Photodiagnosis and Photodynamic Therapy

5-aminolevulinic acid photodynamic therapy inhibits the viability, invasion, and migration of cervical cancer SiHa cells by regulating the miR-152-3p/JAK1/STAT1 axis

Cervical cancer ranks the fourth most prevalent type of cancer worldwide, characterized by a notably low survival rate, particularly in its metastatic stage. Despite 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrating potential anti-tumor effects against cervical cancer, the intricate mechanisms underlying its efficacy necessitate further investigation. Here, the study aims to elucidate the impact of ALA-PDT on the cancer cell viability, invasion and migration, alongside delineating the underlying molecular mechanisms. Cervical cancer SiHa cells were subjected to ALA and red light irradiation, and we then measured the ALA-PDT's effects on cell functions using various assays. The potential interaction between miR-152-3p and JAK1 was explored through bioinformatics analyses and validated by dual-luciferase reporter assays. Post-transfection with miR-152-3p and JAK1 vectors, cellular functions were re-evaluated. The efficacy of ALA-PDT in tumor suppression was further investigated through tumor transplantation experiment in vivo. ALA-PDT markedly suppressed SiHa cell viability, invasion and migration, impacting critical markers of proliferation, apoptosis, and epithelial-mesenchymal transition(EMT). And these effects were echoed by the inhibition of miR-152-3p. JAK1 was identified as a direct target of miR-152-3p, and ALA-PDT was found to regulate the expression levels of miR-152-3p, consequently influencing the JAK1/STAT1 signaling pathway. Augmentation of miR-152-3p expression and inhibition of the JAK1/STAT1 pathway mitigated the anti-cancer effects of ALA-PDT, whereas JAK1 overexpression diminished these effects. In vivo analyses demonstrated that ALA-PDT suppressed tumor growth and modulated the miR-152-3p/JAK1/STAT1 pathway expression. ALA-PDT inhibits the viability, invasion, and migration of cervical cancer SiHa cells by modulating the miR-152-3p/JAK1/STAT1 axis, offering a promising therapeutic avenue for combating invasive cervical cancer.

Surgery combined with photodynamic therapy for early-stage endometrial carcinoma, a report of two cases

Endometrial carcinoma (EC) is one of the most prevalent gynecological malignancies and the onset age of EC tends to be younger. This case report explored the feasibility of surgery combined with photodynamic therapy (PDT) in two young patients with early-stage EC. A 31 years old patient and a 24 years old patient were treated with surgery and PDT, respectively. The intraoperative PDT was performed 3 h after oral administration of 5-aminolevulinic acid (ALA) with intrauterine light irradiation of 630 nm laser light. The patients were followed up for 3 years and 4 months, respectively. There were no signs of recurrence. Intraoperative and intrauterine PDT was feasible and might be used for EC patients who attempt to preserve fertility.

Vulvar intraepithelial neoplasia, grade III, treated with photodynamic therapy: A case report

Vulvar intraepithelial neoplasia (VIN) is a precancerous lesion on the vulvar epidermis that does not invade or metastasize to surrounding stroma; it manifests as atypical intraepithelial hyperplasia on the vulva. Most patients with VIN are diagnosed early, and treatment with standardized therapy often leads to complete regression of symptoms. The treatment of VIN is still a challenge for clinicians because, in most cases, surgery is destructive and risky. However, photodynamic therapy (PDT) was recommended as a new treatment for VIN. Herein, we report the case of a patient with a large-area high-grade VIN lesion complicated by human papillomavirus infection. The patient could not undergo surgical treatment. However, treatment with PDT was performed in our outpatient department. There was slight pain during the treatment after multi-point injection of micro-lidocaine (0.05 mL/dot) was given. No recurrence was noted after 13 months of follow-up. More importantly, scarring and other major side effects were not detected. Therefore, PDT can be a useful alternative treatment for patients with VIN with large lesions or multifocal high-grade VIN.

Evaluation of 5-aminolevulinic acid-mediated photodynamic therapy in postmenopausal women with persistent HPV infection with or without cervical and vaginal low-grade squamous intraepithelial lesions (CIN1/VaIN1)

To analyze the efficacy and safety of photodynamic therapy (PDT) on postmenopausal women with persistent human papillomavirus (HPV) infection with or without low-grade cervical and vaginal intraepithelial neoplasia (CIN1 and VaIN1). The clinicopathological and follow-up data of 86 postmenopausal women with HPV infection (35 cases with chronic cervicitis and 51 cases with CIN1/VaIN1) were collected. All the women in this group met these criteria: menopausal time ≥ 1 year, HPV infection time ≥ 2 years, colposcopy and pathological diagnosis of biopsy ≤ CIN1/VaIN1 before PDT treatment, and 5-aminolaevulinic acid (5-ALA) as photosensitizer treating for 6 times with a week interval. The above patients were followed up 6 months and 12 months after PDT treatment, and the follow-up contents included HPV typing, cytology, colposcopy and pathological examinations. HPV negative conversion rate and lesion remission rate are the evaluation indicators of treatment efficacy. In addition, we also assessed the safety of PDT treatment. At 12-month follow-up, the overall HPV clearance rate was 60% (45/75), of which the negative conversion rate of 16/18 HPV was 41.38% (12/29), and non-16/18 HPV was 71.74% (33/46) (p = 0.009). In patients without lesions, the HPV clearance rate was 51.72% (15/29), while in patients with CIN1/VaIN1 (n = 46), the HPV complete remission rate and lesion regression rate were 65.22% (30/46) and 89.13% (41/46), respectively. In addition, the clearance rate of HPV in lesion regression group was significantly higher than that in lesion persistence/progression group (0.00% vs. 73.17%, p = 0.003). The adverse reactions after PDT treatment were mild, mainly manifested as increased vaginal secretions or burning/tingling. Photodynamic therapy can significantly enhance the elimination rate of persistent HPV infection in postmenopausal women and reduce the progression of CIN1/VaIN1. It could be an effective conservative treatment for persistent HPV infection and CIN1/VaIN1 in postmenopausal women.

Comparison of ALA-PDT and CO2 laser treatment of low-grade vaginal intraepithelial neoplasia with high-risk HPV infection: A non-randomized controlled pilot study

To evaluate the efficacy and safety of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) and CO A total of 163 patients with VAIN1 and hr-HPV infection were divided into PDT Group (n = 83) and CO The overall HPV clearance rate of the PDT Group was significantly higher than that of the CO The efficacy of ALA-PDT appears better than CO

A pilot study of repeated 5-aminolevulinic acid photodynamic therapy for cervical intraepithelial neoplasia by a newly developed intravaginal irradiation system

The pilot study was performed to assess the usefulness of a newly developed patientand physician-friendly intravaginal irradiation system for photodynamic therapy with 5-aminolevulinic acid (5-ALA PDT) for cervical intraepithelial neoplasia (CIN). We used an intravaginal balloon applicator to make the cervix upright and to adjust the position and direction of the laser source in the vagina, resulting in minimal patient discomfort and minimal effort required by the physician during irradiation. Ten outpatients of CIN2 or 3 with high-risk human papillomavirus (HPV) infection without a history of HPV vaccination were treated by 5-ALA PDT. Each patient underwent PDT four times every two weeks. Nine patients showed pathological improvement, and the HPV clearance rate was 80%, and no recurrence was observed at two-years follow-up. Serum anti-HPV16 antibodies were detected in seven patients, and the antibody levels of three patients were high, equivalent to those acquired after HPV vaccination. Our newly developed irradiation system enabled easy repeat 5-ALA PDT in the outpatient clinic resulting in the improvement of CIN lesions and HPV clearance. Our results also suggested that repeated 5-ALA PDT might enhance HPV antibody production in CIN patients.

Efficacy of different 5-aminolevulinic acid photodynamic therapy regimens in managing HSIL/CIN2 among reproductive-age women: A retrospective study

High-grade squamous intraepithelial lesion (HSIL) is a precancerous lesion that requires timely and effective intervention. Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) has emerged as a non-invasive, fertility-preserving alternative to excisional procedures. However, the ALA-PDT regimen remains to be optimized. To compare the efficacy and safety of three treatment strategies-three-session PDT (3PDT), six-session PDT (6PDT), and a single CO This retrospective cohort study included 158 women aged 20-45 years with biopsy-confirmed cervical HSIL/CIN2. Participants received one of three regimens: 3PDT (n = 49), 6PDT (n = 47), or Laser + 6PDT (n = 54). Lesion regression and high-risk HPV (hrHPV) clearance were assessed at 3-6 and 9-12 months post-treatment. A subset of patients was followed up to 18-24 months. Adverse events were also recorded. At the 3-6 months follow-up, the complete remission (CR) rates were 67.35 % (3PDT), 74.47 % (6PDT), and 79.63 % (Laser + 6PDT), with hrHPV clearance rates of 67.35 %, 72.34 %, and 77.78 %, respectively. Differences among groups were not statistically significant (P > 0.05). By 9-12 months, CR rates reached ≥90 % in all groups, and hrHPV clearance exceeded 80 %. At 18-24 months, hrHPV clearance reached 100 % in the 6PDT group, while three patients in the 3PDT group experienced HPV recurrence. All regimens were well tolerated, with only mild adverse events reported. All three ALA-PDT-based regimens were effective and safe in treating HSIL/CIN2 in reproductive-age women. Although not statistically significant, six-session PDT with or without laser pretreatment showed a trend toward higher lesion remission and hrHPV clearance. Individualized treatment decisions based on disease severity, patient preference, and cost factors are recommended to optimize outcomes.

A global approach for the development of photodynamic therapy of peritoneal metastases regardless of their origin

Surgical management of peritoneal metastases raises the problem of the theoretical spread of the entire peritoneal surface. Intraperitoneal photodynamic therapy (IntraPDT) has been limited by the lack of specificity of photosensitizers (PS) and difficulties to bring light into the abdominal cavity. Recent data in ovarian cancer may give development opportunities for IntraPDT. Intraperitoneal PDT could be an option but the level of evidence of research in this topic must increase. Our opinion is that the most important is to have a realistic idea of what we can objectively expect from PDT and the feasibility of its daily application. At the time of personalized medicine, it is mandatory to select population eligible for a targeted PS administration and who could benefit from the process. The design of a specific PS for each subtype of cancers seems essential to avoid side effects on healthy tissue. On the contrary, our progress on lighting solutions can be beneficial for all patients with an indication of IntraPDT regardless of the origin of PM. A common lighting system developed for all cancers eligible for IntraPDT could be adapted with light source of specific wavelength to activate dedicated PS.

The effect of 5-Aminolaevulinic Acid Photodynamic Therapy versus CO2 laser in the Treatment of Cervical Low-grade Squamous Intraepithelial Lesions with High-Risk HPV Infection: A non-randomized, controlled pilot study

There are insufficient studies comparing the efficacy of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) against CO Patients with cervical LSIL and HR-HPV infection were divided into two treatment groups based on their own choice. All patients had a follow-up test including HPV testing, cytology and colposcopy at 4-6 months and 12 months after the treatment. (1) Among 277 patients, 176 patients received 5-ALA PDT and 101 patients received CO The effect of 5-ALA PDT is similar to CO

Efficacy of photodynamic therapy in women with HSIL, LSIL and early stage squamous cervical cancer: a systematic review and meta-analysis

We sought to conduct a systematic review and meta-analysis of randomized and non-randomized clinical trials to assess the efficacy of photodynamic therapy (PDT) in cervical epithelial neoplasia (CIN) and early-stage cervical cancer. Additionally, according to the results, we tried to consider which stage of CIN is more sensitive to PDT. A systematic search was conducted using electronic databases including PubMed, ClinicalTrials.gov, the Cochrane Library, and Google Scholar. all patients had confirmed low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), or an early-stage cervical cancer - the cancer is less than 3 mm deep into the cervix -IA; type of photosensitizer and any type of wavelength. women who were previously treated with PDT; Risk of bias assessment was carried out for each study included in the systematic review using the Cochrane Handbook for Systematic Reviews of Interventions: RoB-2 was used to assess the risk of bias in randomized studies, while ROBINS-I - in non-randomized ones. We identified 2213 publications, but only 6 met the inclusion criteria and were included in the synthesis. PDT is most effective when patients have CIN 2 or photosensitizer is administered intravenously. Based on our systematic review and meta-analysis, it could be concluded that photodynamic therapy may be a practical approach in CIN (LSIL) regression compared with placebo. Nevertheless, we need more evidence and long-term follow-up to answer all questions thoroughly.

Effectiveness of photodynamic therapy in women of reproductive age with cervical high-grade squamous intraepithelial lesions (HSIL/CIN2)

To evaluate the histologic response rate of high-grade squamous intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia 2 (CIN2) of the cervix after photodynamic therapy (PDT) treatment in women with fertility requirements. A retrospective study was carried out comprising 31 female patients aged 20-38 years with histologically confirmed HSIL/CIN2 with high-risk human papillomavirus (hrHPV) infection. Patients were treated with three sessions of 20% 5-aminolevulinic acid (5-ALA) PDT at intervals of 7-14 days. All patients had a follow-up including cytology, HPV testing and colposcopy-directed biopsy after PDT treatment at the 6-month and 12-month follow-up points. The main outcome measure was efficacy, defined as complete histologic remission 12 months after PDT. Secondary outcomes were the remission of HPV infection and the adverse effects of PDT treatment. At the 12-month follow-up, 21 out of 27 patients (77.78%) and 4 out of 27 patients (14.81%) showed histologic disappearance and histologic regression, respectively. Only 7.41% (2/27) patients persisted with HSIL/CIN2. In addition, no patients progressed to CIN3 or carcinoma. The total baseline HPV remission rate was 62.96% (17/27). The remission rate of HPV16/18 was statistically significant compared to the other hrHPV (57.14% vs. 100%, p = 0.016) in the group with HISL/CIN2 disappearance. Adverse events were mild, with increased vaginal secretion and abdominal pain being the most common complaints. There was no report of adverse events such as vaginal bleeding, colporrhagia, ulcer, or abdominal pain after PDT treatment. 5-ALA-PDT shows a favorable efficacy and safety profile and represents a promising alternative to observation and surgical procedures in patients with HSIL/CIN2 who have fertility requirements.

Efficacy and safety of photodynamic therapy mediated by 5-aminolevulinic acid for the treatment of cervical intraepithelial neoplasia 2: A single-center, prospective, cohort study

Photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (5-ALA) is a minimally-invasive treatment for cervical intraepithelial neoplasia (CIN). The present study was carried out to investigate the effect of 5-ALA-PDT on CIN2 and the factors influencing outcome of 5-ALA-PDT. Patients diagnosed as CIN2 who met the inclusion criteria were enrolled in this study sequentially from January 2019 to April 2020. Patients were treated by PDT or cryotherapy according to their intentions. The primary endpoint was pathological regression. The secondary endpoint was HPV clearance. Affecting factors of the efficacy of PDT and adverse events were also assessed during treatment. A total of 210 patients were enrolled, including 97 patients in PDT group and 101 patients in cryotherapy group, with 12 patients excluded. There was no statistical difference in population characteristics. The pathological regression rate in PDT group was 92.0% (80/87), compared with 81.4% (79/97) in cryotherapy group (P < 0.05). The HPV clearance rate was 64.4% (56/87) in PDT group and 57.8% (56/97) in cryotherapy group (P = 0.36). The main side effects of PDT were abdominal pain (24.1%, 21/87) and increased vaginal secretions (23.0%, 20/87). On univariate analysis, the risk for lesions persisting at 6 months after PDT was increased by recurrent genital tract inflammation (P = 0.004), smoking or passive smoking (P = 0.020), and multicentric lesions (P = 0.020). PDT can be a safe and efficient treatment for CIN2. Risk factors for persisting HSIL after PDT include recurrent genital tract inflammation, smoking or passive smoking, and multicentric lesions.

