{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T18:36:04Z","timestamp":1778610964124,"version":"3.51.4"},"reference-count":78,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP25K18783"],"award-info":[{"award-number":["JP25K18783"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21K07287"],"award-info":[{"award-number":["JP21K07287"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22K07527"],"award-info":[{"award-number":["JP22K07527"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22K18378"],"award-info":[{"award-number":["JP22K18378"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K06493"],"award-info":[{"award-number":["JP23K06493"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K08901"],"award-info":[{"award-number":["JP23K08901"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP24K10163"],"award-info":[{"award-number":["JP24K10163"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP24K10500"],"award-info":[{"award-number":["JP24K10500"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In Japan, neuropsychological symptoms after human papillomavirus (\n                    <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\n                    ) vaccinations were publicized as \u201cadverse effects,\u201d leading to vaccine hesitancy. Anti\u2010vaccine activists claimed that adjuvants in\n                    <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\n                    vaccines could cause an immune\u2010mediated neurological disease. Adjuvants in the bivalent\n                    <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\n                    vaccine (\n                    <jats:styled-content style=\"fixed-case\">2vHPV<\/jats:styled-content>\n                    ) and quadrivalent\n                    <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\n                    vaccine (\n                    <jats:styled-content style=\"fixed-case\">4vHPV<\/jats:styled-content>\n                    ) are\n                    <jats:styled-content style=\"fixed-case\">AS04<\/jats:styled-content>\n                    [composed of aluminum (Al) hydroxide (\n                    <jats:styled-content style=\"fixed-case\">AH<\/jats:styled-content>\n                    ) and monophosphoryl lipid A (\n                    <jats:styled-content style=\"fixed-case\">MPL<\/jats:styled-content>\n                    )] and Al hydroxyphosphate sulfate (\n                    <jats:styled-content style=\"fixed-case\">AHS<\/jats:styled-content>\n                    ), respectively. We determined whether\n                    <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\n                    vaccinations in mice could reproduce alleged immunopathology. We injected mice intramuscularly with\n                    <jats:styled-content style=\"fixed-case\">2vHPV<\/jats:styled-content>\n                    ,\n                    <jats:styled-content style=\"fixed-case\">4vHPV<\/jats:styled-content>\n                    , two hepatitis B virus vaccines containing\n                    <jats:styled-content style=\"fixed-case\">AH<\/jats:styled-content>\n                    or\n                    <jats:styled-content style=\"fixed-case\">AHS<\/jats:styled-content>\n                    , or a varicella\u2010zoster virus vaccine (\n                    <jats:styled-content style=\"fixed-case\">vVZV<\/jats:styled-content>\n                    ) containing an adjuvant\n                    <jats:styled-content style=\"fixed-case\">AS01<\/jats:styled-content>\n                    (comprising\n                    <jats:styled-content style=\"fixed-case\">MPL<\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">QS<\/jats:styled-content>\n                    \u201021). Histologically, 12\u2009weeks after vaccinations, all four Al\u2010containing vaccine groups had Al\u2010laden macrophage accumulation at the injected muscle; no groups had abnormalities in any other organs, including the brain, heart, liver, and kidney. Immunologically, although the four Al\u2010containing vaccine groups had continuously increased levels of several cytokines, including interferon (\n                    <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\n                    )\u2010\u03b2, cytokine profiles were not associated with muscle pathology. No groups exhibited any clinical signs, except for the\n                    <jats:styled-content style=\"fixed-case\">vVZV<\/jats:styled-content>\n                    group, which lost body weight temporarily following each injection. Weight loss in the\n                    <jats:styled-content style=\"fixed-case\">vVZV<\/jats:styled-content>\n                    group was associated with increased levels of cytokines, including interleukin (\n                    <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                    )\u201018. Experiments using\n                    <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                    \u201018 receptor\u2010deficient mice and\n                    <jats:styled-content style=\"fixed-case\">AS01<\/jats:styled-content>\n                    injection alone demonstrated that\n                    <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                    \u201018 and\n                    <jats:styled-content style=\"fixed-case\">AS01<\/jats:styled-content>\n                    contributed to weight loss. Since\n                    <jats:styled-content style=\"fixed-case\">2vHPV<\/jats:styled-content>\n                    containing\n                    <jats:styled-content style=\"fixed-case\">AS04<\/jats:styled-content>\n                    (\n                    <jats:styled-content style=\"fixed-case\">AH<\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">MPL<\/jats:styled-content>\n                    ) did not induce weight loss,\n                    <jats:styled-content style=\"fixed-case\">QS<\/jats:styled-content>\n                    \u201021, but not\n                    <jats:styled-content style=\"fixed-case\">MPL<\/jats:styled-content>\n                    , in\n                    <jats:styled-content style=\"fixed-case\">AS01<\/jats:styled-content>\n                    seemed responsible for weight loss, demonstrating the safety of\n                    <jats:styled-content style=\"fixed-case\">MPL<\/jats:styled-content>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/cas.70213","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T10:49:29Z","timestamp":1759747769000},"page":"3309-3325","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparative Cytokine and Histology Studies on\n                    <scp>HPV<\/scp>\n                    and Other Viral Vaccinations: No Pathogenicity of\n                    <scp>HPV<\/scp>\n                    Vaccine Adjuvants"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4610-9808","authenticated-orcid":false,"given":"Reona","family":"Shiro","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Kindai University Faculty of Medicine  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumitaka","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Microbiology Kindai University Faculty of Medicine  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiichi","family":"Omura","sequence":"additional","affiliation":[{"name":"Department of Microbiology Kindai University Faculty of Medicine  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ah\u2010Mee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Arts and Sciences Kindai University Faculty of Medicine  