Low-grade Intraepithelial Lesion Research Articles

Impact of Low-grade Intraepithelial Lesions with High-risk Human Papillomavirus (Part II); Are LSIL Only to be Followed-up? Alternative Management

One of the determining factors that result in the development of cervical cancer is the persistence of high - risk human papillomavirus (HR - HPV). The low - grade intraepithelial lesions are a manifestation of this virus infection. Despite the effectiveness and safety of the HPV vaccine, coverage is still limited; thus, various options have been presented that offer to help reduce the persistence of HPV infection.

Impact of Low-grade Intraepithelial Lesions with High-risk Human Papillomavirus (Part I)

One of the cervical cancer screening tests that has been prevalent in low- and mid-level income countries has been the cytology test, which uses a system of standardized reports such as the Bethesda. This system allows the detection of anomalies in squamous epithelial cells, including the squamous intraepithelial lesion (SIL), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), invasive squamous cell carcinoma, and adenocarcinoma. This categorization in two levels (LSIL and HSIL) has allowed to differentiate the carcinogenic potential of the human papillomavirus (HPV). LSIL are described as transient changes associated with an infection caused by HPV and asymptomatic infections with viral vacuolization within a two-year interval with no specific treatment. In case of HSIL, reference is made to its pre-cancer potential. Several factors have an impact in the onset of a LSIL: the presence of HPV (as one of the key etiologic agents) and other risk factors such as hormones, microbiome, first intercourse at early age, multiple sexual partners, other infections, immune status, and tobaco. All that contribute to the transient nature of the infection, or to its persistence, which in turn may promote the development and progression into an HSIL. The persistence of a high-risk HPV infection (HR-HPV) (or more rarely of low-grade too) plays an important role in the development of cervical cancer.

The Impact of Tamoxifen Usage in Breast Cancer Patients on the Development of Histopathological Lesions in the Cervix Uteri.

Background and Objectives: The purpose of the present study was to compare the results of colposcopic biopsies in patients with breast cancer and those who tested positive for HPV in cervix uteri cytological screenings, with a control group of HPV-positive individuals without breast cancer. Additionally, through this study, we aimed to investigate the impact of tamoxifen treatment, an anti-oestrogen drug used following breast cancer treatment, on histopathological changes. Breast cancer is the most common type of cancer and cause of death in women worldwide. Cervical cancer ranks as the second most prevalent form of cancer among women globally, with prevalence rates ranking just behind those of breast cancer. Human papillomavirus (HPV) positivity is a requirement for the development of cervical cancer, although it is not the sole factor responsible. Materials and Methods: A comparison was made between the histopathological results of 52 patients diagnosed with breast cancer, who tested positive for HPV in routine cervical cytological screenings and underwent colposcopic biopsy, and 230 cases without any abnormalities. A study was conducted to compare healthy individuals between the ages of 30 and 65 who were diagnosed with breast cancer and those who did not have breast cancer. The participants underwent HPV screening as part of the national cervical cytology screening programme. Results: The average age of those diagnosed with breast cancer was 46.73 ± 7.54; in comparison, the average age of participants in the control group was 47.49 ± 7.95. There was no statistically significant difference in age between the two groups (p: 0.530). A total of 51 cases (98.1%) of breast cancer were found to have actively used the anti-oestrogen drug tamoxifen for a duration ranging from at least 6 months to 5 years. One patient (1.9%) in the breast cancer group did not use tamoxifen. During routine cervical cytological screenings, it was observed that both breast cancer cases and healthy cases tested positive for HPV. The most commonly detected types of HPV in both groups were HPV 16 and 18, with rates of 73.1% noted in the breast cancer group and 92.6% noted in the healthy group, results consistent with the rates found in the general population. HPV 16 was found in 58.7% of participants in the control group and 42.3% of participants in the breast cancer group. There was a statistically significant difference between the two groups (p: 0.032). There was no statistically significant difference observed between the two groups in terms of normal, high-grade cervical intraepithelial lesions (HGSILs); low-grade cervical intraepithelial lesions (LGSILs); and chronic cervicitis histopathological lesions based on colposcopic and endocervical biopsy results, smear cytology, and HPV results (p-values of 0.913 and 0.877, respectively). Conclusions: Our study results indicate that tamoxifen treatment, an anti-oestrogen drug administered for chemoprevention purposes in the management of breast cancer, does not lead to an increase in abnormal histological changes in the cervix uteri. In all cases of breast cancer, gynaecological examination and cervical cytological screening should be advised.