Ferroptosis promotes 5-aminolevulinate acid-based photodynamic therapy in cervical cancer

Cervical cancer has the highest incidence rate among all gynecologic malignancies. Photodynamic therapy (PDT) is a minimal invasive treatment widely used in various tumors. Intracellular generation of reactive oxygen species (ROS) is the essential effect in PDT, which also plays a pivotal role in ferroptosis. We hypothesize that ferroptosis inducer could enhance 5-Aminolevulinic acid (5-ALA) based PDT in cervical cancer. In vitro efficacy of 5-ALA-based photodynamic therapy was assessed via viability and apoptosis of cervical cancer cell line SiHa. Ferroptosis related markers were detected in SiHa cells received 5-ALA-PDT treatment. Anti-tumor effects of ferroptosis inducer sorafenib on 5-ALA-based photodynamic therapy were evaluated in both cell line and mouse model. Efficacy of 5-ALA-based photodynamic therapy was validated in SiHa cervical cancer cells. Increased intracellular generation of ROS and lipid ROS, accompanied by decreased GPX4 expression was observed after 5-ALA-PDT treatment, indicating ferroptosis triggered by photodynamic therapy. Ferroptosis inducer sorafenib, a clinical approved cancer drug, promotes 5-ALA-based photodynamic therapy in SiHa cells. In vivo combined anti-tumor effect of sorafenib and 5-ALA-based photodynamic therapy was confirmed in cervical cancer xenografts. We identified that 5-ALA-PDT inhibited cell viability and induced ferroptosis in cervical cancer. Ferroptosis inducer sorafenib promotes 5-ALA-based photodynamic therapy. These findings may provide new insights into mechanisms of photodynamic therapy and cervical cancer treatment in the future.

A prospective study of photodynamic therapy for cervical squamous intraepithelial lesion

To evaluate the efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) for the treatment of cervical squamous intraepithelial lesion (SIL). We prospectively screened and enrolled patients with cervical SIL and persistent high-risk human papilloma virus (HR-HPV) infection to receive ALA-PDT from March 27, 2019, to January 23, 2020, at Beijing Youan Hospital, China. The primary outcome was the remission rate of SIL and HPV. The secondary outcome was the symptom improvement and adverse events of ALA-PDT in these cases. 54 patients with cervical SIL and persistent HR-HPV infection were enrolled and divided these individuals into three groups: high-grade squamous intraepithelial lesion (HSIL) group (10 patients), low-grade squamous intraepithelial lesion (LSIL) group (33 patients), and simple HR-HPV infection group (11 patients). 49 of 54 patients finished six sessions treatment and 46 of 49 patients complete the follow-up. After six sessions' treatment, HR-HPV remission rates were 71.43 %(5/7)in the simple HR-HPV infection group, 63.64 %(14/22) in the LSIL group, and 50 %(4/8) in the HSIL group. The histology remission rates were 80 %(4/5) in the simple HR-HPV infection group, 69.57 %(16/23)in the LSIL group, and 75 % (6/8) in the HSIL group. Symptoms improvement rates in the simple HR-HPV infection, LSIL group, and HSIL group were 100 %(5/5), 66.67 %(5/15) and 71.43 %(5/7). No severe adverse events or systemic side effects were observed in treatment. Topical ALA-PDT is an effective and safe treatment for cervical SIL.

Successful treatment by a chlorin e6 derivative mediated photodynamic therapy combined holmium laser for cervical and vaginal giant condyloma acuminata and low-grade intraepithelial neoplasia:A case report

Photodynamic therapy (PDT) is proved effective for treating low-grade squamous intraepithelial lesions (LSIL) and condylomata acuminata (CA). 5-Aminolevulinicacid (5-ALA) is the most common applied photosensitizer, but high rate of unbearable pain and relative long incubation time were reported. Here, we report a 27-year-old woman suffering from cervical and vaginal giant CA with LSIL involving the whole right vaginal fornix, cervical surface, and vaginal wall. Holmium yttrium aluminum garnet (Ho: YAG) laser was first applied to remove the giant CA lesions. STBF, a derivative of chlorin e6 (Ce6) was then applied on suspicious lesions as a new photosensitizer for 1 h. Lesions were exposed to LED illumination with a wavelength of 630 nm and light dose of 200-284 J/cm

Laser ablation combined with photodynamic therapy for complex vaginal HSIL after repeat cervical conizations: a case report

Cervical and vaginal high-grade squamous intraepithelial lesions (HSIL) are typically managed by excision or ablation. However, surgical excision is restricted in young women. In this case report, complex vaginal HSIL was diagnosed in a 38-year-old woman who previously received two conization treatments of cervical HSIL. The patient underwent two courses of CO₂ laser ablation for cervical and vaginal lesions, followed by two courses of PDT to residual lesions in the vaginal vault. Six months' follow-up revealed pathological cure and HPV clearance. Laser ablation combined with PDT is an effective treatment for patients with concomitant cervical and vaginal HSILs.

Evaluation of the efficacy of topical photodynamic therapy against cervical HPV infection

Persistent high-risk HPV (hr-HPV) infection is a leading cause of cervical cancer. Currently, there are no specific treatment available that can eradicate the HPV virus. Studies demonstrate that photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) is highly effective for treating precancerous lesions and HPV infection of the cervix and vagina. To evaluate the efficacy of ALA PDT for patients with hr-HPV infections but without precancerous cervical lesions. Thirty-one patients with persistent hr-HPV infection for over one year were treated with topical ALA PDT. HPV tests, cytological examinations or colposcopy-guided biopsies were performed before and after treatment. Symptoms and adverse reactions related to PDT were also evaluated. Six-month follow-up showed that the effective rate in treating simple HPV infection was >70 %. Subgroup analysis demonstrated that the presence of vaginitis, absence of significant cervical pathological changes, Type III transformation zone, and a prior history of cervical surgery were all significantly associated with persistent HPV positivity after PDT (p < 0.05). Further multivariate analysis confirmed that vaginitis and the lack of mucosal abnormalities in cervical pathology independently predicted persistent HPV positivity after PDT. In HPV-related koilocytic atypia, Ki-67 expression extended beyond the normal proliferative zone, with positive nuclei throughout the epithelium. This may indicate a mechanism for improved HPV clearance after PDT. No severe adverse events occurred during the treatment. Post-treatment evaluation revealed no structural damage or invasive alterations to the cervix. ALA-PDT is a highly effective and safe non-invasive field-directed treatment option for patients with hr-HPV infection.

Effect of topical photodynamic therapy with 5-aminolevulinic acid in the treatment of high-risk cervical low-grade squamous intraepithelial lesions

This study aimed to investigate the clinical efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of high-risk cervical low-grade squamous intraepithelial lesion (LSIL) and to analyze the influence of different risk factors on the efficacy. The clinical data of 173 patients with persistent cervical LSIL and high-risk human papillomavirus (HR-HPV) infection were retrospectively analyzed. After treatment, HPV and TCT were reexamined every 3 months, and colposcopic biopsy was performed if necessary. At 6 months of follow-up, the HPV clearance rate, complete remission (CR) rate, persistence rate, and progression rate were 73.41%, 89.60%, 8.09%, and 2.31%, respectively. The HPV clearance rate showed an upward trend with time. Moreover, the CR rates of patients with 41-50 years old group, positive HPV16/18 genotyping, and type 3 transformation zone (TZ) were 77.14%, 84.52%, and 83.33%, respectively; these rates were significantly lower compared to patients without the corresponding high-risk factors (P = 0.021, 0.045, 0.042), but had no significant effect on HPV clearance rate. A subgroup analysis based on TCT results revealed no significant effect on the efficacy of ALA-PDT in the treatment of high-risk cervical LSIL. Furthermore, the 6-month CR rate and 2-year HPV clearance rate of the patients with both positive HPV16/18 genotyping and TZ3 were significantly lower than those of the patients without the two high-risk factors (73.53% vs. 94.74%, P = 0.010; 78.95% vs. 97.67%, P = 0.028, respectively). ALA-PDT is a safe and effective treatment for high-risk cervical LSIL. Its efficacy could be affected by patient age, HPV type, and cervical TZ type.

Evaluation of the efficacy and safety of 5-aminolevulinic acid-mediated photodynamic therapy in women with high-risk HPV persistent infection after cervical conization

To evaluate the efficacy and safety of photodynamic therapy (PDT) in women with high-risk human papillomavirus (hr-HPV) persistent infection after cervical conization, including loop electrosurgical excision procedure (LEEP) and cold knife conization (CKC). The clinicopathological and follow-up data of 76 women with hr-HPV persistent infection after cervical conization (54 cases with LEEP and 22 cases with CKC) were collected. All the women in this group met these criteria: postoperative pathological diagnosis of LEEP/CKC showed high grade squamous intraepithelial lesions (HSIL) with negative incisal margin, hr-HPV persistent infection after LEEP/CKC ≥ 1 year, colposcopy and histopathology showed no intraepithelial lesions before PDT, and 5-aminolaevulinic acid (5-ALA) as photosensitizer treating for 6 times with an interval of 7-10 days. The above patients were followed up 6 months and 12 months after PDT, and the follow-up contents included Roche Cobas HPV classification test, cytology, colposcopy, and pathological examinations. HPV negative conversion rate is an index to evaluate the efficacy of PDT. In addition, we also assessed the safety of PDT. Six months after PDT, the overall HPV clearance rate was 59.21% (45/76). The HPV negative conversion rates in patients ≤ 50 years old group and > 50 years old group were 68.52% (37/54) and 36.36% (8/22), respectively (P=0.009). But there was no significant difference in HPV clearance rate between the HPV16/18 infection group and other hr-HPV infection group (P=0.3326). 12 months after PDT, 1 case underwent hysterectomy because of progression to HSIL, and 7 cases lost follow-up. The overall HPV clearance rate was 88.24% (60/68). The negative conversion rates of HPV16/18 and other hr-HPV infection groups were 76.00% (19/25) and 95.35% (41/43), respectively (P=0.0458). However, the HPV negative conversion rate was not correlated with the patient's age (P=0.2383). The adverse reactions after PDT were mild, mainly manifested as increased vaginal secretions or burning/tingling. Photodynamic therapy could be an effective treatment for patients with hr-HPV persistent infection after cervical conization and it could promote the negative conversion of hr-HPV and prevent the recurrence progression of cervical intraepithelial neoplasia (CIN) after LEEP/CKC.

Efficacy of photodynamic therapy for cervical intraepithelial neoplasia grade 3: a retrospective study

This study aimed to evaluate the histologic response rate of high-grade squamous intraepithelial lesion (HSIL), also referred to as cervical intraepithelial neoplasia 3 (CIN 3), following treatment with 5-aminolevulinic acid photodynamic therapy (ALA-PDT). A retrospective analysis was conducted on 49 patients diagnosed with CIN 3 and treated with ALA-PDT between March 2022 and December 2024. Patients received either ALA-PDT alone or in combination with the Loop Electrosurgical Excision Procedure (LEEP) or CO Among the 44 patients with complete follow-up, the total response rate was 85.19% (23/27) for ALA-PDT alone and 88.24% (15/17) for combination therapy, yielding an overall response rate of 86.36% (38/44). The double-negative rate (negative for both HPV and histopathology) was 100%. When stratified by age group, pathology-negative outcomes-considered effective treatment responses-were observed in 100% of patients younger than 20, 80% of those aged 21-30, 93.7% in the 31-40 age group, and 100% in patients over 40. The total effective rates across different cervical transformation zones (TZ) were 75% (18/24) for TZ1, 100% (12/12) for TZ2, and 100% (8/8) for TZ3. Negative HPV conversion rates were 82.35% (28/34) in the HPV16/18-positive group, 80% (8/10) in the non-HPV16/18 group, and 73.33% (11/15) in the multiple high-risk HPV group. ALA-PDT demonstrates favorable efficacy and stability in patients with HSIL/CIN 3, offering clinicians an additional option for managing these cervical lesions.

A micro-Raman spectroscopy study of inflammatory condition of human cervix: Probing of tissues and blood plasma samples

The present study explores the application of the micro-Raman spectroscopy technique to discriminate normal and cervicitis condition from cervical malignancy by analyzing the Raman signatures of tissues and plasma samples of the same subjects. The Raman peaks from tissue samples at 1026 cm

The effect of local photodynamic therapy with 5-aminolevulinic acid in the treatment of vaginal intraepithelial lesions with high-risk HPV infection

Recent data has shown increased rate of vaginal intraepithelial neoplasia (VAIN) in younger individuals. Traditional VAIN treatments exert adverse effects on the anatomy and functions of the vagina. Topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a novel, non-invasive targeted therapy for intraepithelial lesions. Here, we aimed to investigate the efficacy and safety of ALA-PDT in VAIN with high-risk HPV (HR-HPV) infection. This study enrolled a total of 82 HR-HPV-positive women diagnosed with VAIN, who were receiving ALA-PDT. The effect of ALA-PDT was evaluated using HPV genotyping and Thinprep cytologic test (TCT). Besides, colposcopy directed biopsies were performed in all patients at 3-month follow-up, and in patients with positive HR-HPV and/or abnormal TCT results during the follow-up period. Our data showed that the HPV clearance rate was 53.7% (44/82) at 6-month follow-up and 67.1% (55/82) at 12-month follow-up. Patients with HPV16/18 combined with other HR-HPV (HPV16/18 & other HR-HPV) infection, those with a history of hysterectomy and/or older age were had significantly lower HPV clearance rate. Besides, the lesion complete remission (CR) rate was 90.2% (74/82). These results show that HPV16/18 & other HR-HPV infection was associated with significantly lower CR rates. Throughout the follow-up, 2 cases had persistent lesions (2.4%), 6 cases had partial remission (7.3%), 2 cases recurred (2.7%) but none of the patients had disease progression. Taken together, our data showed that ALA-PDT is an effective, safe, and alternative treatment for VAIN patients with HR-HPV infection. However, the ALA-PDT efficacy was relatively poor in patients with older age, HPV16/18 & other HR-HPV infection and/or those with a history of hysterectomy.