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cong Thanh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Microbiology Kindai University Faculty of Medicine  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ijaz","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Microbiology Kindai University Faculty of Medicine  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandesh","family":"Rimal","sequence":"additional","affiliation":[{"name":"Department of Microbiology Kindai University Faculty of Medicine  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology Kindai University Faculty of Medicine  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4512-7975","authenticated-orcid":false,"given":"Noriomi","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Kindai University Faculty of Medicine  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1798-714X","authenticated-orcid":false,"given":"Ikuo","family":"Tsunoda","sequence":"additional","affiliation":[{"name":"Department of Microbiology Kindai University Faculty of Medicine  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30667"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(10)70230\u20108"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1917338"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv302"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30716"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13071339"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6733a2"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.32481\/djph.2023.04.008"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.05.110"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743\u2010422X\u20109\u201052"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2510"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15071884"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541\u2010018\u20100089\u2010x"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.16020"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.29413"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djab080"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(21)02178\u20104"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.16167"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.22513"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/124.9.1821"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/124.5.974"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2009.08.005"},{"key":"e_1_2_11_24_1","unstructured":"National Attorneys Association for the HPV Vaccine Lawsuits in Japan \u201cOpinion on the Creation of HPV Vaccine Fact Sheet \u201dhttps:\/\/sadd02d49008ac59f.jimcontent.com\/download\/version\/1622256046\/module\/8054396754\/name\/210122\u201002%20factsheet\u2010opinion.pdf."},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(98)02326\u20105"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15714"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.6.5.723"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1293132"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25063460"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241612937"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.07.006"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010160648"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201005627\u20108"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201010980\u20100"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.805302"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.09.024"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2009.06.010"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.00377"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep36943"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2015.12.067"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.04.018"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.09.012"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1300392110"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06939"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2009.03.005"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1631"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1098"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13326"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/1348\u20100421.13108"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.04.006"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.12.010"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010023\u201001867\u20108"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030649"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611523104"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.971745"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1415"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2013.59"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2013.12.001"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.146.2.431"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.683011"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2019.152905"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570\u2010020\u201000244\u20103"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10081339"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit365"},{"key":"e_1_2_11_65_1","unstructured":"The Centers for Disease Control and Prevention CDC WONDER https:\/\/wonder.cdc.gov\/vaers.html."},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI16721"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2019.07.029"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400422"},{"key":"e_1_2_11_69_1","unstructured":"The Jackson Laboratory \u201cBody Weight Information for B6J (000664) \u201dhttps:\/\/www.jax.org\/jax\u2010mice\u2010and\u2010services\/strain\u2010data\u2010sheet\u2010pages\/body\u2010weight\u2010chart\u2010000664."},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpmb.30"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1177\/026119299902700106"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.06.005"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.38.448"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9030289"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.117242"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976\u20100105.177703"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.727"},{"key":"e_1_2_11_78_1","unstructured":"European Medicines Agency \u201cGardasil: EPAR\u2014Scientific Discussion \u201dhttps:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010discussion\/gardasil\u2010epar\u2010scientific\u2010discussion_en.pdf."},{"key":"e_1_2_11_79_1","unstructured":"Pharmaceuticals and Medical Devices Agency \u201cThe Documents on Gardasil Aqueous Suspension for Intramuscular Injection and Aqueous Suspension for Intramuscular Injection Syringes 2.6 The Summary Text and Summary Table on Nonclinical Studies\u2014Toxicity \u201dhttps:\/\/www.pmda.go.jp\/drugs\/2011\/P201100122\/170050000_22300AMX00600000_J100_1.pdf."}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70213","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T10:25:50Z","timestamp":1764584750000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.70213"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,6]]},"references-count":78,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/cas.70213"],"URL":"https:\/\/doi.org\/10.1111\/cas.70213","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,6]]},"assertion":[{"value":"2025-07-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}