Host Nuclear Genome Copy Number Variations Identify High-Risk Anal Precancers in People Living With HIV.

People living with HIV (PLWH) have substantially increased incidence of anal precancer and cancer. There are very little data regarding genomic disturbances in anal precancers among PLWH. In this study, specific chromosomal variants were identified in anal squamous intraepithelial lesions. Overall, 63 anal biopsy specimens (27 low-grade intraepithelial lesions [LSIL] and 36 high-grade intraepithelial lesions [HSIL]) were collected from PLWH obtained as part of anal cancer screening in our NYC-based health system. Data on patient demographics, anal cytological, and high-risk human papillomavirus (HR-HPV) diagnoses were collected. Specimens were tested for a panel of chromosomal alterations associated with HPV-induced oncogenesis using fluorescence in situ hybridization, and analyses compared the associations of these alterations with clinical characteristics. Gains of 3q26, 5p15, 20q13, and cen7 were detected in 42%, 31%, 31%, and 19% of HSIL compared with 7%, 0%, 4%, and 0% of LSIL, respectively. If at least 1 abnormality was observed, 89% had a 3q26 gain. In lesions with 5p15 gains, 20q13 gains co-occurred in 91% of cases, while cen7 gain only co-occurred with the other 3 alterations. The sensitivity and specificity of any alteration to predict HSIL were 47% (95% CI: 30%-65%) and 93% (95% CI: 76%-99%), respectively. Genomic alterations seen in HPV-associated cancers may help distinguish anal LSIL from HSIL. 3q26 amplification may be an early component of anal carcinogenesis, preceding 5p16, 20q13, and/or chr7. Insights into potential genomic biomarkers for discriminating high-risk anal precancers are shared.

Methylation markers for anal cancer screening: A repeated cross-sectional analysis of people living with HIV, 2015-2016.

People living with HIV (PLWH) are at highest risk of anal cancer and will benefit from optimized screening for early disease detection. We compared host DNA methylation markers in high-grade squamous intraepithelial lesions (HSIL) versus samples negative for intraepithelial lesions (NILM) or low-grade intraepithelial lesions (LSIL) in PLWH. We recruited PLWH identifying as male aged ≥18 years undergoing high-resolution anoscopy (HRA) in Seattle, Washington, 2015-2016. Anal brush samples were collected for HPV detection, genotyping, and pyrosequencing methylation (host genes ASCL1, PAX1, FMN2, and ATP10A); clinical data were abstracted from medical records. We assessed associations between methylation and presence and extent of HSIL using generalized estimating equation logistic regression, adjusting for age, CD4 count and HIV viral load. Marker panels using HPV DNA and methylation were also evaluated to predict prevalent HSIL. We analyzed 125 samples from 85 participants (mean age 50.1; standard deviation 11.0 years). ASCL1 (adjusted odds ratio [aOR] per 1 unit increase mean percent methylation: 1.07, 95% CI: 1.01-1.13) and FMN2 (aOR per 1 unit increase mean percent methylation: 1.14, 95% CI: 1.08-1.20) methylation were significantly associated with HSIL versus NILM/LSIL. ASCL1 (aOR: 1.06, 95% CI: 1.01-1.11) and FMN2 (aOR: 1.13, 95% CI: 1.08-1.17) methylation were positively associated with increasing HSIL extent. A panel combining methylation (ASCL1 and FMN2) and HPV DNA (HPV16, HPV18, and HPV31) demonstrated best balance of sensitivity (78.2%) and specificity (73.9%) for HSIL detection compared with methylation or HPV alone. Increasing levels of DNA methylation of ASCL1 and FMN2 were positively associated with HSIL detection in PLWH. Host gene methylation testing shows promise for HSIL screening and triage.

