5‐Aminolevulinic Acid Photodynamic Therapy for Non‐Lesional Persistent High‐Risk HPV Infection: A Comparative Cohort Study With Interferon

Persistent high-risk human papillomavirus (HR-HPV) infection drives cervical carcinogenesis, yet effective treatments for patients without histologically confirmed cervical lesions are lacking. Although five-aminolevulinic acid photodynamic therapy (ALA-PDT) effectively treats cervical lesions and associated HR-HPV, its efficacy for clearing HR-HPV in non-lesional patients is unclear. We aim to compare the efficacy of ALA-PDT versus interferon (IFN) in treating persistent HR-HPV infection in patients without cervical lesions. This real-world cohort study included 157 patients receiving three sessions of ALA-PDT and 114 patients receiving 3 courses total of IFN therapy. The primary outcome was HR-HPV complete clearance at 6- and 12-month post-treatment. At 6 months, complete clearance rates were 56.9% (82/144) in the PDT group versus 15.3% (13/85) in the IFN group (p < 0.001). At 12 months, rates were 67.0% (59/88) versus 28.3% (26/92) (p < 0.001). Generalized estimating equations (GEE) analysis confirmed PDT was significantly superior to IFN in reducing persistent infection risk (adjusted odds ratio [aOR] = 0.114, 95% CI: 0.054-0.242, p < 0.001). Longer infection duration (≥ 24 vs. 6-23 months) (aOR = 2.334, 95% CI: 1.352-4.030, p = 0.002) and increasing age (per year) (aOR = 1.025, 95% CI: 1.003-1.048, p = 0.027) were independently associated with higher persistence risk. Adverse events (mild pain and vaginal discharge) occurred in 5.1% of patients. ALA-PDT demonstrates superior and sustained efficacy over IFN for clearing persistent HR-HPV infection in patients without cervical lesions. Older age and longer infection duration are significant risk factors for treatment failure.