High-grade Squamous Intraepithelial Lesion Group Research Articles

Microbiome markers in HPV-positive and HPV-negative women of reproductive age with ASCUS and SIL determined by V4 region of 16S rRNA gene sequencing.

Human papilloma virus (HPV) is the most common sexually transmitted infection worldwide. Cervicovaginal microbiota plays an important role in HPV infection and is associated with the development of squamous intraepithelial lesions (SIL). The natural history of cervical cancer involves reversible changes in the cervical tissue from a normal state, in which no neoplastic changes are detected in the squamous epithelium, to varying states of cellular abnormalities that ultimately lead to cervical cancer. Low-grade SIL (LSIL), like another cytological category - atypical squamous cells of undetermined significance (ASCUS), may progress to high-grade SIL (HSIL) and invasive cervical cancer or may regress to a normal state. In this work, we studied cervical canal microbiome in 165 HPV-positive and HPV-negative women of a reproductive age with ASCUS [HPV(+) n = 29; HPV(-) n = 11], LSIL [HPV(+) n = 32; HPV(-) n = 25], HSIL [HPV(+) n = 46], and the control group with negative for intraepithelial lesion malignancy (NILM) [HPV(-) n = 22]. HPV16 is the most prevalent HPV type. We have not found any differences between diversity in studied groups, but several genus [like Prevotella (p-value = 0.026), Gardnerella (p-value = 0.003), Fannyhessea (p-value = 0.024)] more often occurred in HSIL group compared by NILM or LSIL regardless of HPV. We have found statistically significant difference in occurrence or proportion of bacterial genus in studied groups. We also identified that increasing of the ratio of Lactobacillus iners or age of patient lead to higher chance to HSIL, while increasing of the ratio of Lactobacillus crispatus lead to higher chance to LSIL. Patients with a moderate dysbiosis equally often had either of three types of vaginal microbial communities (CST, Community State Type) with the prevalence of Lactobacillus crispatus (CST I), Lactobacillus gasseri (CST II), and Lactobacillus iners (CST III); whereas severe dysbiosis is linked with CST IV involving the microorganisms genera associated with bacterial vaginosis and aerobic vaginitis: Gardnerella, Fannyhessea, Dialister, Sneathia, Anaerococcus, Megasphaera, Prevotella, Finegoldia, Peptoniphilus, Porphyromonas, Parvimonas, and Streptococcus.

Is the Anal Component of the Anogenital HPV-Related Disease Overlooked During the Surveillance of Patients Treated for Cervical Intraepithelial Neoplasia?

To investigate the anal component of the anogenital Human Papillomavirus (HPV) related disease during surveillance of patients treated for cervical intraepithelial neoplasia (CIN). Patients were analyzed within two groups according to the histopathological examination of the cervical biopsies: Low-Grade Squamous Intraepithelial Lesion (LSIL) and High-Grade Squamous Intraepithelial Lesion (HSIL) groups. Anal specimens were also collected in the first-year follow-up visit. All patients had cervical high-risk HPV (HR HPV) infection at admission. At the first-year follow-up, positive HR HPVs were found in 47% of cervical samples. Despite this clearance, the anal HPV infection rate after the first year was 42.5% and 39.6% in LSIL and HSIL groups. Amongst the HSIL group, anal HR HPV positivity was observed in 29.6% of cases without any cervical HPV infection. A group of women cured of high-grade lesions have ongoing anal HPV infection. It is reasonable to propose that detecting anal HPV could impact the patient's treatment process. Therefore, prospective studies are needed to investigate this group of women's clinical outcomes and define the clearance rate of cervical HPV infection when anal HPV persists.

Detection rate and clinical characteristics of vulvar squamous intraepithelial lesion

