Treatment Of Cervical Intraepithelial Neoplasia Research Articles

Comparison between Single Versus Twice Application of Topical 85% Trichloroacetic Acid in the Treatment of Cervical Intraepithelial Neoplasia; A Randomized Clinical Trial on Efficacy and Tolerability.

Purpose:To compare the efficacy and safety of up to two-time administration of 85% TCA, as a promising alternative therapy to conservative and surgical management of grade one to three CINs. Methods:In this two-armed randomized clinical trial, a total of 53 patients with biopsy-proven CIN lesions were allocated to two groups of TCA treatment. The first group (n=26) received a single dose of local therapy with 85% TCA while the second group (n=27) was treated on two separate occasions with a two-week interval. Two participants (one in each group) were lost to follow-up. At the two-month follow-up after TCA application, a colposcopy-guided biopsy was performed for all patients and the pathological specimens were studied by a single experienced pathologist to determine the post-intervention grading of CIN. Results:Two groups were comparable in terms of age and base-line lesion grading, as CIN 1 lesions comprised the majority of cases (54%), followed by CIN 2(37%). While our sample was a poor representative of CIN3 lesions (7%), no significant difference was noticed between the single and twice TCA treated groups with a response rate of 52% and 54% respectively (either complete remission to normal histology or regression to any low-grade lesion). Either separate analysis (with respect to the base-line grading within each treatment group) or combined analysis (regardless of CIN sub-group) could not generate any statistical significance. The second dose of TCA did not increase the frequency of reported adverse events. Conclusion:The second dose of topical 85% TCA does not seem to increase the CIN response rate more so than its single dose. However, further controlled clinical trials with larger samples are warranted to verify current findings. The use of TCA was not limited by any major side effect, therefore, the potential to achieve an increased efficacy with more frequent TCA applications is appealing.

Inhibitory Effect of Salvia miltiorrhiza Extract and Its Active Components on Cervical Intraepithelial Neoplastic Cells.

The effective treatment of cervical intraepithelial neoplasia (CIN) can prevent cervical cancer. Salvia miltiorrhiza is a medicinal and health-promoting plant. To identify a potential treatment for CIN, the effect of S. miltiorrhiza extract and its active components on immortalized cervical epithelial cells was studied in vitro. The H8 cell was used as a CIN model. We found that S. miltiorrhiza extract effectively inhibited H8 cells through the CCK8 method. An HPLC–MS analysis revealed that S. miltiorrhiza extract contained salvianolic acid H, salvianolic acid A, salvianolic acid B, monomethyl lithospermate, 9‴-methyl lithospermate B, and 9‴-methyl lithospermate B/isomer. Salvianolic acid A had the best inhibitory effect on H8 cells with an IC50 value of 5.74 ± 0.63 μM. We also found that the combination of salvianolic acid A and oxysophoridine had a synergistic inhibitory effect on H8 cells at molar ratios of 4:1, 2:1, 1:1, 1:2, and 1:4, with salvianolic acid A/oxysophoridine = 1:2 having the best synergistic effect. Using Hoechst33342, flow cytometry, and Western blotting analysis, we found that the combination of salvianolic acid A and oxysophoridine can induce programmed apoptosis of H8 cells and block the cell cycle in the G2/M phase, which was correlated with decreased cyclinB1 and CDK1 protein levels. In conclusion, S. miltiorrhiza extract can inhibit the growth of H8 cells, and the combination of salvianolic acid A (its active component) and oxysophoridine has a synergistic inhibitory effect on H8 cells and may be a potential treatment for cervical intraepithelial neoplasia.

Evidence to Support Change of Clinical Pathway Following Colposcopy Treatment for Cervical Intraepithelial Neoplasia in Canada

