Cervical cancer, the fourth most common female malignancy and one of the main causes of female cancer-related fatalities, poses a significant challenge and affects the quality of life and safety of women globally [1]. Despite a consistent decline in cervical cancer incidence and mortality rate in recent years, there were still 604,000 new cases and 342,000 deaths worldwide in 2020. Among these cases, a significant disparity exists between the incidence and mortality rate, with 90% occurring in developing countries [2]. Persistent high-risk human papillomavirus (HR-HPV) infection is the primary risk of cervical intraepithelial lesions and cervical cancer [3], in particular, HPV16 and 18 infections, which can be detected using Cobas HPV testing that detects HPV16, 18, and 12 other types of HR-HPV [4,5].

According to the 5th edition of the World Health Organization (WHO) Classification of Female Genital Tumors [6], cervical intraepithelial lesions are classified into two categories: low-grade squamous intraepithelial lesions (LSIL), including cervical intraepithelial neoplasia grade 1 (CIN1), and high-grade squamous intraepithelial lesions (HSIL), encompassing CIN2 and CIN3. Research findings indicate that approximately 20–30% of HSIL cases may progress to invasive cervical cancer over a 10-year follow-up period [7]. Therefore, active intervention measures are typically required to treat HSIL. However, controversy exists regarding LSIL or CIN1 management [5]. In general, approximately 22% of LSIL cases remain stable, 66% of LSIL cases can be cleared without treatment, and 12% of LSIL cases progress to HSIL within 2 years [8]. But persistent HR-HPV infection significantly increases the risk of persistent or progressive lesions in LSIL patients, while reducing the possibility of lesion regression [9]. Therefore, implementing appropriate intervention strategies is crucial for LSIL associated with HR-HPV in order to promote the clearance of cervical lesions and HPV, thereby reducing the occurrence of cervical precancerous lesions and cervical cancer.

Currently, the available intervention methods for LSIL include resection (e.g. loop electrosurgical excision procedure, LEEP) or ablation. However, both procedures may lead to intraoperative and postoperative bleeding. Following surgery, issues such as cervical anatomical structural damage and cervical stenosis may arise, potentially affecting fertility and leading to complications, including premature birth, premature membrane rupture, low birth weight, and other adverse pregnancy outcomes [10].

Photodynamic therapy (PDT) is a combination approach that relies on the interplay between light, photosensitizer and oxygen [11]. Topical ALA-PDT that utilizes predrug 5-aminolevulinic acid (ALA) is markedly advantageous for its high selectivity towards lesion tissue and minimally invasive characteristics [12]. After ALA-PDT treatment, the number of local CD4+ lymphocytes increases, thereby regulating local immunity and improving the body's antiviral ability, and ultimately promoting HPV clearance [13].

This retrospective study aimed to compare the effects of ALA-PDT, LEEP and observation methods on lesions and HPV clearance in patients with cervical LSIL and HR-HPV infection. The findings could provide valuable evidence for utilizing PDT in the field of cervical lesions.