Evaluating photodynamic therapy protocols for high-grade cervical neoplasia: A comparative study

Cervical cancer has the infection by the Human Papillomavirus (HPV) as one of the main conditions for its development. Photodynamic Therapy (PDT) is a non-invasive treatment that combines the interaction between oxygen, light, and a photosensitizing molecule, resulting in cellular damage. HPV - infected cells because they are metabolically more active, can be better affected by this technique, promoting an alternative topic treatment for Cervical Intraepithelial Lesions (CIN). The present prospective and randomized study compared three PDT protocols applied to 31 patients with high-grade CIN and infected by HPV. Protocols used LEDs with a wavelength of 630 nm and a fluence of 150 J/cm

The effect of high-risk HPV E6/E7 mRNA on the efficacy of topical photodynamic therapy with 5-aminolevulinic acid for cervical high-grade squamous intraepithelial lesions

E6 and E7 high-risk human papillomavirus (HR-HPV) oncoproteins are closely associated with the initiation and progression of cervical cancer (CC) and pre-cancerous lesions. Cervical high-grade squamous intraepithelial lesions (HSIL), as pre-cancerous lesions, have a 5% chance of progressing to invasive cancer. Topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a novel non-invasive targeted therapy for intraepithelial lesions. Herein, we analyzed the effect of HR-HPV E6/E7 mRNA on ALA-PDT for cervical HSIL. A retrospective analysis of 148 HR-HPV-positive patients diagnosed with cervical HSIL and receiving ALA-PDT was carried out. ALA-PDT was performed with 20% ALA thermosensitive gel, and irradiation at wavelength of 635 nm and density of 80-100 J/cm At the 6-month follow up, the complete remission (CR) rate of patients' lesions was 86.5% (128/148), whereas the total HPV clearance rate was 72.3% (107/148). It was evident that positive E6/E7 mRNA before treatment had a significant effect on HPV clearance rate (66.3% VS 81.4%, P = 0.045) and CR rate (80.9% VS 94.9%, P = 0.015). The E6/E7 mRNA associated with HPV16/18 and HPV16/18 combined with other HR-HPV (HPV16/18 and other HR-HPV) affected HPV clearance (P = 0.035) and lesions CR (P = 0.039), respectively. Moreover, persistently positive E6/E7 mRNA after treatment was closely associated with poor efficacy (HPV clearance rate: P = 0.000, CR rate: P = 0.000). Throughout the follow up period, two cases recurred but none of the patients progressed. This study has shown that ALA-PDT is an effective, safe, and alternative treatment for cervical HSIL, especially for the patients of childbearing age. However, its efficacy is relatively poor in patients with persistently positive E6/E7 mRNA before and after treatment, who are relatively insensitive to ALA-PDT.

Efficacy and safety of photodynamic therapy mediatied by 5-aminolevulinic acid for the treatment of cervical intraepithelial neoplasia 3(CIN 3): A single-center, prospective, cohort study

Cervical intraepithelial neoplasia grade 3(CIN 3) is a precancerous lesion condition with high progression rate and is advised to be treated immediately. Because traditional treatments have limited effects or complications, here we evaluated the efficacy and safety of topical 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT). This study consisted of 56 female patients diagnosed with CIN3. A 20 % 5-ALA jelly formation was topically applied to the cervix, followed by 635 nm PDT at 7-14 days intervals. Cytology, human papillomavirus (HPV) genotyping, colposcopy, and pathology were assessed after treatment. Among the 56 patients in our study, 26.8 % (15/56) patients had disease remission after just one course PDT, 69.6 % (39/56) patients had partial remission to CIN2, which suggested a response to the therapy and should be treated with more course. The total pathological regression rate was 89.3 %(50/56). Although6 patients did CKC finally, none of the pathology suggest cervical cancer and 2 of them were LSIL. The HPV clearance rate during the 6-month follow-up was 51.8 %. 4 patients had recurrent disease during the 2-year follow-up time point. The most common adverse event was increased vaginal discharge, other side effects include abdominal pain, vulvar pruritus, and vaginal bleeding. No severe adverse effect was observed during the treatment. ALA-PDT is a treatment option for CIN 3 which meet certain conditions, with the main goal to preserve the struction and founction of cervix.

Comparative analysis of photodynamic therapy and conization for cervical high-grade squamous intraepithelial lesion: A systematic review and meta-analysis

This review aims to compare the effectiveness of photodynamic therapy (PDT) with conization, including loop electrosurgical excision procedure (LEEP) and cold-knife conization (CKC), in treating cervical high-grade squamous intraepithelial lesions (HSIL). PubMed, Cochrane Library, Google Scholar, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched. The outcomes assessed were complete response (CR) rate, human papillomavirus (HPV) eradication rate, recurrence rate, and adverse events (AEs). 9 studies were included. A total of 312 patients received PDT, while 380 underwent conization (LEEP/CKC). There was no significant difference between PDT and conization in the CR rate at 3-6 months (OR: 1.64 [0.97, 2.76]; P = 0.06), 12-month CR (OR: 0.49 [0.13, 1.90]; P = 0.30), HPV eradication rate at 3-6 months (OR: 1.40 [0.95, 2.07]; P = 0.09), HPV eradication rate at 12 months (OR: 0.92[0.47, 1.82]; P = 0.81), or 12-month recurrence rate (OR: 2.97 [0.62, 14.25]; P = 0.17). However, the rate of AEs, including vaginal bleeding (OR: 0.10 [0.03, 0.33]; P = 0.0002), cervical canal adhesion (OR: 0.16 [0.03, 0.90]; P = 0.04), and cervical scar formation (OR: 0.04 [0.01, 0.30]; P = 0.002), was significantly lower with PDT than with conization. The degree of heterogeneity was not high. Based on our systematic review and meta-analysis, it could be concluded that PDT may be a practical approach for cervical HSIL regression compared to conization (LEEP/CKC). However, further high-quality, controlled trials are needed to confirm these findings.

Hiporfin photodynamic therapy for early-stage cervical cancer: A case report

A 28-year-old female patient, diagnosed with stage IA1 cervical cancer, received PDT treatment with intravenous injection of Hiporfin, a HpD type photosensitizer. The patient's human papillomavirus (HPV) and cytology testing results were negative at the 3-month. At 6 months, the lesions on the cervical surface and within the cervical canal had completely resolved. There were no signs of recurrence or HPV infection during the 12-month follow-up period. There were no serious adverse events reported during or after the PDT treatment.

Assessment of systemic reaction to inflammation induced by photodynamic therapy in cervical intraepithelial neoplasia

Photodynamic therapy is a curative treatment of human papillomavirus-associated diseases that provides a selective effect leading to the destruction of pathological cells containing the virus. The retrospective study aimed to determine the role of systemic inflammatory reaction induced by photodynamic stimulation in low- and high-squamous intraepithelial lesion treatment. 143 patients with confirmed human papillomavirus-associated cervical intraepithelial neoplasia underwent photodynamic therapy with Photolon and activation in the range of 662 nm. All patients underwent colposcopy, histologic study, HPV DNA analysis, CBC, and immunogram. The chi-square criterion was used to evaluate differences before, 5 days post, and 3 months after PDT; a P value <0.05 was considered significant. A complete regression in patients with low-squamous intraepithelial lesion (n=117) was achieved 3 months after PDT in 89.7% of cases (105/117) while it persisted in 12 patients. Complete regression in patients with high-squamous intraepithelial lesion (n=26) was achieved in 92.3% (24/26), one patient retained with the lesion, and another one had partial regression in the form of lower grade lesion. On the 5th day post-PDT, the formation of dense fibrin in photodynamic effect was noted on colposcopy, and changes in CBC, accompanied by statistically significant neutrocytosis, increased ESR and other indicators of reactive inflammation were recorded. Patients noted increased body temperature up to 37.8±0.5°C in 88% of cases. One of the mechanisms of PDT`s antitumor and antiviral action is the development of acute inflammation in response to cytotoxic action on cells and vascular response in the form of pathological area devascularization. Such reactive inflammation activates all parts of the immune system. Changes on day 5 post-PDT in inflammatory parameters in CBC and IL-1, IL-6 and TNF-α markers correlate with the clinical picture of the post-photodynamic effect.

Efficacy and safety of photodynamic therapy mediatied by 5-aminolevulinic acid for the treatment of vaginal high-grade intraepithelial lesions

Vaginal high-grade squamous intraepithelial lesion (HSIL) (vaginal intraepithelial neoplasia [VAIN] grade 2-3) is clinically, a precancerous lesion condition with an estimated progression rate of 10%-20%. Therefore, treatment is recommended. Because traditional treatments have limited effects, high expense and complications, here we evaluated the efficacy and safety of topical 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT). This study consisted of 56 female patients diagnosed with vaginal HSIL. A 20% 5-ALA jelly formation was topically applied to the vaginal wall, followed by 635 nm PDT at 7-14 days intervals. Cytology, human papillomavirus (HPV) genotyping, colposcopy, and pathology were assessed after treatment. Among the 56 patients in our study, 47 (83.9%) had VAIN 2 and 9 (16.1%) had VAIN 3. 35 patients underwent three courses of PDT treatment, 19 experienced six courses, and two experienced nine courses. The total pathological regression rate was 87.5%, and the HPV clearance rate during the 6-month follow-up was 41.9%. Lesions located in the vaginal stump after hysterectomy seem to be difficult to treat. 9%(4/44) and 23%(7/30) patients had recurrent disease during the 6-month and 1-year follow-up time point. The most common adverse event was increased vaginal discharge, other side effects include abdominal pain, vulvar pruritus, and vaginal bleeding. No severe adverse effect was observed during the treatment. Photodynamic therapy mediatied by 5-aminolevulinic acid is an effective and safe treatment for vaginal HSIL with minimal side effects.

Effects of photodynamic therapy mediated by emodin in cervical carcinoma cells

Cervical cancer is a worldwide public health problem, and improved selective therapies and anticancer drugs are urgently needed. In recent years, emodin has attracted considerable attention due to its anti-inflammatory, antineoplastic, and proapoptotic effects. Furthermore, emodin may be used as a photosensitizing agent in photodynamic therapy. Interest in photodynamic therapy for cancer treatment has increased due to its efficiency in causing tumor cell death. This study aimed to analyze the effect of emodin combined with photodynamic therapy in cervical carcinoma cell lines. At first, emodin presented cytotoxicity in concentration and time-dependent manners in all the specific cell lines analyzed. SiHa, CaSki, and HaCaT cancer cells presented more than 80% cell viability in concentrations below 30 µmol/L. Fluorescence microscopy images showed efficient cellular uptake of emodin in all analyzed cell lines. A significant decrease in cell viability was observed in SiHa, CaSki, and HaCaT cell lines after treatment of emodin combined with photodynamic therapy. These decreases were accompanied by increased ROS production, caspase-3 activity, and fluorescence intensity of autophagic vacuoles. This suggests increased ROS production led to cell death by apoptosis and autophagy. Additionally, after the combination of emodin and photodynamic therapy in SiHa cells, we observed the overexpression of 22 target genes and downregulation of two target genes of anti-cancer drugs. These results show the promising potential for applications that combine emodin with photodynamic therapy for cervical cancer treatment.

Application of 5-aminolevulinic acid photodynamic therapy for vaginal intraepithelial neoplasia, a report of six cases

Vaginal intraepithelial neoplasia (VAIN) has a high-risk for recurrence and may precede genital cancers, such as vaginal cancer and/or other invasive diseases. Human papillomavirus (HPV)-induced VAIN may occur after loop electrosurgical excision procedures (LEEPs) or panhysterectomy. 5-aminolevulinic acid (ALA) photodynamic therapy (ALA-PDT) has demonstrated utility in preventing the recurrence of cervical intraepithelial neoplasia (CIN); however, evaluation of its effect on VAIN has not been performed. The effectiveness of ALA-PDT was evaluated in 6 women diagnosed with HPV-induced VAIN. Lesion treatment was performed 3 h after ALA using light at a wavelength of 635 nm and light density of 80 mw/cm Six women, aged 49-54 years, who were diagnosed VAIN grade 1/2 or 2 after LEEP or panhysterectomy or no surgery underwent ALA-PDT (range, 4-8 treatments). Four of the 6 women were HPV negative on retesting 3-4 months after ALA-PDT. Most patients exhibited no signs of recurrence during the follow-up period. Direct use of ALA-PDT or after panhysterectomy did not necessarily lead to a negative result; however, ALA-PDT after LEEP or panhysterectomy combined with LEEP yielded a satisfactory curative effect on VAIN. Although recurrence rates need to be monitored in longer-term studies, the absence of post-treatment complications in this study supports the potential utility of the technique.

Fluorescence imaging of lymphangioma circumscriptum of the vulva with aminolevulinic acid and target-type narrow band ultraviolet light

Lymphangioma circumscriptum of the vulva is a rare lymphatic disorder. Defining the precise location of the lesion is required to select an appropriate treatment. Herein we present photodynamic diagnosis of lymphangioma circumscriptum of the vulva with aminolevulinic acid and target-type narrow band ultraviolet light device.

Effectiveness of photodynamic therapy with 5-aminolevulinic acid on HPV clearance in women without cervical lesions

High-risk HPV (hrHPV) not only increases the risk of cervical precancerous lesions and cervical cancer, but also adds psychological burden to HPV-positive women. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive and highly tissue-selective therapy. We aim to investigate the clinical efficacy of ALA-PDT for elimination of cervical hrHPV infection in HPV-positive women without cervical lesions. A total of 57 hrHPV-positive women without pathologically proved cervical lesions received three treatments of ALA-PDT in total. HPV DNA testing and pap cytology were performed in all patients. Patients with positive HPV16/18 or abnormal TCT results received colposcopic biopsy during the follow-up. hrHPV clearance rate was 56.1 % (32/57) at 3-month follow-up and 68.1 % at 6-month follow-up. 100 % of HPV 18 and 87.5 % of HPV16 infections were cleared while the clearance rate was 48.8 % among those positive for 12 other high-risk types. Multivariate analysis showed HPV16/18 infection was associated with significantly higher clearance rate. HPV clearance rate in patients with multiple-type HPV infection was significantly lower than that in patients with single-type HPV infections. ALA-PDT is effective on treating hrHPV infection in patients with no cervical lesions. HPV16/18 positive cases can benefit most from ALA-PDT. Multitype-infected women need more sessions of 5- ALA-PDT to eradicate hrHPV infection.

