Squamous Intraepithelial Lesions Research Articles

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

ObjectiveThe 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. MethodsA 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. ResultsOf 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. ConclusionsThe efficacy of ALA-PDT was similar to that of surgery in treating recurrent cervical HSIL following surgery, with fewer side effects.

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

BackgroundVaginal 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. ObjectivesTo evaluate the efficacy and safety of Carbon dioxide (CO2) laser, 5-aminolevulinic acid photodynamic therapy (PDT) and PDT combined with CO2 laser pretreatment for VaIN1 with HR-HPV infection, and analyze the factors affecting the clearance of HR-HPV. MethodsPatients 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 CO2 laser (laser Group), 15 patients received three times PDT (PDT Group) and 15 patients received CO2 laser once and PDT three times (laser + PDT Group). HPV testing, cytology and colposcopy examinations at 3–6 months and 9–12 months after treatment were analyzed to assess the outcomes of the treatment. Results: 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. ConclusionFor 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 CO2 laser pretreatment may not increase the benefit of ALA-PDT treatment of VaIN1. Older age, menopause, more times of pregnancies, and multiple vaginal lesions might affect HR-HPV regression.

Single-cell RNA sequencing of cervical exfoliated cells reveals potential biomarkers and cellular pathogenesis in cervical carcinogenesis

Cervical cancer (CC) is a common gynecological malignancy. Despite the current screening methods have been proved effectively and significantly decreased CC morbidity and mortality, deficiencies still exist. Single-cell RNA sequencing (scRNA-seq) approach can identify the complex and rare cell populations at single-cell resolution. By scRNA-seq, the heterogeneity of tumor microenvironment across cervical carcinogenesis has been mapped and described. Whether these alterations could be detected and applied to CC screening is unclear. Herein, we performed scRNA-seq of 56,173 cervical exfoliated cells from 15 samples, including normal cervix, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and malignancy. The present study delineated the alteration of immune and epithelial cells derived during the cervical lesion progression. A subset of lipid-associated macrophage was identified as a tumor-promoting element and could serve as a biomarker for predicting the progression of LSIL into HSIL, which was then verified by immunofluorescence. Furthermore, cell–cell communication analysis indicated the SPP1-CD44 axis might exhibit a protumor interaction between epithelial cell and macrophage. In this study, we investigated the cervical multicellular ecosystem in cervical carcinogenesis and identified potential biomarkers for early detection.

Effects of 5-aminolevulinic acid photodynamic therapy for cervical low-grade squamous intraepithelial lesions with HR-HPV infections.

To determine the effectiveness and safety of 5-aminolevulinic acid mediated photodynamic therapy (5-ALA PDT) in HR-HPV infected patients with cervical low-grade squamous intraepithelial lesions (LSIL) and to explore possible factors affecting treatment outcomes. This retrospective study included 96 patients with histologically confirmed cervical LSIL and high-risk human papillomavirus (HR-HPV) infection. They received 5-ALA PDT treatment once a week for a total of 3 courses. All patients were evaluated by cytology tests, HPV DNA assay, colposcopy, and biopsy at 2 weeks, 3 months, and 6 months checkpoint. The chi-square test were used to evaluate the differences in various clinical data, and a p value <0.05 was considered statistically significant. At 2 weeks, 3 months, and 6 months checkpoint, colposcopies showed that the cervical iodine-unstained area under VILI (visual inspection with Lugol's iodine) significantly reduced (p < 0.01) with no structure changes. At 3 months and 6 months checkpoint, the pathological regression rate reached 87.5% (84/96) and 94.79% (91/96), while the HR-HPV clearance rates reached 80.21% (77/96) and 93.75% (90/96) respectively. We also examined the efficacy in the HPV 16/18-related group and non-HPV 16/18-related group. The HR-HPV clearance rate in the HPV16/18 group [94.87% (37/39)] was significantly higher than that of the non-HPV 16/18 group [70.17% (40/57)]. However, at 6 months after treatment, the clearance rate of the HPV 16/18 group [94.87% (37/39)] showed no statistical difference from the non-HPV 16/18 group [92.30% (53/57)]. Topical 5-ALA PDT can effectively eliminate HR-HPV infection and treat low-grade cervical squamous intraepithelial lesions, it offers an alternative treatment option for patients with LSIL, especially for those with fertility requirements and who wish to preserve cervical structure or function.

