Real-world outcomes of photodynamic therapy for HPV-associated lower genital tract lesions: a 2024-2025 gynecology follow-up cohort study.

BACKGROUND: Persistent high-risk human papillomavirus (hrHPV) infection drives lower genital tract intraepithelial lesions. 5-aminolevulinic acid photodynamic therapy (5-ALA-PDT) is a minimally invasive, tissue-preserving option, but real-world effectiveness remains variably reported. METHODS: We analyzed de-identified standardized gynecology follow-up forms from 2024-2025 for patients treated with 5-ALA-PDT for HPV-associated lower genital tract disease. Outcomes at 3 months were genotype-specific clearance of HPV-16 and HPV-18 among baseline-positive patients and cytology normalization to negative for intraepithelial lesion or malignancy (NILM) among those with abnormal baseline ThinPrep cytology (TCT). Logistic regression explored predictors of post-treatment HPV clearance. RESULTS: Overall, 714 patients were included; 635 (88.9%) had complete baseline and follow-up testing plus documented PDT protocol parameters (mean age 45.8 ± 12.6 years). The cervix was the most common treatment site (52.9%); median number of sessions was 4 (IQR 3-6) using 20% 5-ALA. At 3 months, HPV-16 cleared in 162/217 (74.7%), and HPV-18 cleared in 46/61 (75.4%); clearance for other HPV types was 337/566 (59.5%). Among patients with abnormal baseline TCT, 314/329 (95.4%) normalized to NILM. In multivariable analysis, a higher number of baseline HPV types predicted reduced clearance (adjusted OR 0.70, 95% CI 0.50-0.97); age <40 years was associated with clearance only in univariate analysis (OR 1.96, 95% CI 1.17-3.27) but was not significant after adjustment. CONCLUSIONS: In this retrospective routine-care cohort, 5-ALA-PDT was associated with substantial early HPV-16/18 clearance and high short-term cytologic normalization. Multitype HPV infection may be a risk factor and warrant closer surveillance.