The effect of local photodynamic therapy with 5-aminolevulinic acid for the treatment of cervical low-grade squamous intraepithelial lesions with high-risk HPV infection: A retrospective study

High-risk HPV infection is the main cause of cervical cancer and pre-cancerous lesions. The current principle of clinical management of cervical low-grade squamous intraepithelial lesion is observation for 2 years. Progression to high-grade squamous intraepithelial lesion warrants intervention. Primary treatment option is surgical excision which may have a negative impact on fertility. Topical photodynamic therapy is a non-invasive and targeted therapy. We investigated the clinical efficacy of this therapy for cervical low-grade squamous intraepithelial lesion with high-risk HPV infection. A retrospective study consisting of 258 female patients aged 21-69 years with a histologically confirmed cervical low-grade squamous intraepithelial lesion with high-risk HPV infection was carried out. Subjects were treated with three sessions of 20 % 5-aminolevulinic acid photodynamic therapy at intervals of 7-14 days. Three months after treatment, the effect was evaluated through HPV typing, Thinprep cytology and colposcopy directed biopsy. Six months after treatment, the photodynamic therapy effect was evaluated by HPV genotyping and Thinprep cytology first, the pathological examination would be performed at the 6-month follow-up point if the cytological results indicated the risk of high-grade squamous intraepithelial lesions. Three months after treatment, among 258 low-grade squamous intraepithelial lesion with high-risk HPV infection patients, total baseline HPV remission rates was 64.34 % (166/258). The remission rate of HPV16/18 group was not statistically significant compared to the HPV non-16/18 group (73.13 % vs 61.26 %, p = 0.081).The remission rates of the 50 age group (67.28 %vs46.34 %, p = 0.001). The total lesion regression rate wa treatment, among 258 low-grade squamous intraepithelial lesion with high-risk HPV infection patients, total baseline HPV remission rates was 64.34 % (166/258). The remission rate of HPV16/18 group was not statistically significant compared to the HPV non-16/18 group (73.13 % vs 61.26 %, p = 0.081).The remission rates of the 50 age group (67.28 %vs46.34 %, p = 0.001). The total lesion regression rate was 84.88 % (219/258). 12.8 % (33/258) of patients did not progress. Only 2.33 % (6/258) patients progressed to high-grade squamous intraepithelial lesion and accepted loop electrosurgical excision procedure. The patients >50 age group had significant higher progression rate than the patients ＜50 age group (p＜0.05). Six months after treatment, except for 6 patients who progressed to high-grade squamous intraepithelial lesion and underwent surgical treatment, the total baseline HPV remission rates was up to 82.54 % (208/252). 5-aminolevulinic acid photodynamic therapy was highly effective and did not appear to create cervical damage.. It might be an ideal treatment for cervical low-grade squamous intraepithelial lesion with high-risk HPV infection, but this requires additional clinical trials.

Feasibility study of 5-aminolevulinic acid mediated photodynamic therapy of persistent vaginal high-risk HPV infection of post-hysterectomy patients

Patients after hysterectomy are at higher risk for developing VaIN. However, there are no standard treatments for HPV infection and VaIN after hysterectomy and relative studies are limited. Thus we aim to evaluate the feasibility of 5-aminolevulinic acid photodynamic therapy (5-ALA-PDT) for the treatment of persistent vaginal infection with high-risk HPV (HR-HPV) in post-hysterectomy patients. Thirty-eight patients aged 43-70 years old with persistent vaginal stump HR-HPV infection with or without histological vaginal intraepithelial neoplasia (VaIN1) during follow-up after hysterectomy were recruited. Twenty patients received three times of ALA-PDT (PDT Group). Eighteen patients did not receive any treatments (Control Group). HPV testing, cytology, and colposcopy were performed in all patients 4-6 months and 12 months after treatment. HR-HPV remission rates of the PDT Group were 40% (8/20) and 66.67% (12/18) at the 4-6 month and 12-month follow-up, respectively, both were significantly higher than that of the Control Group (11.11% (2/18) and 6.23% (1/16), respectively; P < 0.05). For the PDT Group, the regression rate of VaIN1 was 100% (7/7) at 4-6 months, while VaIN1 recurred in two cases (28.6%) at the 12-month due to persistent HR-HPV infection. No persistence or progression of VaIN1 was noted. For the Control group, the spontaneous regression rate of VaIN1 was 50% (3/6) at 4-6 months and one patient progressed into VaIN2. At the 12-month follow-up point, one patient reccurred and the disease regression, persistence and recurrence rates were 40% (2/5), 40% (2/5) and 20% (1/5), respectively. Adverse reactions were mild after PDT treatment. 5-ALA-PDT is a safe, non-invasive, and effective option for post-hysterectomy patients who have persistent HR-HPV infection.

The effect of local photodynamic therapy with 5-aminolevulinic acid in treating different grades of cervical intraepithelial neoplasia

Cervical intraepithelial neoplasia (CIN) is a precursor lesion of cervical cancer. Traditional treatments for CIN might have negative effects on cervical anatomical structure and physiological function. Topical 5-aminolevulinic acid photodynamic therapy (5-ALA PDT) is a novel, non-invasive targeted therapy for intraepithelial lesions. This study aims to evaluate and compare the efficacy and safety of 5-ALA PDT for different grades of CIN. A retrospective study of 183 patients aged 19-50 with histologically confirmed CIN and receiving ALA-PDT was conducted. ALA-PDT was performed with 20% ALA thermosensitive gel and irradiation at a wavelength of 635 nm and density of 80-100 J/cm The HPV clearance rate was 71.0% (130/183) at the six-month follow-up and 84.5% (147/174) at the 12-month follow-up. The complete lesion remission (CR) rate was 90.2% (165/183). No statistically significant differences concerning the CR rate (P>0.05) or HPV clearance rates (P>0.05) were observed in CIN I, CIN II, and CIN III. In women with CIN III, gland involvement was revealed to be associated with a significantly lower HPV clearance rate (63.16% vs. 92.60%, P= 0.036) at the 12-month follow-up. Our study showed that the atypical vessels seemed to be a risk factor for HPV clearance rate in the CIN II group at six-month follow-up, although the difference was not statistically significant (P= 0.089). During the follow-up, 13 cases had persistent lesions (7.1%), four cases recurred (2.3%), and none of the patients progressed. The study also showed that the efficacy of PDT in the treatment of patients with CIN III involving glands was comparable to that of CKC (P>0.05). ALA-PDT is an effective andsafe treatment for CIN, and responseis unaffected by the grade of lesions. However, for patients with atypical vessels and glandular involvement, the effect of PDT seems to be poorer.

Efficacy of photodynamic therapy with 5-aminolevulinic acid for the treatment of cervical high-grade squamous intraepithelial lesions with high-risk HPV infection: A retrospective study

The current principle of clinical management of cervical high-grade squamous intraepithelial lesion(HSIL) is surgical excision. However excisional procedures of the uterine cervix may have a negative impact on fertility. Topical photodynamic therapy(PDT) is a non-invasive and selective tissue destruction. We investigated the clinical efficacy of PDT for cervical HSIL with high-risk human papilloma virus(HPV) infection. A retrospective study consisting of 96 patients aged 20-50 years with a histologically confirmed cervical HSIL with high-risk HPV infection from July 2018 to June 2022 was carried out. Patients were treated with six times of 20% 5-aminolevulinic acid photodynamic therapy (5-ALA PDT) at intervals of 7-14 days. Three months after treatment, the effect was evaluated through HPV typing and colposcopy directed biopsy. Six and twelve months after treatment, TCT and HPV tests were carried out. Three months after 5-ALA PDT treatment, among 96 HSIL with high-risk HPV infection patients, the total lesion regression rate was 89.58%(86/96), and the HPV clearance rate was 79.17 % (76/96) at 3 months follow-up. At 6 and 12 months follow-up, the patients who was HSIL pathological regression and negative HPV at 3 months follow-up continued negative results in both TCT and HPV. All patients with ineffective 5-ALA PDT treatment had persistent HPV infections. There was no significant difference in the HSIL regression rate and HPV clearance rate among different age groups. The main side effects of PDT were abdominal pain and increased vaginal secretions. Univariate analysis showed that the different severity of cervical cytology was associated with lesion regression rate in 5-ALA PDT treatment. The HSIL regression rate of TCT<ASC-H was higher than that of TCT≧ASC-H(94.59% vs 72.72%; P<0.01).Multicentric lesions,the proportion of visible lesion size in ectocervical size≥24.59%, size of visible lesion ≥1.23cm 5-ALA PDT can be a safe and efficient treatment for cervical HSIL who wish to preserve fertility. 5-ALA PDT did not appear to create cervical damage and have negligible side effects. But we need evaluate the type of transformation zone, the visible lesion size, the location of lesion,baseline status of TCT and histological results before 5-ALA PDT treatment.

Personalized approach to management of high-grade squamous intraepithelial lesion

Cervical cancer ranks 4th place among malignant neoplasms in the world in 2020. HPV is the main reason for cervical cancer. The «Gold standard» of cervical screening is an «HPV-testing + PAP-test» co-test. The immune system can clear HPV infection. Pathway of cervical cancer development is investigated, but immunity recognition of HPV is still incompletely studied. Toll-like receptors (TLRs) are membrane receptors on the cell membranes and membrane organelles. TLRs ligands could be bacterial, viral pathogens or toxins. When a ligand binds to TLRs, cytokines production is triggered. Chronic inflammation process down-regulates TLRs expression. This helps develop HPV infection. The current paper demonstrates how photodynamic therapy induces TLRs gene expression. A personal approach to estimating photodynamic therapy by an innate immune response in a clinical case is described. A 43-year-old woman with high-grade squamous intraepithelial lesion and 33rd type of HPV infection turned into a private clinic. The patient had complex check-ups before we defined a treatment strategy. Photodynamic therapy was performed as a non-invasive fertility-preserving treatment. We tested TLRs 2/3/4/8 gene expression before and after photodynamic therapy in 2 h, one week and 6-month periods. PDT induces TLRs gene expression in a 6-month period. HPV elimination was achieved. The patient has no atypical cells in liquid-based cytology investigation after PDT.

FT-IR combined with PSO-CNN algorithm for rapid screening of cervical tumors

Cervical cancer is the most common gynecological malignancy.. Early and accurate identification of the stage of cervical cancer patients can greatly improve the cure rate. In this study, serum sample data were collected from patients with cervical cancer, CIN (cervical intraepithelial neoplasia) I, CIN II, CIN III and hysteromyoma using FT-IR (Fourier-transform infrared spectroscopy) technology. PSO-CNN model for early screening of cervical cancer was designed using a particle swarm algorithm to automatically build a CNN structure with variable number of layers and variable layer class parameters. The experimental results showed that PSO-CNN was the best compared with the classical Lenet, AlexNet, VGG16 and GoogLeNet deep learning models, and the accuracy of PSO-CNN in discriminating five types of samples can reach 87.2%. This study showed that FT-IR technology combined with PSO-CNN model had great potential for non-invasive, rapid and accurate identification of patients with cervical cancer, and can provide a reference for intelligent diagnosis of other diseases.

Clinical outcome of photodynamic therapy for the treatment of cervical intraepithelial neoplasia grade 2

Five-aminolaevulinic acid photodynamic therapy (ALA-PDT) was used to treat 79 cervical intraepithelial neoplasia 2 (CIN 2) patients who desired preservation of fertility ,between Oct 2018 and Dec 2020. Three months after treatment, among the 65 patients who returned for follow-up, full recovery and improvement rates were 43/65 and 16/65, respectively, resulting in a total response rate of 90.77%. This suggests that ALA-PDT is worthy of clinical application, even as monotherapy. The result of immune testing also indicated significant promotion of CD4+T expression during the recovery process, highlighting the importance of immune responses in different prognoses.

Therapeutic effects of topical photodynamic therapy with 5-aminolevulinic acid on cervical high-grade squamous intraepithelial lesions

Topical photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) is a non-invasive option for treatment of Cervical Intraepithelial Neoplasia (CIN). We investigated the clinical efficacy and safety of ALA-PDT in treatment of patients with cervical high-grade squamous intraepithelial lesion (HSIL) and evaluated the factors that effect the efficacy of PDT. A total of 99 patients (average age: 30 years (18-45 years old)) with cervical HSIL and high-risk Human Papilloma Virus (hr-HPV) infections and who had received ALA-PDT were enrolled in this retrospective study. Before ALA-PDT, cervical exfoliated cells from all patients were obtained for HPV genotyping, liquid-based cytology test (LBC) and PAX1 methylation (PAX1 At 6 months after treatment, total HPV clearance and lesions complete remission (CR) rates were 64.6% (64/99) and 88.9% (88/99), while at 1-year of follow-up, they were 81.3% (65/80) and 92.5% (74/80), respectively. At 1-year follow-up, HPV clearance rate was higher, relative to 6 months after ALA-PDT (p <0.05). At 6 months after treatment, HPV clearance and CR rates in the PAX1 hypermethylation (PAX1 ALA-PDT is an effective, safe treatment approach for patients with cervical HSIL and hr-HPV infections. Patients with PAX1

Evaluation of 5-aminolevulinic acid-mediated photodynamic therapy on cervical low-grade squamous intraepithelial lesions with high-risk HPV infection

The treatment options for low-grade squamous intraepithelial neoplasia (LSIL) of the cervix with high-risk HPV infection have not been standardized. Studies show that photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA-PDT) might be effective. In this retrospective study, the clinical efficacy and safety of ALA-PDT in the treatment of LSIL were evaluated. ALA-PDT was performed in 55 LSIL patients aged 21-45 years who also showed high-risk HPV infection and cervical ectropion. HPV test, cytology, colposcopy and pathology were examined before and after treatment. Meanwhile, PDT-related symptoms and adverse reactions were also reviewed. At 6-month follow-up after PDT, except for 5 patients who showed the persistence of LSIL lesions, the pathological regression ratio of 90.1% (50/55) was achieved. No HPV-DNA was detected in exfoliated cervical cells in 81.8% (45/55) patients. Among them, the HPV clearance ratio of I Degree cervical ectropion was 96.2%, significantly higher than that of II Degree (70.8%) and III Degree (60%). Significant shrunk of cervical ectropion and reduction of vaginal secretions after PDT were seen in 78.0% patients. ALA-PDT is a safe and effective therapeutic option for patients of reproductive age who suffer from LSIL with high-risk HPV infection and cervical ectropion.

Photodynamic therapy with HiPorfin for cervical squamous intraepithelial lesion at childbearing age

To evaluate the clinical efficacy and safety of HiPorfin® photodynamic therapy (PDT) in the treatment of young women at reproductive age with high-grade squamous intraepithelial lesion (HSIL) of the cervix. Prospective study of 41 patients aged 28.8 ± 4.6 years old with cervical intraepithelial neoplasia (CIN) Ⅱ-Ⅲ at Peking University Shenzhen Hospital from March 2019 to January 2023. HiPorfin® (2 mg/kg) was infused intravenously, and 48-72 h later, 630-nm laser irradiation was performed in cervical canal and cervical surface with an irradiation dose of 100-120 J/cm All 41 patients with no recurrence had been observed at least 12 months follow-up period after PDT. The number of nulliparous women was 30 (30/41, 73.2 %). CIN Ⅱ were 22 cases (22/41,53.7 %) and CIN Ⅲ were 19 cases (19/41,46.3 %). Complete response (CR) was in 95.5 % (21/22) patients with CIN Ⅱ and 78.9 % (15/19) patients with CIN Ⅲ at 6 months follow-up. Meanwhile, CR rate was 100.0 % (22/22) and 84.2 % (16/19) in CIN Ⅱ and CIN Ⅲ group respectively at 12 months. Pre-treatment, all patients (41/41,100 %) were Human papilloma virus (HPV) positive. HPV eradication rate was 63.4 % (26/41), 73.2 % (30/41) and 92.7 % (38/41) at 3, 6 and 12 months after PDT respectively. Before treatment, cytology ≥ atypical squamous cells of undetermined significance (ASCUS) was 78.0 % (32/41). Negative conversion ratio of cytology was 75.0 % (24/32), 90.6 % (29/32) and 100.0 % (32/32) at 3, 6 and 12 months after PDT respectively. There were no serious adverse effects in patients during and after PDT. HiPorfin-PDT is a promising and organ-saving approach for cervical HSIL, which also eradicates HPV infection effectively and can be a beacon of hope for the young women with fertility preservation requirement.