ObjectivesHuman papillomavirus (HPV) testing can be incorporated into the post-treatment pathway of cervical intraepithelial neoplasia (CIN) to confirm disease-free status. To inform a post-treatment strategy based on risk of recurrence, we modelled disease and economic outcomes. MethodsThe current Alberta, Canada, post-treatment care pathway—cytology testing with colposcopy assessment—was compared with 6 other scenarios incorporating cytology, HPV testing, or both tests at different time points in a modelling study based on a microsimulation program. Input parameter values for the screening participation, screening age groups, and follow-up options and test compliance for HPV, cytology, and colposcopy were varied, based on Alberta cervical cancer screening program data. Health outcomes over the short- and long-term were projected, which incorporated the increasing population-level coverage of HPV vaccination. Lifetime incremental cost-effectiveness ratios (ICERs) were used to evaluate economic outcomes and descriptive statistics compared with numbers of tests, visits, and procedures as well as changes in incidence and mortality rates between the scenarios. ResultsAt 5 years after implementation of the “HPV testing alone at 6 and 18 months” post-treatment pathway, the number of colposcopies dropped by 36% and the number of pre-cancer treatments, by 6%. Lifetime ICERs were CAD $6170 versus $248,495 per quality-adjusted life-year compared with the status quo pathway. Cervical cancer incidence and mortality rates decreased significantly and similarly in all scenarios. ConclusionStrategies that involve HPV testing in CIN post-treatment follow-up care are expected to be more cost effective with improved clinical outcomes than traditional cytology and colposcopy-based follow-up.

Associations between cervical intraepithelial neoplasia during pregnancy, previous excisional treatment, cone-length and preterm delivery: a register-based study from western Sweden

BackgroundExcisional treatment of cervical intraepithelial neoplasia (CIN) has been associated with increased risk of preterm delivery (PTD), although the underlying mechanism is as yet unclear. Studies on formalin-fixed excised tissue indicate that the risk increases with cone-length, but the magnitude of increase is uncertain, especially in case of minor excisions (≤10 mm), as well compared to women with untreated CIN during pregnancy. This study assesses the impact of cone-length at previous treatment for CIN as well as diagnosis of CIN during pregnancy on the risk of PTD.MethodsA register-based cohort study in western Sweden linking cervical cytology, histology, and treatment data from the Swedish National Cervical Screening Registry to data on obstetric outcomes in singleton pregnancies 2008–2016 from the Swedish Medical Birth Registry. These groups were compared for PTD and other obstetric outcomes: (1) women with one excisional treatment (n=3250, including a subgroup (n=2408) with cone-length measured before fixation; (2) women with untreated CIN diagnosed during pregnancy (n=1380); and (3) women with normal cytology (n=42,398). Logistic regression analyses were adjusted for socioeconomic and health-related confounders.ResultsTreated women had increased risk of PTD (adjusted odds ratio (aOR) 1.60, 95% confidence interval (CI) 1.21–2.12), spontaneous PTD (aOR 1.95, 95% CI 1.40–2.72) and preterm prelabor rupture of membranes (pPROM) (aOR 2.74, 95% CI 1.66–4.51) compared to the CIN during pregnancy group. ORs were similar when compared to the normal cytology group. Risks of these outcomes increased with cone-length. Mean cone-length was 9.1 mm. Cone-length ≤10 mm was associated with increased risk of PTD (aOR 1.41, 95% CI 1.02–1.94), spontaneous PTD (aOR 1.73, 95% CI 1.18–2.54), and pPROM (aOR 2.44, 95% CI 1.40–4.28), compared to the CIN during pregnancy group. The PTD risk was similar for cone-lengths 3–10 mm, thereafter increasing by 15% with each additional millimeter.ConclusionsThis study suggests that all excisional treatment, including small cones, are associated with increased risk of PTD and pPROM. Risks increase further with cone-length. In women of reproductive age, clinicians should aim to remove all CIN but minimal healthy cervical tissue.Cone-length should be recorded at treatment, for future prenatal risk estimation.

Co-Delivery of p53 Restored and E7 Targeted Nucleic Acids by Poly (Beta-Amino Ester) Complex Nanoparticles for the Treatment of HPV Related Cervical Lesions.

The p53 gene has the highest mutation frequency in tumors, and its inactivation can lead to malignant transformation, such as cell cycle arrest and apoptotic inhibition. Persistent high-risk human papillomavirus (HR-HPV) infection is the leading cause of cervical cancer. P53 was inactivated by HPV oncoprotein E6, promoting abnormal cell proliferation and carcinogenesis. To study the treatment of cervical intraepithelial neoplasia (CIN) and cervical cancer by restoring p53 expression and inactivating HPV oncoprotein, and to verify the effectiveness of nano drugs based on nucleic acid delivery in cancer treatment, we developed poly (beta-amino ester)537, to form biocompatible and degradable nanoparticles with plasmids (expressing p53 and targeting E7). In vitro and in vivo experiments show that nanoparticles have low toxicity and high transfection efficiency. Nanoparticles inhibited the growth of xenograft tumors and successfully reversed HPV transgenic mice’s cervical intraepithelial neoplasia. Our work suggests that the restoration of p53 expression and the inactivation of HPV16 E7 are essential for blocking the development of cervical cancer. This study provides new insights into the precise treatment of HPV-related cervical lesions.

