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
Abstract
Background 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. Case presentation 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—a cervical quadrant spatially distinct from the original CIN3 lesions. This finding raises the possibility of de novo 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. Conclusions 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.