Analysis of the Differences between Bethesda Groups according to Conventional Smear and Liquid-Based Cytology Methods in Cervicovaginal Cytology: A Single-Center Experience with 165,915 Cases

Introduction: Liquid-based cytology (LBC) has replaced conventional smear (CS) in the world. In this study, through a series with a large number of cases, we aimed to make a comparison and general evaluation in all groups, primarily epithelial abnormalities, according to LBC and CS methods. This study was carried out in a private pathology laboratory located in a metropolitan city, where cytological materials sent from many clinics were examined. Material and Methods: There were 165,915 cases whose smears were examined between 2012 and 2020, most of them conventional (131,224 CS, 34,691 LBC). Cases were evaluated on the basis of the Bethesda 2014 classification and divided into sub-diagnostic categories after they were divided into two main groups as “with epithelial abnormalities” and “without.” χ2 and Fischer’s precision statistical tests were conducted using SPSS 23.0 package. In the CS process, cervical samples were obtained using an endocervical brush and a spatula. Cells were directly spread onto the slides and promptly fixed in 95% ethanol, followed by staining with the standard Papanicolaou stain. For LBC ThinPrep, cervical specimens were gathered using a cervix brush. The brush was washed in a vial and discarded. Finally, cells were isolated through vacuum filtration and transferred to the slide using air pressure. Results: Squamous cell abnormalities (atypical squamous cells of undetermined significance [ASC-US], atypical squamous cells – cannot exclude high-grade squamous intraepithelial lesion [ASC-H], low-grade squamous intraepithelial lesion [LSIL], high-grade squamous intraepithelial lesion [HSIL], squamous cell carcinoma, atypical glandular cells of undetermined significance) were reported in 5,696 (3.43%) cases. ASC (ASC-US + ASC-H)/SIL ratio (1.36/2.04) was found to be 0.67 (recommended Bethesda ratio is <3). ASC-US (p < 0.001), ASC-H (p < 0.001), and HSIL(p < 0.001) detection rate of LBC was found to be significantly higher than CS. ASC-US (1.8/1.2), ASC-H (0.08/0.008), and HSIL (0.6/0.3) case ratios of LBC/CS were found to be significantly higher in LBC. LSIL (1.72/1.66) rate was similar. Conclusion: LBC is superior to CS in detecting epithelial lesions. In addition to being used as a screening method, it is clear that it makes a great contribution to reducing cervical carcinomas due to HPV typing. Definitive comments regarding comparison of methods on reactive changes and microorganism detection are challenging. Preanalytical factors might account for these situations.

Focused ultrasound versus the loop electrosurgical excision procedure to treat women with cervical high-grade squamous intraepithelial lesions under 40: a retrospective study

BackgroundThis study aimed to compare the efficacy of focused ultrasound (FUS) and the loop electrosurgical excision procedure (LEEP) for the treatment of cervical high-grade squamous intraepithelial lesions (HSILs) among women of reproductive age.MethodsCase records of patients aged < 40 years who were treated for cervical HSILs using either FUS or LEEP from September 1, 2020 to May 31, 2022 were retrospectively reviewed. Patients were followed up for cure, recurrence, human papillomavirus (HPV) clearance, and complications within 1 year of treatment. Odds ratios and 95% confidence intervals were determined using univariate and multivariate logistic regression models to analyze the association between disease evidence or HPV clearance and treatment modalities or other covariates.ResultsOf the 1,054 women who underwent FUS or LEEP, 225 met our selection criteria. Among the selected women, 101 and 124 received FUS and LEEP, respectively. There was no significant difference between the FUS and LEEP groups in the cure rate during the 3–6 months of follow-up (89.11% vs. 94.35%, P = 0.085) and recurrence rate during the 6–12 months follow-up (2.22% vs. 1.71%, P = 0.790). Both groups exhibited enhanced cumulative HPV clearance rates; however, the rates were not significantly different between the FUS and LEEP groups (74.23% vs. 82.79%, P = 0.122 during the 3–6 months follow-up; 84.95% vs. 89.17%, P = 0.359 during the 6–12 months follow-up). Furthermore, the incidence of complications caused by the FUS and LEEP techniques was comparable (5.0% vs. 5.6%, P = 0.818).ConclusionsWe found that FUS and LEEP have similar efficacy, safety, and reliability in treating women (aged < 40 years) with HSILs.

