{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T01:04:09Z","timestamp":1794359049347,"version":"4.9.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The prophylactic vaccines available to protect against infections by HPV are well tolerated and highly immunogenic. People with HIV have a higher risk of developing HPV infection and HPV-associated cancers due to a lower immune response, and due to viral interactions. We performed a systematic review of RCTs to assess HPV vaccines efficacy and safety on HIV-infected people compared to placebo or no intervention in terms of seroconversion, infections, neoplasms, adverse events, CD4+ T-cell\u00a0count and HIV viral load. The vaccine-group showed a seroconversion rate close to 100% for each vaccine and a significantly higher level of antibodies against HPV vaccine types, as compared to the placebo group (MD\u2009=\u20094333.3, 95% CI 2701.4; 5965.1 GMT EL.U.\/ml for HPV type 16 and MD\u2009=\u20091408.8, 95% CI 414.8; 2394.7 GMT EL.U.\/ml for HPV type 18). There were also no differences in terms of severe adverse events (RR\u2009=\u20090.6, 95% CI 0.2; 1.6) and no severe adverse events (RR\u2009=\u20090.6, 95% CI 0.9; 1.2) between vaccine and placebo groups. Secondary outcomes, such as CD4\u2009+\u2009T-cell count and HIV viral load, did not differ between groups (MD\u2009=\u200914.8, 95% CI \u2212\u00a035.1; 64.6 cells\/\u00b5l and MD\u2009=\u20090.0, 95% CI \u2212\u00a00.3; 0.3 log10 RNA copies\/ml, respectively). Information on the remaining outcomes was scarce and that did not allow us to combine the data. The results support the use of the HPV vaccine in HIV-infected patients and highlight the need of further RCTs assessing the effectiveness of the HPV vaccine on infections and neoplasms.<\/jats:p>","DOI":"10.1038\/s41598-021-83727-7","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T11:04:56Z","timestamp":1614683096000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Efficacy and safety of human papillomavirus vaccination in HIV-infected patients: a systematic review and meta-analysis"],"prefix":"10.1038","volume":"11","author":[{"given":"Antonella","family":"Zizza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Banchelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Guido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Marotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Di Gennaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Mazzucco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanna","family":"Pistotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"D\u2019Amico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,2]]},"reference":[{"key":"83727_CR1","doi-asserted-by":"publisher","first-page":"I1","DOI":"10.1016\/j.vaccine.2013.07.026","volume":"31","author":"FX Bosch","year":"2013","unstructured":"Bosch, F. X. et al. Comprehensive control of human papillomavirus infections and related diseases. Vaccine 31, I1\u2013I31 (2013).","journal-title":"Vaccine"},{"key":"83727_CR2","unstructured":"International Agency for Research on Cancer (IARC). IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological agents. Volume 100 B. A review of human carcinogens. IARC Monogr. Eval. Carcinog. Risks Hum. 100, 1\u2013441 (2012)."},{"key":"83727_CR3","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1002\/ijc.27485","volume":"131","author":"P Guan","year":"2012","unstructured":"Guan, P. et al. Human papillomavirus types in 115,789 HPV-positive women: A meta-analysis from cervical infection to cancer. Int. J. Cancer. 131, 2349\u20132359 (2012).","journal-title":"Int. J. Cancer."},{"key":"83727_CR4","doi-asserted-by":"crossref","unstructured":"Scarbrough Lefebvre, C. D., Van Kriekinge, G., Gon\u00e7alves, M. A. & de Sanjose, S. Appraisal of the burden of genital warts from a healthcare and individual patient perspective. Public Health 125, 464\u2013475 (2011).","DOI":"10.1016\/j.puhe.2011.01.016"},{"key":"83727_CR5","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1093\/infdis\/jix105","volume":"217","author":"D Novakovic","year":"2018","unstructured":"Novakovic, D. et al. A prospective study of the incidence of Juvenile-onset recurrent respiratory papillomatosis after implementation of a national HPV vaccination program. J. Infect. Dis. 217, 208\u2013212 (2018).","journal-title":"J. Infect. Dis."