Test of cure and beyond: superiority of thermal ablation over LLETZ in the treatment of high-grade CIN

PurposeAmong the treatment modalities for high-grade cervical intraepithelial neoplasia (CIN), large-loop excision of the transformation zone (LLETZ) is the commonest offered in the UK, whereas thermal ablation (TA) has not been common in several decades, despite several notable advantages. TA and LLETZ are both routinely undertaken in our colposcopy unit, and extensive follow-up data have been used to interrogate outcomes between the two modalities and determine whether one modality may be preferred over the other.MethodsUp to 8 years of follow-up data (cytology and histology) were collected for patients who have undergone LLETZ or TA and failed post-treatment test of cure (ToC). These data were analysed and used to plot Kaplan–Meier survival curves, in order to compare outcomes: negative cytology, dyskaryosis, low- and high-grade CIN and invasive squamous cell carcinoma.Resultsi) Very few women treated with TA developed recurrent high-grade CIN in the follow-up period; (ii) LLETZ-treated women had a significantly higher rate of recurrence than those treated by TA; (iii) women who failed both virology and cytology components of post-treatment ToC had higher recurrence than those who failed only one, and the rate of recurrence was highest in those treated by LLETZ (> 65%).ConclusionTA is an effective treatment of high-grade CIN, with a high chance of achieving double-negative ToC and low recurrence relative to LLETZ. We recommend the wider adoption of TA, so that young women of reproductive age have a choice of treatment with no reported adverse effects on pregnancy outcomes.

Cryotherapy and LEEP are Effective Treatment for CIN Lesions in HIV+ and HIV- Women in Western Kenya

Cervical cancer is the third most common cancer worldwide and the most common cancer among Kenyan women, with an age-standardized incidence rate of 33.8% in 2018. Cervical intraepithelial neoplasia (CIN) caused by human papillomavirus (HPV) in HIV+ women is over twice as likely to progress in severity compared to HIV- women. Conflicting reports exist as to the efficacy of cryotherapy or loop electrosurgical excision procedure (LEEP) as treatment for CIN among HIV+ women. This study assesses the results of cryotherapy or LEEP for CIN among HIV+ compared to HIV- women in Western Kenya.

Healing pattern of the cervical stroma following cold coagulation treatment for cervical intraepithelial neoplasia: A case report.

Cold coagulation of the cervix for cervical intraepithelial neoplasia (CIN), when compared with cervical excision, has previously demonstrated comparable cure rates and a reduction in the rate of spontaneous preterm birth. In the present report the healing pattern in the cervices of two women after cold coagulation is described. Both women underwent cold coagulation due to CIN3, which was found on pre-treatment cervical punch biopsies. They were followed up after cold coagulation and at 7 and 18 months, respectively, they underwent cervical excision. The histopathological slides from the excised specimen were reviewed, which represents the healed cervix after cold coagulation. A clear boundary of collagenisation was noted in the superficial stroma, which appeared to stop at the junction with the healthy muscular stroma. The collagenised superficial stroma depth, which represents the area that was thermally ablated and has now healed, measured 1.6 and 1.5 mm for the two women, respectively, which is less compared with that typically removed by cervical excision. Observations from these two cases indicate that cold coagulation does not appear to disrupt the deep tissue architecture of the cervix and could therefore explain the reduced levels of adverse obstetric morbidity in patients who underwent cold coagulation ablative treatment of the cervix, which has been previously reported.

