Analysis of the Results of Severe Intraepithelial Squamous Cell Lesions and Preinvasive Cervical Cancer Phototheranostics in Women of Reproductive Age

Abstract

(1) Purpose: To investigate the efficacy and safety of using PDT in the treatment of severe intraepithelial squamous lesions of the cervix and preinvasive cervical cancer associated with HPV in women of reproductive age. (2) Methods: The examination and treatment of 45 patients aged 22–49 years with morphologically confirmed HPV-associated cervical intraepithelial neoplasia of a severe degree (17 patients) and preinvasive cervical cancer (28 patients) were performed. All patients underwent PDT of the cervix using a chlorin e6 photosensitizer; after which, the affected areas of the cervix were evaluated using video and spectral fluorescence diagnostics. PDT effectiveness was assessed on the basis of colposcopy data, a cytological examination of exo- and endocervix and PAP test scrapings or the liquid cytology method, and polymerase chain reaction for HPV carriage 4 weeks after PDT, as well as on the basis of histological and immunohistochemical studies of biopsy materials 5 weeks after PDT. The expression levels of the Ki-67 and p16 markers in the affected areas of the cervix were also assessed. (3) Results. All patients included in the study tolerated the intravenous administration of the photosensitizer well, with no side effects or allergic reactions observed. In 88.2% of patients with CIN III/HSIL and in 85.7% of women with preinvasive cervical cancer, the effect of the treatment was noted after the first PDT procedure, while complete regression of the dysplasia foci was observed in 15 women (88.2%) with CIN III/HSIL and in 25 patients (89.3%) with preinvasive cervical cancer. Partial regression to the form of LSIL/CIN I was noted in two cases (11.8%) in the CIN III/HSIL group and in three cases (10.7%) in the group of patients with preinvasive cervical cancer. After PDT, a statistically significant decrease in the expression of the Ki-67 and p16 levels relative to the initial values was noted. (4) Conclusions. The results obtained indicate the high efficiency of PDT with intravenous administration of the chlorin photosensitizer for the treatment of intraepithelial lesions of the cervix with a selective effect on pathologically altered tissue. The use of this approach makes it possible to preserve the normal anatomical and functional characteristics of the cervix, which is especially important for maintaining the fertility of patients.

Differential Analysis of Pregnancy Outcomes After Treatment of HIFU and LEEP in Patients with Cervical High-Grade Squamous Intraepithelial Lesions

“…Several studies have shown that treatment with ablation has no significant adverse effects on pregnancy outcomes, including preterm birth and PROM. 22 , 23 Although it is important to protect fertility, reducing the persistence or recurrence of precancerous lesions is equally important. Some research suggests that persistence of HPV infection and positive endocervical margins are risk factors for the persistence or recurrence of CIN, and there is no significant association with the type of therapy.…”

Devices and Methods for Dosimetry of Personalized Photodynamic Therapy of Tumors: A Review on Recent Trends

“…Another approach to optimizing PDT treatment parameters on tumor tissue, including spot diameter and radiation fluence, was implemented through numerical simulation of laser radiation propagation with varying fluence and spot diameter in cervical tissue and the monitoring of PS photobleaching and hemoglobin oxygenation degree on phantoms (optical models) imitating the optical properties of cervical tumor tissue [88]. Based on an analysis of all the data obtained and considering the depth of the cervical lesion established through histological examination, the most appropriate laser radiation energy parameters for PDT (spot diameter and radiation fluence) for cervical dysplasia and cancer in 107 patients were determined, thus minimizing side effects and preventing disease progression and recurrence [13,14,52].…”

“…This approach enabled the PDT process to be monitored at all stages of treatment. At Ce6 concentrations of 0.8-1.2 mg/kg, fluorescence images of the cervix exhibited well-defined contrast between pathologic and normal surrounding tissue, allowing for the assessment of PS distribution over the entire measured area with a resolution of 1 mm [13,14,52]. In a separate study, fluorescence diagnostics and 5-ALA-and hexyl aminolevulinate-PDT (HAL-PDT) were employed to examine cervical dysplasia and vulvar leukoplakia in both continuous and pulsed laser irradiation modes.…”

“…Photodynamic therapy (PDT) is one of the prospective methods for the treatment of precancerous and cancerous diseases, which already today shows high antitumor and antiviral efficacy. PDT works on the principle of light-induced activation of photosensitizers (PSs) and leads to cancer cell death mediated by reactive oxygen species (ROS), which ensures tumor growth cessation by triggering apoptosis and/or necrosis processes in the area of laser exposure, damage to blood vessels within the tumor that feed it and deliver oxygen, and has both local cytotoxic and systemic immunomodulatory effects [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16].…”