},{"key":"83727_CR6","unstructured":"World Health Organization (WHO). GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. Lyon, France, International Agency for Research on Cancer, http:\/\/globocan.iarc.fr\/Pages\/fact_sheets_cancer.aspx (2014)."},{"key":"83727_CR7","doi-asserted-by":"publisher","first-page":"F168","DOI":"10.1016\/j.vaccine.2012.06.045","volume":"30","author":"LA Denny","year":"2012","unstructured":"Denny, L. A. et al. Human papillomavirus, human immunodeficiency virus and immunosuppression. Vaccine 30, F168\u2013F174 (2012).","journal-title":"Vaccine"},{"key":"83727_CR8","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1177\/0956462413491735","volume":"25","author":"SA Denslow","year":"2014","unstructured":"Denslow, S. A., Rositch, A. F., Firnhaber, C., Ting, J. & Smith, J. S. Incidence and progression of cervical lesions in women with HIV: A systematic global review. Int. J. STD. AIDS 25, 163\u2013177 (2014).","journal-title":"Int. J. STD. AIDS"},{"key":"83727_CR9","doi-asserted-by":"publisher","first-page":"903","DOI":"10.2217\/fvl.13.69","volume":"8","author":"D Konopnicki","year":"2013","unstructured":"Konopnicki, D., De Wit, S. & Clumeck, N. HPV and HIV coinfection: a complex interaction resulting in epidemiological, clinical and therapeutic implications. Future Virol. 8, 903\u2013915 (2013).","journal-title":"Future Virol."},{"key":"83727_CR10","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.virol.2013.08.018","volume":"446","author":"SM Tugizov","year":"2013","unstructured":"Tugizov, S. M. et al. HIV-associated disruption of mucosal epithelium facilitates paracellular penetration by human papillomavirus. Virology 446, 378\u2013388 (2013).","journal-title":"Virology"},{"key":"83727_CR11","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1097\/QAD.0000000000001765","volume":"32","author":"G Liu","year":"2018","unstructured":"Liu, G., Sharma, M., Tan, N. & Barnabas, R. V. HIV-positive women have higher risk of human papilloma virus infection, precancerous lesions, and cervical cancer. AIDS 32, 795\u2013808 (2018).","journal-title":"AIDS"},{"key":"83727_CR12","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1200\/JCO.2017.74.9291","volume":"36","author":"V Col\u00f3n-L\u00f3pez","year":"2018","unstructured":"Col\u00f3n-L\u00f3pez, V. et al. Anal cancer risk among people with HIV infection in the United States. J. Clin. Oncol. 36, 68\u201375 (2018).","journal-title":"J. Clin. Oncol."},{"key":"83727_CR13","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1097\/OLQ.0b013e31822154f9","volume":"38","author":"AG Nyitray","year":"2011","unstructured":"Nyitray, A. G. et al. The prevalence of genital HPV and factors associated with oncogenic HPV among men having sex with men and men having sex with women and men: The HIM study. Sex. Transm. Dis. 38, 932\u2013940 (2011).","journal-title":"Sex. Transm. Dis."},{"key":"83727_CR14","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1093\/jnci\/92.18.1500","volume":"92","author":"M Frisch","year":"2000","unstructured":"Frisch, M., Biggar, R. J. & Goedert, J. J. Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J. Natl. Cancer Inst. 92, 1500\u20131510 (2000).","journal-title":"J. Natl. Cancer Inst."},{"key":"83727_CR15","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1093\/infdis\/jis695","volume":"207","author":"E Irungu","year":"2013","unstructured":"Irungu, E. et al. Immune response to hepatitis B virus vaccination among HIV-1 infected and uninfected adults in Kenya. J. Infect. Dis. 207, 402\u2013410 (2013).","journal-title":"J. Infect. Dis."},{"key":"83727_CR16","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1089\/apc.2014.0121","volume":"28","author":"NF Crum-Cianflone","year":"2014","unstructured":"Crum-Cianflone, N. F. & Wallace, M. R. Vaccination in HIV-infected adults. AIDS Patient Care STDS. 28, 397\u2013410 (2014).","journal-title":"AIDS Patient Care STDS."