Traditional Chinese Medicine Erhuang Suppository for Treatment of Persistent High-risk Human Papillomavirus Infection and Its Impact on Transcriptome of Uterine Cervix.

OBJECTIVE: High-risk human papillomavirus (HR-HPV) infection is the chief cause of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. The Erhuang suppository (EHS) is a traditional Chinese medicine (TCM) prepared from realgar (As2S2), Coptidis rhizoma, alumen, and borneolum syntheticum and has been used for antiviral and antitumor purposes. However, whether EHS can efficiently alleviate HR-HPV infection remains unclear. This study was conducted to evaluate the efficacy of EHS for the treatment of persistent HR-HPV infection in the uterine cervix. METHODS: In this study, we evaluated the therapeutic efficacy of EHS in a randomized controlled clinical trial with a 3-month follow-up. Totally, 70 patients with persistent HR-HPV infection were randomly assigned to receive intravaginal administration of EHS or placebo. HPV DNA, ThinPrep cytologic test (TCT), colposcopy, and safety evaluation were carried out after treatment. Microarray analysis was performed to compare transcriptome profiles before and after EHS treatment. A K14-HPV16 mouse model was generated to confirm the efficiency of EHS. RESULTS: After 3 months, 74.3% (26/35) of the patients in the treatment group were HPV negative, compared to 6.9% (2/29) in the placebo group. High-throughput microarrays revealed distinct transcriptome profiles after treatment. The differentially expressed genes were significantly enriched in complement activation, immune response, and apoptotic processes. The K14-HPV16 mouse model also validated the remarkable efficacy of EHS. CONCLUSION: This study demonstrated that EHS is effective against HR-HPV infection and cervical lesions. Additionally, no obvious systemic toxicity was observed in patients during the trial. The superior efficacy and safety of EHS demonstrated its considerable value as a potential cost-effective drug for the treatment of HPV infection and HPV-related cervical diseases.

Clinical efficacy of a new therapeutic option for lower genital tract lesions: 5-ALA photodynamic therapy.

The study utilized 5-ALA-PDT to treat patients with CIN or VaIN and assessed their clinical response, HPV clearance, and influencing factors after photodynamic therapy (PDT). This study involved 56 patients who received 5-ALA-PDT in a single center from May 2020 to March 2022, including 12 patients with CIN, 30 patients with VaIN, and 14 patients with both CIN and VaIN. Follow-up were conducted within 6 and 12 months after treatment to evaluate the clinical effectiveness of PDT. The assessment criteria included histological response (ER, elimination rate, RR, regression rate) and HPV clearance. Additionally, factors that could potentially influence the outcomes were analyzed. After PDT, the histological response showed an ER of 48.2% (27/56) and a RR of 80.4% (45/56) within 6 months of follow-up. The elimination rate increased to 69.6% (39/56) within 12 months, along with a regression rate of 82.1% (46/56). The rates of HPV clearance were observed to be 37.5% (21/56) and 44.6% (25/56) within 6 and 12 months, respectively. The study also revealed that HPV clearance significantly influenced histologic elimination within 6 months (p < 0.001) and histologic regression within 12 months (p < 0.01). Furthermore, premenopausal women exhibited a higher HPV clearance rate compared to postmenopausal women (61.5% vs. 30.0%, p = 0.036). 5-ALA PDT can be considered as an available option for the treatment of lower genital squamous intraepithelial lesions. The efficacy of its histologic response depends on HPV clearance. Additionally, it has been found that premenopausal women may benefit more from this treatment.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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 %. CONCLUSIONS: ALA-PDT is recommendable for treating high-grade squamous intraepithelial lesions, especially in patients with fertility requirements.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147).

PURPOSE: We report the results of a randomized phase II trial of imiquimod, a topical immune-response modulator versus imiquimod plus a 9-valent human papillomavirus (HPV) vaccine (9vHPV) versus clinical surveillance in cervical intraepithelial neoplasia (CIN2/3) patients. PATIENTS AND METHODS: We randomly allocated 133 patients with untreated CIN2/3 in equal proportions to a 4-month treatment with self-applied vaginal suppositories containing imiquimod (Arm B) or imiquimod plus a 9vHPV (Arm C) versus clinical surveillance (Arm A). The main outcome was efficacy, defined as histologic regression to CIN1 or less. Secondary outcomes were HPV clearance and tolerability. Exploratory objectives included the comparison of cervical CD4/CD8 T-cell infiltration at baseline, mid-study, and posttreatment by flow cytometry among study arms. RESULTS: Of the 114 evaluable patients 77% and 23% harbored CIN2 and CIN3, respectively. Regression to CIN1 or less was observed in 95% of patients in the imiquimod group (Arm B) compared with 79% in the control/surveillance (Arm A); P = 0.043 and 84% in the imiquimod+9vHPV group (Arm C; P = 0.384 vs. Arm A). Neither of the treatment-arm differences from Arm A reached the prespecified α = 0.025 significance level. No significant differences were noted in the secondary outcome of rate of HPV clearance. The number of tissue-resident memory CD4/CD8 T cells in cytobrush samples demonstrated a >5-fold increase in Arm B/imiquimod when compared with Arm A/surveillance (P < 0.01). In contrast, there was no significant difference in T-cell responses among participants in Arm C when compared with Arm A. Imiquimod treatment was well tolerated. CONCLUSIONS: Although imiquimod induced a higher regression to CIN1 or less and significant increases in CD4/CD8 T cells infiltrating the cervix, it did not meet its prespecified statistical outcome for efficacy. A higher regression rate than expected was observed in the surveillance arm of this prospective trial. Future clinical trials with imiquimod targeting CIN3 patients are warranted.

