{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T07:58:11Z","timestamp":1768031891234,"version":"3.49.0"},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00283"],"award-info":[{"award-number":["PI19\/00283"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Regional Development Fund","award":["PI19\/00283"],"award-info":[{"award-number":["PI19\/00283"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: The objectives were to evaluate the safety and immunogenicity of the nonavalent human papillomavirus (nHPV) vaccine in adult Spanish women living with HIV (WLHIV); the prevalence of anal and cervical dysplasia and nHPV vaccine genotypes in the anus and cervix; and risk factors for high-risk HPV (HR-HPV) infection in anal mucosa. Methods: In this single-center, open-arm, non-randomized clinical trial, the nHPV vaccine was administered at 0, 2, and 6 months to WLHIV enrolled between February 2020 and November 2023, measuring vaccine antibody titers pre-vaccination and at 2, 6, and 7 months after the first dose. Cervical and anal cytology and HPV PCR genotyping studies were performed. Women with abnormal cytology and\/or anal or cervical HPV infection at baseline underwent high-resolution anoscopy and\/or colposcopy. Results: A total of 122 participants were included with mean age of 49.6 years: 52.5% smoked; 10.7% had anal-genital condylomatosis; 38.5% were infected by HR-HPV in the anus and 25.4% in the cervix, most frequently HPV 16; 19.1% had anal intraepithelial neoplasia 1-(AIN1); and 3.1% had cervical intraepithelial neoplasia 1 and 2 (CIN1\/CIN2). Vaccine administration did not modify viral\u2013immunological status (CD4 [809 \u00b1 226.8 cells\/uL vs. 792.35 \u00b1 349.95; p = 0.357]) or plasma HIV load (3.38 \u00b1 4.41 vs. 1.62 \u00b1 2.55 cop\/uL [log]; p = 0.125). Anti-HPV antibodies ([IQR: 0\u20130] vs. 7.63 nm [IQR: 3.46\u201319.7]; p = 0.0001) and seroconversion rate (8.2% vs. 96.7% [p = 0.0001]) were increased at 7 versus 0 months. There were no severe vaccine-related adverse reactions; injection-site pain was reported by around half of the participants. HR-HPV infection in the anus was solely associated with a concomitant cervix infection (HR 5.027; 95% CI: 1.009\u201325.042). Conclusions: nHPV vaccine in adult WLHIV is immunogenic and safe.<\/jats:p>","DOI":"10.3390\/vaccines12080838","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T11:43:44Z","timestamp":1721907824000},"page":"838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety and Immunogenicity of the Nonavalent Human Papillomavirus Vaccine in Women Living with HIV"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6394-5728","authenticated-orcid":false,"given":"Carmen","family":"Hidalgo-Tenorio","sequence":"first","affiliation":[{"name":"Infectious Disease Unit, Hospital Universitario Virgen de las Nieves, IBS-Granada, 18012 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6768-963X","authenticated-orcid":false,"given":"Raquel","family":"Moya","sequence":"additional","affiliation":[{"name":"Internal Medicine, Complejo Hospitalario de Ja\u00e9n, 23007 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Omar","sequence":"additional","affiliation":[{"name":"Infectious Disease Unit, Complejo Hospitalario de Ja\u00e9n, 23007 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8995-8271","authenticated-orcid":false,"given":"Leopoldo","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Hospital Universitario San Cecilio, IBS-Granada, 18012 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"SamPedro","sequence":"additional","affiliation":[{"name":"Microbiology Department, Hospital Universitario Virgen de las Nieves, IBS-Granada, 18012 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9106-2028","authenticated-orcid":false,"given":"Javier","family":"L\u00f3pez-Hidalgo","sequence":"additional","affiliation":[{"name":"Pathology Department, Hospital Universitario Virgen de las Nieves, IBS-Granada, 18012 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coral","family":"Garcia-Vallecillos","sequence":"additional","affiliation":[{"name":"Infectious Disease Unit, Hospital Universitario Virgen de las Nieves, IBS-Granada, 18012 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"G\u00f3mez-Ronquillo","sequence":"additional","affiliation":[{"name":"Infectious Disease Unit, Hospital Universitario Virgen de las Nieves, IBS-Granada, 18012 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/QAD.0000000000000062","article-title":"High rates of anal dysplasia in HIV-infected men who have sex with men, women, and heterosexual men","volume":"28","author":"Gaisa","year":"2014","journal-title":"AIDS"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.ajog.2015.03.034","article-title":"Prevalence of anal human papillomavirus infection and anal HPV-related disorders in women: A systematic review","volume":"213","author":"Stier","year":"2015","journal-title":"Am. J. Obs. Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/jnci\/djs491","article-title":"Annual report to the nation on the status of cancer, 1975\u20132009, featuring the burden and trends in human papillomavirus (HPV)-associated cancers and HPV vaccination coverage levels","volume":"105","author":"Jemal","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_4","first-page":"324","article-title":"Genital infections due to the human papillomavirus","volume":"37","year":"2019","journal-title":"Enferm. Infecc. Microbiol. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"728","DOI":"10.7326\/0003-4819-148-10-200805200-00005","article-title":"Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992\u20132003","volume":"148","author":"Patel","year":"2008","journal-title":"Ann. Intern. Med."},{"key":"ref_6","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":"Silverberg","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e692","DOI":"10.1093\/cid\/ciac581","article-title":"Incidence and Clearance of Anal Human Papillomavirus Infection in 16 164 Individuals, According to Human Immunodeficiency Virus Status, Sex, and Male Sexuality: An International Pooled Analysis of 34 Longitudinal Studies","volume":"76","author":"Wei","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Gonz\u00e1lez, A., Cachay, E., Ocampo, A., and Poveda, E. (2022). Update on the Epidemiological Features and Clinical Implications of Human Papillomavirus Infection (HPV) and Human Immunodeficiency Virus (HIV) Coinfection. Microorganisms, 10.","DOI":"10.3390\/microorganisms10051047"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hidalgo-Tenorio, C., Calle-G\u00f3mez, I., Moya-Meg\u00edas, R., Rodr\u00edguez-Granges, J., Omar, M., L\u00f3pez Hidalgo, J., and Garc\u00eda-Mart\u00ednez, C. (2023). HPV Infection of the Oropharyngeal, Genital and Anal Mucosa and Associated Dysplasia in People Living with HI. Viruses, 15.","DOI":"10.3390\/v15051170"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17382","DOI":"10.7448\/IAS.15.2.17382","article-title":"Highly active antiretroviral therapy and cervical dysplasia in HIV-positive women in South Africa","volume":"15","author":"Firnhaber","year":"2012","journal-title":"J. Int. AIDS Soc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1097\/QAD.0b013e3283023f78","article-title":"Marked increase in the incidence of invasive anal cancer among HIV-infected patients despite treatment with combination antiretroviral therapy","volume":"22","author":"Piketty","year":"2008","journal-title":"AIDS"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1097\/QAI.0b013e31817aebfe","article-title":"Incidence and epidemiology of anal cancer in the multicenter AIDS cohort study","volume":"48","author":"Wiley","year":"2008","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1097\/01.olq.0000162366.60245.02","article-title":"Increased incidence of squamous cell anal cancer among men with AIDS in the era of highly active antiretroviral therapy","volume":"32","author":"Diamond","year":"2005","journal-title":"Sex. Transm. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/sj.bjc.6605756","article-title":"Changing patterns of cancer incidence in the early- and late-HAART periods: The Swiss HIV Cohort Study","volume":"103","author":"Franceschi","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_15","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":"Schutten","year":"2012","journal-title":"Sex. Transm. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hidalgo-Tenorio, C., Rivero-Rodriguez, M., Gil-Anguita, C., Lopez De Hierro, M., Palma, P., Ram\u00edrez Taboada, J., Esquivias, J., L\u00f3pez-Ruz, M.A., Javier-Mart\u00ednez, R., and Pasquau-Lia\u00f1o, J. (2014). Antiretroviral therapy as a factor protective against anal dysplasia in HIV-infected males who have sex with males. PLoS ONE, 27.","DOI":"10.1371\/journal.pone.0092376"},{"key":"ref_17","first-page":"555","article-title":"High prevalence and incidence of HPV-related anal cancer precursor lesions in HIV-positive women in the late HAART era","volume":"36","author":"Esquivias","year":"2018","journal-title":"Enferm. Infecc. Microbiol. Clin."},{"key":"ref_18","unstructured":"Panel de Expertos del Grupo de Estudio de Sida (GESIDA) (2024, May 01). Documento de Consenso Sobre Diagn\u00f3stico y Tratamiento de Las Infecciones de Transmisi\u00f3n Sexual en Adultos, Ni\u00f1os y Adolescentes (ACTUALIZACI\u00d3N MARZO 2017). Available online: http:\/\/www.gesida-seimc.org."},{"key":"ref_19","unstructured":"(2023). Versi\u00f3n 12, European AIDS Clinical Society. Guidelines."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hidalgo-Tenorio, C., Rivero-Rodriguez, M., Gil-Anguita, C., Esquivias, J., L\u00f3pez-Castro, R., Ram\u00edrez-Taboada, J., de Hierro, M.L., L\u00f3pez-Ruiz, M.A., Mart\u00ednez, R.J., and Lla\u00f1o, J.P. (2015). The role of polymerase chain reaction of high-risk human papilloma virus in the screening of high-grade squamous intraepithelial lesions in the anal mucosa of human immunodeficiency virus-positive males having sex with males. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128165"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1097\/QAD.0b013e328339e592","article-title":"The role of cytology (Pap test) and human papillomavirus testing in anal cancer screening","volume":"24","author":"Salit","year":"2010","journal-title":"AIDS"},{"key":"ref_22","first-page":"560","article-title":"Usefulness of human papillomavirus testing in. anal intraepithelial neoplasia screening in a risk behaviour population","volume":"32","author":"Pereda","year":"2014","journal-title":"Enferm. Infecc. Microbiol. Clin."