Objective: To explore the detection rate, clinical characteristics of vulvar squamous intraepithelial lesion (SIL). Methods: Women diagnosed with vulvar high-grade squamous intraepithelial lesions (HSIL) through colposcopy-guided biopsy from January 1, 2018 to August 31, 2022 in Obstetrics and Gynecology Hospital of Fudan University were included in a 1∶1 ratio with patients diagnosed with vulvar low-grade squamous intraepithelial lesions (LSIL) during the same period. Clinical characteristics including human papillomavirus (HPV) infection rate, genotype, cytology result, colposcopy impression, and lesion location were retrospectively analyzed. Results: (1) The proportion of vulvar SIL detected by colposcopy-guided biopsy increased annually from 2018 to 2022, with rates of 1.64% (740/45 057), 2.34% (1 110/47 402), 2.68% (1 108/41 335), 3.26% (1 536/47 078), 3.31% (667/20 155), with an average rate of 2.57% (5 161/201 027). (2) A total of 1 096 cases of vulvar HSIL and 1 096 cases of vulvar LSIL were included. The overall infection rate of HPV was 92.7% (1 993/2 150), with higher infection rate in vulvar HSIL patients than that in vulvar LSIL patients [96.0% (1 012/1 054) vs 89.5% (981/1 096); χ2=33.62, P<0.001]. Among vulvar HSIL patients, the common HPV genotype from high to low were HPV 16 (66.7%), HPV 52 (14.3%), and HPV 58 (10.0%). For vulvar LSIL patients, the most common HPV genotype were respectively HPV 16 (24.9%), HPV 6 (20.1%) and HPV 52 (17.1%). The overall sensitivity rate of cytology was 53.6%, with no significance difference between vulvar LSIL and HSIL groups (54.3% vs 52.9%; χ2=0.40, P=0.526). The accuracy of colposcopy impression for vulvar HSIL was lower than that for vulvar LSIL [40.2% (163/405) vs 81.7% (380/465); χ2=158.72, P<0.001]. About 57.3% (1 257/2 192) of the patients had concomitant cervical and vaginal lesions, with a higher rate in vulvar HSIL group than that in vulvar LSIL group [62.6% (686/1 096) vs 52.1% (571/1 096); χ2=24.67, P<0.001]. Unifocal lesion was the main type, with no significance difference between vulvar LSIL and HSIL groups [81.4% (381/468) vs 82.5% (386/468); χ2=0.18, P=0.671]. The most common lesion locations were the posterior commissure, followed by labia minora, vaginal vestibule, labia majora, perianal and clitoris. Conclusions: The detection rate of vulvar SIL under colposcopy is about 3%, and the infection rate of HPV is 92.7%. Vulvar SIL, especially vulvar HSIL, is likely to cause concomitant cervical and vaginal lesions. The accuracy of colposcopy in diagnosing vulvar HSIL is low. Therefore a comprehensive and careful examination of the vulva is necessary and suspicious vulvar lesions should be undergone colposcopy-guided biopsy for diagnosis.

Detection of DNA Methylation in Gene Loci ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671 for Diagnosis of Cervical Cancer.

To evaluate the diagnostic value of DNA methylation detection of multiple gene loci in cervical cancer. A total of 61 cases requiring cervical biopsy were selected from the outpatient clinic of Maternal and Child Health Hospital of Hubei Province between January 2018 and December 2019. The patients were divided into four groups based on histopathologic diagnosis: cervical cancer (CC) group, high-grade squamous intraepithelial lesion (HSIL) group, low-grade squamous intraepithelial lesion (LSIL) group, and control group. HPV examination, liquid-based cytology examination, and DNA methylation detection at multiple gene sites were performed. The positive rate of DNA methylation, sensitivity, specificity, area under the curve (AUC), and other efficacy indexes were calculated to evaluate the diagnostic value of DNA methylation detection at multiple gene loci in cervical cancer. The positive rates of DNA methylation in CC, HSIL, LSIL, and control groups were 100%, 88%, 83% and 17%, respectively. The ZNF671 gene had the highest positive rate among the cervical lesion group, with rates of 57%, 76%, and 100% in LSIL, HSIL, and CC groups respectively. The combination of DNA methylation detection at multiple gene loci showed the highest diagnostic efficacy for HSIL and cervical cancer, with AUC value of 0.850 (95% CI:0.746-0.954), a Youden index of 0.654, and a sensitivity and specificity of 85% and 85.4%, respectively. The diagnostic efficacy of the combined detection was significantly higher than that of HPV examination and liquid-based cytology examination (P < 0.05). DNA methylation detection at multiple gene loci is highly effective and diagnostic tool for cervical cancer, and has potential application value in clinical practice.