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.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Topical delivery of drugs in the treatment of high-grade cervical squamous intraepithelial lesions: A meta-analysis.

OBJECTIVE: The present study aims to evaluate the efficacy and effect of localized delivery of drugs in the treatment of high-grade squamous intraepithelial lesion (HSIL) based on a meta-analysis. STUDY DESIGN: Databases including Cochrane Library, PubMed, Embase, Scopus, CNKI, and Wanfang were searched from their inception till August 2022. Randomized controlled trials (RCTs) that compared the efficacy of drugs and surgery in the treatment of HSIL were collected. A meta-analysis was performed using the software of Review Manager (version 5.4.1). RESULTS: Eight RCTs involving 523 patients were included in the meta-analysis. For HSIL, the rate of cervical lesions histological regression was 69.85 % in the surgery group and 59.88 % in the drug group, there was no significant difference between the two groups [OR = 0.45, 95 % CI (0.07, 3.03), P = 0.41]. The histological regression rate of cervical lesions in the placebo group was 37.76 %, and the difference between the drug group and the placebo group was statistically significant [OR = 4.94, 95 % CI (2.65, 9.20), P < 0.00001]. CONCLUSION: A total of four drugs were involved in the eight RCTS included in this study, which were imiquimod, 5-fluorouracil (5-FU), cidofovir and interferon. The results showed that although drug administration was effective in the histological regression of HSIL, the efficacy was less than about 10% of surgical treatment. Considering the recurrence of the disease after surgery and the problems of abortion, premature delivery and premature rupture of membranes after cervical conization in reproductive women, drug therapy can be used as a supplement to surgery or conservative treatment to promote the histological regression of cervical lesions in patients with HSIL.

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

OBJECTIVE: 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. METHODS: 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/cm2 and 100-120 J/cm2 respectively. RESULTS: 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. CONCLUSION: 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.

A phase 1/2a, dose-escalation, safety, and preliminary efficacy study of the RKP00156 vaginal tablet in healthy women and patients with cervical intraepithelial neoplasia 2.

OBJECTIVE: This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, in healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2). METHODS: We conducted a phase 1/2a clinical trial of RKP00156. In step 1, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered transvaginally to 24 healthy women. In step 2, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered once daily for 4 weeks in 62 patients with CIN2. The primary endpoints of this trial were the safety of RKP00156 and the change in the human papillomavirus (HPV) viral load. RESULTS: A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events (AEs). Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a reduction in the HPV viral load was observed in the 25 mg-dose group (-98.61%; 95% confidence interval=-99.83%, 4.52%; p=0.046) after treatment completion in patients with a high HPV viral load, despite a lack of statistical power. No differences in histologic regression and HPV clearance were observed. CONCLUSION: The safety of RKP00156 was proved with no serious AEs. Although the study did not show any significance in histologic regression and HPV clearance, our findings indicate that RKP00156 may have a possibility of short-term inhibitory effect on HPV replication in patients with higher viral loads. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02139267.

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

OBJECTIVE: 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. METHODS: 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/cm2 and 150 J/cm2 respectively. RESULTS: 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. CONCLUSION: 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.

A prospective multicentre controlled study of Gaoweikang (Chinese multiherb extract-based tincture) used in high-risk HPV infections.

