{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T08:58:05Z","timestamp":1793177885808,"version":"4.5.0"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T00:00:00Z","timestamp":1612310400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The objective of this study in MSM living with HIV was to determine the incidence of HSIL and ASCC, related factors, and the response to treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>Data were gathered in 405 consecutive HIV-infected MSM (May 2010-December 2018) at baseline and annually on: sexual behavior, anal cytology, and HPV PCR and\/or high-resolution anoscopy results. They could choose mucosectomy with electric scalpel (from May 2010) or self-administration of 5% imiquimod 3 times weekly for 16 weeks (from November 2013). A multivariate logistic regression model was developed for \u2265HSIL-related factors using a step-wise approach to select variables, with a significance level of 0.05 for entry and 0.10 for exit, applying the Hosmer-Lemeshow test to assess the goodness of fit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The study included 405 patients with a mean age of 36.2 years; 56.7% had bachelor\u00b4s degree, and 52.8% were smokers. They had a mean of 1 (IQR 1\u20137) sexual partner in the previous 12 months, median time since HIV diagnosis of 2 years, and mean CD4 nadir of 367.9 cells\/uL; 86.7% were receiving ART, the mean CD4 level was 689.6 cells\/uL, mean CD4\/CD8 ratio was 0.77, and 85.9% of patients were undetectable. Incidence rates were 30.86\/1,000 patient-years for \u2265high squamous intraepithelial lesion (HSIL) and 81.22\/100,000 for anal squamous cell carcinoma (ASCC). The \u2265HSIL incidence significantly decreased from 42.9% (9\/21) in 2010 to 4.1% (10\/254) in 2018 (p = 0.034). \u2265HSIL risk factors were infection with HPV 11 (OR 3.81; 95%CI 1.76\u20138.24), HPV 16 (OR 2.69, 95%CI 1.22\u20135.99), HPV 18 (OR 2.73, 95%CI 1.01\u20137.36), HPV 53 (OR 2.97, 95%CI 1.002\u20138.79); HPV 61 (OR 11.88, 95%CI 3.67\u201338.53); HPV 68 (OR 2.44, CI 95% 1.03\u20135.8); low CD4 nadir (OR1.002; 95%CI 1\u20131.004) and history of AIDS (OR 2.373, CI 95% 1.009\u20135.577). Among HSIL-positive patients, the response rate was higher after imiquimod than after surgical excision (96.7% vs 73.3%, p = 0.009) and there were fewer re-treatments (2.7% vs 23.4%, p = 0.02) and adverse events (2.7% vs 100%, p = 0.046); none developed ASCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HSIL screening and treatment programs reduce the incidence of HSIL, which is related to chronic HPV infection and poor immunological status. Self-administration of 5% imiquimod as first-line treatment of HSIL is more effective than surgery in HIV+ MSM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0245870","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T14:01:48Z","timestamp":1612360908000},"page":"e0245870","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Risk factors for \u2265high-grade anal intraepithelial lesions in MSM living with HIV and the response to topical and surgical treatments"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6394-5728","authenticated-orcid":true,"given":"Carmen","family":"Hidalgo-Tenorio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen Maria","family":"Garc\u00eda-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Pasquau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Omar-Mohamed-Balgahata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"L\u00f3pez-Ruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"L\u00f3pez-Hidalgo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3n","family":"Gil-Anguita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,2,3]]},"reference":[{"key":"pone.0245870.ref001","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1097\/QAI.0000000000001033","article-title":"Non-AIDS-Defining Cancer Mortality: Emerging Patterns in the Late HAART Era","volume":"73","author":"A Zucchetto","year":"2016","journal-title":"J Acquir Immune Defic Syndr"},{"key":"pone.0245870.ref002","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1093\/cid\/cir1012","article-title":"Risk of anal cancer in HIV infected and HIV-uninfected individuals in North America","volume":"54","author":"MJ Silverberg","year":"2012","journal-title":"Clin Infect Dis"},{"key":"pone.0245870.ref003","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s10350-007-9154-7","article-title":"Invasive anal squamous-cell carcinoma in the HIV-positive patient: outcome in the era of highly active