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1056\/NEJMoa2201048","article-title":"Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer","volume":"386","author":"Palefsky","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/s11908-010-0090-7","article-title":"Evaluation and management of anal intraepithelial neoplasia in HIV-negative and HIV-positive Men who have Sex with Men","volume":"12","author":"Park","year":"2010","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1097\/00007435-200211000-00018","article-title":"Do Condoms Prevent Genital HPV Infection, External Genital Warts, or Cervical Neoplasia? A meta-analysis","volume":"29","author":"Manhart","year":"2002","journal-title":"Sex. Transm. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/QCO.0b013e328334fe5a","article-title":"Anal Cytology screening in HIV-positive men who have sex with men: What\u2019s new and what\u2019s now?","volume":"23","author":"Kenneth","year":"2010","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1056\/NEJMoa0909537","article-title":"Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males","volume":"364","author":"Giuliano","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1086\/656320","article-title":"Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in HIV-1-infected men","volume":"202","author":"Wilkin","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12981-017-0160-0","article-title":"Safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccine in HIV-positive Spanish men who have sex with men (MSM)","volume":"14","author":"Esquivias","year":"2017","journal-title":"AIDS Res. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1093\/cid\/ciy274","article-title":"ACTG A5298: A Randomized, Placebo-Controlled Trial of the Quadrivalent Human Papillomavirus Vaccine in Human Immunodeficiency Virus-Infected Adults Aged 27 Years or Older: AIDS Clinical Trials Group Protocol A5298","volume":"67","author":"Wilkin","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1056\/NEJMoa021641","article-title":"Epidemiologic classification of human papillomavirus types associated with cervical cancer","volume":"348","author":"Bosch","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_32","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":"Solomon","year":"2002","journal-title":"JAMA"},{"key":"ref_33","first-page":"76","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":"32","author":"Darragh","year":"2013","journal-title":"J. Low. Genit. Tract. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/s12985-017-0879-1","article-title":"Fraction of high-grade cervical intraepithelial lesions attributable to genotypes targeted by a nonavalent HPV vaccine in Galicia, Spain","volume":"14","author":"Perez","year":"2017","journal-title":"Virol. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1016\/S0140-6736(21)02178-4","article-title":"The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence: A register-based observational study","volume":"398","author":"Falcaro","year":"2021","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.ygyno.2018.08.033","article-title":"SPERANZA Project: HPV vaccination after treatment for CIN2+","volume":"151","author":"Ghelardi","year":"2018","journal-title":"Gynecol. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Hidalgo-Tenorio, C., Pasquau, J., Omar-Mohamed, M., Sampedro, A., L\u00f3pez-Ruz, M.A., L\u00f3pez Hidalgo, J., and Ram\u00edrez-Taboada, J. (2021). Effectiveness of the Quadrivalent HPV Vaccine in Preventing Anal \u2265 HSILs in a Spanish Population of HIV + MSM Aged >26 Years. Viruses, 13.","DOI":"10.3390\/v13020144"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"101585","DOI":"10.1016\/j.eclinm.2022.101585","article-title":"Immunogenicity, safety, and efficacy of the HPV vaccines among people living with HIV: A systematic review and meta-analysis","volume":"52","author":"Staadegaard","year":"2022","journal-title":"EClinicalMedicine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4954","DOI":"10.1038\/s41598-021-83727-7","article-title":"Efficacy and safety of human papillomavirus vaccination in HIV-infected patients: A systematic review and meta-analysis","volume":"11","author":"Zizza","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zayats, R., Murooka, T.T., and McKinnon, L.R. (2022). HPV and the Risk of HIV Acquisition in Women. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.814948"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/12\/8\/838\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:23:16Z","timestamp":1760109796000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/12\/8\/838"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,25]]},"references-count":40,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["vaccines12080838"],"URL":"https:\/\/doi.org\/10.3390\/vaccines12080838","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,25]]}}}