{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T21:43:34Z","timestamp":1792878214871,"version":"4.5.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009399","name":"Peking University Third Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This prospective study aimed to evaluate the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) for cervical\/vaginal intraepithelial neoplasia (CIN\/VaIN) and explore the predictive value of pretreatment PAX1\/JAM3 methylation status in exfoliated cells for treatment outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 516 patients with histologically confirmed high-grade squamous intraepithelial lesion (HSIL: CIN2\/3, VaIN2\/3) who received ALA-PDT between September 2024 and February 2026 were enrolled. Pretreatment exfoliated cells were collected for HR-HPV detection, ThinPrep cytology test (TCT), and PAX1\/JAM3 methylation analysis via multiplex real-time quantitative PCR. All patients received two courses of ALA-PDT consisting of six treatment sessions in total at 7\u201314-day intervals. Each session was performed with 20% ALA topical application for 3 h followed by irradiation at 80 mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      , 635 nm, for 25\u201330 min. Efficacy was evaluated by pathological regression, HR-HPV clearance at 6\/12 months, and factors influencing outcomes were analyzed using univariate\/multivariate regression and ROC curves.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The overall disease remission rates were 92.21% (CIN2), 88.68% (CIN3), 78.57% (VaIN2), and 66.67% (VaIN3). The HR-HPV clearance rates at 6 months were 60.79% for CIN2, 61.90% for CIN3, 52.38% for VaIN2, and 50.00% for VaIN3; the corresponding 12-month clearance rates were 71.72, 74.36, 58.54, and 50.00%, respectively. Univariate analysis identified prior cervical surgery, HPV16\/18 positivity, TCT \u2265 LSIL, and multiple lesions as adverse factors for CIN2. TCT \u2265 LSIL, and multiple lesions were associated with poorer outcomes in VaIN2\/3. PAX1\/JAM3 hypomethylation was significantly associated with higher remission rates (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001). Pretreatment PAX1\/JAM3 hypermethylation showed predictive value for incomplete response to ALA-PDT. Combined methylation detection showed optimal predictive performance (AUC: 0.861 for CIN2, 0.734 for CIN3, 0.777 for VaIN2, 0.750 for VaIN3).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ALA-PDT is effective for HSIL with favorable HPV clearance. Pretreatment PAX1\/JAM3 methylation status serves as a reliable non-invasive biomarker for predicting PDT efficacy, supporting individualized clinical decision-making.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1828763","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:30:29Z","timestamp":1782365429000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy of 5-aminolevulinic acid photodynamic therapy for the treatment of female lower reproductive tract intraepithelial lesions and its predictive biomarker: DNA methylation"],"prefix":"10.3389","volume":"13","author":[{"given":"Qin","family":"Han","sequence":"first","affiliation":[{"name":"Department of Gynecology, Peking University Third Hospital","place":["Haidian, 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