Optimal number of 5-aminolevulinic acid photodynamic therapy sessions for cervical low-grade squamous intraepithelial lesions with high-risk HPV infection: a retrospective cohort study

Persistent high-risk human papillomavirus (hrHPV) infection is the principal cause of cervical cancer, and although 5-aminolevulinic acid photodynamic therapy (ALA-PDT) has emerged as a minimally invasive treatment for cervical low-grade squamous intraepithelial lesions (LSIL) with hrHPV infection, the optimal number of treatment sessions remains uncertain. We conducted a retrospective cohort study involving 326 women with histologically confirmed cervical LSIL and hrHPV infection from 11 medical centers in China between June 2019 and April 2023 to compare the effectiveness of three-session and six-session ALA-PDT regimens. A total of 268 women completed follow-up and were evaluated 3–6 months after treatment. Overall clinical remission, pathological remission, and hrHPV clearance rates were 77.24%, 91.42%, and 74.25%, respectively. Compared with the three-session regimen, the six-session regimen was associated with significantly higher clinical remission (82.61% vs. 71.54%, P = 0.041) and hrHPV clearance (84.06% vs. 63.85%, p < 0.001), whereas pathological remission did not differ significantly between groups. Subgroup analysis demonstrated that the six-session regimen was associated with significantly improved clinical remission, pathological remission, and hrHPV clearance in women with non-HPV16/18 infection, while no significant differences were observed among those with HPV16/18 infection. These findings suggest that an extended six-session ALA-PDT regimen may provide additional short-term benefit for selected patients with cervical LSIL and hrHPV infection, particularly those with non-HPV16/18 infection. Rather than routinely extending treatment for all patients, treatment duration should be individualized according to baseline characteristics and treatment response. Given the retrospective design and relatively short follow-up, prospective randomized studies with longer-term evaluation are warranted to determine the optimal ALA-PDT treatment strategy.