OBJECTIVE: The aim of the study was to investigate the safety and antiviral efficacy of a Chinese multiherb extract-based tincture (GWK) on a population of patients with high-risk human papilloma (hrHPV) infections and hrHPV-caused cervical low-grade squamous intraepithelial lesions (LSILs). PATIENTS AND METHODS: Patients with persistent hrHPV infection were enrolled in Group A, including A1 subjects, who received the intervention, and A2 subjects, who received the control. Patients with hrHPV infection causing cervical LSIL were enrolled in Group B, which included B1 subjects, who received the intervention, and B2 subjects, who served as the control. For Groups A1 and B1, hrHPV was tested at 3 months (M3) and 6 months (M6) after the intervention. The side effects were also analyzed. RESULTS: At baseline (D0), a total of 99 patients were enrolled in Group A, with 50 subjects in Group A1 and 49 subjects in Group A2. A total of 91 patients were enrolled in Group B, with 45 subjects in Group B1 and 46 subjects in Group B2. There was no significant difference in the characteristics, including average age, age stratification, and HPV genotype. At M6, both Group A1 and Group B1 had a higher hrHPV clearance rate than the control group (A1/A2: 80.0% vs. 20.4%; B1/B2: 64.4% vs. 15.2%, p<0.001). At M6, the effective rates of Group A1 and Group B1 were 84% (42/50) and 68.9% (31/45), respectively. The side effect rates of Groups A1 and B1 were 11.5% (6/52) and 11.1% (5/45), respectively. Most adverse reactions involved local discomfort, including vulvar erythema, vulvar itch, increased vaginal discharge, cervical bleeding, and mild pain in the lower abdomen. Univariate logistic regression analysis showed that the intervention had an OR of 12 (95% CI 4.431-32.50) for clearing persistent HPV infection (p<0.001). For cervical LSIL, the intervention had an OR of 10.1 for clearing persistent HPV infection (95% CI 3.68-27.7) (p<0.001). CONCLUSIONS: The results of this study suggest that the Chinese multiherb extract-based tincture GWK is safe and well tolerated. Furthermore, this preliminary study showed that this Chinese multiherb extract-based tincture is helpful for promoting HPV clearance in cases of persistent HPV and HPV-induced LSIL.

Elimination of Human Papillomavirus and Cervical Pathological Microbiota with Photodynamic Therapy in Women from Mexico City with Cervical Intraepithelial Neoplasia I.

Cervical carcinoma (CC) is the second cause of cancer death in Mexican women. It starts with premalignant lesions known as Intraepithelial Cervical Neoplasia (CIN) that can develop due to infection by Human Papillomavirus (HPV) and other microorganisms. Current CIN therapy involves invasive methods that affect cervix integrity and fertility; we propose the use of photodynamic therapy (PDT) as a strategy with few side effects. In this work, the effectiveness of PDT for CIN I, HPV and pathogenic vaginal microbiota elimination in 29 women of Mexico City with CIN I, CIN I + HPV and HPV diagnosis was determined. After 6 months of PDT application, HPV infection was eliminated in 100% of the patients (P < 0.01), CIN I + HPV in 64.3% (P < 0.01) and CIN I in 57.2% (P > 0.05). PDT also eliminated pathogenic microorganisms: Chlamydia trachomatis in 81% of the women (P < 0.001) and Candida albicans in 80% (P < 0.05), without affecting normal microbiota since Lactobacillus iners was eliminated only in 5.8% of patients and the opportunistic Gardnerella vaginalis in 20%. These results show that PDT was highly effective in eradicating HPV and pathogenic microorganisms, suggesting that PDT is a promising therapy for cervical infections.

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

BACKGROUND: 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. METHODS: 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/cm2. ALA-PDT was conducted every 7-10 days for 4-6 times. Patients were followed up three, six, nine, and twelve months after treatment. The effect was evaluated through HPV genotyping, ThinPrep cytology test (TCT), and colposcopy-directed biopsy. RESULTS: 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). CONCLUSIONS: 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.

A Therapeutic Antigen-Presenting Cell-Targeting DNA Vaccine VB10.16 in HPV16-Positive High-Grade Cervical Intraepithelial Neoplasia: Results from a Phase I/IIa Trial.

PURPOSE: To evaluate the safety, immunogenicity and efficacy of a therapeutic DNA vaccine VB10.16, using a unique modular vaccine technology that is based on linking antigens to CCL3L1 targeting module, in women with HPV16-positive high-grade cervical intraepithelial neoplasia (CIN). PATIENTS AND METHODS: We conducted a first-in-human, open-label, phase I/IIa clinical trial of VB10.16 in subjects with confirmed HPV16-positive CIN 2/3. The primary endpoint was the proportion of participants with adverse events, including dose-limiting toxicities. Secondary outcome measures included measuring the E6/E7-specific cellular immune response. In the Expansion cohort HPV16 clearance, regression of CIN lesion size and grading were assessed during a 12-month follow-up period. RESULTS: A total of 34 women were enrolled: 16 in two dose cohorts and 18 in the expansion cohort. No serious adverse events or dose-limiting toxicities were observed, and none of the subjects discontinued treatment with VB10.16 due to an adverse event. Mild to moderate injection site reactions were the most commonly reported adverse event (79%). HPV16-specific T-cell responses were observed after vaccination in the majority of the subjects. In the expansion cohort, HPV16 clearance was seen in 8 of 17 evaluable subjects (47%). Reductions in lesion size were seen in 16 subjects (94%) and 10 subjects (59%) had regression to CIN 0/1. Correlation between strong IFNγ T-cell responses and lesion size reduction was statistically significant (P < 0.001). CONCLUSIONS: The novel therapeutic DNA vaccine VB10.16 was well tolerated and showed promising evidence of efficacy and strong HPV16-specific T-cell responses in subjects with high-grade CIN.