Discovery and technical validation of high-performance methylated DNA markers for the detection of cervical lesions at risk of malignant progression in low- and middle-income countries

BackgroundCervical cancer remains a leading cause of death, particularly in developing countries. WHO screening guidelines recommend human papilloma virus (HPV) detection as a means to identify women at risk of developing cervical cancer. While HPV testing identifies those at risk, it does not specifically distinguish individuals with neoplasia. We investigated whether a quantitative molecular test that measures methylated DNA markers could identify high-risk lesions in the cervix with accuracy.ResultsMarker discovery was performed in TCGA-CESC Infinium Methylation 450 K Array database and verified in three other public datasets. The panel was technically validated using Quantitative Multiplex-Methylation-Specific PCR in tissue sections (N = 252) and cervical smears (N = 244) from the USA, South Africa, and Vietnam. The gene panel consisted of FMN2, EDNRB, ZNF671, TBXT, and MOS. Cervical tissue samples from all three countries showed highly significant differential methylation in squamous cell carcinoma (SCC) with a sensitivity of 100% [95% CI 74.12–100.00], and specificity of 91% [95% CI 62.26–99.53] to 96% [95% CI 79.01–99.78], and receiver operating characteristic area under the curve (ROC AUC) = 1.000 [95% CI 1.00–1.00] compared to benign cervical tissue, and cervical intraepithelial neoplasia 2/3 with sensitivity of 55% [95% CI 37.77–70.84] to 89% [95% CI 67.20–98.03], specificity of 93% [95% CI 84.07–97.38] to 96% [95% CI 79.01–99.78], and a ROC AUC ranging from 0.793 [95% CI 0.68–0.89] to 0.99 [95% CI 0.97–1.00] compared to CIN1. In cervical smears, the marker panel detected SCC with a sensitivity of 87% [95% CI 77.45–92.69], specificity 95% [95% CI 88.64–98.18], and ROC AUC = 0.925 [95% CI 0.878–0.974] compared to normal, and high-grade squamous intraepithelial lesion (HSIL) at a sensitivity of 70% (95% CI 58.11–80.44), specificity of 94% (95% CI 88.30–97.40), and ROC AUC = 0.884 (95% CI 0.822–0.945) compared to low-grade intraepithelial lesion (LSIL)/normal in an analysis of pooled data from the three countries. Similar to HPV-positive, HPV-negative cervical carcinomas were frequently hypermethylated for these markers.ConclusionsThis 5-marker panel detected SCC and HSIL in cervical smears with a high level of sensitivity and specificity. Molecular tests with the ability to rapidly detect high-risk HSIL will lead to timely treatment for those in need and prevent unnecessary procedures in women with low-risk lesions throughout the world. Validation of these markers in prospectively collected cervical smear cells followed by the development of a hypermethylated marker-based cervical cancer detection test is warranted.

Prognostic potential of PRMT5 and DSG2 proteins in pre-malignant cervical lesions.

Precancerous cervical lesions are metaplastic alterations of epithelial cells of the cervix, eventually developing into cervical cancer. Despite primary and secondary prevention, the burden of cervical cancer remains high globally. Protein arginine methyltransferases (PRMT) represent post-translational modifications that interact with multiple signalling pathways, playing a role in epithelial-mesenchymal transition. In complex with desmoglein-2 (DSG2), a cell adhesion protein, both participate in the progression of dysplastic changes with potential malignant development. The presented study was performed on archival paraffin-embedded blocks from adult women. The studied samples were categorised into low-grade and high-grade intraepithelial lesions. Immunohistochemical analysis was used to observe subcellular localisation, immunoreaction intensity, and percentage of PRMT5- and DSG2-expressing cells, followed by statistical analysis. Preliminary results identified statistically significant differences between the expression and subcellular localisation of proteins in question in low-grade and high-grade squamous intraepithelial lesions. The primary goal of the presented study is to perceive the involvement of PRMT5 and DSG2 in the initiation and progression of cervical lesions. Our observations indicate the potential of the assessed proteins as prognostic markers. However, further studies of PRMT5 and DSG2 are required to provide greater insight into cervical carcinogenesis.

Human papillomavirus genotyping for predicting disease progression in women with biopsy-negative or cervical intraepithelial neoplasia grade 1 of low-grade intraepithelial lesion cytology

ObjectiveOur study used human papillomavirus (HPV) genotyping to assess the disease occurrence probability in women with a low-grade squamous intraepithelial lesion (LSIL) without histologically confirmed cervical intraepithelial neoplasia grade 2...