Immune-priming mechanisms of photodynamic therapy in cervical high-grade squamous intraepithelial lesions and translational implications for ovarian near-infrared photoimmunotherapy

Photodynamic therapy (PDT) offers lesion control with tissue preservation, which is important for patients seeking to avoid excision in cervical high-grade squamous intraepithelial lesions (HSIL). This review examines evidence for aminolaevulinate- and hexaminolaevulinate-based PDT as a tissue-preserving treatment for cervical HSIL and explores the biological rationale for translating near-infrared photoimmunotherapy (NIR-PIT) to intraperitoneal ovarian cancer. We summarise mechanisms by which PDT and NIR-PIT induce immunogenic cell death and engage cGAS-STING signalling, and review cervical clinical data demonstrating histologic regression, high-risk human papillomavirus clearance, and favourable tolerability. For ovarian cancer with peritoneal dissemination, we discuss how antigen-targeted NIR-PIT aligns with the immunobiology of immune-excluded serosal disease by promoting local cytotoxicity and systemic immune activation. Key translational considerations are outlined, including antigen selection, immune responsiveness, and rational combination strategies with immunomodulatory agents. Emphasis is placed on biological mechanisms and immune correlates relevant to treatment response. Overall, this review highlights the shared immunological foundations of PDT and NIR-PIT while defining distinct clinical contexts for cervical HSIL and investigational intraperitoneal ovarian cancer therapy.

Efficacy and safety of photodynamic therapy for vaginal intraepithelial neoplasia: A systematic review and meta-analysis

Vaginal Intraepithelial Neoplasia (VaIN) is a precancerous condition that can progress to vaginal cancer if untreated. Photodynamic Therapy (PDT), recognized for its minimally invasive nature and favorable side effect profile, is increasingly employed for VaIN treatment; however, comprehensive evidence synthesis on its efficacy and safety remains limited. This study aims to comprehensively evaluate the efficacy and safety of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) in treating VaIN. We systematically searched PubMed, Embase, Web of Science, and Cochrane Library databases for studies evaluating PDT efficacy in VaIN. Primary outcomes were complete response (CR) rate and HPV clearance rate; secondary outcomes included recurrence rate and adverse events (AE). Meta-analysis was performed using Stata 18.0. Nine trials (421 patients) were included. Pooled outcomes: 6-month CR:87% (95% CI: 78%-94%), 12-month CR:84% (95% CI:76%-91%); 6-month HPV clearance:61% (95% CI:55%-66%), 12-month:73% (95% CI:67%-78%); 6-month HPV16/18 clearance:71% (95% CI:61%-80%), 12-month:76% (95% CI:63%-88%); 6-month recurrence:4% (95% CI:2%-8%), 12-month:7% (95% CI:0%-24%); AEs: Increased vaginal discharge (20%, 95% CI: 8%-36%), itching (25%, 95% CI: 1%-62%), burning sensation (23%, 95% CI: 1%-57%), abdominal pain (7%, 95% CI: 0%-21%), and mild vaginal bleeding (0%, 95% CI: 0%-3%). No serious AEs. ALA-PDT demonstrates high efficacy and favorable safety in treating VaIN. However, as current evidence primarily stems from single-arm studies, future high-quality multicenter randomized controlled trials are essential to confirm these findings and directly compare ALA-PDT with standard therapies.

Establishment of C-33A cervical carcinoma spheroids on Japanese quail CAM: relevance in assessment of photodiagnosis and photodynamic therapy mediated by hypericin

Cervical cancer is the most common type of cancer in women. The present study aims to establish a reliable model of human cervical cancer microtumours (C-33A) growing on the chorioallantoic membrane (CAM) of quail embryos to test the efficacy of anticancer drugs. Cultrex®, an extracellular matrix, was used as a scaffold for C-33A spheroids. Hypericin, a natural perylene quinone, was used in this study as a model photosensitizer for photodiagnosis and photodynamic therapy (PDT). Fluorescence pharmacokinetics were recorded to verify the robustness of the model. The changes in vessel growth parameters were determined after weak PDT (405 nm, 2 min and 285 mW/cm

A non-inferiority study of 5-aminolevulinic acid photodynamic therapy (5-ALA-PDT) for high-grade squamous intraepithelial lesions of the cervix in patients of childbearing age: A non-randomized controlled prospective study

The objective of this study was to compare the effectiveness of 5-aminolevulinic acid photodynamic therapy (5-ALA-PDT) and loop electrosurgical excision procedure (LEEP) for treating cervical high-grade intraepithelial lesions (HSIL) in patients of childbearing age. We conducted a prospective study of 67 women diagnosed with cervical HSIL from January 2022 to June 2024 in Minhang Hospital, Affiliated to Fudan University. A total of 60 patients were finally included in this clinical trial. They were assigned to two groups. 30 cases received 5-ALA-PDT, and 30 cases underwent LEEP. All patients were followed up at 6 months and 12 months after treatment, including HPV testing, cytology, and colposcopy examination. 6 months after treatment, the HPV clearance rates in the 5-ALA-PDT group were similar to the LEEP group, both groups were 80.00 % (P = 1.00). The cure rates in both groups were 80.00 %, and the improvement rates were 20.00 % (P = 1.00). 12 months after treatment, the HPV clearance rate in the 5-ALA-PDT group was marginally higher than the rate observed in the LEEP group (90.00 % vs. 83.33 %, P = 0.448). The cure rate in the 5-ALA-PDT group was marginally higher than that in the LEEP group (86.67 % vs. 83.33 %, P = 0.718). The incidence of adverse reactions in the 5-ALA-PDT group was significantly lower than that in the LEEP group for the treatment of cervical HSIL (3.33 % vs. 30.00 %, P < 0.05). For patients of reproductive age with cervical HSIL, 5-ALA-PDT treatment for cervical HSIL is an effective and safe treatment option.

Treatment of HPV Infection-Associated Low Grade Cervical Intraepithelial Neoplasia with 5-Aminolevulinic Acid-Mediated Photodynamic Therapy

To investigate the efficacy of 5-aminoketovalic acid (5-ALA) photodynamic therapy (PDT) in the treatment of patients with low cervical intraepithelial neoplasia (CINI) combined with high-risk human papillomavirus ((HR-HPV), and the factors affecting the efficacy. 80 patients with CINI and HR-HPV infection were selected for the study. They received once weekly 5-ALA-PDT for either three or six treatments. To evaluate the clinical efficacy of 5-ALA-PDT treatment, follow-up evaluations were conducted at 3, 6 and 12 months, utilizing thinPrep cytology test(TCT)and colposcopic histopathological biopsy for the detection of HPVDNA. Following PDT, HR-HPV remission rates at 3, 6 and 12 months were 75.32%, 80.52%, and 81.82%, respectively. Complete remission rate of CINI was 94.81% (73/77 patients). There was no statistically significant difference in the remission rate of HR-HPV between 3 and 6 treatments with PDT (P > 0.05). Likewise, there was no difference in the remission rate comparing patients ≤40 years old and those >40 years old (P > 0.05). However, the remission rate was statistically greater in patients with normal vaginal microecology compared to patients with vaginal microecologic imbalance (P = 0.004). Not only can 5-ALA-PDT effectively clear CINI, but it also can clear HR-HPV. Vaginal microecological imbalance can reduce the effect of PDT on HR-HPV, whereas differences in age or frequency of PDT do not affect the remission rate of PDT on HR-HPV.

Efficacy of hematoporphyrin injection (HpD) photodynamic therapy in the treatment of widespread extramammary Paget's disease

Photodynamic therapy (PDT) utilizing Hematoporphyrin Derivative (HpD) injection has been demonstrated as an efficacious treatment for various conditions, including Bowen's disease, subtypes of basal cell carcinomas, and actinic keratosis. While surgical resection is considered the primary treatment option for extramammary Paget's disease (EMPD), some patients may not be suitable candidates for surgical intervention. ALA-PDT may have some benefits in treating EMPD in select patients, while Hematoporphyrin Derivative-Photodynamic Therapy (HpD-PDT) has demonstrated promising potential as a cancer treatment. We present one case of vulvar extramammary Paget's disease (EMPD), that is a female patient with lesions in the vulva and involving the urethra. Due to advanced age, underlying diseases, the extensive affected area, and the specific location of the vulvar lesion, the patients were unable to undergo surgical treatment. Therefore, the patient declined traditional wide local excision and instead opted for hematoporphyrin photodynamic therapy. Treatment eliminated the tumor, but it recurred locally after 1.5 years of follow-up. Localized small-scale recurrence at the affected site can be treated with surgical resection or photodynamic therapy to achieve complete clearance of the lesion. However, the patient refuses further examination and treatment. EMPD has a high recurrence rate, but we propose that hematoporphyrin photodynamic therapy is an effective alternative to conventional surgery for treating this condition, even in case of recurrence.

Comparison of photodynamic therapy and LEEP in women of reproductive age with cervical squamous intraepithelial neoplasia 2 (CIN2): A prospective observational study in China

Non-invasive treatments, such as 5-Aminolevulinic acid photodynamic therapy (5-ALA-PDT), has gained increasing attention among women with cervical intraepithelial neoplasia grade 2 (CIN2) who have fertility requirements. To compare the effectiveness of 5-ALA-PDT and loop electrosurgical excision procedure (LEEP) in patients with CIN2, we conducted this prospective cohort study in Chinese patients with CIN2. 229 patients with CIN2 were enrolled. They were divided into the PDT Group (n=94) and LEEP Group (n=135) according to the patient's willingness. Patients were evaluated at the 3-, 6-, 12- and 18-month follow-up periods, using cytology, HPV testing, and colposcopy examination. At the 3-month follow-up, the rates of disease regression to normal or CIN1 in the PDT group were 76.6% (72/94) and 13.8% (13/94), respectively, whereas in the LEEP group, they were 80.7% (109/135) and 11.1% (15/135), respectively. Logistic regression analysis revealed that the transformation zone type 3 was the only risk factor for both the PDT (OR=3.68; 95% CI, 2.43-5.26; P=0.008) and LEEP groups (OR=2.34; 95% CI, 1.84-4.53; P=0.02). The treatment efficacy in the PDT group increased gradually and peaked at the 18-month follow-up point with disease disappearance and regression rates of 90.4% and 8.5%, respectively. The disease disappearance and regression rates in the LEEP group were highest at the first half year posttreatment, with disease disappearance and regression rates of 87.4% and 12.6%, respectively. The hrHPV-negative rates in the PDT group and LEEP group were the highest at the 18-month follow-up (78.7% and 74.8%). There was no significant difference in the disappearance or regression rates between the two groups at the follow-up points (P > 0.05). Our study revealed that both 5-ALA PDT therapy and LEEP were highly effective at treating CIN2. 5-ALA-PDT, as a non-invasive treatment, could be an effective option for CIN2 patients with fertility preservation needs.

Comparison of the efficacy of photodynamic therapy alone and photodynamic therapy after laser pretreatment for high-grade cervical intraepithelial lesions in women of childbearing age: a prospective study

The objective of this study was to compare the effectiveness of photodynamic therapy(PDT)and photodynamic therapy after laser pretreatment for treating cervical high-grade intraepithelial lesions(HSIL) in patients of childbearing age. We conducted a prospective study of 68 women diagnosed with cervical HSIL from January 2022 to June 2024 in Minhang Hospital Affiliated to Fudan University. A total of 60 patients were included in this clinical trial. They were randomly assigned to two groups.30 cases received 5-ALA-PDT, and 30 cases underwent photodynamic therapy after laser pretreatment. All patients were followed up at 6 months and 12 months after treatment, including HPV testing, cytology, and colposcopy examination. 6 months after treatment, the rate of HPV clearance in the PDT after laser pretreatment (86.67%)was marginally higher than the PDT(80.00%)group(P= 0.488). The cure rate after six months of treatment was 86.67% in the PDT after laser pretreatment group and 80.00% in the PDT group (P = 0.488). After 12 months, the HPV clearance rate in the PDT after laser pretreatment group was found to be 93.33%, while the rate in the PDT group was 90.00%(P = 0.640). After 12 months, the cure rate was 90.00% in the PDT after laser pretreatment group and 86.67% in the PDT group (P = 0.688). For patients of reproductive age with cervical HSIL, laser therapy prior to PDT treatment does not result in a substantial enhancement of the cure rate or HPV clearance rate of cervical high-grade intraepithelial lesions.

Evaluation of topical photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) for cervical intraepithelial neoplasia with human papillomavirus (HPV) infection: a retrospective comparative study versus loop electrosurgical excision procedure (LEEP)

Cervical intraepithelial neoplasia (CIN), driven by persistent human papillomavirus (HPV) infection, necessitates effective treatments that balance oncological efficacy with fertility preservation. This retrospective study evaluated 5-aminolevulinic acid photodynamic therapy (ALA-PDT) versus loop electrosurgical excision procedure (LEEP) in 171 patients with HPV-associated CIN. Participants were stratified into LSIL-PDT (n = 61), HSIL-PDT (n = 42), and HSIL-LEEP (n = 68) groups, with outcomes assessed at 6 months. ALA-PDT demonstrated superior lesion remission (HSIL: 83.3 % vs. LEEP's 64.7 %, p < 0.05) and HPV clearance (78.6 % vs. 60.3 %, p < 0.05), particularly against HPV16/18 infections (OR=0.351, 95 %CI:0.132-0.93). Crucially, ALA-PDT preserved cervical integrity, with 8/103 patients achieving uncomplicated pregnancies post-treatment, compared to 6/68 LEEP-treated patients, among whom adverse outcomes (e.g., preterm birth) occurred. The study highlights ALA-PDT's dual advantage: targeted eradication of high-risk HPV strains and minimal collateral tissue damage, critical for reproductive-age patients. Innovations include validating genotype-specific efficacy and demonstrating fertility preservation without compromising oncological outcomes. These findings position ALA-PDT as a safer, precision-based alternative to traditional excisional methods, offering significant clinical implications for CIN management and long-term patient quality of life. Future research should expand cohorts to confirm durability and explore broader applications in lower genital tract pathologies.