Value of p16 Expression in the Detection of High-Grade Squamous Intraepithelial Lesion of Cervix

Background: Cervical intraepithelial neoplasia (CIN) is usually a precancerous condition but, if left untreated, can develop into invasive cervical cancer. CIN2 and CIN3 are combinedly termed high-grade squamous intraepithelial lesions (HSIL). There are few screening tests based on cytology in detecting HSIL, but they are mostly less accurate. There is over-expression of p16 in pre-cancer and cancer of the cervix. The purpose of this study was to determine the value of p16 expression in the detection of HSIL. Methods: It was a cross-sectional study conducted in the colposcopy clinic of the Department of Obstetrics and Gynecology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from October 2021 to March 2022. The study included 72 HSIL patients detected by colposcopy and had subsequent cervical biopsy and p16 immunohistochemistry. Results: Majority (45.8%) of the patients were found within the 30-39 years age group, 44.4% of the participants were illiterate, and 76.4% came from the middle-income group. Colposcopy-directed cervical Punch or Loop electrosurgical excision procedure (LEEP) biopsy revealed that 70.5% of patients had HSIL, and the rest (64.3%) suffered from LSIL. Positive p16 results were significantly higher among the HSIL group (84.1%) compared to those other than the HSIL group (3.6%) (p&lt;0.001). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the p16 in the detection of HSIL were 84.1%, 96.4%, 79.4%, and 88.9%, respectively. Conclusions: Immunohistochemistry for p16 has a high diagnostic value in detecting HSIL patients. Therefore, this could be recommended for appropriate management of patients with CIN to avoid misdiagnosis and the over or under-treatment.

Determining the relationship between serum acute phase reactants and cervical premalignant lesions: a cohort study.

Acute phase reactants play a role in the progression and prognosis of many malignant and premalignant tumors. This study investigated the diagnostic value of certain reactants as markers for cervical premalignant lesions. Despite advanced screening and vaccination programs, cervical cancer remains a serious health problem worldwide. We aimed to determine the possible relationship between premalignant cervical disease and serum acute phase reactant levels. This study included 124 volunteers who underwent cervical cancer screening. We divided the patients into three groups according to cervical cytology and histopathological findings as follows: no cervical lesion, low-grade neoplasia, or high-grade neoplasia. We included women aged 25-65 years with benign smear or colposcopy results, low- and high-grade squamous intraepithelial lesions. The benign group was based only on cytology findings, whereas the other groups were based on histopathology findings. Demographic data and serum albumin, fibrinogen, ferritin, and procalcitonin levels were evaluated in the three groups. We found significant differences among the three groups in terms of age, albumin level, albumin/fibrinogen ratio, and procalcitonin level. The regression analysis revealed lower serum albumin levels in the low- and high-grade squamous intraepithelial lesion groups compared with the benign group. This is the first study to evaluate the importance of serum inflammatory markers in cervical intraepithelial lesions. Our results indicate that serum albumin level, albumin/fibrinogen ratio, procalcitonin level, and neutrophil values differ among cervical intraepithelial lesions.

Relationship Between Immunohistochemical CD3, CD4, CD5, CD8, and PD1 Staining and Histopathological Diagnosis of Cervical Lesions in Patients With Abnormal Colposcopic Findings.

This study aimed to analyse the relationship between clinicopathological factors in cervical intraepithelial lesions and abnormal colposcopic findings. Thirty high-grade squamous intraepithelial lesion (HSIL) and thirty low-grade squamous intraepithelial lesion (LSIL) patients who underwent biopsy due to abnormal colposcopic findings were included in the study. The immunoreactivity of CD3, CD4, CD5, CD8, and PD-1 was analysed immunohistochemically in tumor-infiltrating lymphocytes (TILs) and stromal lymphocytes. In TILs, CD3, CD4, CD5, CD8, and PD-1 were highly stained in 20/30 (66.6%), 16/30 (53.3%), 15/30 (50.0%), 24/30 (80.0%), and 13/30 (43.3%) of the cases for the HSIL group, while 7/30 (23.3%), 4/30 (13.3%), 5/30 (16.6%), 9/30 (30.0%), and 5/30 (16.6%) were in the LSIL group, respectively. CD3, CD4, CD5, CD8, and PD-1 immunostainings for TILs were higher in the HSIL group (p=0.001, p=0.001, p=0.006, p˂0.001, p=0.024, respectively). Only PD-1 was significantly higher in lymphocytes in the stroma (p=0.001). CD3, CD4, and CD8 also show a positive correlation with the Ki-67 proliferation index. CD3, CD4, CD5, and CD8 may contribute to PD-1-mediated tumour control. Immunohistochemical staining plays a key role in evaluating the tumour microenvironment.