The role of endocervical curettage in the diagnosis of cervical intraepithelial neoplasia in human papillomavirus positive patients.

The role of endocervical curettage (ECC) in the diagnosis of cervical intraepithelial neoplasia (CIN) is a controversial topic. Investigate the role of ECC in the diagnosis of CIN in human papillomavirus (HPV) positive patients. Retrospective. A tertiary training and research hospital. This study included patients who were referred for colposcopy between 2018-2022 because of abnormal screening results. ECC results, age, cytology, HPV status, and colposcopic impression of the patients were extracted from the medical records. Multinomial logistic regression analyses were performed to identify factors that could predict CIN on ECC. The likelihood of high-grade squamous intraepithelial lesions (HSIL) in ECC in patients with cervical biopsy results of normal and low-grade squamous intraepithelial lesion (LSIL). 2895 women. In patients with normal and LSIL cervical biopsy results, HSILs were detected in 6.7% of ECC results. There was no difference in the detection rates of CIN in ECC among groups with smear results negative for intraepithelial lesions or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), and LSIL. The likelihood of HSIL being observed in ECC was 2.2 times higher in patients with HPV16. The probability of LSIL disanois was 2.3 times higher in women aged 50-59 years and 2.8 times higher in women ≥ 60 years compared to the reference group of <30 years. The probability of LSIL was 2.3 and HSIL by ECC was 2.2 times higher in both age categories (P<.012 and P=.032, respectively) than the reference group of <30 years. Regardless of colposcopic findings, ECC should be performed in patients with smear results of NILM who are positive for HPV16, in patients with smear results of ASC-US and LSIL who are positive for any oncogenic type of HPV and in patients 50 and above with any result of smear or any oncogenic HPV type. We did not have the components of the HPV types in mixed groups.

Prevalence, risk factors and genotype distribution of human papillomavirus infection among women with and without invasive cervical cancer: Findings from a hospital-based study in Bihar, India.

Background Human papillomavirus (HPV) infection is largely responsible for the development of invasive cervical cancer (ICC). Its prevalence, risk factors and genotype distribution among women residing in Bihar (third most populous Indian state) with and without ICC are not well known. Methods In this hospital-based study, we followed up 1439 participants with cytology and HPV report. HPV detection and genotyping were performed using the TaqMan-based real-time PCR method. Clinical and sociodemographic data were collected and analysed using statistical methods. Results The overall prevalence of HPV infection was 37.3% (537/1439) and 11 different types of HPV genotypes were observed. Higher HPV positivity was found in premalignant, intraepithelial and invasive malignant lesions of the cervix; 73.8% (93/126) of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and high-grade squamous intraepithelial lesions (HSIL) and 93.4% (114/122) of invasive malignancies were infected with HPV in comparison to only 26.1% (245/938) of negative for intraepithelial lesion or malignancy (NILM) cytology. Moreover, HPV was found in 95.2% (236/248) of histologically confirmed cases of carcinoma cervix. HPV16 and HPV18 infections were reported in 78.2% (194/248) and 8.9% (22/248), respectively. The remaining patients had infection with other high-risk strains/co-infection with multiple strains or were HPV-negative. Various socio-demographic factors including women >50 years of age, >10 years of marriage and high parity were significantly associated with HPV infection. Conclusion Our data suggest that HPV16 infection may be the major cause for ICC among women residing in Bihar. Our findings may serve as a baseline for developing an appropriate screening and vaccination strategy for Bihar.