Efficacy of Lactococcus lactis strain Plasma on clearance of anal HPV infection in men who have sex with men: A single-center, double-blinded, randomized placebo-controlled trial (CLEAR HPV study)

Background: Anal cancer is a human papillomavirus-related cancer; specifically, it is preceded by high-grade squamous intraepithelial lesions, which are less likely to regress spontaneously than low-grade intraepithelial lesions. Although most human papillomavirus (HPV) infections are thought to clear spontaneously, anal HPV infection persists, especially in people living with HIV. Preliminary results from a recent small randomized placebo-controlled trial of oral bacteriotherapy using a high dose of probiotics demonstrated clearance of anal high-risk HPV (hr-HPV) infection and lower onset of new high-grade squamous intraepithelial lesions among people living with HIV. Lactococcus lactis strain Plasma is a lactic acid bacterium directly activating plasmacytoid dendritic cells and inducing release of type I and III interferons via Toll-like receptor 9 stimulation. Based on these findings, oral bacteriotherapy with LC-plasma may contribute to clearing anal hr-HPV infection and reducing anal precancerous lesions by activating innate and acquired immune responses. This randomized placebo-controlled trial aims to investigate the efficacy and safety of LC-plasma therapy in clearing anal hr-HPV infection and reducing anal precancerous lesions among men who have sex with men with or without HIV infection. Methods: Participants with anal hr-HPV infection will be included and receive test capsules. A total of 150 patients will be included in the intervention group with follow-up, which will consist of HPV genotype test, cytology by anal pap smear, and biopsy with high-resolution anoscopy. The primary endpoint will be the clearance rate of the hr-HPV genotype infection at the anal site at 180 days. The secondary endpoints will be changes in anal epithelial neoplasia detected using high-resolution anoscopy at 180 days; change in abnormal cytology by anal pap smear at 180 days; change in hr-HPV genotype at the anal site at 180 days; change or percentage change in peripheral blood CD4 positive T-lymphocyte numbers in HIV-infected participants at 180 days; changes in quantitative hepatitis B surface antigen levels at 180 days in the HBV-infected participants; and adherence to the study drugs. Conclusion: This randomized controlled study will provide data on the efficacy and safety of LC-plasma as a treatment for anal HPV infection and grade 2 or 3 anal intraepithelial neoplasia.

Pre-Malignant Lesions of Cervix in Female Attending a Tertiary Hospital of Nepal

Introduction: Cervical cancer is killing Nepali women in gross even though cervical cancer is preventable with time-tested screening strategies in Nepal. Detection of premalignant lesions of cervix is preliminary step for early treatment and to minimise the tragedy of death. The aim of this research is to corelate the Pap smear, colposcopy and guided biopsy findings with histopathology to detect premalignant lesion of cervix.Methods: A prospective observational study conducted among 145 women attending gynaecology OPD with symptoms during reproductive age 21-65 years. Collection of Pap smear was conducted by conventional method, colposcopy and guided biopsy in selected women were performed and the sample was sent to pathology department for histopathological confirmation.Results:The pre-malignant lesions in cytology were ASCUS (Atypical Squamous Cells of Undetermined Significance) 11%, ASC-H (Atypical Squamous cell- cannot exclude High Grade)1.3 %, LSIL (Low Grade Intraepithelial Lesion)28.2 %, and HSIL (High Grade Intraepithelial Lesion) 7.5 %. The colposcopy detected 54.4% atypical transformation zone. The histopathology detected Cervical Intra-epithelial Neoplasia I (CIN I) 26.1%, CIN II 11.7%, and CIN III 7.5%. The sensitivity of Pap smear and colposcopy was 83%, the specificity of Pap smear was 88%, and colposcopy was 98%.The positive predictive value(PPV)were 89% and 98 %, negative predictive value(NPV) were 81%and 83%.and accuracy was 88 % and 98% in Cytology and Colposcopy.Conclusions:Pap smear and colposcopy were effective tools to detect premalignant lesions of cervix in comparison to histopathological findings.

PRAME expression by Immunohistochemistry and Reverse Transcription Quantitative PCR in conjunctival melanocytic lesions -A comprehensive clinicopathologic study of 202 cases and correlation of cytogenetics with PRAME expression in challenging conjunctival melanocytic lesions.