Expression of epithelial–mesenchymal transition markers in squamous cell carcinoma of the uterine cervix: A cross-sectional study

Background: Cervical cancer is the fourth most common cancer in women worldwide. Epithelial– mesenchymal transition (EMT) is a phenomenon related to carcinogenesis, which is characterized by morphological changes from neoplastic epithelial cells to mesenchymal cells, resulting in increased motility and invasiveness of neoplastic cells. To observe the expression of three EMT markers (cytokeratin 19 [CK1]), vimentin, and Ras homolog gene family member C [RhoC]) in individuals with a normal cervix, patients with high-grade squamous intraepithelial lesion (HSIL), and patients with squamous cell carcinoma (SCC) and determine the association with the histological grade and clinical/radiological stage of cervical cancer. Methods: Seventy participants were included in the study: 10 individuals with a normal cervix, 30 patients with HSIL, and 30 patients with newly diagnosed SCC. Immunohistochemistry for CK19, vimentin, and RhoC was performed in all groups. The association of the expressions of the three markers between the groups was analyzed. P values of &lt; 0.005 were considered statistically significant. Results: The mean age of the normal cervix, HSIL, and SCC groups was 46.2 ± 16.12, 49.10 ± 10.13, and 56.27 ± 9.29 years, respectively. CK19 showed a weak basal cell positivity in 80% of the individuals with a normal cervix. Meanwhile, 93.3% and 100% of the patients with HSIL and SCC, respectively, were positive for CK19; the association of the expressions between the groups was insignificant. Vimentin was negative in the normal cervix group and positive in the HSIL (33.3%) and SCC (73.3%) groups; the association of the expressions between the groups was significant. RhoC was positive in the normal cervix, HSIL, and SCC groups (10%, 20%, and 83.33%, respectively), and the association of the expressions between them was significant. There was no significant association found between the expression of vimentin or RhoC and the histopathological grade or FIGO stage. Conclusion: An increased expression of CK19 in patients with HSIL and SCC of the cervix highlights the role of basal cells in cervical carcinogenesis. The expression of vimentin and RhoC in individuals with a normal cervix and patients with HSIL and SCC indicates EMT.

Human papillomavirus (HPV) integration signature in cervical lesions: identification of MACROD2 gene as HPV hot spot integration site.

High-risk HPV is clearly associated with cervical cancer. Integration of HPV DNA into the host genome is considered a key event in driving cervical carcinogenesis. However, the mechanism on how HR-HPV integration influences the host genome structure has remained enigmatic. In our study, 25 DNA samples including 11 from fresh-frozen cervical carcinomas and 14 from fresh-frozen high-grade squamous intraepithelial lesion (HSILs) were detected using the method of HPV capture combined with next generation sequencing. We calculated the frequency in each viral gene or region and found that breakpoints were prone to occur in L1 and L2 instead of E2 in the cervical cancer (P = 0.0004 and P = 5.15 × 10-40) and HSIL group (P = 2.1 × 10-32 and P = 7.06 × 10-13). The results revealed that HPV16 showed a strong tendency toward intronic region (P = 5.02 × 10-64) but a subtle tendency toward intergenic region (P = 0.04). The most frequent integration site was in the MACROD2 gene (introns 2, 4, 5, 6, 8 and 9), which in MACROD2 functional domain. Our results revealed that MACROD2 is HPV hot spot integration site in cervical lesions, and its deficiency alter DNA repair and sensitivity to DNA damage thought impaired PARP1 activity resulting in chromosome instability.

The Human Papillomavirus Infection Characteristics for Patients with Cervical Intraepithelial Neoplasia in Yunnan, China: A Sampling Survey Analysis.