antiretroviral therapy","volume":"51","author":"A Wexler","year":"2008","journal-title":"Dis Colon Rectum"},{"key":"pone.0245870.ref004","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1097\/QAD.0000000000001546","article-title":"Impact of screening and antiretroviral therapy on anal cancer incidence in HIV-positive MSM","volume":"31","author":"N Blaser","year":"2017","journal-title":"AIDS"},{"key":"pone.0245870.ref005","first-page":"ciz831","article-title":"Routine screening of anal cytology in HIV-infected subjects and the impact on invasive anal cancer. A prospective cohort study","volume":"4","author":"B Revollo","year":"2019","journal-title":"Clin Infect Dis"},{"key":"pone.0245870.ref006","doi-asserted-by":"crossref","first-page":"e0224183","DOI":"10.1371\/journal.pone.0224183","article-title":"ART is key to clearing oncogenic HPV genotypes (HR-HPV) in anal mucosa of HIV-positive MSM","volume":"14","author":"C Hidalgo-Tenorio","year":"2019","journal-title":"PLoS One"},{"key":"pone.0245870.ref007","doi-asserted-by":"crossref","first-page":"e2510","DOI":"10.1002\/jia2.25110","article-title":"Evidence of synergistic relationships between HIV and Human Papillomavirus (HPV): systematic reviews and meta-analyses of longitudinal studies of HPV acquisition and clearance by HIV status, and of HIV acquisition by HPV status","volume":"21","author":"KJ Looker","year":"2018","journal-title":"Journal of the international AIDS Society"},{"key":"pone.0245870.ref008","doi-asserted-by":"crossref","first-page":"e436","DOI":"10.1016\/S2214-109X(18)30567-9","article-title":"Circumcision to prevent HIV and other sexually transmitted infections in men who have sex with men: a systematic review and meta-analysis of global data","volume":"7","author":"T Yuan","year":"2019","journal-title":"Lancet Glob Health"},{"key":"pone.0245870.ref009","first-page":"257","article-title":"Anal intraepithelial neoplasia: diagnosis, screening, and treatment","volume":"32","author":"RV Siddharthan","year":"2019","journal-title":"Ann Gastroenterol"},{"key":"pone.0245870.ref010","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1111\/j.1463-1318.2010.02258.x","article-title":"What should we do about anal condyloma and anal intraepithelial neoplasia? Results of a survey","volume":"13","author":"D Dindo","year":"2011","journal-title":"Colorectal Dis"},{"key":"pone.0245870.ref011","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1111\/hiv.12352","article-title":"The effectiveness of electrocautery ablation for the treatment of high-grade anal intraepithelial neoplasia in HIV-infected men who have sex with men","volume":"17","author":"J Burgos","year":"2016","journal-title":"HIV Med"},{"key":"pone.0245870.ref012","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1097\/DCR.0b013e318227833e","article-title":"Long-term follow-up of infrared coagulator ablation of anal high-grade dysplasia in men who have sex with men","volume":"54","author":"RN Goldstone","year":"2011","journal-title":"Dis Colon Rectum"},{"key":"pone.0245870.ref013","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1097\/QAD.0b013e32833d466c","article-title":"A double-blind, randomized controlled trial of the use of imiquimod cream for the treatment of anal canal high-grade anal intraepithelial neoplasia in HIV-positive MSM on HAART, with long-term follow-up data including the use of open-label imiquimod","volume":"24","author":"PA Fox","year":"2010","journal-title":"AIDS"},{"key":"pone.0245870.ref014","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1001\/jama.287.16.2114","article-title":"The 2001 Bethesda system: terminology for reporting results of cervical cytology","volume":"287","author":"D Solomon","year":"2002","journal-title":"JAMA"},{"key":"pone.0245870.ref015","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/LGT.0b013e31825c31dd","article-title":"The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology","volume":"16","author":"TM Darragh","year":"2012","journal-title":"J Low Genit Tract Dis"},{"key":"pone.0245870.ref016","volume-title":"Applied categorical data analysis","author":"DH Freeman","year":"1987"},{"key":"pone.0245870.ref017","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1097\/QAD.0000000000002218","article-title":"Incidence and time trends of anal cancer among people living with HIV in Australia","volume":"33","author":"F Jin","year":"2019","journal-title":"AIDS"},{"key":"pone.0245870.ref018","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1097\/QAD.0000000000001546","article-title":"Impact of screening