},{"key":"83727_CR17","doi-asserted-by":"publisher","first-page":"e20181902","DOI":"10.1542\/peds.2018-1902","volume":"143","author":"C Spinner","year":"2019","unstructured":"Spinner, C. et al. Human papillomavirus vaccine effectiveness and herd protection in young women. Pediatrics 143, e20181902 (2019).","journal-title":"Pediatrics"},{"key":"83727_CR18","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1093\/infdis\/jiz280","volume":"220","author":"JA Bogaards","year":"2019","unstructured":"Bogaards, J. A., van der Weele, P., Woestenberg, P. J., van Benthem, B. H. B. & King, A. J. Bivalent Human Papillomavirus (HPV) vaccine effectiveness correlates with phylogenetic distance from HPV vaccine types 16 and 18. J. Infect. Dis. 220, 1141\u20131146 (2019).","journal-title":"J. Infect. Dis."},{"key":"83727_CR19","doi-asserted-by":"publisher","first-page":"343","DOI":"10.2174\/1381612826666200212115840","volume":"26","author":"M Guido","year":"2020","unstructured":"Guido, M. et al. Universal Human Papillomavirus Vaccination and its Impact on the Southern Italian Region. Curr. Pharm. Des. 26, 343\u2013357 (2020).","journal-title":"Curr. Pharm. Des."},{"key":"83727_CR20","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1056\/NEJMoa1917338","volume":"383","author":"J Lei","year":"2020","unstructured":"Lei, J. et al. HPV vaccination and the risk of invasive cervical cancer. N. Engl. J. Med. 383, 1340\u20131348 (2020).","journal-title":"N. Engl. J. Med."},{"key":"83727_CR21","first-page":"e123","volume":"3","author":"the PRISMA Statement","year":"2009","unstructured":"the PRISMA Statement. Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G. & PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses. Open Med. 3, e123\u2013e130 (2009).","journal-title":"Open Med."},{"key":"83727_CR22","unstructured":"Higgins, J. P. & Green, S. Cochrane Handbook for Systematic Reviews of Interventions, 5.1.0 (Wiley, New York, 2011)."},{"key":"83727_CR23","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","volume":"7","author":"R DerSimonian","year":"1986","unstructured":"DerSimonian, R. & Laird, N. Meta-analysis in clinical trials. Control Clin. Trials 7, 177\u2013188 (1986).","journal-title":"Control Clin. Trials"},{"key":"83727_CR24","unstructured":"Sch\u00fcnemann, H., Bro\u017cek, J., Guyatt, G. & Oxman, A. GRADE handbook for grading quality of evidence and strength of recommendations. The GRADE Working Group https:\/\/gdt.gradepro.org\/app\/handbook\/handbook.html (2013)."},{"key":"83727_CR25","doi-asserted-by":"publisher","first-page":"5745","DOI":"10.1016\/j.vaccine.2013.09.032","volume":"31","author":"L Denny","year":"2013","unstructured":"Denny, L. et al. Safety and immunogenicity of the HPV-16\/18 AS04-adjuvanted vaccine in HIV-positive women in South Africa: A partially-blind randomised placebo-controlled study. Vaccine 31, 5745\u20135753 (2013).","journal-title":"Vaccine"},{"key":"83727_CR26","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s12981-017-0160-0","volume":"14","author":"C Hidalgo-Tenorio","year":"2017","unstructured":"Hidalgo-Tenorio, C. et al. Safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccine in HIV-positive Spanish men who have sex with men (MSM). AIDS Res. Ther. 14, 34 (2017).","journal-title":"AIDS Res. Ther."},{"key":"83727_CR27","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1097\/QAI.0b013e3181de8d26","volume":"55","author":"MJ Levin","year":"2010","unstructured":"Levin, M. J. et al. Safety and immunogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine in HIV-infected children 7 to 12 years old. J. Acquir. Immune Defic. Syndr. 55, 197\u2013204 (2010).","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"83727_CR28","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1093\/cid\/ciy274","volume":"67","author":"TJ Wilkin","year":"2018","unstructured":"Wilkin, T. J. et al. 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. Clin. Infect. Dis. 67, 1339\u20131346 (2018).","journal-title":"Clin. Infect. Dis."},{"key":"83727_CR29","unstructured":"New York State Department of Health AIDS Institute. Human Papillomavirus (HPV) in Patients with HIV. Clinical Guidelines Program. New York, NY: New York State Department of Health https:\/\/www.hivguidelines.org\/sti-care\/hpv-infection\/#tab_7 (2018)."},{"key":"83727_CR30","unstructured":"NCT04270773. Immunogenicity and Safety of a 9-valent Human Papillomavirus Vaccine in HIV-positive Women (9-VPH-MVIH). https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04270773 (Ongoing study July 2020)."