pathologiques, Hôpital Saint-Antoine, GH HUEP, AP-HP. 14. Faculté de Médecine Sorbonne Université. 15. Clinical and Therapeutic Research on HIV/AIDS, ANRS (France Recherche Nord et Sud Sida-HIV et Hépatites), Paris, France.
Abstract
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.
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.
Authors: Chunqing Lin; Jiri Slama; Paula Gonzalez; Marc T Goodman; Ningshao Xia; Aimée R Kreimer; Ting Wu; Nancy A Hessol; Yurii Shvetsov; Ana P Ortiz; Beatriz Grinsztejn; Anna-Barbara Moscicki; Isabelle Heard; María Del Refugio González Losa; Erna M Kojic; Maarten F Schim van der Loeff; Feixue Wei; Adhemar Longatto-Filho; Zizipho A Mbulawa; Joel M Palefsky; Annette H Sohn; Brenda Y Hernandez; Katina Robison; Steve Simpson; Lois J Conley; Alexandra de Pokomandy; Marianne A B van der Sande; Racheal S Dube Mandishora; Lays P B Volpini; Alessandra Pierangeli; Byron Romero; Timothy Wilkin; Silvia Franceschi; Carmen Hidalgo-Tenorio; Reshmie A Ramautarsing; Ina U Park; Fernanda K Tso; Sheela Godbole; Kathleen W M D'Hauwers; Borek Sehnal; Lynette J Menezes; Sandra A Heráclio; Gary M Clifford Journal: Lancet Infect Dis Date: 2019-06-13 Impact factor: 25.071
Authors: Rebecca G Nowak; Nicaise Ndembi; Wuese Dauda; Paul Jibrin; Søren M Bentzen; Chinedu H Nnaji; Oluwole Olaomi; Teresa M Darragh; Jonathan Madukwe; Trevor A Crowell; Stefan D Baral; William A Blattner; Manhattan E Charurat; Joel M Palefsky; Kevin J Cullen Journal: J Glob Oncol Date: 2019-07