Clinical Performance of DNA and RNA Based HPV Tests for Test of Cure (TOC) Post Treatment for Cervical Intraepithelial Neoplasia (CIN) - a Retrospective Study

Clinical Performance of DNA and RNA Based HPV Tests for Test of Cure (TOC) Post Treatment for Cervical Intraepithelial Neoplasia (CIN) - a Retrospective Study

The Role of IL-2, IL-4, IL-10 and IFN-<i>γ</i> Cytokines Expression in the Microenvironment of Cervical Intraepithelial Neoplasia

Objective: To investigate the role of IL-2, IL-4, IL-10 and IFN-γ cytokines in the microenvironment of cervical intraepithelial neoplasia. Methods: 180 patients participating were enrolled in this trial, where 50 cases are in control group, 50 cases are in low-grade squamous intraepithelial lesion (LSIL) group, 50 cases are in high-grade squamous intraepithelial lesion (HSIL) group, and 30 cases have cervical carcinoma. ELISA methods are used to detect the expression of IL-2, IL-4, IL-10 and IFN-γ in the lavage fluid, and all data is analyzed using one-way analysis of variance. Results: The expression of IL-2 and IFN-γ in cervical lavage fluid gradually decreases with the aggravation of the lesion. The expression of IL-4 and IL-10 increases by the aggravation of pathological changes. There were statistically significant differences in IL-2 level among the four groups. IFN-γ levels are significantly different between the cervical cancer group and the other groups, also between HSIL and LSIL group, and between HSIL and the control group, but no statistically significant difference was observed in IFN-γ e between LSIL and the control group. The expressions of IL-4 and IL-10 between the cervical cancer group and the other groups were significantly different, and also between HSIL and the control group. But there was no statistically significant difference between LSIL and the control group, HSIL and LSIL. Conclusion: The cytokines of IL-2, IL-4, IL-10 and IFN-γ in the microenvironment of the cervix play an important role in the occurrence and development of cervical intraepithelial neoplasia. This study may provide the evidence for diagnosis and treatment of cervical intraepithelial neoplasia.

ПЕРВЫЕ РЕЗУЛЬТАТЫ ЛЕЧЕНИЯ ЦЕРВИКАЛЬНОЙ ИНТРАЭПИТЕЛИАЛЬНОЙ НЕОПЛАЗИИ В РЕСПУБЛИКЕ ТАДЖИКИСТАН

Objective: To assess the clinical results of cervical intraepithelial neoplasia (CIN) treatment following the outcomes of the first pilot implementation of visual screening in the Republic of Tajikistan. Methods: The study was conducted from 2016 to 2020. The piloting included the population of two large districts of Kushoniyon and B. Gafurov, with a total number of 608,700 people, which is 6.74% of the country's total population. The target group of this screening included healthy women aged 30-49 years, numbering 72574 people. As a result of communication campaigns with the target group of both districts, 69391 women participated in visual screening; the overall screening coverage was 94.2%. Of the 2958 women referred for diagnosis, in 164 cases (0.24%) CIN was identified and morphologically confirmed. Results: Tajikistan, along with piloting imaging screening, has adopted a "detection-diagnosis-treatment" strategy, which involves treatment after histological confirmation of CIN. Additionally, electrosurgical loop excision/conization was adopted as the primary method, regardless of the degree of CIN involvement. Patients with CIN in 136 (82.9%) cases underwent electrosurgical loop excision, in 21 cases – conization (12.8%), and in 7 (4.3%) cases, at the insistence of the women themselves – hysterectomy. In the long-term follow-up period from 6 months to 2 years, in 159 (96.9%) cases, a favorable course of CIN was noted after the above procedures, and in 5 (3.1%) cases, relapse occurred. Patients with relapses received re-surgical treatment using electrosurgical excision/conization with a satisfactory outcome. Conclusion: The "detection-diagnosis-treatment" strategy adopted by Tajikistan has shown its high efficiency in detecting precancerous pathology and the success of CIN treatment by electrosurgical excision/conization, which contributes to the healing of the population from precancerous pathology. Keywords: Cervical intraepithelial neoplasia, visual screening, VIA/VILI visual method, colposcopic examination, electrosurgical loop excision/conizatio.