ObjectiveThis study aimed to analyze the status of human papillomavirus (HPV) infections in women in Yunnan in the south of China and their correlation with the grade of cervical intraepithelial neoplasia (CIN).MethodsA total of 281 patients with CIN and HPV infection, diagnosed at Kunming Kingmed Institute for Clinical Laboratory between January 2019 and June 2021, were enrolled as the subjects of the study and underwent HPV genotyping and cervical histopathology.ResultsThe mean age of the 281 patients was 42.3 years, and the median age was 42 years. There were 79 patients in the low-grade squamous intraepithelial lesion (LSIL) group, and 202 patients in the high-grade squamous intraepithelial lesion (HSIL) group. The proportion of 30–45 years old in HSIL group was 58%. Overall, single infections accounted for 76%, and HR-HPV infections accounted for 90.1%. The most common HR-HPV subtypes in the two CIN groups were almost the same, including HPV16, HPV58 and HPV52. The most common LR-HPV subtype in the two CIN groups was HPV43. There were no significant differences in ethnic and single or multiple infection rates among different CIN groups. Single infection of HPV43 and HPV81 was found in minority HSIL patients.ConclusionHPV infection in Yunnan was dominated by single infection and HR-HPV. Patients aged 30 to 45 years were in the high incidence of HSIL, and the most common HR-HPV subtypes were HPV16, HPV58, and HPV52. Single LR-HPV infection exists in minority HSIL patients.

Does mode of delivery impact the course of cervical dysplasia in pregnancy? A review of 219 cases

ObjectiveThe prevalence of cervical intraepithelial neoplasia (CIN) in pregnancy is about 1%.The aim of this study was to analyze the regression, persistence and progression rates of cervical dysplasia in pregnancy and the impact of delivery mode. Study designIn this retrospective study, data from pregnant patients with abnormal cytology findings, who presented to a colposcopic outpatient clinic of a university hospital within the last 10 years, were analyzed. Information on cytology, histology and Human Papillomavirus (HPV) status during pregnancy and postpartum and mode of delivery was collected. Results219 women, who were assessed with cytology and /or biopsy antepartum and postpartum between January 2010 and July 2020, were included in the study. Antepartum patients presented with low grade squamous intraepithelial lesions (LSIL) in 37% and high grade squamous intraepithelial lesions (HSIL) in 53%. During pregnancy biopsy was performed in 78 patients (36%). Postpartum evaluation revealed an overall regression rate of 39%. Persistence rates were especially high in the HSIL group with 70 %. HSIL regressed in 28 %. Progression to invasive disease was rare and seen in two patients postpartum only. 141 women delivered vaginally (VD) and 51 received a cesarean section (CS). Regression rates were similar: 36 % and 47 %. There was no significant difference in progression or persistence rates. ConclusionOur study demonstrates that mode of delivery does not influence the course of SIL. SIL show high rates of regression and persistence, progression to invasive disease is rare.

Analysis of Distributions of HPV Infection in Females with Cervical Lesions in the Western District of Beijing Chaoyang Hospital.

Objective To analyze the distribution of human papilloma virus (HPV) infection in women with cervical lesions of different grades and analyze the relationship of high-risk HPV and cervical lesions in order to facilitate targeted prevention. Methods The infection status of HPV subtype was statistically analyzed in patients who underwent colposcopy examination from April 2017 to June 2019. Results The infection rate of HPV was 81.4% in chronic cervicitis, 82.9% in 1ow-grade squamous intraepithelial lesion (LSIL), 63.7% in HSIL (high-grade squamous intraepithelial lesion), and 50% in cervical squamous cell carcinoma (CSCC). Among the 16 high-risk HPV types, the top six HPV types with the comprehensive infection rates were HPV16 > HPV52 > HPV58 > HPV18 > HPV51 > HPV53 in turn, and the infection rates were 23.3%, 14.8%, 13.3%, 9.8%, 9.2%, and 8.8%, respectively. The infection rates of HPV16 in chronic cervicitis group, LSIL group, and HSIL group were significantly different. There was no significant difference in the injection rates of HPV52, HPV58, and HPV18 among the three groups. HPV infection rates were highest in the 31–40 years old group, followed by the 41–50 years old group. Conclusion The distribution of different types of HPV varies in different tissue types, which can be used to develop relevant vaccines to achieve better prevention and treatment of cervical cancer.

The Role of IL-2, IL-4, IL-10 and IFN-&amp;lt;i&amp;gt;γ&amp;lt;/i&amp;gt; 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.

