{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:10:38Z","timestamp":1788844238239,"version":"build-2803163510"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2077143 and 42507651"],"award-info":[{"award-number":["2077143 and 42507651"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2025AFD075"],"award-info":[{"award-number":["2025AFD075"]}],"id":[{"id":"10.13039\/501100003819","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>Background<\/jats:title>\n                    <jats:p>Cervical intraepithelial neoplasia grade 3 (CIN3) is a high-grade precancer, and 5-aminolaevulinic acid-mediated photodynamic therapy (ALA-PDT) offers a fertility-preserving alternative for young patients. However, complete lesion regression does not eliminate the latent oncogenic risk of persistent HPV16, and real-world evidence of invasive carcinoma arising after long-term loss to follow-up (LTFU) post-PDT remains scarce. This case report aims to share this clinical observation and provide real-world evidence supporting risk-stratified post-treatment surveillance for patients with isolated persistent HPV16 after histological CIN3 remission.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      A 32-year-old parous woman with TZ2 CIN3 at the 9\/12 o'clock cervical positions achieved histological remission after two cycles of standardized ALA-PDT, yet retained isolated HPV16 infection. Despite repeated clinical reminders, she discontinued all surveillance for 20 consecutive months. Upon voluntary re-presentation, newly developed invasive squamous cell carcinoma was confirmed at the 6 o'clock position\u2014a cervical quadrant spatially distinct from the original CIN3 lesions. This finding raises the possibility of\n                      <jats:italic>de novo<\/jats:italic>\n                      malignant transformation from persistent HPV16; however, pre-existing occult multifocal disease cannot be excluded in the absence of viral clonality or HPV integration-site molecular evidence. Multimodal staging indicated theoretical eligibility for fertility-sparing radical trachelectomy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Isolated persistent HPV16 retains long-term malignant potential despite resolved precancerous lesions, and can drive spatially separate invasive carcinoma. Because this inference is based on a single observational case without supporting molecular data, risk-stratified intensified surveillance should be further validated in larger cohorts. Standardized follow-up adherence interventions are required to prevent irreversible fertility loss and advanced disease secondary to discontinuous monitoring.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1954126","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:26:37Z","timestamp":1788841597000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Possible spatially-distinct de novo invasive cervical carcinoma in the setting of isolated persistent HPV16 after ALA-PDT-mediated histological clearance of CIN3"],"prefix":"10.3389","volume":"13","author":[{"given":"Huihui","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Gynecology, Laoshan Branch, Affiliated Hospital of Qingdao University","place":["Qingdao, 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