A case of extra-mammary Paget’s disease of the cervix mimicking a high-grade squamous intraepithelial lesion

A case of extra-mammary Paget’s disease of the cervix mimicking a high-grade squamous intraepithelial lesion

Conservative management of cervical intraepithelial neoplasia 2 and prediction of its progression - a retrospective study.

Cervical intraepithelial neoplasia 2 (CIN2) evolution is controversial, and some of them regress spontaneously in a two-year follow-up. The purpose of this work was to evaluate the percentage of CIN2 progression or persistence during a 24-month follow-up, using clinical predictors such as human papillomavirus (HPV) genotype and cytology results. This is a retrospective case-control study and included patients of reproductive age who had a new diagnosis of CIN2 who were monitored for lesion regression (Group 1, n=72 patients), and progression or persistence (Group 2, n=36 patients). A multinominal logistic regression was preferred to evaluate the impact that various categorical risk elements can lead to outcomes of persistence or progression of CIN2. We also performed a linear regression to assess the risk of CIN2 progression or persistence using the interaction between clinical predictors. A previous cervical cytology indicative of high-grade squamous intraepithelial lesion (HSIL) [relative risk ratio (RRR): 3.85, 95% confidence interval (CI): 1.66-8.90] or atypical squamous cells, cannot exclude HSIL (ASC-H) can highly raise the probability of a CIN2 progression or persistence. The presence of HPV16 increased the risk of CIN2+ with 3.77 (95% CI: 0.78-5.00), the presence of HPV18 increased the probability of CIN2+ with 4.39 (95% CI: 1.35-14.33), and other high-risk HPV (HR-HPV) strains increased the probability of CIN2+ with 3.62. The highest risk issue was produced by the interaction between HSIL* HPV16, ASC-H* HPV16, and ASC-H* HPV18. When discussing follow-up for CIN2 lesions, it is important to offer careful consideration and monitoring of patients with a previous HSIL or ASC-H cytology, with or without HPV 16, 18 or other HR-HPV strains, as their presence significantly increased the risk of CIN2 progression and persistence.

The role of cervical elastography in the differential diagnosis of preinvasive and invasive lesions of the cervix.

This study aims to evaluate the role of cervical elastography in the differential diagnosis of preinvasive and invasive lesions of the cervix. A total of 95 women participated in this prospective study and were divided into the following groups: 19 healthy subjects (group 1) with normal cervicovaginal smear (CVS) and negative human papillomavirus test (HPV DNA), 19 women with normal cervical biopsy and normal final pathological result of cervical biopsy (group 2), 19 women with low-grade squamous intraepithelial lesion (LSIL) (group 3), 19 women with high-grade squamous intraepithelial lesion (HSIL) (group 4), and 19 women with cervical cancer (group 5). Clinical, demographic, histopathological, and elastographic results were compared between these groups. Comparing groups, age (40.42 ± 8.31 vs. 39.53 ± 8.96 vs. 38.79 ± 9.53 vs. 40.74 ± 7.42 vs. 54.63 ± 12.93, p < 0.001 respectively), gravida (1.74 ± 1.33 vs. 2.16 ± 1.68 vs. 2.21 ± 1.96 vs. 2.53 ± 1.93 vs. 4.63 ± 2.17 p < 0.001 respectively), parity (1.37 ± 0.68 vs. 1.68 ± 1.20 vs. 1.58 ± 1.30 vs. 2.00 ± 1.67 vs. 3.37 ± 1.61, p < 0.001 respectively), and the proportion of patients at menopause (10.5% vs., 15.8% vs. 10.5% vs. 5.3% vs. 57.9%, p < 0.01 respectively), a statistically significant difference was found (Table1). However, no statistically significant difference was found in the number of abortions, BMI, mode of delivery, smoking, additional disease status, history of surgery, and family history (p > 0.05) (Table2. As a result of the applied roc analysis, mean cervical elastographic stiffness degree (ESD) was found to be an influential factor in predicting cervical cancer (p < 0.05). The mean cut-off value was 44.65%, with a sensitivity of 94.7% and a specificity of 96.1% (Table7). Measurement of ESD by elastography is a low-cost, easily applicable, and non-invasive indicator that can distinguish cervical cancer from normal cervical and preinvasive lesions. However, it is unsuitable for determining preinvasive cervical lesions from normal cervix.