Expression and Analysis of Rsf-1 and P16 in Cervical Intraepithelial Neoplasia

Objective: The molecular mechanism in the occurrence and progression of cervical intraepithelial neoplasia (CIN) is of great theoretical significance to improve the early diagnosis, treatment and prognostic judgement of CIN in clinical practice. The current study aimed to detect the expression of remodel and space factor-1 (Rsf-1) and P16 in CIN, and to analyze the expression of Rsf-1 and P16 in different stages of CIN and to investigate the possible correlation. Methods: A total of 110 samples of CIN were collected from the Department of Pathology, the First Affiliated Hospital of Bengbu Medical College in 2018. Rsf-1 and P16 was detected by immunohistochemical staining in pathological tissue sections. The correlation between Rsf-1 expression and P16 expression in CIN was further analyzed. Results: The immunohistochemical results of 110 cases of CIN showed that the positive rate of P16 and Rsf-1 gradually increases with the grade of CIN increases. The expression of P16 was significantly different between different CIN grade (p = 0.011). The expression of Rsf-1 was also significantly different in different CIN grade (p = 0.015). Conclusions: Rsf-1 and P16 was highly expressed or over-expressed in high-grade CIN, and the positive rate of their expression increased with the increase in CIN grade.

Ultrasonic Elastography Combined with Human Papilloma Virus Detection Based on Intelligent Denoising Algorithm in Diagnosis of Cervical Intraepithelial Neoplasia.

The aim of this research was to study the application of ultrasonic elastography combined with human papilloma virus (HPV) detection based on bilateral filter intelligent denoising algorithm in the diagnosis of cervical intraepithelial neoplasia (CIN) and provide a theoretical basis for clinical diagnosis and treatment of CIN. In this study, 100 patients with cervical lesions were selected as research objects and randomly divided into control group and experimental group, with 50 cases in each group. Patients in control group and experimental group were diagnosed by ultrasonic elastography combined with HPV detection. The experimental group used the optimized image map of bilateral filter intelligent denoising algorithm for denoising and optimization, while the control group did not use optimization, and the differences between them were analyzed and compared. The diagnostic effects of the two groups were compared. As a result, the three accuracy rates of the experimental group were 95%, 95%, and 98%, respectively; the three sensitivity rates were 96%, 92%, and 94%, respectively; and the three specificity rates were 99%, 97%, and 98%, respectively. In the control group, the three accuracy rates were 84%, 86%, and 84%, respectively; the three sensitivity rates were 88%, 84%, and 86%, respectively; and the three specificity rates were 81%, 83%, and 88%, respectively. The accuracy, sensitivity, and specificity of experiment group were significantly higher than those of control group, and the difference was statistically significant (P < 0.05). In summary, the bilateral filter intelligent denoising algorithm has a good denoising effect on the ultrasonic elastography. The ultrasonic image processed by the algorithm combined with HPV detection has a better diagnosis of CIN.

Successfully Pregnancy Outcome After LLETZ in Women with Cervical Intraepithelial Neoplasia: A Case Series

BACKGROUND: Human papillomavirus (HPV) has an important role in cervical cancer development and the incidence of cervical intraepithelial neoplasia (CIN) was 1.3–2.7/1000 pregnancies. The HPV and its treatments such as loop electrosurgical excisional procedure (LEEP) or large loop electrosurgical excisional procedure (LLETZ) have an association with poor obstetric outcomes. CASE REPORT: Here, we present four case studies of successful live birth after treatment of CIN. We reported that four patients had been performed LLETZ, with abnormal colposcopy results and liquidbased cytology results were one ASCUS, one ASCH, and two HSIL. The histopathology results were one CIN 1, one CIN 2, and two CIN 3. There was a higher rate of pregnancy for treated women than untreated women. The higher the CIN grades, the more prevalence of cesarean section rate. CONCLUSION: The HPV testing or cotesting at 3-year intervals is recommended after treatment due to the sensitivity of HPV testing. Although pregnancy could delay the progression of precancerous lesions, it is recommended to follow the individualized algorithm in the ASCCP guideline to reduce the risk of cervical cancer progression.

Evaluation of the Factors Affecting the Cure Rate of Cervical Intra-Epithelial Neoplasia Recurrence Using Defective Models.

