Background/Objectives: This study aims to fill certain knowledge gaps by assessing the clinical effectiveness of PDT in a large group of women with HPV-related cervical lesions and examining how different patient factors affect treatment results. Methods: 811 women aged from 19 to 76 were retrospectively analyzed who were treated by PDT of HPV infection with atypical squamous cells and HPV-related cervical lesions. PDT was performed using chlorin e6–based systemic photosensitizers. Irradiation was carried out at 662 nm. The endocervical dose was 334 J/cm² and the ectocervical dose was 291 J/cm². Results: Overall HPV clearance was 91.1%, lesion remission 95.3%, and complete response 88.3%, with the highest complete response observed in the HSIL group compared with HPV-positive ASC. Multivariable models showed that multiple HPV infection (especially >3 genotypes) and pregnancy history were associated with lower odds of complete response, while younger age (18–25 years) and TZ2 were associated with higher odds of complete response. Conclusions: PDT using chlorin e6–based photosensitizers demonstrated high clinical and virological effectiveness across HPV-related cervical abnormalities, including HSIL, supporting its role as an organ-preserving treatment option. Multiple HPV genotypes and pregnancy history may identify patients at increased risk of incomplete response and warrant closer follow-up or tailored treatment strategies.