Expression of fascin in association with p16 and Ki-67 in cervical lesions: immunohistochemical study Expression of fascin in association with p16 and Ki-67 in cervical lesions: immunohistochemical study

Annual gynecological examination with cervical cancer screening and HPV vaccination ensures the appropriate prevention of the onset and progression of cervical cancer. Currently, efforts are being made to find new diagnostic and prognostic biomarkers. Fascin, an actin-bundling protein, promotes cellular migration. Its overexpression has been observed in many types of squamous carcinomas and was usually correlated with aworse prognosis and metastasis. However, the data on fascin expression in cervical lesions are limited. This study focuses on the quantitative evaluation of fascin expression, the immunoreaction intensity and subcellular localization of fascin expression in low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinomas (SCC). Fascin expression was also correlated with the routinely used diagnostic markers p16 and Ki-67. Biopsy specimens (n = 67) of LSIL, HSIL and SCC were taken from adult women in the age range 20-86 years. Fascin expression was detected by immunohistochemical analysis and quantified using morphometric software. Analysis of variance confirmed statistically significant differences in the percentage of fascin-positive cells between the LSIL, HSIL and SCC groups. Finally, the results showed asignificant positive correlation between fascin expression and p16 and Ki-67 expression.

Evaluation of dynamic thiol-disulfide balance in preinvasive lesions of the cervix.

This study aimed to determine the potential clinical use of dynamic thiol-disulfide balance in cases with preinvasive lesions of the cervix. One hundred and sixteen patients with high-grade squamous intraepithelial lesion, 100 patients with low-grade squamous intraepithelial lesion, and 110 healthy controls were enrolled in the study. A fully automated colorimetric system was used to determine the levels of thiol-disulfide parameters. The ischemia-modified albumin, total oxidant-antioxidant capacity, and oxidative stress index of the retrieved cases were further analyzed. Native thiol and total thiol levels are significantly lower in the high-grade squamous intraepithelial lesion group according to control group (p: 0.004 and 0.015, respectively). Disulfide level is significantly increased in the high-grade squamous intraepithelial lesion group compared to control group (p: 0.004). Oxidative stress index levels in high-grade squamous intraepithelial lesion group were observed as significantly higher according to the control group (p: 0.014). Ischemia-modified albumin levels in the high-grade squamous intraepithelial lesion group were observed as significantly higher compared to the control group (p: 0.020). Disulfide levels are positively correlated with risk type of Human papillomavirus (r: 0.420, p < 0.001). The analysis of dynamic thiol-disulfide balance revealed considerable oxidative damage in patients with Human papillomavirus-related cervical precursor lesions compared to women with ordinary cytology specimens. Therefore, investigation of thiol-disulfide balance with presented method represents a new promising test for early diagnosis and management of women at high risk for cervical cancer.

Identification of autophagy-associated miRNA signature for the cervical squamous cell cancer and high-grade cervical intraepithelial lesions

Cervical cancer markedly threatens women's health worldwide and currently ranks fourth leading cause of cancer mortality in women according to recent global cancer statistics. Recent advances have proven that not only tumor suppressor and oncogenes but also non-coding RNAs including micro RNAs (miRNAs) have significant impact in the development and progression of cervical cancers. Previous studies have identified many cancer-specific miRNAs for the early detection of cervical cancers. However, the diagnostic and prognostic use of autophagy-associated miRNAs for the cervical squamous cell cancer (SCC) cases and high-grade squamous intraepithelial lesion (HSIL) have not been uncovered. In the present study, we revealed that miRNAs are differentially expressed in both cervical SCC and HSIL. A total of 35 HSIL, 35 cervical SCC and 30 healthy controls were enrolled for the present study. Total RNA including miRNAs were isolated from the FFPE tissue samples and miRNA expression levels were quantified by quantitative PCR. Predicted miRNA targets of autophagy related genes were determined using miRNA-target prediction algorithms. MiR-143, miR-372, miR-375 and miR-30c were markedly downregulated in HSIL and cervical SCC. MiR-130a was significantly upregulated in the cervical SCC group compared to HSIL and control groups. MiR-30a, miR-520e, miR-548c and miR-372 were significantly associated with the overall survival of cervical SCC patients and these miRNAs were determined to be significant diagnostic markers as revealed by ROC analysis. Together, these results indicate that autophagy-associated miRNAs are potentially valuable for the differential diagnosis and targeted therapy to cervical cancer.

Correlation between melatonin concentration and cytokines in cervical mucus in positive samples for the presence of human papillomavirus.