Deep Learning in High-Resolution Anoscopy: Assessing the Impact of Staining and Therapeutic Manipulation on Automated Detection of Anal Cancer Precursors.

High-resolution anoscopy (HRA) is the gold standard for detecting anal squamous cell carcinoma (ASCC) precursors. Preliminary studies on the application of artificial intelligence (AI) models to this modality have revealed promising results. However, the impact of staining techniques and anal manipulation on the effectiveness of these algorithms has not been evaluated. We aimed to develop a deep learning system for automatic differentiation of high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion in HRA images in different subsets of patients (nonstained, acetic acid, lugol, and after manipulation). A convolutional neural network was developed to detect and differentiate high-grade and low-grade anal squamous intraepithelial lesions based on 27,770 images from 103 HRA examinations performed in 88 patients. Subanalyses were performed to evaluate the algorithm's performance in subsets of images without staining, acetic acid, lugol, and after manipulation of the anal canal. The sensitivity, specificity, accuracy, positive and negative predictive values, and area under the curve were calculated. The convolutional neural network achieved an overall accuracy of 98.3%. The algorithm had a sensitivity and specificity of 97.4% and 99.2%, respectively. The accuracy of the algorithm for differentiating high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion varied between 91.5% (postmanipulation) and 100% (lugol) for the categories at subanalysis. The area under the curve ranged between 0.95 and 1.00. The introduction of AI to HRA may provide an accurate detection and differentiation of ASCC precursors. Our algorithm showed excellent performance at different staining settings. This is extremely important because real-time AI models during HRA examinations can help guide local treatment or detect relapsing disease.

Features of the systemic influence of cervical cancer on peripheral blood and hemostasis according to the tumor histological subtype

Aim. To identify the features of the systemic effect on hematopoiesis and the blood coagulation system of different histological subtypes of cervical cancer (CC).Materials and methods. A single-center retrospective cohort study of 428 patients (61 patients with high grade squamous intraepithelial lesion (carcinoma in situ) and 367 patients with CC) examined from 1997 to 2022 in the Polyclinic of P. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiology Center, Ministry of Health of Russia. The age of patients was from 18 to 90 years (median age – 42 [34; 51] years). Patients were divided into 4 groups: group 1 – patients with high grade squamous intraepithelial lesion and 3 groups depending on tumor’s histological subtype (squamous cell, glandular squamous cell, adenocarcinoma). Demographic and clinical data were analyzed including laboratory tests (general blood count, biochemical blood test and iron metabolism and coagulograms (total 32 variables)) compared to clinical and surgical stages of CC.Results. High grade squamous intraepithelial lesion does not have a systemic effect on the parameters of general, biochemical blood tests and hemostasis (p &gt;0.05). On the other hand, statistically significant changes were found in the parameters of routine laboratory blood tests, which correlate with the results of microinvasive analysis of CC, thus revealing the systemic effect of a malignant tumor: at p ≤0.001 for thrombin time, total protein, alkaline phosphatase levels; at p ≤0.05 for alanine aminotransferase, aspartate aminotransferase, C-reactive protein, serum iron and urea levels. Among patients with CC, statistically significant (p&lt;0.001) correlations were obtained between hematological, hemostasiological and biochemical blood parameters. Of statistical significance, the presence of the glandular component in the tumor increases the systemic effect of CC on blood parameters, hemostasis, markers of inflammation and iron metabolism: leukocytosis and maximum erythrocyte sedimentation rate values compared to CC, high fibrinogen and the level of soluble fibrin-monomer complexes which increased activation of coagulation hemostasis along the common coagulation pathway (thrombin time) (p&lt;0.001). It leads to an increase in the risk of venous thromboembolic complications in this category of patients.Conclusion. The identified changes in blood parameters made it possible to reveal the unique biological characteristics of each histological subtype of CC, including biochemical ones, which will help in developing an improved diagnosis of CC depending on the histological subtype and stage of the disease, along with developing preventive measures and treatment methods adapted to each specific case.

