{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T10:46:03Z","timestamp":1792752363616,"version":"4.5.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP 17lk0201019."],"award-info":[{"award-number":["JP 17lk0201019."]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While human papillomavirus (HPV)\u2013specific T-cell responses are believed to contribute to regression of HPV-associated cervical neoplasia, their role has not been fully elucidated. We investigated HPV type 16 (HPV16) E7-specific T-cell responses in the cervix and peripheral blood and their association with pathological outcomes in cervical intraepithelial neoplasia grade 2 (CIN2).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human papillomavirus type 16 E7-specific T-cell responses in cervical lymphocytes (CxLs) and peripheral blood mononuclear cells (PBMCs) were quantified using overlapping peptide (OLP) pools of E7 in 38 subjects with HPV16-positive CIN2 with defined pathological outcomes. Breadth and human leukocyte antigen (HLA) restriction of these responses were assessed using single OLPs on in vitro\u2013expanded PBMCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Human papillomavirus type 16E7-specific T-cell responses were detected in over 30% of CxL samples but rarely detected in PBMCs unless expanded in vitro. Higher magnitudes of E7-stimulated responses in CxLs, along with elevated nonspecific background responses, were associated with pathological regression of CIN2 lesions. The E7-specific T-cell responses in expanded PBMCs varied in breadth among subjects and were mediated by both CD4+ and CD8+ T cells with diverse HLA restrictions. Importantly, response breadth was significantly greater in subjects with lesion regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Human papillomavirus\u2013specific T-cell responses are preferentially localized at the site of infection and maintained at low frequencies in peripheral blood. The magnitude of local E7-stimulated response in CxLs and the breadth of E7-specific responses in expanded PBMCs were associated with pathological regression of CIN2. These associations support a potential role for E7-specific T-cell responses in the regression of HPV-related cervical neoplasia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag505","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:27:22Z","timestamp":1791199642000},"source":"Crossref","is-referenced-by-count":0,"title":["Association of Human Papillomavirus Type 16 E7-specific T-Cell Responses in Cervical Lymphocytes and Peripheral Blood With Regression of High-Grade Cervical Intraepithelial Neoplasia Lesions"],"prefix":"10.1093","author":[{"given":"Kaori","family":"Nakayama-Hosoya","sequence":"first","affiliation":[{"name":"AIDS Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security , Tokyo ,","place":["Japan"]},{"name":"Morishita Jintan Co., Ltd. Department of Corporate Planning, , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1919-8830","authenticated-orcid":false,"given":"Kei","family":"Kawana","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nihon University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9260-2505","authenticated-orcid":false,"given":"Saki","family":"Kamata","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nihon University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Tomita","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nihon University School of Medicine , Tokyo 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,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nihon University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2177-4344","authenticated-orcid":false,"given":"Keisuke","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nihon University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizunobu","family":"Igimi","sequence":"additional","affiliation":[{"name":"Department of Applied Biology and Chemistry, Tokyo University of Agriculture , Tokyo 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