This study examined PRAME expression by immunohistochemistry and reverse transcription quantitative PCR (RT-qPCR) in 202 histologically unequivocal conjunctival melanocytic lesions: 76 nevi, 29 benign melanoses, 25 low-grade conjunctival intraepithelial melanocytic lesions (LGCMIL), 26 high-grade conjunctival melanocytic intraepithelial lesions/in-situ melanoma (HGCMIL) and 46 invasive melanomas. PRAME score 0 was seen in 96% of nevi (73/76), 96% of benign melanoses (28/29) and 88% of LGCMIL (22/25). PRAME score 4 was seen in 50% HGCMIL (13/26) and 76% invasive melanomas (35/46). PRAME score 4 had sensitivity of 50% and specificity of 100% in differentiating between HGCMIL and benign melanosis/LGCMIL. PRAME score 4 had sensitivity of 76% and specificity of 100% in differentiating between melanoma and nevi. Relative quantification of PRAME mRNA expression by RT-qPCR was performed on 49 (24%) cases: 17 nevi, 3 benign melanoses, 5 LGCMIL, 9 HGCMIL, and 15 invasive melanomas. The analysis generated two distinct groupings with 'high' relative PRAME expression for the HGCMIL and invasive melanoma and 'low/zero' expression for nevi, benign melanosis and LGCMIL. Thirty-three challenging conjunctival melanocytic lesions that had previous FISH analysis were studied: 18 nevi, 12 melanomas in a nevus, 2 nevoid melanomas, 1 in-situ melanoma. All nevi (100%) showed concordance between negative FISH and PRAME (scores 0-3). 4/13 (31%) melanomas (in-situ, invasive, isolated, and in association with nevus) showed concordance between positive FISH and PRAME score 4. In conclusion, PRAME score 4 has 100% specificity for diagnosis of HGCMIL and melanoma. PRAME is limited in its sensitivity in the evaluation of challenging melanocytic lesions.

Evaluation of 1,030,482 Cervical Smear Results in Brazilian Population.

The objective was to determine the prevalence of abnormal cytologic smears in a large population of a Brazilian city. Retrospective study of cervical cytology results performed at a private laboratory in São Paulo - Brazil. A total of 1,030,482 cytology tests were performed between January 2010 and December 2015. Among the satisfactory cytologies, we observed abnormal results in 8.9% (91,371). Analyzing the proportion of exams with altered results over the years, there was no change in these rates. We observed that the proportion of abnormal exams decreased with increasing age. Atypical squamous cells of undetermined significance, possibly non-neoplastic (ASC-US) cytology was the most common abnormality found in the general population with 73.19%, followed by low-grade intraepithelial lesion (LSIL) with 20.5%; these 2 cytological abnormalities add up to 93.69 % of all abnormal results. There was an increase in ASC-US with advancing age, a decrease in prevalence of LSIL, especially after the age of 30 and high-grade intraepithelial lesion (HSIL) shows two peaks of elevation, respectively in the age groups of 30-39 years and over 70 years. Women under the age of 30 showed a higher prevalence of cytological abnormalities, however most of these changes are low-grade lesions. In older women, cytological abnormalities are largely high-grade lesions, requiring greater care to prevent progression to cancer.

Comparison of Ki67 index and P16 expression in different grades of cervical squamous intraepithelial lesions.

the assessment of P16 expression and Ki-67 proliferative index is now proposed as an adjunct test for the diagnosis of high-risk precursor lesions for cervical cancer. The aim of the present study was to elucidate the quality expression of P16 and quantification Ki-67 index in different types of cervical intraepithelial neoplasia and also to determine the cutoff for Ki67 index to predict the severity of CIN lesions. This cross-sectional study was conducted on patients with colposcopic indication. Selected samples with different CIN grades were examined for P16 and Ki-67 index by immunohistochemical (IHC) methods. All LSIL (CIN I) cases were negative for P16, while in 58.7% of HSIL cases (CIN 2/3), P16 was positive. The mean Ki67 index in the present study was 3.13 ± 2.65 in the upper two/third of the squamous epithelium in the LSIL group and 19.04 ±36.40 in the HSIL group, which was statistically significant. Also, the mean Ki67 index in full thickness squamous epithelium in HSIL group was significantly higher than LSIL. The sensitivity of P16 and Ki67 index in our study was 58.73%, 66.67% and the specificity was 100% and 100%, respectively. Assessment of P16 expression and Ki67 index can be used to distinguish low grade (CIN1) intraepithelial lesion from high grade (CIN2/3) intraepithelial or precancerous lesions.

Characterization of Human Papillomavirus 16 from Kinshasa (Democratic Republic of the Congo)-Implications for Pathogenicity and Vaccine Effectiveness.