Analysis of the efficacy of photodynamic therapy in treating cervical lesions and HPV infections and its influencing factors

To evaluate the efficacy of photodynamic therapy (PDT) in patients with human papillomavirus (HPV) infection and cervical lesions, meanwhile factors influencing the efficacy of PDT were analyzed. A retrospective analysis was performed on 110 patients with HPV infection and cervical lesions. All patients underwent HPV genotyping, ThinPrep Cytology Test (TCT), and pathological examination, the changes before and after PDT treatment for 6 months were analyzed. In evaluating the therapeutic effect, if HPV is completely eliminated or cervical lesions return to normal, it was counted in the negative conversion rate; If HPV is partially eliminated or cervical lesions are downgraded but not return to normal, it was counted in the effective rate. Meanwhile, patients were grouped according to HPV vaccination history, menopausal status, transformation zone type and previous HPV infection history, and the therapeutic effects of anti-HPV and cervical lesion were compared among different groups. After PDT, the negative conversion rate of HPV was 45.45 % with an effective rate of 64.54 %; the negative conversion rate of TCT was 63.51 % with an effective rate of 68.91 %; and the negative conversion rate of pathology was 72.22 % with an effective rate of 79.62 %. The HPV negative conversion rate (78.57 % vs. 35.36 %) and TCT negative conversion rate (83.33 % vs. 57.14 %) in the vaccinated population were significantly higher than those in the unvaccinated population (p < 0.05). The non-menopausal population showed significantly higher TCT negative conversion rate (72.00 % vs. 45.83 %) and effective rate (78.00 % vs. 45.83 %), as well as pathological negative conversion rate (85.36 % vs. 30.76 %) and effective rate (87.80 % vs. 46.15 %) compared with the menopausal population (p < 0.05). Patients with type Ⅰ and Ⅱ transformation zone (TZ) show significantly better outcomes than those with TZ3 in anti-HPV treatment and cervical lesion management (p < 0.05). Patients without a history of HPV infection had significantly higher TCT negative conversion rate (73.33 % vs. 35.89 %) and effective rate (73.33 % vs. 46.15 %) than those with a previous infection history (p < 0.05). PDT shows good therapeutic effects in both HPV infection and cervical lesions. In addition, better therapeutic effects are observed in populations with a history of HPV vaccination, non-menopausal populations, populations without previous HPV infection, and those with type Ⅰ or Ⅱ cervical transformation zones.

Combination of photodynamic therapy and estrogen cream for menopause women with cervical low-grade squamous intraepithelial lesion with human papillomavirus infection

In menopausal women, decreased estrogen levels lead to genital tract mucosal atrophy and reduced mucosal immune function. Low-grade squamous intraepithelial lesions (LSIL) associated with persistent or newly acquired high-risk HPV infection may progress silently to high-grade squamous intraepithelial lesions (HSIL) and eventually cervical cancer. This study aimed to evaluate the efficacy and safety of photodynamic therapy combined with estrogen in the treatment of menopausal women with LSIL and high-risk HPV infection. A retrospective controlled study was conducted to compare LSIL regression and HPV clearance among three treatment groups: photodynamic therapy plus estrogen, interferon gel plus estrogen, and estrogen alone. Therapeutic outcomes were assessed using ThinPrep cytology (TCT), HPV testing, and colposcopic pathology at 3, 6, and 12 months post-treatment. The rates of LSIL regression and HPV clearance in the photodynamic therapy plus estrogen group were significantly higher than those in both the interferon gel plus estrogen group and the estrogen-alone group at 3, 6, and 12 months (p < 0.05). Furthermore, the interferon gel plus estrogen group showed improved outcomes compared to estrogen alone, with statistically significant differences (p < 0.05). Photodynamic therapy combined with estrogen cream is an effective and safe treatment approach for menopausal women with LSIL and high-risk HPV infection.

Efficacy of 5-aminolevulinic acid photodynamic therapy versus observation for cervical low-grade squamous intraepithelial lesion with type 3 transformation zone

The treatment for patients with cervical low-grade squamous intraepithelial lesion (LSIL) and type 3 transformation zone (TZ) had limitations. The aim of this study was to compare the efficacy of new approach 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and observation in those patients. This study retrospectively analyzed data from 236 patients (aged 25-45 years) with cervical LSIL and type 3 TZ. Participants were divided into ALA-PDT and observation groups, and were followed up for 1-year post-diagnosis. Outcomes were compared and factors influencing LSIL regression and human papillomavirus (HPV) clearance were analyzed. The LSIL regression rate was 89.8 % in the ALA-PDT group, significantly higher than 68.4 % in the observation group (P < 0.05). The ALA-PDT group demonstrated a significantly higher HPV clearance rate of 69.5 % compared to 39.0 % in the observation group (P < 0.05). No significant correlation was found between baseline clinical characteristics and LSIL regression or HPV clearance in either group. ALA-PDT is effective in promoting LSIL regression and HPV clearance. ALA-PDT may be considered as a viable treatment option for women with type 3 TZ, persistent LSIL and high-risk HPV infection, The efficacy of ALA-PDT is not affected by clinical characteristics, suggesting its benefit for patients with various clinical risk factors.

Frequency shift Raman-based sensing of serum MicroRNA for ultrasensitive cervical cancer diagnosis

Cervical cancer is the most common gynaecological tumor. The development of a sensor for the ultrasensitive detection of cervical cancer is significant in guaranteeing its prognosis. Herein, we proposed a novel surface-enhanced Raman scattering (SERS) analysis platform using a frequency shifts-based sensing model for rapid and ultrasensitive microRNA (miRNA) assay. During the analysis process, miR-21 can be captured by the single-stranded DNA (ssDNA) modified on the platform which is complementary pairing with miR-21. The connection of miR-21 can lead to the variation of the molecular weight and result in the deformation extent of the Raman report molecule 6Thioguanine (6TG); thus, the peak at 1301 cm

Effect of 5-aminolevulinic acid photodynamic therapy versus loop electrosurgical excision procedure for cervical intraepithelial neoplasia grade 2 treatment

Both the traditional loop electrosurgical excision procedure (LEEP) and the newly developed 5-aminolevulinic acid photodynamic therapy (ALA-PDT) are used to treat high-grade squamous intraepithelial lesions. However, the clinical efficacy and safety of these two therapies have rarely been compared. Thus, this study aimed to compare the clinical efficacy and safety of the two treatment regimens. One hundred and twenty patients in two groups (60 + 60) with grade 2 cervical intraepithelial neoplasia (CIN2) were voluntary treated with photodynamic therapy or LEEP between June 2020 and December 2022. Follow-up was conducted at 3, 4-6, and 7-12 months after treatment. Although the total effective rate of LEEP was higher during the first 6 months after treatment, both the total effective rate of lesion degradation and the double-negative rate of high-risk HPV16/18 and liquid-based cervical cytology by ALA-PDT treatment increased with time and finally exceeded those of LEEP at 7-12 months. ALA-PDT may be more promising than LEEP for treating patients with CIN2 because of the better CIN2 degradation and high-risk HPV negativity, less damage, and greater fertility conservation, especially after 6 months.

Comparison of 5-ALA-PDT and LEEP of cervical squamous intraepithelial neoplasia (CIN2) with high-risk human papillomavirus infection in childbearing age women: A non-randomized controlled polit study

5-Aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) is a possible minimally-invasive treatment for high-grade cervical intraepithelial neoplasia (HSIL). The present study was carried out to assess the effect of 5-ALA-PDT and loop electrosurgical excision procedure (LEEP) in cervical squamous intraepithelial neoplasia (CIN2) combined with high-risk human papillomavirus (HR-HPV) infection. In this study, 190 patients with CIN2 and HR-HPV infection were finally included. They were divided into the LEEP Group (n = 116) and PDT Group (n = 74) according to gynecologist's recommendation and patient's willingness. All patients were followed up at 4-6 months and 12 months after treatment, including HPV testing, cytology, and colposcopy examination. (1) 4-6 months after treatment, the pathological regression rate was 97.30 % (72/74) in the PDT group and 98.28 % (114/116) in the LEEP group (P = 0.952). The HPV clearance rate was 81.08 % (60/74) in the PDT group and 80.17 % (93/116)in the LEEP group (P = 0.877). (2) 12 months after treatment, the pathological regression rate was 93.24 % (69/74) in the PDT group and 96.55 % (112/116) in the LEEP group (P = 0.486). The recurrence rate of CIN2 was 4.05 % (3/74) in the PDT group and 1.72 % (2/116) in the LEEP group (P = 0.608). The HPV clearance rate was 90.54 % (67/74) in the PDT group and 89.66 % (104/116)in the LEEP group (P = 0.843). The reinfection rate of HR-HPV was 5.41 % (4/74) in the PDT group and 1.72 % (2/116) in the LEEP group (P = 0.322). (3) The adverse reactions in the PDT Group were slightly lower than that in the LEEP Group (P = 0.4956), but the incidence of vaginal bleeding in the PDT group was lower than that in the LEEP group during follow-up. The effectiveness of 5-ALA-PDT is similar to LEEP for CIN2 with less side effects. Therefore, 5-ALA-PDT, a non-invasive treatment, may be an effective method for CIN2 patients of childbearing age.

Effect of vaginal microbial infections on the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy for vaginal intraepithelial neoplasia

Vaginal intraepithelial neoplasia (VAIN) is a precancerous condition with significant potential for malignant transformation. The 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is considered as a novel approach to treat VAIN. Recent studies have shown that an imbalance in the vaginal microbiota can affect the progression of VAIN. Thus, the effect of imbalanced microbiota on the efficacy of ALA-PDT for treating VAIN needs to be determined. Sixty-five female patients diagnosed with VAIN were recruited. 5-aminolevulinic acid was applied topically to the vaginal wall, followed by 635 nm red light at intervals of 7-14 days. Cytological inspections, high risk human papillomavirus (HR-HPV) genotyping, vaginal colposcopy examinations, histopathology and culture and identification of vaginal microflora were performed before and after treatment. Among the 62 patients, the complete remission rate (CRR) of vaginal wall lesions was 85.5 %, and the HR-HPV clearance rate was 61.3 %. In the balanced vaginal microbiota group, the CRR of vaginal wall lesions reached 97.2 %, with an HR-HPV clearance rate of 75.1 %. In the imbalanced vaginal microbiota group, the CRR of vaginal wall lesions was only 65.5 %, with an HR-HPV clearance rate of 48.3 %. There was a trend of improved clearance of lesions and HR-HPV when the vaginal microbiota was balanced (p= 0.002 and p= 0.038, respectively). During the process of clinical treatment and the 1-year follow-up period, all patients experienced minimal adverse reactions. The findings of this study demonstrate that ALA-PDT is a clinically effective and safe treatment for VAIN, and the vaginal microbiota's status is a key factor affecting the efficacy of ALA-PDT for VAIN.

Effect of photodynamic therapy on vaginal intraepithelial neoplasia grade one: A retrospective cohort study

To evaluate the efficacy of photodynamic therapy (PDT) for vaginal intraepithelial neoplasia grade 1 (VaIN1) related to high-risk (Hr)-human papillomavirus (HPV). Participants aged 25-65 years treated for VaIN1 between March 2022 and September 2022 were retrospectively analyzed into three groups. The PDT and follow-up groups were matched 1:1 for gravidity, HPV type, and quadrants involved. The PDT and CO After matched, the lesion and Hr-HPV clearance rates of the PDT group (89.5%, 89.5%, 92.1%, and 81.6%, 84.2%, 89.5%) were significantly higher than those of the follow-up group (31.6%, 50.0%, 63.2%, and 21.1%, 26.3%, 31.6%, P < 0.05) at 6, 12, and 24 months. But the lesion clearance rates did not differ significantly between the PDT (68.9%, 82.2%, and 91.1%) and CO Compared with CO

Comparison of efficacy of ALA-PDT and CO2 laser in the treatment of vaginal intraepithelial neoplasia II (VaIN II)

To compare and analyze the efficacy as well as adverse effects of 5-aminolevulinic acid photodynamic therapy (5-ALA-PDT) and carbon dioxide (CO₂) laser therapy in the treatment of vaginal intraepithelial neoplasia II (VaIN II), and assess the feasibility, safety, and influencing factors of ALA-PDT. A retrospective review was conducted on the clinical data of 79 patients with VaIN II (PDT group = 37, Laser group = 42) who were treated at the Gynecology Department of the Affiliated Hospital of Qingdao University from January 2022 to January 2024. Follow-up evaluations were carried out at 3, 6, and 12 months after treatment. During these follow-ups, human papillomavirus (HPV) testing, cervical liquid-based cytology (TCT), colposcopy, and vaginal lesion biopsy were utilized to assess key outcomes, including the lesion reversal rate, HPV clearance, and treatment-related adverse reactions in both groups. The lesion reversal rates following ALA-PDT treatment were 83.3 %, 86.1 %, and 88.2 % at 3, 6, and 12 months, respectively. There was no significant difference when compared to the laser group. However, the negative HPV conversion rates at 6 and 12 months after ALA-PDT treatment were 73.5 % and 87.5 %, respectively, which were significantly higher than those observed in the CO For the treatment of VaIN II, ALA-PDT exhibits equivalent lesion reversal rates and superior HPV clearance compared to CO

Hematoporphyrin derivative-photodynamic therapy (HpD-PDT) for extensive vulvar and vaginal Bowen's disease: A case report

Bowen's disease (BD) is an intraepithelial squamous cell carcinoma (SCC) that commonly affects older individuals, with the vulva being a prevalent site in women. Lesions within the vagina pose a particular challenge for surgical treatment, often compromising both functional integrity and cosmesis. Photodynamic therapy (PDT) is an emerging, safe, and non-invasive technique utilizing a photosensitizer and a specific light source, widely applied in the treatment of malignancies and skin diseases. We report the case of a 74-year-old woman presenting with a large, dark brown patch on the vulva, histopathologically confirmed as BD. The patient also had lesions within the vagina. Hematoporphyrin derivative-photodynamic therapy (HpD-PDT) was administered, with an optical fiber used for targeted treatment of the vaginal lesions. Complete resolution of the lesions was observed after a single treatment. A follow-up biopsy at 7 months post-treatment revealed no residual tumor cells. The patient remains disease-free at 2 years follow-up and continues to be monitored. This case suggests that HpD-PDT is a viable treatment option for BD, and may be particularly advantageous for elderly patients with extensive or vaginally located lesions, where preserving function and cosmesis is paramount.

Topical 5-aminolevulinic acid photodynamic therapy for cervical high-grade squamous intraepithelial lesions

To evaluate the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of high-grade squamous intraepithelial lesions of the cervix (HSIL). This retrospective study included 22 female patients with histologically confirmed HSIL and high-risk human papillomavirus (HR-HPV) infections. Patients were treated with ALA-PDT once a week for a total of 6 times. All patients had a follow-up period of 3 months and 6 months. The assessment of effectiveness of ALA-PDT was performed by ThinPrep cytology test (TCT), HPV DNA assay, HPV E6/E7 mRNA examination, colposcopy, biopsy, and immunohistochemistry detection. Three months after 5-ALA PDT, the histologic disappearance rate was 81.82% (18/22), while the HPV clearance rate was 54.55% (12/22). At the 6 months checkpoint, the HSIL disappearance rate was 90.91% (20/22) and the HPV clearance rate was 86.36% (19/22). Before PDT, 68.18% of patients (15/22) were confirmed with TCT abnormalities, while only one patient (1/22, 4.55%) was abnormal in the TCT test at 6 months checkpoint. All participants were found HPV E6/E7 mRNA positive initially, while the HPV E6/E7 mRNA negative rate was 90.91% (20/22) at 6 months checkpoint. Additionally, we found a significant difference of the expression of CD4+ and CD8+ T cells and HPV E6 and E7 proteins before ALA-PDT and at 3 months follow-up (P < 0.01). No severe side effects were seen. Topical 5-ALA PDT is an effective treatment for cervical HSIL with HR-HPV infection.

