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

ABSTRACT

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.