Human Papillomavirus (HPV) type 16 is the main etiological agent of cervical cancer worldwide. Mutations within the virus genome may lead to an increased risk of cancer development and decreased vaccine response, but there is a lack of information about strains circulating in Sub-Saharan Africa. Endocervical cytology samples were collected from 480 women attending a voluntary cervical cancer screening program at Monkole Hospital and four outpatient centers in Kinshasa, Democratic Republic of the Congo (DRC). The prevalence of HPV infection was 18.8% and the most prevalent high-risk types were HPV16 (12.2%) followed by HPV52 (8.8%) and HPV33/HPV35 (7.8% each). HPV16 strains were characterized: 57.1% were classified as C lineage; two samples (28.6%) as A1 and one sample belonged to B1 lineage. HPV33, HPV35, HPV16, and HPV58 were the most frequent types associated with low-grade intraepithelial lesion while high-grade squamous intraepithelial lesions were predominantly associated with HPV16. Several L1 mutations (T266A, S282P, T353P, and N181T) were common in Kinshasa, and their potential effect on vaccine-induced neutralization, especially the presence of S282P, should be further investigated. Long control region (LCR) variability was high with frequent mutations like G7193T, G7521A, and G145T that could promote malignancy of these HPV16 strains. This study provides a helpful basis for understanding HPV16 variants circulating in Kinshasa and the potential association between mutations of LCR region and malignancy and of L1 and vaccine activity.

Evaluation of Sirtuin1 Overexpression by Immunohistochemistry in Cervical Intraepithelial Lesions and Invasive Squamous Cell Carcinoma.

Cervical cancer is one of the most common genital cancers in the woman with approximately half a million new cases per year. Development of invasive squamous cell carcinoma (SCC) is the result of persistent and frequent human papilloma virus infection in premalignant lesions of cervix. Thereby identification of biomarkers that could predict progression of dysplastic mucosa to invasive cancer is of great clinical significance. Overexpression of SIRT1 has been reported to induce tumorogenesis in several organs. We evaluated SIRT1 expression in normal squamous epithelium of cervix, low-grade and high-grade cervical intraepithelial lesions and invasive SCC. A total of 104 cases were selected including 34 low-grade cervical intraepithelial lesions (CINs), 37 high-grade CINs, and 35 cases of invasive SCC. The normal cervical epithelium showed negative or weak SIRT1 positivity only in basal layers. SIRT1 cytoplasmic expression was found in 13 of 34 (38.2%) of low-grade CINs, 31 of 37 (83.8%) of high-grade CINs and all 35 (100%) cases of invasive SCC. Expression between 2 groups of CIN was statistically significant ( P =0.001). Thus, SIRT1 appears to be a promising biomarker for predicting the progression of CIN to invasive SCC.

Serum Levels of Galectin-9 are Increased in Cervical Cancer Patients and are Higher in Advanced Clinical Stages.

PurposeCervical cancer (CC) is the second most frequent cancer in undeveloped countries. Serum biomarkers could be useful for evaluation of the treatment response and as a complementary means to improve diagnosis. The expression of galectin-9 is altered in cancer tissue, and higher concentrations are found in the serum of cancer patients. The objectives of this study were (a) to determine the serum galectin-9 concentration in patients with intraepithelial lesions and CC, (b) to determine if the concentration was related to the clinicopathological characteristics and (c) to determine if the galectin-9 concentration was related to its expression level in tumour tissue.Patients and MethodsIn all, 222 serum samples from women with different diagnoses, including premalignant lesions and CC, as well as samples from women with normal cytology were included in the study. The serum galectin-9 concentration was determined by ELISA. To evaluate the expression level of galectin-9 in CC tissue, immunohistochemistry was performed in 34 CC biopsy specimens.ResultsThe galectin-9 concentration in the serum of CC patients (8.171 ng/mL) was increased compared with serum from women with normal epithelia (4.654 ng/mL) and those with low-grade (4.806 ng/mL) and high-grade (5.354 ng/mL) intraepithelial lesions (p value < 0.0001). The area under the ROC curve considering the CC group and the control group was 0.882. The optimal cut-off value was ≥6.88 ng/mL, the specificity obtained was 100%, and the sensitivity was 68.2%. In the CC group, the analysis of the clinical stage showed an increase of galectin-9 in the advanced stage IV group. Serum galectin-9 was not related to the level of galectin-9 expression in tissue, which suggests that galectin-9 is not secreted by tumour cells.ConclusionThe serum galectin-9 concentration is related to cancer progression, as the level of this protein is higher in patients with advanced-stage disease.

The Modeling Analysis and Effect of CHI3L1 and CD31-Marked Microvessel Density in the Occurrence and Development of Cervical Squamous Cell Carcinoma.