Comparative study of photodynamic therapy (PDT) of cervical low-grade squamous intraepithelial lesion (LSIL)

Prevention of high-risk HPV (HR-HPV) infection and effective medical intervention of persistent HPV infection and precancerous lesions are critical for the prevention of cervical cancer. The aim of this retrospective comparative study was to evaluate the outcomes of ALA PDT and observation only in the management of low-grade squamous intraepithelial lesions (LSIL). In PDT Group (n = 138), ALA PDT was applied to patients with colposcopic biopsy confirmed cervical LSIL accompanied with HR-HPV infection longer than 1 year or HPV 16/18 subtype infection. Cervical LSIL only patients received 3 times of ALA PDT and those with concurrent cervical canal or vaginal lesions received 6 times ALA PDT. Control Group (n = 69) received observation only. Colposcopy, TCT and HPV typing were performed before and after treatment. Patients were followed up for up to two years. The observation group showed 26.1%, 34.8% and 53.6% HR-HPV negative conversion at 3-6, 12 and 24 months, respectively. LSIL regression rate of the observation group was 33.33%, 36.23% and 65.22% at 3-6, 12 and 24 months, respectively. There was 62.32%, 80.56% and 89.22% patients achieved HPV clearance at 3-6, 12 and 24 months after PDT treatment, respectively. The LSIL remission rate was 89.86%, 94.40% and 96.08% at 3-6, 12 and 24 months after ALA PDT, respectively. The abnormal TCT (≧ ASCUS) was reduced from 92% to 10.1%, 4.6% and 3.9% at 3-6, 12 and 24 months after ALA PDT, respectively. The patient age was not a factor affecting the clearance of HPV infection and the LSIL regression rate of PDT treatment. This study demonstrates that the application of multiple ALA PDT treatments has added value in achieving both short-term and long-term HPV and lesion clearance.

Successful pregnancy and delivery after HiPorfin photodynamic therapy for cervical high-grade squamous intraepithelial lesion

The study analyzed HiPorfin-Photodynamic therapy (PDT) for young women with cervial high-grade squamous intraepithelial lesion (HSIL) and evaluated the impact of PDT on their pregnancy and delivery. Retrospective analysis of 4 patients (21-33 years old) were treated with HiPorfin® (2 mg/kg) PDT in 2019-2022. 1 patient suffered from cervical intraepithelial neoplasia (CIN)Ⅱ and 3 patients from CIN Ⅲ. 630 nm laser light irradiated the cervical surface and endocervical canal with light dose of 150 J/cm The median observation time period was 40.5 months. Cure rate, HPV eradication rate and negative conversion rate of cytology were all 100.0 % at 3, 6 and 12 months. All cervical canal lesions completely turned negative. No recurrence occurred during the long-term follow-up period. None of patients suffered from infertility. Three patients delivered vaginally and one delivered by C-section to healthy infants at term. HiPorfin® PDT for cervical HSIL was proved to be a safe method without adverse effects on female fertility and allowing these women to have healthy, full-term children.

Comparative study of topical 5-aminolevulinic acid photodynamic therapy and surgery for recurrent cervical high-grade squamous intraepithelial lesions following surgery

The study aimed to compare the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and surgery in treating recurrent cervical high-grade squamous intraepithelial lesions (HSIL) after surgery due to precancerous lesions. A total of 41 patients with recurrent cervical HSIL after surgery for precancerous lesions were studied retrospectively. Patients underwent ALA-PDT or surgery and were followed up at 3, 6, 9 and 12 months and then every six months after that. Clinical data were collected and the efficacy and safety of the two treatment methods were compared. Of the 41 patients with recurrent cervical HSIL after conization, 15 cases received ALA-PDT and 26 received surgery. At the six-month follow-up, the lesions' complete remission (CR) rate was 93.33 % in ALA-PDT group and 88.46 % in the surgery group. The human papillomavirus (HPV) clearance rates were 66.67 % and 73.08 %, respectively. No significant differences concerning the lesions' CR rate and the HPV clearance rate were observed between the two groups (P>0.05). At the twelve-month follow-up, the HPV clearance rates were 80.00 % and 91.67 %. No significant differences concerning the HPV clearance rate were observed between the two groups (P>0.05). In the surgery group, the HPV clearance rate and the lesions' CR rate were lower in patients over 45 years of age (25.00% vs. 81.82 %, P = 0.031; 50.00% vs. 95.45 %, P = 0.052). During the follow-up, there was no significant difference in the recurrence rate between the two groups (P>0.05). In addition, none of the patients progressed. In women treated with ALA-PDT, there was no vaginal bleeding, and no harmful effects on the cervical organizational structure or functions compared to the surgery group, and two women delivered successfully after ALA-PDT treatment. The efficacy of ALA-PDT was similar to that of surgery in treating recurrent cervical HSIL following surgery, with fewer side effects.

Comparative study of topical 5-aminolevulinic acid photodynamic therapy and surgery in treating vaginal high-grade squamous intraepithelial lesions following hysterectomy

To compare the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and surgery in treating vaginal high-grade squamous intraepithelial lesions (HSIL) after hysterectomy due to cervical cancer (CC) or precancerous lesions. A retrospective study was performed comprising 41 women with histologically confirmed vaginal HSIL after hysterectomy for CC or cervical HSIL. Patients were treated with surgery or ALA-PDT and were followed up at 3, 6 and 12 months and then every six months afterwards. Clinical data were collected and the efficacy and safety of the two groups were analyzed. Of the 41 patients with vaginal HSIL after hysterectomy, 18 were treated with ALA-PDT and 23 underwent surgery. There was no significant difference in the lesions' complete remission (CR) rate or the human papillomavirus (HPV) clearance rate between the ALA-PDT group and the surgery group (P > 0.05). In the surgery group, the clearance rate of HPV16/18 was higher than that of other high-risk HPV (HR-HPV) and HPV16/18 combined with other HR-HPV (87.50 % vs. 45.45 % vs. 0.00 %, P = 0.014). No significant difference in the recurrence rate between the two groups was noted (P > 0.05). And none of the patients progressed. In the surgery group, one patient developed significant thickening of the vaginal stump, and one patient had increased vaginal discharge. In women treated with ALA-PDT, there was no vaginal bleeding or harmful effects on the organizational structure or functions compared to the surgery group. The efficacy of ALA-PDT was comparable to that of surgery in treating vaginal HSIL following hysterectomy due to CC or cervical HSIL, with fewer side effects.

Evaluation of the effectiveness and safety of photodynamic therapy in the treatment of precancerous diseases of the cervix (neoplasia) associated with the human papillomavirus: A systematic review

This study provides an overview of the effectiveness and safety of PDT for the treatment of HPV-associated precancerous cervical conditions and contains recent findings from relevant research studies. A comprehensive literature search of MEDLINE/PubMed, Cochrane Central Library, and Google Scholar was conducted, including analytic epidemiological studies, and 11 papers were included. The narrative synthesis approach was used to summarize the results of the included studies. Studies were critically appraised using The Joanna Briggs Institute (JBI) tool for assessing the risk of bias. The results of the study demonstrate that CRR for HPV remission ranges from 66.7 % to 92.73 %, whereas for CIN1 it fluctuates from 57.1 % to 83.3 %. The frequency of recurrence of the disease ranged from 3.3 % to 8.9 % during the follow-up period of up to 2 years. Adverse events were observed in 8 (66 %) studies and the most common were cervical stenosis, abdominal pain, vaginal pain, and focal edema. Five types of topical and intravenous applications along with lasers of various wavelengths and intensities were mostly used. However, all studies demonstrated relatively similar results. According to the results, PDT has demonstrated favorable outcomes, but no impressive effect on the treatment of CIN. It should be emphasized, that the effectiveness of PDT for the treatment of HPV-associated CIN may vary depending on some variables, including the kind of PDT agent used, the dosage, duration and frequency of PDT administration, the severity and location of the lesions, and the host immunological response.

Comparative study of treatment efficacy in severe intraepithelial squamous cell lesions and preinvasive cervical cancer by conization and chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy

Cervical cancer (CC) occupies a leading position in incidence among young women of reproductive age. In this connection, it is urgent to search for the most effective approaches to the diagnosis and treatment of this pathology. The purpose of the study was to evaluate the effectiveness of the PDT method using Cе6 with the control of the photobleaching using video and spectral fluorescence diagnostic methods, to develop the method of fluorescence-assisted systemic photodynamic therapy mediated with chlorin e6 for treatment CIN 3 and CIS. A randomized comparative clinical study was conducted involving 94 women aged 18 to 49 years with histologically verified severe intraepithelial squamous cell lesions of the cervix or preinvasive cervical cancer. The patients were included in 2 groups: in the first group conization of the cervix was performed with curettage of the remaining part of the cervical canal; patients in the second group underwent the chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy. The absolute majority of patients in the main group after the first course of chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy showed normalization of cytological parameters and colposcopic picture, while women from the comparison group showed signs of cervical lesions statistically significantly more often. These changes corresponded to the dynamics of the proliferation markers expression in the cells of intraepithelial squamous cell lesions. Also, patients of the second group who were planning a pregnancy had better reproductive outcomes after treatment compared to those of the first group. In general, higher clinical efficacy and safety of the use of the chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy in the treatment of intraepithelial squamous cell lesions and preinvasive cervical cancer have been established compared to the use of standard treatment methods.

Comparative study of topical 5-aminolevulinic acid photodynamic therapy and surgery for the treatment of vulvar squamous intraepithelial lesion

Vulvar squamous intraepithelial lesion (SIL) is a precursor lesion of vulvar squamous cell carcinoma. The current clinical treatments for vulvar SIL cause damage to the vulvar structure, chronic pain and psychological distress. Topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a novel, non-invasive therapy for intraepithelial lesions. The objective of this study was to compare the clinical efficacy and safety of ALA-PDT with local surgical resection for vulvar SIL. A total of 56 patients with vulvar SIL were enrolled in this retrospective study. Among them, 16 patients received local resection and 40 patients received ALA-PDT. HPV genotyping and ThinPrep cytologic test (TCT) were used to evaluate treatment efficacy. In addition, colposcopy-directed biopsy was performed in all patients at 3-month follow-up and in patients with positive high-risk human papillomavirus (HR-HPV) and/or abnormal TCT results during the follow-up. At 3-month follow-up and in HSIL group the complete remission (CR) rate of the ALA-PDT group and surgery group was 90.6% (29/32) and 87.5% (14/16) (P = 1.000), respectively. The HPV clearance rate of the ALA-PDT group and surgery group was 45.2% (14/31) and 43.8% (7/16) (P = 0.927), respectively. The average numbers of ALA-PDT treatments were 5.34 for HSIL patients and 4.88 for LSIL patients, respectively. The CR rate of HSIL patients and LSIL patients was 90.6% (29/32) and 75.0% (6/8) (P = 0.550), respectively. The HPV clearance rate of HSIL patients and LSIL patients was 45.2% (14/31) and 37.5% (3/8) (P = 1.000), respectively. The ALA-PDT group showed similar clinical efficacy and milder adverse effects compared with the surgical group. ALA-PDT showed similar clinical efficacy as surgery in the treatment of vulvar SIL, but with milder adverse effects and maintaining the integrity of the vulvar structure.

Efficacy and influencing factors of CO2 laser, topical photodynamic therapy versus therapy combined with CO2 laser pretreatment for vaginal low-grade squamous intraepithelial lesions with high-risk HPV infection

Vaginal intraepithelial neoplasia (VaIN) is a group of diseases of squamous epithelial dysplasia and carcinoma in situ occurring in the vagina, which is associated with high-risk human papillomavirus (HR-HPV) infection. To evaluate the efficacy and safety of Carbon dioxide (CO Patients with HR-HPV infection and pathological diagnosis of VaIN1 and received laser or PDT or PDT combined with laser pretreatment were recruited. A total of 45 patients received one to three times CO There was no significant difference in regression rate of VaIN1 among the laser Group, the PDT Group and the laser + PDT Group (3-6 month follow-up: 57.78% vs 73.3% vs 80 %, 9-12 month follow-up: 68.89% vs 80% vs 86.67 %, P>0.05). HR-HPV remission rates were also similar in the three groups (3-6 month follow-up: 26.67% vs 46.67% vs 46.67 %, 9-12 month follow-up: 40 % in all groups, P>0.05). Compared to HR-HPV negative group, patients in the HR-HPV positive group were older and had more pregnancies. Menopause and multiple vaginal lesions were more common in the HR-HPV positive group. Adverse reactions were mild in the PDT Group. The laser Group and the laser + PDT Group had more adverse effects, such as increased vaginal secretion, vaginal bleeding, scarring and local pain. For patients with VaIN1 at risk of progression, ALA-PDT presents itself as a viable choice for those who are well-informed and can consent to its costs and benefits. The addition of CO

Nanoparticles loading porphyrin sensitizers in improvement of photodynamic therapy for ovarian cancer

Ovarian cancer, the malignant tumor with the highest mortality rate in gynecological tumors, leads to a poor prognosis due to tumor metastasis. At present, the main treatment for ovarian cancer is the combination of cytoreduction surgery and chemotherapy. But the surgery is insufficient to solve the extensive transfer of tumor in the abdominal cavity and a large proportion of ovarian cancer cases have shown resistance to chemotherapy. Photodynamic therapy (PDT) is a viable treatment option for a wide range of applications, especially in malignant tumors. Porphyrin sensitizers, as the most widely used photosensitive agents, have the following advantages: short photosensitive period and high singlet oxygen production. However, most studies have found that it is difficult to achieve high loading rates of photosensitive agents, thus effective concentration in target tissue is suboptimal and the lethal ability is greatly reduced. In this article, we review several studies that nanoparticles loading porphyrin sensitizers for photodynamic therapy of ovarian cancer. We collected relevant literature from PUBMED and reviewed their research content. The application of nanotechnology to PDT in ovarian cancer can reduce the non-specific toxicity of photosensitive agents and increase stability and delivery efficiency. The combination with nanotechnology can cover the shortcomings of photodynamic therapy, but the specific efficacy still needs a large number of experiments to prove.

Rapid identification of cervical adenocarcinoma and cervical squamous cell carcinoma tissue based on Raman spectroscopy combined with multiple machine learning algorithms

Cervical cancer has a long latency, and early screening greatly reduces mortality. In this study, cervical adenocarcinoma and cervical squamous cell carcinoma tissue data were collected by Raman spectroscopy, and then, the adaptive iteratively reweighted penalized least squares (airPLS) algorithm and Vancouver Raman algorithm (VRA) were used to subtract the background of the collected data. The following five feature extraction algorithms were applied: partial least squares (PLS), principal component analysis (PCA), kernel principal component analysis (KPCA), isometric feature mapping (isomap) and locally linear embedding (LLE). The k-nearest neighbour (KNN), extreme learning machine (ELM), decision tree (DT), backpropagation neural network (BP), genetic optimization backpropagation neural network (GA-BP) and linear discriminant analysis (LDA) classification models were then established through the features extracted by different feature extraction algorithms. In total, 30 types of classification models were established in this experiment. This research includes eight good models, airPLS-PLS-KNN, airPLS-PLS-ELM, airPLS-PLS-GA-BP, airPLS-PLS-BP, airPLS-PLS-LDA, airPLS-PCA-KNN, airPLS-PCA-LDA, and VRA-PLS-KNN, whose diagnostic accuracy was 96.3 %, 95.56 %, 95.06 %, 94.07 %, 92.59 %, 85.19 %, 85.19 % and 85.19 %, respectively. The experimental results showed that the model established in this article is simple to operate and highly accurate and has a good reference value for the rapid screening of cervical cancer.