Predictive Value of Various Atypical Cells for the Detection of Human Papillomavirus in Cervical Smears.

It is thought that numerous genotypes of human papillomavirus (HPV) are associated with various atypical cells, such as multinucleated cells, koilocytes, binucleated cells, parakeratotic cells, and giant cells, in the cervix. We previously showed the specificity of HPV genotypes for koilocytes and multinucleated cells. Therefore, in this study, we analyzed the association among HPV genotypes and binucleated cells, parakeratotic cells, and giant cells in Papanicolaou (Pap) smears. We detected HPV genotypes and atypical cells in 651 cases of liquid-based cytology with an abnormal Pap smear. The HPV genotypes associated with atypical cells were evaluated using stepwise logistic regression with backward elimination and a likelihood ratio test for model construction. Polymerase chain reaction was used to determine the HPV genotypes in whole liquid-based cytology samples and microdissected cell samples from Pap smear slides. Binucleated cells were significantly associated with HPV genotype 42. Moreover, parakeratotic cells were significantly associated with certain HPV genotypes, such as HPV40. However, it was difficult to detect specific HPV genotypes by the manual microdissection-polymerase chain reaction method despite the presence of binucleated cells and parakeratotic cells. Thus, the presence of binucleated cells, parakeratotic cells, and giant cells in Pap smears may not be predictive of cervical lesions above low-grade squamous intraepithelial lesions or infection with highly carcinogenic HPV genotypes.

Prevalence of high-risk human papillomavirus infection and genotype distribution among Kazakhstani women with abnormal cervical cytology

Aim This study aimed to identify the prevalence and distribution of high-risk human papillomavirus (HR-HPV) types among Kazakhstani women with abnormal cervical cytology. Methods A cross-sectional study was performed from May 2019 to June 2020. Cervical samples were collected from women in the different regions of Kazakhstan. Results A total of 316 patients’ samples were analysed for HR-HPV using real-time multiplex PCR. Cervical cytology abnormalities were reported according to the Bethesda classification. HPV detection by cytology showed a statistically significant association with HPV status and the number of HPV infection types (p < .05). Among women with abnormal cervical cytology, 62.4% were positive for HPV infection of those 79.4% had low-grade squamous intraepithelial lesions (LSIL), and 20.6% had high-grade squamous intraepithelial lesions (HSIL). Among patients with LSIL, 77.4% had HPV16 and 58.8% were infected with HPV18. Among patients with HSIL, 41.2% had HPV18 and 22.6% – HPV16. Conclusions There is a high prevalence of HR-HPV types among Kazakhstani women with abnormal cervical cytology. The most identified types were HPV16, 18, 31, 33 and 52. There is an emergency need to implement an HPV vaccination program to prevent cervical lesion development.

Epidemiology and genotypes analysis of human papillomavirus infection in Beijing, China

BackgroundThis study aimed to investigate the epidemiology of high-risk human papillomavirus (HPV) in the female population in Beijing, China, and identify the relationship between HPV genotypes and host factors.MethodsHPV testing was performed on women aged 15–89 (mean age 38.0 ± 10.9 years) from Beijing in 2020. High-risk HPV genotyping real-time polymerase chain reaction was used to determine HPV genotypes. The overall prevalence, age-specific prevalence, genotype distribution, and the correlation between HPV genotypes and cervical cytology were analyzed.ResultsAmong the 25,344 study participants, the single and double infection rates were 18.8% (4,777/25,344) and 4.2% (1,072/25,344), respectively. A total of 6,119 HPV-positive individuals were found to have 91.6% negative results for intraepithelial lesion or malignancy (NILM), 5.8% atypical squamous cells of undetermined significance (ASC-US), 0.9% low-grade squamous intraepithelial lesion (LSIL), and 1.7% high-grade squamous intraepithelial lesion (HSIL). In single HPV infections, the HPV16 genotype was highly associated with cervical cytology severity (χ2 trend = 172.487, P < 0.001). Additionally, HPV infection rates increased gradually with age, and statistical differences were observed across age groups (χ2 = 180.575; P < 0.001). High-risk HPV genotypes were highly prevalent in women below 25 years of age and those aged 55–59 years. Cluster analysis revealed that the 13 HPV genotypes could be roughly divided into two groups in a single infection; however, patterns of infection consistent with biological characteristics were not observed.ConclusionHigh-risk HPV was found in 24.1% of outpatients, with HPV52, HPV58, HPV16, HPV39, and HPV51 being the most common high-risk genotypes. Single high-risk HPV infection was predominant. HPV16, HPV39, HPV51, and HPV52 were associated with cervical lesion progression. HPV16 infection was especially worrying since it aggravates cervical lesions. Because the infection rates of the 13 HPV genotypes differed by age, the peak HPV infection rate should not guide vaccination, screening, and prevention programs. Instead, these initiatives should be tailored based on the regional HPV distribution characteristics. Moreover, it was determined that Beijing’s populace needed to receive treatment for HPV39 infection.