Background: Treatment of cervical intraepithelial neoplasia is very important since if it remains untreated, it may progress to cervical cancer. It is usually treated with excisional surgery. This study aimed to find the factors affecting the cure rate of cervical intraepithelial neoplasia recurrence after surgery using defective models. Study design: A retrospective cohort study. Methods: Excisional surgery was performed on 307 patients with high-grade cervical intraepithelial neoplasia, from 2009 to 2017. The patients were followed up until recurrence based on histopathology report. Hematologic factors were measured before surgery. The cure rates were estimated using defective models with a Gamma frailty term and the results were compared. Results: Neutrophil-to-lymphocyte ratio (NLR) ( P 15 mm 2 and NLR of 15 mm 2 and NLR of >1.9, 79% among patients with an excised mass size of 1.9. Conclusion: Cervical intraepithelial neoplasia must be identified and treated before its progress. Excision of more tissues during excisional surgery, especially when the NLR of the patient is high, can help to prevent cervical intraepithelial neoplasia recurrence.

Abstract P043: A double-blind randomized, placebo-controlled trial of oral administration with human papillomavirus (HPV) type 16 E7-expressing Lactobacillus-based vaccine, BLS-ILB-E710c, for the treatment of cervical intraepithelial neoplasia (CIN2/3)

Abstract Background - Despite preventive HPV vaccines is implemented worldwide, current treatments for high grade cervical intraepithelial neoplasia are ablative, and no pharmacological treatments are available. Here we evaluated safety of BLS-ILB-E710c, HPV 16 E7-expressing Lactobacillus-based vaccine, and explored its efficacy for histopathological regression in women with CIN2/3. Methods - Safety and efficacy of BLS-ILB-E710c were assessed in CIN2/3 associated with HPV16 and its related HPV types in a randomized, double-blind, placebo-controlled phase 2b study. Total of 116 patients was recruited from fourteen hospitals in South Korea, and were randomized (2:1) to receive 1000 mg BLS-ILB-E710c or placebo for 5 days at 1, 2, 4, and 8 weeks. The primary endpoint was histopathological regression to CIN1 or normal pathology at 16 weeks after the first dose. Full analysis set (FAS) and Per-protocol set (PPS) analyses were based on patients receiving at least one oral vaccination, and on patients receiving four rounds of oral vaccination without protocol violations, respectively. The safety population included all patients who enrolled. The trial is registered at clinicaltrials.gov (number NCT03274206). Findings - Total of 116 patients were randomized, and 113 received either BLS-ILB-E710c (n=75) or placebo (n=38). The oral vaccination was well tolerated and no serious vaccine-related AEs occurred. No differences were showed between the BLS-ILB-E710c and placebo groups for patient background and adverse events. In the full analysis set (FAS) no statistically significant difference was noted between the two groups of histopathological regression at 16 weeks. However, the distribution by Bethesda system (for cervical cytology) in CIN2 patients showed significant differences between two groups (P=0.0304), which can affect histopathological regression. Sub-group analysis in FAS is performed to reduce the bias; histopathological classification (CIN2, CIN3) and cytological classification (≤ASCUS, LSIL, HISL). Therefore, in CIN3 sub-group, BLS-ILB-E710c recipients showed 13.33% of higher histopathological regression at 32 weeks than placebo recipients, and interestingly represented the statistically significant difference when histopathological regression at 32 weeks compared with 16 weeks (percentage point difference 34.87 [95% CI 7.78–61.96]; P=0.0216). In BLS-ILB-E710c recipients of CIN3 sub-group with histopathological regression, E7-specific CD8+ T lymphocyte immune responses were induced at 32 weeks (P= 0.0323). In addition, in HSIL sub-group, BLS-ILB-E710c recipients showed higher histopathological regression at 32 weeks than placebo recipients in similar with CIN3 sub-group analysis. Interpretation – Based on the finding this study, BLS-ILB-E710c could induce the local immune response by recruiting HPV16 E7-specific CD8+ T cells to cervical lesions, leading to histologic regression. To assess the efficacy of BLS-ILB-E710c as a novel Lactobacillus-based oral vaccine, it is necessary to define the population and time frame for phase 3 trial. Citation Format: Jae Kwan Lee, Seung Hun Song, Young Tae Kim, Chi-Heum Cho, Chan Joo Kim, Young-Chul Park. A double-blind randomized, placebo-controlled trial of oral administration with human papillomavirus (HPV) type 16 E7-expressing Lactobacillus-based vaccine, BLS-ILB-E710c, for the treatment of cervical intraepithelial neoplasia (CIN2/3) [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P043.