Long-term follow-up of photodynamic therapy of cervical intraepithelial neoplasia grade 2 (CIN2)

To determine the long-term efficacy and safety of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) for treating cervical intraepithelial neoplasia grade 2 (CIN2) as well as the suitability of ALA-PDT in treating of cervical lesions divided into cervical transformation zone type 3. We included 81 patients diagnosed with CIN2 at the Department of Gynecology of the Affiliated Hospital of Qingdao University with data collected between January 2019 and January 2021 following ALA-PDT. Furthermore, we analyzed the superiority of ALA-PDT in fertility preservation among women of childbearing age based on follow-up data from 11 patients with fertility requirements. Our findings confirmed the long-term efficacy of ALA-PDT for CIN2 treatment, with an overall efficacy of 95.83 % (23/24) at follow-up of 25-36 months. Moreover, the cervical transformation zone type 3 improvement and human papillomavirus (HPV)-negative efficacy were 69.2 % (18/26) and 82.4 % (14/17), respectively. ALA-PDT is recommended for consenting patients with cervical transformation zone type 3. Additionally, women without primary infertility could experience natural pregnancy and full-term birth of more than one baby following ALA-PDT for CIN2 treatment, with a satisfaction rate of ≈100 %. ALA-PDT is recommendable for treating high-grade squamous intraepithelial lesions, especially in patients with fertility requirements.

Efficacy of 5-aminolevulinic acid and LED photodynamic therapy in cervical intraepithelial neoplasia: A clinical trial

5-Aminolaevulinic acid (5ALA) is a precursor of the strong sensitizer protoporphyrin IX (PpIX) in the heme synthesis pathway. We conducted aclinical trial designed to evaluate the efficacy and safety of 5ALA photodynamic therapy (PDT) using a light-emitting diode (LED) in patients with cervical intraepithelial neoplasia (CIN). Data for 51 CIN patients who underwent 5ALA-PDT between 2012 and 2017 were prospectively analysed. After a 20 % 5ALA jelly formulation was topically applied to the cervix, the region was irradiated with red light at approximately 633 nm to excite PpIX for treatment. We estimated outcomes by cytology, pathology, and human papilloma virus (HPV) testing after PDT. Patients underwent two PDT sessions at one-week intervals during outpatient treatment and achieved favourable results without photosensitivity and severe adverse events. Over a long follow-up period, 96.1 % of all patients showed some positive effects, including approximately 70 % with a complete response (CR), 10 % with a partial response, and 15 % with downgrades. The HPV clearance rate in patients with CR was 79.4 %. Recurrence occurred in five patients who mostly remained HPV-positive after PDT. Based on our study, topical 5ALA-PDT using an LED light source potentially represents a safe treatment for CIN on an outpatient basis.

Effect of berberine associated with photodynamic therapy in cell lines

Cervical cancer is a serious worldwide health problem. In view of the potentially harmful effects of current conventional therapies, photodynamic therapy may be an option as it is a minimally invasive therapy and can promote selective cytotoxic activity for neoplastic cells in the target tissue., Berberine (BBR) as an isolated molecule is a natural compound that has antineoplastic properties and potential action as a photosensitizer agent. The purpose of this study was to evaluate the use of berberine as a photosensitizer in photodynamic therapy (PDT) protocols and observe the effects produced by this association in cervical carcinoma cells and in immortalized keratinocytes. Incubation with 2.5 μM berberine promoted less than 10 % of cellular death in both cell lines studied. In addition, by fluorescence microscopy, we demonstrated that berberine was internalized by the cells, and after a period of 48 h, it was still present in the intracellular environment preferentially localized in the cytoplasm. After photodynamic therapy using berberine as a photosensitizer and visible light activation at 447 (±10) nm, we observed a phototoxic effect, which resulted in 19.84 % cell viability for Caski cells and 47.22 % cell viability for HaCaT. Treatment with berberine associated with photodynamic therapy promoted an increase in the production of reactive species of oxygen (ROS) and caspase-3 activity, indicating a preferential cell death mechanism by caspase-dependent apoptosis. Therefore, we demonstrated that berberine is an efficient photosensitizer and that its association with photodynamic therapy may be a potential anticancer treatment strategy for cervical cancer.

High-risk HPV clearance and CIN 3 treated with MAL-PDT: A case report

High-grade cervical intraepithelial neoplasia (CIN) is the precursor to cervical cancer. HPV (human papillomavirus) infection is strongly related with this disease. The CIN treatment is generally excision of the transformation zone (ETZ). Photodynamic therapy (PDT) has also shown to be a promising treatment. We are reporting a case of a 33-years-old patient with high-grade CIN 3 treated with topical MAL (methyl aminolevulinate) PDT. Was applied 2.5 g of 20 % (w/w) MAL cream overnight and the cervix was illuminated twice, with three weeks apart, using a probe with LEDs simultaneously with a cylindrical laser fiber emitting both at 630 nm, with a fluency of 150 J/cm

Pluronic-based graphene oxide-methylene blue nanocomposite for photodynamic/photothermal combined therapy of cancer cells

A nanocomposite containing methylene blue (MB), graphene oxide (GO) and Pluronic F127 (PF127) had been developed for combined photothermal therapy (PTT) and photodynamic therapy (PDT). In this study, GO was firstly loaded with MB to form GO-MB by a self-assembly method, and then the surface was modified with PF127 to form GO-MB/PF127 nanocomposite (GO-MB/PF127) by a thin-film hydration method. The structure and properties of the nanocomposite were characterized by Ultraviolet-Visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, transmission electron microscope (TEM), dynamic light scattering (DLS) and zeta potential. The results showed that the as-prepared nanocomposite exhibited high stability in aqueous solution, high release rate of MB from the nanocomposite under acidic conditions. In addition, when excited by 808 nm near infrared (NIR) light and 660 nm light emitting diode (LED) source, GO in GO-MB/PF127 caused photothermal ablation of cancer cells while MB produced singlet oxygen (

Clinical efficacy of photodynamic therapy combined with CO2 laser in the treatment of vulvar squamous intraepithelial lesions

Comprehensive research data on the combination of 5-aminolevulinic acid (5-ALA) photodynamic therapy (PDT) and CO This study was a retrospective study. The subjects were 165 patients diagnosed with VSIL in the People's Hospital of Zhengzhou University. According to the patients' personal choice, they were divided into 5-ALA PDT group (n = 37), CO2 laser group (n = 78) and 5-ALA PDT combined with CO2 laser group (n = 50). The general condition, treatment times and adverse reactions of patients in each group were analyzed. All patients underwent HPV, TCT and colposcopy at 3 months and 6 months after treatment to evaluate the therapeutic effect, and biopsy was performed again if necessary. There was no statistically significant difference in the HPV negative conversion rates and lesions complete remission (CR) rates of both vulvar low-grade squamous intraepithelial lesions (VLSIL) and vulvar high-grade squamous intraepithelial lesions (VHSIL) patients among the three groups at 3 months after treatment. Regarding VLSIL, the HPV negative conversion rates for both the 5-ALA PDT group (51.7 %) and the combination group (51.9 %) were significantly higher than the CO The integration of 5-ALA PDT with CO₂ laser therapy not only reduces the overall treatment duration but also enhances treatment efficacy. Therefore, it is a promising option for treating VSIL.

Aminolevulinate photodynamic therapy (ALA-PDT) combined with fire needle for vulva lymphangioma circumscriptum

Lymphangioma is a rare benign lymphatic system proliferation, especially in the vulva. The general treatment principle is determined by clinical manifestations, lesion size, anatomic location, and complications. Treatment options include surgical excision, carbon dioxide laser, cryotherapy, electrocoagulation, and sclerosing agent injection. In the absence of evidence to guide the choice of significant treatment modalities, treatment options are often based on the experience of the treatment team and the patient's preferences. This study presents a case of primary vulva lymphangioma circumscriptum treated with fire needle therapy, photodynamic therapy, and cryotherapy. Furthermore, the combination of fire needle and photodynamic therapy demonstrated exceptional comprehensive effects in pain, wound healing and cosmetic.

Effect and rational application of topical photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) for treatment of cervical intraepithelial neoplasia with vaginal intraepithelial neoplasia

Lesions in both the cervix and vagina require an efficacious non-invasive treatment therapy such as 5-Aminolevulinic acid photodynamic therapy(5-ALA-PDT). In this study, we evaluate clinical efficacy and safety of 5-ALA PDT for cervical intraepithelial neoplasia with vaginal intraepithelial neoplasia (CIN & VAIN). A retrospective analysis was performed on 48 patients diagnosed with CIN & VAIN and receiving 5-ALA PDT. All patients were first followed up at 3, 6 and 12 months after treatment, then every 6 months thereafter. Out of 1051 patients referred for CIN (4.56%), 48 were diagnosed with CIN&VAIIN. The patients had statistically significant average vaginal and cervical lesion areas of 1.22 and 0.41 cm 5-ALA-PDT is a non-invasive, effective, and safe therapy for treating CIN & VAIN and can maintain the structural and functional integrity of target organs. However, its efficacy is relatively poor in patients with endocervical canal lesions involvement, atypical vessels, and HPV16/18 and other hrHPV infection.

Long-term outcomes of photodynamic therapy for a positive resection margin after conization for cervical intraepithelial neoplasia grade 3

Positive resection margins after conization or loop electrosurgical excision procedure (conization/LEEP) are associated with increased risks of recurrence or residual cervical intraepithelial neoplasia (CIN). Herein, we investigated the long-term outcomes of photodynamic therapy (PDT) for incomplete excision of CIN3. We retrospectively reviewed the medical charts of 73 patients treated with PDT between 2000 and 2011. Patients who underwent conization/LEEP before PDT within 6 months were included. The primary outcomes were the complete response (CR) rate after 1 year and human papillomavirus (HPV) eradication rate at 6 months after PDT. A total of 34 patients with positive resection margins were finally enrolled. The median patient age was 33 years. Carcinoma in situ was diagnosed in 25 patients and CIN3 in 7 patients. The CR rate was 97.1% after 1 year. Except for one case of a persistent disease, there was no recurrence or newly developed disease during the median follow-up of 84 months (range, 12-224 months). The HPV eradication rate of PDT following conization/LEEP after 6 months was 96.9% (31/32). Photosensitivity was identified in five patients and cervical stenosis in one patient. In conclusion, PDT could be an effective therapeutic option for patients with a positive resection margin after conization/LEEP for CIN3. It could reduce the residual or recurrence rate of CIN lesions with tolerable adverse events.

Photodynamic therapy for early-stage cervical cancer treatment

The aim of this article is a retrospective analysis of PDT effectiveness in the treatment in early-stage cervical cancer and also analysis of HPV elimination via PDT MATERIAL AND METHODS: A total of 28 patients were analyzed retrospectively, all with PDT treatment for early-stage cervical cancer. Patients underwent one PDT session or a multi-course PDT approach. This depended on individual reaction and response to therapy after the first session. A multi-course approach was performed over two months. Treatments were performed from 2015 to 2020. Relapse-free probability was assessed for these patients by Kaplan Meier estimator at 60 months and HPV elimiantion was also examined.. HPV elimination was in 82% of cases in three-month period after PDT (R The article demonstrates treatment results for CC and detected a five-year period relapse-free probability after PDT. Patients completing a multi-treatment PDT protocol for invasive cervical cancer can achieve both high response rate and relapse-free survival.

Application of one-dimensional hierarchical network assisted screening for cervical cancer based on Raman spectroscopy combined with attention mechanism

Cervical cancer is one of the most common malignant tumors among women, and its pathological change is a relatively slow process. If it can be detected in time and treated properly, it can effectively reduce the incidence rate and mortality rate of cervical cancer, so the early screening of cervical cancer is particularly critical and significant. In this paper, we used Raman spectroscopy technology to collect the tissue sample data of patients with cervicitis, Low-grade Squamous Intraepithelial Lesion, High-grade Squamous Intraepithelial Lesion, Well differentiated squamous cell carcinoma, Moderately differentiated squamous cell carcinoma, Poorly differentiated squamous cell carcinoma and cervical adenocarcinoma. A one-dimensional hierarchical convolutional neural network based on attention mechanism was constructed to classify and identify seven types of tissue samples. The attention mechanism Efficient Channel Attention Networks module and Squeeze-and-Excitation Networks module were combined with the established one-dimensional convolutional hierarchical network model, and the results showed that the combined model had better diagnostic performance. The average accuracy, F1, and AUC of the Principal Component Analysis-Squeeze and Excitation-hierarchical network model after 5-fold cross validations could reach 96.49%±2.12%, 0.97±0.03, and 0.98±0.02, respectively, which were 1.58%, 0.0140, and 0.008 higher than those of hierarchical network. The recall rate of the Principal Component Analysis-Efficient Channel Attention-hierarchical network model was as high as 96.78%±2.85%, which is 1.47% higher than hierarchical network. Compared with the classification results of traditional CNN and ResNet for seven types of cervical cancer staging, the accuracy of the Principal Component Analysis-Squeeze and Excitation-hierarchical network model is 3.33% and 11.05% higher, respectively. The experimental results indicate that the model established in this study is easy to operate and has high accuracy. It has good reference value for rapid screening of cervical cancer, laying a foundation for further research on Raman spectroscopy as a clinical diagnostic method for cervical cancer.

Chinese expert consensus on the clinical applications of aminolevulinic acid-based photodynamic therapy in female lower genital tract diseases (2022)

With the younger onset age of female lower genital tract diseases, there are increasing demands for protecting organ and tissue structures to preserve fertility and, therefore, effective fertility-sparing treatments that cause minimal normal tissue damage and less adverse reactions are urgently needed. This study is aimed at reviewing information and achieving consensus on recommendations on the clinical applications of aminolevulinic acid-based photodynamic therapy (ALA-PDT) in female lower genital tract diseases. Members of the expert panel held online and in-person meetings to discuss and revise drafts created by the steering committee based on the literature review and the clinical experiences of the expert panel. Opinions of the experts were transcribed and discussed in detail to ensure that the consensus statement best reflects the current advances in the field and the experts' view. After numerous rounds of meetings, experts unanimously agreed on the importance of ALA-PDT in the treatment of cervical squamous intraepithelial lesions (SIL), vaginal SIL, vulvar SIL, vulvar lichen sclerosus (VLS), and condyloma acuminatumon (CA). Experts also reached consensus on the recommended treatment regimen and treatment methods. This consensus aimed to provide practical basis and guidance for the clinical applications of ALA-PDT in female lower genital tract diseases in China. Of note, this is the only expert consensus prepared by board-certified specialists in gynecology and obstetrics in China. More evidence-based clinical studies should be made to update and expand the current recommendations.