A Promising New Model: Establishment of Patient-Derived Organoid Models Covering HPV-Related Cervical Pre-Cancerous Lesions and Their Cancers.

The lack of human-derived in vitro models that recapitulate cervical pre-cancerous lesions has been the bottleneck in researching human papillomavirus (HPV) infection-associated pre-cancerous lesions and cancers for a long time. Here, a long-term 3D organoid culture protocol for high-grade squamous intraepithelial lesions and cervical squamous cell carcinoma that stably recapitulates the two tissues of origin is described. Originating from human-derived samples, a small biobank of cervical pre-tumoroids and tumoroids that faithfully retains genomic and transcriptomic characteristics as well as the causative HPV genome is established. Cervical pre-tumoroids and tumoroids show differential responses to common chemotherapeutic agents and grow differently as xenografts in mice. By coculture organoid models with peripheral blood immune cells (PBMCs) stimulated by HPV antigenic peptides, it is illustrated that both organoid models respond differently to immunized PBMCs, supporting organoids as reliable and powerful tools for studying virus-specific T-cell responses and screening therapeutic HPV vaccines. In this study, a model of cervical pre-cancerous lesions containing HPV is established for the first time, overcoming the bottleneck of the current model of human cervical pre-cancerous lesions. This study establishes an experimental platform and biobanks for in vitro mechanistic research, therapeutic vaccine screening, and personalized treatment for HPV-related cervical diseases.

Evaluation of combination of ALA-PDT and interferon for cervical low-grade squamous intraepithelial lesion (LSIL)

BackgroundCervical LSIL is a precancerous disease which requires regular follow-up. High risk patients need active interventions. Interferon and topical PDT have been used in the treatment of cervical LSIL. The aim of this study was to evaluate the combination use of topical PDT and interferon in the treatment of cervical LSIL. Materials and methodsA prospective study was carried out involving 159 women with cervical LSIL and high risk human papillomaviruses (hr-HPV) infection. Patients were divided into three groups. Group 1-receiving interferon suppository only, Group 2-receiving 19 mg/cm2 ALA plus post PDT interferon, and Group 3-receiving 38 mg/cm2 ALA plus post PDT interferon. The primary endpoint was pathological regression. The secondary endpoints were the HPV negative conversion rate and the adverse effects of treatment. ResultsAt 6–12 months after PDT, for Group 1, the effective rate, CR rate and HPV negative conversion rate was 48.3 %, 43.3 % and 24.0 %, respectively. For Group 2, the effective rate, CR rate and HPV negative conversion rate were 89.3 %, 71.4 %, and 72.4 %, respectively. For Group 3, the effective rate, CR rate and HPV negative conversion rate were 91.5 %, 66.1 %, and 64.4 %, respectively, significantly higher than those of interferon only group. Two ALA dose group study showed similar efficacy. No patient experienced serious adverse effects. ConclusionsALA-PDT combined with interferon therapy was feasible and tolerable. Two ALA dose groups showed similar outcomes in treating cervical LSIL.