},{"key":"83727_CR31","unstructured":"NCT03626467. A Clinical Trial to Evaluate the Immunogenicity of the Nonavalent Vaccine Against Human Papillomavirus in Men Infected by HIV Who Have Sex With Men. GESIDA 10017 (GESIDA10017). https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03626467 (Ongoing study July 2020)."},{"key":"83727_CR32","unstructured":"NCT03284866. HPV Vaccine Therapy in Reducing High-Grade Cervical Lesions in Patients With HIV and HPV (COVENANT). https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03284866 (Ongoing study July 2020)."},{"key":"83727_CR33","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1080\/14787210.2017.1392854","volume":"15","author":"M Poljak","year":"2017","unstructured":"Poljak, M., \u0160terbenc, A. & Lunar, M. M. Prevention of human papillomavirus (HPV)-related tumors in people living with human immunodeficiency virus (HIV). Expert Rev. Anti Infect. Ther. 15, 987\u2013999 (2017).","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"83727_CR34","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1186\/s12879-016-1706-9","volume":"16","author":"EE M\u00fcller","year":"2016","unstructured":"M\u00fcller, E. E. et al. The prevalence of human papillomavirus infections and associated risk factors in men-who-have-sex-with-men in Cape Town South Africa. BMC Infect. Dis. 16, 440 (2016).","journal-title":"BMC Infect. Dis."},{"key":"83727_CR35","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.jaut.2017.03.011","volume":"80","author":"A Lopez","year":"2017","unstructured":"Lopez, A. et al. Vaccination recommendations for the adult immunosuppressed patient: A systematic review and comprehensive field synopsis. J. Autoimmun. 80, 10\u201327 (2017).","journal-title":"J. Autoimmun."},{"key":"83727_CR36","unstructured":"World Health Organization (WHO). Human papillomavirus vaccines: WHO position paper, May 2017. Wkly. Epidemiol. Rec. 92, 241\u2013268 (2017)."},{"key":"83727_CR37","unstructured":"European AIDS Clinical Society (EACS). EACS Guidelines version 10.0. Brussels: EACS https:\/\/www.eacsociety.org\/files\/2019_guidelines-10.0_final.pdf (2019)."},{"key":"83727_CR38","doi-asserted-by":"publisher","first-page":"698","DOI":"10.15585\/mmwr.mm6832a3","volume":"68","author":"E Meites","year":"2019","unstructured":"Meites, E. et al. Human papillomavirus vaccination for adults: Updated recommendations of the advisory committee on immunization practices. MMWR Morb. Mortal. Wkly. Rep. 68, 698\u2013702 (2019).","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"83727_CR39","doi-asserted-by":"crossref","unstructured":"Bergman, H. et al. Comparison of different human papillomavirus (HPV) vaccine types and dose schedules for prevention of HPV-related disease in females and males. Cochrane Database Syst. Rev. 2019, CD013479 (2019).","DOI":"10.1002\/14651858.CD013479"},{"key":"83727_CR40","doi-asserted-by":"crossref","unstructured":"Arbyn, M., Xu, L., Simoens, C. & Martin-Hirsch, P. P. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst. Rev. 5, CD009069 (2018).","DOI":"10.1002\/14651858.CD009069.pub3"},{"key":"83727_CR41","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1177\/0956462419852224","volume":"30","author":"Y Zhan","year":"2019","unstructured":"Zhan, Y., Liu, X., Feng, Y., Wu, S. & Jiang, Y. Safety and efficacy of human papillomavirus vaccination for people living with HIV: A systematic review and meta-analysis. Int. J. STD. AIDS 30, 1105\u20131115 (2019).","journal-title":"Int. J. STD. AIDS"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83727-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83727-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83727-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T04:45:40Z","timestamp":1670042740000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83727-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,2]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["83727"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-83727-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,2]]},"assertion":[{"value":"27 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4954"}}