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).

OBJECTIVE: 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). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: Topical 5-ALA PDT is an effective treatment for cervical HSIL with HR-HPV infection.

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.

Echinacea angustifolia and Echinacea purpurea Supplementation Combined with Vaginal Hyaluronic Acid to Boost the Remission of Cervical Low-Grade Squamous Intraepithelial Lesions (L-SILs): A Randomized Controlled Trial.

Background and Objectives: Echinacea angustifolia and purpurea have known immunomodulatory effects which boost viral clearance, including HPV infection. However, evidence regarding the improvement due to Echinacea-based supplements of cervical HPV-related pathologies is still lacking. The aim of this study is to evaluate the efficacy of Echinacea supplementation on the remission of cervical low-grade squamous intraepithelial lesions (L-SIL). Materials and Methods: A single-blind 1:1:1 parallel randomized controlled trial was conducted at the Colposcopy Unit of a tertiary care referral center. Reproductive-aged women were allocated either to (a) an oral supplement based on Echinacea extracts plus vaginal hyaluronic acid-based soft gel capsules, (b) the Echinacea supplement alone, or (c) vaginal hyaluronic acid-based soft gel capsules alone for 3 months. The primary outcome was the regression of cervical intraepithelial neoplasia (CIN)-1 for each treatment arm at 3, 6 and 12 months after the diagnosis. Secondary outcomes included changes in the epithelialization, pap smear, colposcopic parameters, histological reports, and vaginal health indexes (VHI) in the study groups. Results: 153 women (52 for arm A, 50 for arm B and 51 for arm C) completed the follow-up and were included in the analysis. There were no significant differences in both primary and secondary outcomes for the three groups after 3 months. At the 6-month follow-up, the number of persistent CIN-1 diagnoses was significantly lower in arm A (15/51), rather than in arm B (23/48, p = 0.03) and C (27/49, p = 0.03). Similarly, the same effect was seen after 12 months for treatment A (5/51) relative to B (15/48, p = 0.03) and C (14/48, p = 0.03). Colposcopic, histological and vaginal parameters were all significantly improved at 6 and 12 months for arm A relative to B and C, while no beneficial effects were seen after 3 months. Conclusions: Echinacea extracts supplementation in women with L-SIL/CIN-1 significantly boosts HPV lesion clearance, reducing the overall amount of diagnosis, histological, colposcopic and vaginal parameters after 6 and 12 months. However, a limited sample size reduces the quality of evaluated evidence, emphasizing the need for additional studies to validate these findings.

Effects of folate supplementation on recurrence and metabolic status of cervical intraepithelial neoplasia grade 2/3 in overweight and obese women: a randomized double-blind placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Inconsistent evidence showed that folate supplementation may be associated with reduced risk of cancer due to improved metabolic profiles and reduced markers of oxidative stress and inflammation. The aim of this investigation was to quantify the effects of folate supplementation on the recurrence and other metabolic factors of women with cervical intraepithelial neoplasia grade 2/3 (CIN2/3). METHODS: This randomized, double-blind, placebo-controlled clinical trial was performed among 60 overweight/obese women with CIN2/3. Definitive CIN2/3 confirmation was done via biopsy, pathological diagnosis, as well as colposcopy. Participants were randomly assigned to the intervention group to take 5 mg/day folate supplements or placebo group (n = 30 in each group) for 12 weeks. RESULTS: The results of the current study showed a non-significant decrease in recurrence of CIN2/3 in the folate group in comparison with the placebo group (3.3% vs. 16.7%, P = 0.08). Compared with the placebo, folate supplementation significantly decreased plasma homocysteine (Hcy) levels (P < 0.001), serum insulin values (in the crude model) (P = 0.01), and homeostasis model assessment of insulin resistance (P = 0.01). Also, folate supplementation resulted in a significant improvement in the quantitative insulin sensitivity check index (P = 0.002) and total antioxidant capacity (P = 0.04) and a significant reduction in high-sensitivity C-reactive protein (P = 0.015) in comparison with the placebo group. CONCLUSIONS: In conclusion, folate supplementation for 12 weeks among overweight/obese women with CIN2/3 showed a non-significant decrease in its recurrence and had beneficial effects on insulin sensitivity, inflammation, and oxidative stress markers.