Background Chitinase-3-like protein 1 (CHI3Ll) has been identified as a novel tumor marker in several cancers. The objective of this study was to detect the expression of Chitinase-3-like protein 1 (CHI3L1) and CD31-labeled microvessel density (MVD) in cervical squamous cell carcinoma (CSCC) and to assess its prognostic impact. Methods Elivision™ plus immunohistochemical method was used to detect CHI3L1 expression and MVD in different cervical tissues. We analyzed the relationship between CHI3L1 and MVD in CSCC tissues and investigated the relationship between CHI3L1, MVD, and clinicopathological parameters. Univariate and multivariate survival analyses were performed to assess the impact on progression-free survival (PFS) and overall survival (OS). Results The positive expression rate of CHI3L1 protein in CSCC tissues (69.9%, 72/103) was significantly higher than that in high-grade cervical intraepithelial lesions (53.3%, 32/60), low-grade cervical intraepithelial lesions (25%, 15/60), and normal cervical tissues (16.7%, 10/60). MVD values ranged from 6 to 64 in CSCC, and no microvascular formation was observed in normal cervical tissues, high-grade intraepithelial lesions, or low-grade intraepithelial lesions. The high expression of CHI3L1 and MVD was significantly correlated with the invasion depth, differentiation degree, vascular invasion, and lymph node metastasis of CSCC (all P < 0.05). In CSCC, the expression of MVD in the CHI3L1 high-expression group (41.35 ± 9.056) was significantly higher than that in the CHI3L1 low-expression group (23.26 ± 11.000, P < 0.05). On univariate Kaplan–Meier analysis, FIGO stage, tumor diameter, lymph node metastasis, vascular invasion, CHI3L1, and MVD of CSCC were related to the prognosis of PFS and OS (all P < 0.05); however, CHI3L1 and MVD were not independent prognostic factors. Conclusion CHI3L1 may be involved in the progression of cervical cancer. Its high expression can promote neovascularization in the tumor microenvironment. CHI3L1 is a potential therapeutic target in the context of cervical cancer.

Cytopathological characteristics for provoked lesions of squamous epithelia of digestive system in animal models

Purpose of the study. Investigation of morphological characteristics of changes in the epithelium of foregut in experimental animals put under conditions of provoked carcinogenesis.Materials and methods. The method of chronic experiment on animals is applied: 40 female non-linear white rats, which are divided into 4 equal groups (n = 10). The first (I) and second (II) control groups of animals were exposed to mechanical trauma of the oral mucosa with additional application of 0.9 % NaCl solution and 1 % aqueous dimethyl sulfoxide (DMSO) solution with a frequency of 2 times a week. The third group of animals, i.e. the main group (4-NQO), was subjected to mechanical traumatization of the oral mucosa with additional application of 1 % DMSO aqueous solution containing 0.1 mg/ml of 4 nitroquinoline-N-oxide, with a frequency of 2 times a week. The fourth group of animals was intact. On the 1st, 7th, 10th, 14th day from the beginning of the experiment, and then every 14 days, cytological material was taken from the oral mucosa and stained with Papanicolaou stain. To compare the emerging changes, the histological picture of the organs of the foregut was studied.Results. Animals from the main group (4-NQO) showed a lag in body weight gain over the standard variance in the control (I and II) and intact groups. Atypical cells of indeterminate significance appeared in smears starting from 42 days of the experiment. Starting from the 56th day of the experiment, atypical cells (1–2 in the field of view), described in Bethesda terms as low-grade intraepithelial lesions, were detected in smears obtained from the main group of animals (4-NQO). Parabasal cells of the squamous epithelium with atypical large (more than 3 times compared to the reference) nuclei, anisonucleosis, with variable contours of the nuclear membrane within one cell, coarse chromatin were recognized as diagnostically significant.Conclusion. The severity of morphological changes in foregut epithelium in the direction of the precancerous state is significantly higher in the main group with prolonged exposure to carcinogenic factor, compared with the control and intact groups (р &lt; 0.05). Thus, the effectiveness of modeling the conditions of provocation of carcinogenesis of the epithelium of the upper digestive tube in experimental animals was studied and proved by mechanical traumatization of the oral mucosa with additional application of carcinogen (4-NQO). This model of provocation of carcinogenesis will be used in the next study of neoplastic processes of the female reproductive system.