The human papillomavirus (HPV) is the main causative agent of cervical cancer, characterized by neoplastic lesions in the cervix. Based on the morphology of the cells of the uterine cervix, the findings are classified as negative intraepithelial lesions for malignancies, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions (HSILs), atypical squamous cells of undetermined significance and atypical squamous cells of undetermined significance without excluding HSILs (ASCs-H). The progression of neoplastic lesions is related to the cervix's microenvironmental inflammatory process and mediated by the expression and stimulation of cytokines. Cervical mucus is a viscous liquid secretion composed of proteins, inorganic components, pro-and anti-inflammatory agents, and an important protective barrier. This study aimed to quantify and correlate cytokines IL-6, IL-8, and IL-10 and Melatonin in cervical mucus. According to the results, a decrease in MLT was observed in LSIL, HSI, and ASC-H groups than in the NILM group. The cytokines IL-6 and IL-8 showed greater expression in the LSIL and HSIL groups than the NILM group. HSIL group showed a negative correlation between the MLT and IL-6 and IL-8 concentrations. In the ASC-US group, IL8 level was positively correlated to MLT levels. We suggest that IL-6, IL-8, and MLT levels in HSIL groups are decisive for the progression of neoplastic lesions in HPV infections. New cervical cancer treatment strategies may include cytokine and melatonin control targets for effective immunotherapy.

A prospective study of photodynamic therapy for cervical squamous intraepithelial lesion

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

Association Between Vulvar Squamous Intraepithelial Lesions and Psychiatric Illness.

The aims of the study were to describe and to compare demographics and the prevalence of psychiatric disorders among patients with low- and high-grade vulvar squamous intraepithelial lesions. A retrospective chart review was performed for patients presenting to a vulvar diseases clinic between 1996 and 2019 (N = 2,462). Intake questionnaire data were entered into a deidentified database. Results were compared between 80 patients with biopsy-confirmed high-grade squamous intraepithelial lesions (HSILs) and 48 patients with biopsy-confirmed low-grade squamous intraepithelial lesions (LSILs). Bivariate analysis was performed to compare demographics and psychiatric treatment and outcomes across HSIL and LSIL groups. Among 128 patients with vulvar disease, 80 (62.5%) had HSILs and 48 (37.5%) had LSILs. Patients with HSILs were significantly older (HSIL median [interquartile range] = 49.0 (39.0-61.0) vs LSIL = 36.0 [29.0-53.0], p = .006). There were no significant differences between groups across race/ethnicity, education, marital status, or self-reported household income categories. Forty percent of HSIL patients reported depression compared with 20.8% of LSIL patients (p = .03), whereas 31.3% of HSIL patients and 8.3% of LSIL patients reported anxiety (p = .002). Bipolar disorder was reported in 3.8% of HSIL patients and no LSIL patients (p = .29). There were no differences in the proportion of patients receiving psychiatric counseling, medications, or hospitalizations between groups. Squamous intraepithelial lesions of the vulva are associated with psychiatric disorders above age-matched national averages; these disorders are more prominent in the HSIL group. Combining mental health services with ongoing disease treatment seem to be part of a comprehensive approach to caring for this patient population.

Application of p16, p63, cyclin D1 immunostaining and nuclear morphometric analysis for assessment of cervical dysplasia

Background/Aim. Human papilloma virus (HPV) infection is the main etiological factor for the development of cervical precancerous dysplastic squamous intraepithelial lesions (SIL). The virus oncoproteins affect several proteins included in cell proliferation. The aim of this study was to evaluate application of immunohistochemical markers related to proteins of the cell cycle and, also, application of nuclear morphometric analysis for assessment of cervical dysplasia. Methods. Retrospective study included 78 women with detection of presence of high-risk HPV by polymerase chain reaction (PCR), with histopathology diagnosis low-grade SIL (LSIL) or high-grade SIL (HSIL). Immunohistochemical staining for p16, p63, cyclin D1 and morphometric analysis of the nuclear surface area were performed. The control group consisted of ten women without SIL and without HPV infection. This study was conducted in accordance with the Helsinki Declaration. Results. Comparing immunohistochemical expression of p16 and p63, highly statistically significant differences (p &lt; 0.001) were established among the control, LSIL and HSIL groups, while cyclin D1 showed significant statistical difference (p &lt; 0.05). Great variations were observed in nuclear morphology and nuclear surface area that had highly statistically significant differences (p &lt; 0.001) among the control, LSIL and HSIL groups. Conclusion. This study demonstrated that immunohistochemical analysis of p16, p63 and cyclin D1 are important for diagnosis of dysplastic changes in cervical epithelium. Also, morphometric analysis of the nuclear surface area demonstrated a high significance for diagnosis of cervical dysplasia.