Muramyl peptides in the complex treatment of cervical intraepithelial neoplasia associated with human papillomavirus

Research objective: the use of an immunomodulator III generation with a wide range of action (muramyl peptide drug Liastenum) to increase the effectiveness of treatment of cervical intraepithelial neoplasia grade I associated with human papilloma virus (HPV) and to reduce the recurrence of cervical pathology.Materials and methods. The study included 60 women with histologically confirmed cervical intraepithelial neoplasia associated with highly oncogenic HPV. The mean age of patients was 25.92 ± 0.61 years. The first group included 30 women who received traditional treatment, the second group included 30 women who additional received Liastenum 0.002 g intramuscularly 1 time per day, 5 injections per course, after that patients took 1 tablets Liastenum twice a day for 20 days.Traditional treatment included antibiotic therapy (doxycycline monohydrate), metronidazole, nystatin in standard dosage. Patients with herpes viruses received valaciclovir 500 mg twice/day for 5 days. Evaluation of treatment efficacy was performed at 6 and 12 months with co-testing, fluid cytology, HPV quantification, and colposcopy.Results. There was a significant decrease in the exposure level of highly oncogenic HPV in the second group compared to the first: after 12 months in the first group HPV was not detected in 2 women (6.67%), and in the second group HPV was no detected in 17 women (56.67%) (p &lt; 0.05). Improvement of the colposcopic picture occurred in 70% of patients in the second group, and in 12 (40.0%) of patients colposcopic conclusion on the Swedish scale was less than 3 points after 12 months of observation. Only 8 (26.67%) women received improvement of the colposcopic picture with a score of 3 points on the Swedish scale in the first group, which was significantly different from the second group (p &lt; 0.05).Conclusions. Advanced therapy with muramyl peptide Liastenum in the treatment of cervix for 12 months can increase the effectiveness of HPV elimination, improves the colposcopic picture by reducing the area of cervical lesions and normalized cytological picture in 70% of patients with cervical intraepithelial neoplasia grade I.

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

BackgroundLesions 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). MethodsA 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. ResultsOut 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 cm2 respectively. 4 patients were lost during follow-up. The patients’ complete remission (CR) rate was 88.64% (39/44) at 3–6 months after treatment, while the total HPV clearance rate was 46.34 and 60.98% at 3- and 12-months follow-up,respectively. HPV16/18 combined with other high-risk human papillomaviruses (hrHPV) (HPV16/18 and other hrHPV) infection exhibited a lower HPV clearance rate (P = 0.006). The treatment time in high-grade intraepithelial neoplasia (HSIL) was higher than that of low-grade intraepithelial neoplasia (LSIL). Notably, atypical vessels and endocervical canal lesions involvement significantly affected 5-ALA PDT. Moreover, 5 patients had residual lesions (11.36%) during follow-up, one patient presented recurrence (2.56%), while 4 had successful pregnancy. Conclusions5-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.

History of Surgical Treatment for Cervical Intraepithelial Neoplasia

History of Surgical Treatment for Cervical Intraepithelial Neoplasia

The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia

BackgroundVaginal microbiota (VMB) composition is altered in women with cervical intra-epithelial neoplasia (CIN) compared to healthy controls and is associated with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This observational study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines.MethodsWe sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMP levels in matched vaginal secretions. Analyses were performed to compare the bacterial composition and immune analyte levels before and after CIN excision and in healthy controls.ResultsWomen with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV 21/103, 20% vs 1/39, 3%, p = 0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV 19/103, 20% vs 1/39, 3%, p = 0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls, and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1β and IL-8 remained significantly elevated pre- (p < 0.0001 and p = 0.0014, respectively) and post-treatment (p < 0.0001 and p = 0.0035, respectively) compared to untreated controls. Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p < 0.0001); however, their levels remained lower than controls post-treatment.ConclusionsWomen with CIN have an increased prevalence of Lactobacillus sp. depletion, high-diversity VMB composition, and higher levels of proinflammatory cytokines and AMPs compared to normal controls. Surgical excision of the disease reduces levels of vaginal AMPs but does not alter VMB composition or cytokine levels. These findings suggest that women with CIN have an inherent predisposition to a high-diversity proinflammatory environment that is not corrected by disease excision. The failure to re-establish a Lactobacillus-enriched CST may explain why women remain at high risk of pre-invasive and invasive disease recurrence.