Laparoscopic Abdominal Cerclage: Ensuring the Best Fertility Outcome

Study Objective To present the case of a patient undergoing fertility treatment, who required a Laparoscopic Abdominal Cerclage to improve fertility outcome. Design Descriptive video of Laparoscopic placement of Benson Cerclage. Setting Patient was in lithotomy position during surgery. One umbilical 5 mm port was used for the camera. Two 5 mm accessory ports were placed on both lower quadrants, and a left lateral 5 mm port was placed. A 5 mm Mersilene suture was used and tied with a posterior knot to avoid friction with bladder. Patients or Participants Only one patient was selected for this video. Interventions A laparoscopic abdominal cerclage (Benson) was placed in a patient with history of cervical cone due to a low-grade intraepithelial lesion at 22 years old. She underwent an IVF cycle due to idiopathic infertility. A frozen embryo was programmed, knowing that a cerclage needed to be placed after 12 weeks gestation. The cerclage (McDonald) was placed on an extremely short cervix (1 cm). She suffered a 2nd trimester loss due to rupture of membranes with Klebsiella positive culture. In preparation for next frozen embryo transfer, we recommended placement of an abdominal cerclage via laparoscopy. Measurements and Main Results The patient was seen after the laparoscopic procedure, with a vaginal ultrasound confirming the adequate placement of the abdominal cerclage. The patient will undergo frozen embryo transfer in the next months. Conclusion Initially, we informed the patient that, due to her gynecologic history, a cerclage was to be placed once a pregnancy reached the first trimester. We explained that given her extremely short cervix, an abdominal cerclage was needed to improve the outcome of her next frozen embryo cycle. To present the case of a patient undergoing fertility treatment, who required a Laparoscopic Abdominal Cerclage to improve fertility outcome. Descriptive video of Laparoscopic placement of Benson Cerclage. Patient was in lithotomy position during surgery. One umbilical 5 mm port was used for the camera. Two 5 mm accessory ports were placed on both lower quadrants, and a left lateral 5 mm port was placed. A 5 mm Mersilene suture was used and tied with a posterior knot to avoid friction with bladder. Only one patient was selected for this video. A laparoscopic abdominal cerclage (Benson) was placed in a patient with history of cervical cone due to a low-grade intraepithelial lesion at 22 years old. She underwent an IVF cycle due to idiopathic infertility. A frozen embryo was programmed, knowing that a cerclage needed to be placed after 12 weeks gestation. The cerclage (McDonald) was placed on an extremely short cervix (1 cm). She suffered a 2nd trimester loss due to rupture of membranes with Klebsiella positive culture. In preparation for next frozen embryo transfer, we recommended placement of an abdominal cerclage via laparoscopy. The patient was seen after the laparoscopic procedure, with a vaginal ultrasound confirming the adequate placement of the abdominal cerclage. The patient will undergo frozen embryo transfer in the next months. Initially, we informed the patient that, due to her gynecologic history, a cerclage was to be placed once a pregnancy reached the first trimester. We explained that given her extremely short cervix, an abdominal cerclage was needed to improve the outcome of her next frozen embryo cycle.

Comparison of Cervical Cancer Screen Results on Female-to-Male Transgender Patients With Female Patients.

There are limited data on cervical screen results from female-to-male (FTM) transgender patients. Herein, we compiled demographic information and cervical screen testing on FTM transgender patients and compared with age-appropriate controls. A search of our previous and current databases was performed for Papanicolaou (Pap) tests from patients taking testosterone and/or with a diagnosis of gender dysphoria, transsexualism, or transvestism. Patient data were reviewed. Relative risks of abnormal Pap smear and human papillomavirus (HPV) infection were calculated against age-matched controls. Eighty-nine Pap tests from FTM transgender individuals were identified, with a mean age of 31.3 years (range, 21-60 years). The Pap test diagnoses were distributed as follows: negative for intraepithelial lesion (n = 84, 94.4%), atypical squamous cells of undetermined significance (n = 0), low-grade intraepithelial lesion (n = 4, 4.5%), and high-grade squamous intraepithelial lesion (n = 1, 1.1%). Fifty (56.2%) patients had concurrent high-risk HPV testing with four (8%) positive results. Relative risk was 0.625 (95% confidence interval [CI], 0.25-1.59; P = .32) for an abnormal Pap test and 0.55 (95% CI, 0.19-1.52; P = .24) for HPV compared with 267 age-matched controls. Of note, 13.5% of patients older than 21 years had documentation of never having a prior Pap test in our medical record. In our study, FTM transgender individuals were not at a higher or lower risk of HPV infection or abnormal Pap test result compared with women. However, larger studies are needed to support our findings.