and antiretroviral therapy on anal cancer incidence in HIV-positive MSM","volume":"31","author":"Swiss HIV Cohort Study","year":"2017","journal-title":"AIDS"},{"key":"pone.0245870.ref019","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1097\/DCR.0000000000001384","article-title":"Risk of Invasive Anal Cancer in HIV-Infected Patients with High-Grade Anal Dysplasia: A Population-Based Cohort Study","volume":"62","author":"Y Arens","year":"2019","journal-title":"Dis Colon Rectum"},{"key":"pone.0245870.ref020","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1186\/1471-2458-13-946","article-title":"The Study of the Prevention of Anal Cancer (SPANC): design and methods of a three-year prospective cohort study","volume":"13","author":"DA Machalek","year":"2013","journal-title":"BMC Public Health"},{"key":"pone.0245870.ref021","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1136\/sextrans-2015-052444","article-title":"Prolonged antiretroviral therapy is associated with fewer anal high-grade squamous intraepithelial lesions in HIV-positive MSM in a cross-sectional study","volume":"93","author":"A Libois","year":"2017","journal-title":"Sex Transm Infect"},{"key":"pone.0245870.ref022","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1097\/OLQ.0b013e31825aa764","article-title":"Use of highly active antiretroviral therapy is associated with lower prevalence of anal intraepithelial neoplastic lesions and lower prevalence of human papillomavirus in HIV-infected men who have sex with men","volume":"39","author":"EM Van Der Snoek","year":"2012","journal-title":"Sex Transm Dis"},{"key":"pone.0245870.ref023","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1097\/QAD.0000000000001639","article-title":"Risk factors for anal high-grade squamous intraepithelial lesions in HIV-positive MSM: is targeted screening possible?","volume":"31","author":"ML Siegenbeek van Heukelom","year":"2017","journal-title":"AIDS"},{"key":"pone.0245870.ref024","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1097\/OLQ.0000000000000475","article-title":"Anal Dysplasia Screening and Treatment in a Southern Human Immunodeficiency Virus Clinic","volume":"43","author":"WG Willeford","year":"2016","journal-title":"Sex Transm Dis"},{"key":"pone.0245870.ref025","first-page":"jiz623","article-title":"Study group. Incidence and clearance of anal HPV-16 and HPV-18 infection, and their determinants, among HIV-infected men who have sex with men in France","volume":"22","author":"CJ Alberts","year":"2019","journal-title":"J Infect Dis"},{"key":"pone.0245870.ref026","first-page":"377","article-title":"Retrospective analysis of alpha-human papillomavirus (HPV) types in tissue samples from anogenital dysplasias\u2014introduction of the RICH (Risk of HPV-related Carcinoma in HIV+\/- patients) score","volume":"8","author":"JA Hildebrand","year":"2019","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"pone.0245870.ref027","unstructured":"Direcci\u00f3n general de Salud P\u00fablica, Calidad e Innovaci\u00f3n. Sistema de Informaci\u00f3n sobre nuevos diagn\u00f3sticos de VIH. Regsitro Nacional de Casos de SIDA. Noviembre 2019. htt:\/\/www.mscbs.gob.es."},{"key":"pone.0245870.ref028","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1136\/sextrans-2014-051810","article-title":"Imiquimod 5% cream for five consecutive days a week in an HIV-infected observational cohort up to 32 weeks in the treatment of high-grade squamous intraepithelial lesions","volume":"91","author":"EM Van der Snoek","year":"2015","journal-title":"Sex Transm Infect"},{"key":"pone.0245870.ref029","doi-asserted-by":"crossref","first-page":"e334","DOI":"10.1111\/jdv.14895","article-title":"Imiquimod anal tampons treatment of anal intraepithelial neoplasia","volume":"32","author":"C Salas-M\u00e1rquez","year":"2018","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"pone.0245870.ref030","first-page":"257","article-title":"Anal intraepithelial neoplasia: diagnosis, screening, and treatment","volume":"32","author":"RV Siddharthan","year":"2019","journal-title":"Ann Gastroenterol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0245870","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T14:02:20Z","timestamp":1612360940000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0245870"}},"subtitle":[],"editor":[{"given":"Luca","family":"Giannella","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,2,3]]},"references-count":30,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0245870","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,3]]}}}