Objective: To explore the relationship between the expression of the T-cell activation suppressor-immunoglobulin variable region (VISTA) and the development of cervical squamous cell carcinoma (CSCC), and the impact on the prognosis of CSCC patients. Methods: Cervical tissue samples from 116 CSCC, including 23 cervical intraepithelial neoplasia (CIN) grade I, 23 CIN grade Ⅱ-Ⅲ, and 23 chronic cervicitis patients, were collected from the First Hospital of Soochow University between March 2014 and April 2019. The expression of VISTA in each group was detected by immunohistochemistry (IHC). Survival data of CSCC patients were obtained by follow-up. The survival analysis was performed by Kaplan-Meier method, and survival differences between groups were compared by Log rank test. Prognostic impact factors were analyzed using a multifactorial Cox proportional hazards model. Results: The positive rate of VISTA expression in CSCC group was 32.8% (38/116), and which of grade Ⅱ-Ⅲ was 17.4% (4/23). VISTA expression results showed no positive expression patients in the cervical intraepithelial neoplasia grade I and chronic cervicitis groups. The differences between the CSCC group and other groups were statistically significant (P<0.01). In 116 CSCC patients, VISTA expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis (P<0.01). The mean survival time of patients in the VISTA positive expression group was 30.7 months, and the 3-year survival rate was 44.7% (17/38). However, the mean survival time of the patients in the VISTA negative expression group was 49.1 months, and the 3-year survival rate was 87.2% (68/78). The Cox regression model found that VISTA expression positivity (P=0.001) and FIGO stage (P=0.047) were prognostic factors for CSCC, and patients with VISTA-positive CSCC had a 4.130-fold risk of death higher than those with VISTA-negative expression. Conclusions: The VISTA protein is highly expressed in CSCC tissues, and its expression level is closely related to the occurrence and development of CSCC. The expression of VISTA can be used as an independent predictor of CSCC prognosis and can provide a strong basis for the treatment of CSCC with immune checkpoint inhibitors.
Female ; Humans ; Carcinoma, Squamous Cell/pathology* ; Clinical Relevance ; Neoplasm Staging ; Prognosis ; Uterine Cervical Dysplasia/pathology* ; Uterine Cervical Neoplasms/pathology* ; Uterine Cervicitis/pathology*

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ²=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ²=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.
Female ; Humans ; Adult ; Middle Aged ; Cervix Uteri/pathology* ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections/diagnosis* ; Cell Wall Skeleton ; Persistent Infection ; Powders ; Uterine Cervical Dysplasia/pathology* ; Immunotherapy ; Papillomaviridae

Adenocarcinoma ; pathology ; Adult ; Aged ; Carcinoma in Situ ; pathology ; Carcinoma, Squamous Cell ; pathology ; Cervical Intraepithelial Neoplasia ; pathology ; Cervix Uteri ; pathology ; Early Detection of Cancer ; Female ; Humans ; Middle Aged ; Uterine Cervical Dysplasia ; pathology ; Uterine Cervical Neoplasms ; pathology ; Vaginal Smears ; classification ; Young Adult

OBJECTIVETo evaluate the performance of computer-assisted imaging system in the detection of cervical squamous intraepithelial lesion and quality-assurance.

METHODSManual PAP screening (n = 140 580) and image-assisted screening (n = 32 885) were compared for the detection rates of squamous cell abnormalities, the atypical squamous cells (ASC) to squamous intraepithelial lesion (SIL) ratio, the positive rates of high risk human papillomavirus (HR-HPV) test in the case of atypical squamous cells of undetermined significance (ASC-US), and the correlation between cytopathology and histopathology.

RESULTSCompared with manual screening, computer-assisted imaging system showed increased overall positive detection by 0.32%, decreased detection of ASC by 0.21%, increased detection of low-grade squamous intraepithelial lesion (LSIL) by 0.22%, increased detection of high-grade squamous intraepithelial lesion or worse (HSIL) by 0.31%, and decreased ASC to SIL ratio from 2.59 to 1.60. Computer-assisted imaging system did not change the HR-HPV positive rate of the patients who were ASC-US, or the coincidence rate between cytopathology and histopathology. Moreover, the productivity of the laboratory operation increased 58.33%.

CONCLUSIONComputer-assisted imaging system significantly increases the overall positive detection rate of cervical SIL, improves accuracy and work efficiency of screening, decreases the ASC/SIL rate, and strengths the quality-assurance of laboratory testing.