Is robotic-assisted vaginectomy a better choice in vaginal high-grade squamous intraepithelial lesions than conventional laparoscopic surgery?

BackgroundVaginectomy has been shown to be effective for select patients with vaginal high-grade squamous intraepithelial lesions (HSIL) and is favored by gynecologists, while there are few reports on the robotic-assisted laparoscopic vaginectomy (RALV). The aim of this study was to evaluate the safety and treatment outcomes between RALV and the conventional laparoscopic vaginectomy (CLV) for patients with vaginal HSIL.MethodsThis retrospective cohort study was conducted in 109 patients with vaginal HSIL who underwent either RALV (RALV group) or CLV (CLV group) from December 2013 to May 2022. The operative data, homogeneous HPV infection regression rate and vaginal HSIL regression rate were compared between the two groups. Student’s t-test, the Mann-Whitney U test, Pearson χ2 test or the Fisher exact test, Kaplan-Meier survival analysis and Cox proportional-hazards models were used for data analysis.ResultsThere were 32 patients in the RALV group and 77 patients in the CLV group. Compared with the CLV group, patients in the RALV group demonstrated less estimated blood loss (41.6 ± 40.3 mL vs. 68.1 ± 56.4 mL, P = 0.017), lower intraoperative complications rate (6.3% vs. 24.7%, P = 0.026), and shorter flatus passing time (2.0 (1.0–2.0) vs. 2.0 (2.0–2.0), P < 0.001), postoperative catheterization time (2.0 (2.0–3.0) vs. 4.0 (2.0–6.0), P = 0.001) and postoperative hospitalization time (4.0 (4.0–5.0) vs. 5.0 (4.0–6.0), P = 0.020). In addition, the treatment outcomes showed that both RALV group and CLV group had high homogeneous HPV infection regression rate (90.0% vs. 92.0%, P > 0.999) and vaginal HSIL regression rate (96.7% vs. 94.7%, P = 0.805) after vaginectomy. However, the RALV group had significantly higher hospital costs than that in the CLV group (53035.1 ± 9539.0 yuan vs. 32706.8 ± 6659.2 yuan, P < 0.001).ConclusionsBoth RALV and CLV can achieve satisfactory treatment outcomes, while RALV has the advantages of less intraoperative blood loss, fewer intraoperative complications rate and faster postoperative recovery. Robotic-assisted surgery has the potential to become a better choice for vaginectomy in patients with vaginal HSIL without regard to the burden of hospital costs.

Effectiveness of trichloroacetic acid versus electrocautery for the treatment of anal high-grade squamous intraepithelial lesions in persons with HIV

Purpose This study aimed to compare trichloroacetic acid (TCA) versus electrocautery (ECA) for the treatment of anal high-grade squamous intraepithelial lesions (HSIL). Methods This is an observational, single-center study. All subjects with HIV who had anal HSIL treated with TCA or ECA from 2010 to 2022 were included. Effectiveness was evaluated by on-treatment analysis, defining response as the resolution of HSIL and recurrence as a new diagnosis of HSILs during follow-up. A propensity score analysis was used to adjust for confounding factors. Results In total, 227 and 260 HSIL episodes were treated with ECA and TCA, respectively. Response was observed in 61.7% (95% CI: 55.3–68) of cases treated with ECA and in 73.1% (95% CI: 67.8–78.5) with TCA (p = .004). The effectiveness of TCA was higher in large and multifocal HSILs. Side effects were common with both treatments, but no serious events were described. Tolerability was good in 77.1% and 80.7% of patients treated with ECA and TCA, respectively. At 24 months, recurrent HSIL were observed in 36.3% (95% CI: 27.3–45) and 28% (95% CI: 20.2–35.8) in the ECA and TCA groups (p = .049). A nadir CD4 cell count ≤200 cells/µl was found to be a risk factor for recurrence (OR: 1.77; 95% CI: 1.12–2.78). Conclusions In this study, treatment with TCA showed high effectiveness, low recurrence and good tolerability. Considering the benefits of TCA, it could be considered one of the first-line treatments for anal HSIL.