Carcinoma, Squamous Cell ; pathology ; Cervical Intraepithelial Neoplasia ; pathology ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Papillomaviridae ; isolation & purification ; Papillomavirus Infections ; pathology ; Uterine Cervical Dysplasia ; pathology ; Uterine Cervical Neoplasms ; pathology ; Vaginal Smears ; methods

Objective: To investigate the natural regression and related factors of high-grade squamous intraepithelial lesion (HSIL) in the cervix of childbearing age women, and to evaluate the applicability of conservative management for future fertility needs. Methods: This study included 275 patients of reproductive age with fertility needs, who were diagnosed as HSIL by biopsy from April 30, 2015 to April 30, 2022, including 229 cases (83.3%) cervical intraepithelial neoplasia (CIN) Ⅱ and 46 cases (16.7%) CIN Ⅱ-Ⅲ. They were followed-up without immediate surgery in the First Affiliated Hospital of Nanjing Medical University. The median follow-up time was 12 months (range: 3-66 months). The regression, persistence and progression of lesions in patients with HSIL were analyzed during the follow-up period, the influencing factors related to regression and the time of regression were analyzed. Results: (1) Of the 275 HSIL patients, 213 cases (77.5%, 213/275) experienced regression of the lesion during the follow-up period. In 229 CIN Ⅱ patients, 180 cases (78.6%) regressed, 21 cases (9.2%) persisted, and 28 cases (12.2%) progressed. In 46 CIN Ⅱ-Ⅲ patients, 33 cases (71.7%) regressed, 12 cases (26.1%) persisted, and 1 case (2.2%) progressed to invasive squamous cell carcinoma stage Ⅰ a1. There was no significant difference in the regression rate between the two groups (χ²=1.03, P=0.309). (2) The average age at diagnosis, age <25 years old at diagnosis were independent influencing factor of HSIL regression in univariate analysis (all P<0.05). There was no significant difference between HSIL regression and pathological grading, the severity of screening results, human papillomavirus (HPV) genotype, colposcopy image characteristics, number of biopsies during follow-up and pregnancy experience (all P>0.05). (3) The median regression times for patients aged ≥25 years and <25 years at diagnosis were 15 and 12 months, respectively. Kaplan-Meier analysis showed that age ≥25 years at diagnosis significantly increased the median regression time compared to <25 years (χ²=6.02, P=0.014). Conclusions: For HSIL patients of childbearing age, conservative management without immediate surgical intervention is preferred if CINⅡ is fully evaluated through colposcopy examination. Age ≥25 years at diagnosis is a risk factor affecting the prognosis of HSIL patients.
Pregnancy ; Humans ; Female ; Adult ; Cervix Uteri/pathology* ; Uterine Cervical Neoplasms/pathology* ; Uterine Cervical Dysplasia/pathology* ; Biopsy ; Colposcopy/methods* ; Squamous Intraepithelial Lesions/pathology* ; Carcinoma in Situ/pathology* ; Papillomaviridae/genetics* ; Papillomavirus Infections/diagnosis* ; Squamous Intraepithelial Lesions of the Cervix/pathology*

OBJECTIVE: To evaluate of liquid based cytology test (LCT) in avoiding medical tangles. METHODS: One thousand five hundred five thirty one cases, which were collected from out-patients of precancerous lesions of uterine cervix, were randomly divided into three groups based on different smear preparation: LCT method was used in two groups (one with ThinPrep kit and one with ArtoBrain kit), conventional Papauicolaou smear (PS) was used in one group. All cases of abnormal cervical smears were identified by cytologic test underwent colposcopic examination and colopscopically multiple biopsy. Results of test were analyzed by software SPSS 11.0. RESULTS: Significant diference were found between LCT method and PS method compared by index of satifacation, sensitivity, specificity, accuracy, false negative rate and erroneous diagnosis rate (P < 0.05, but no difference were found between two LCT groups (ThinPrep kit and ArtoBrain kit). CONCLUSION LCT method can improve diagnostic level of precancerous lesions of uterine cervix either tested by ThinPrep kit or ArtoBrain kit, so have the powerfull value to avoid medical tangles.
Adult ; Aged ; Biopsy/methods* ; Carcinoma, Squamous Cell/pathology* ; Cervix Uteri/pathology* ; Female ; Humans ; Mass Screening/methods* ; Medical Errors/prevention & control* ; Middle Aged ; Sensitivity and Specificity ; Uterine Cervical Neoplasms/pathology* ; Vaginal Smears/methods* ; Young Adult ; Uterine Cervical Dysplasia/pathology*

Objective: To explore the relationship between abnormal expression of fragile histidine triad (FHIT) gene and methyl-CpG-binding protein 2 (MeCP2) as well as their interaction on cervical cancerization. Methods: A total of 73 patients with cervical squamous cell carcinoma (SCC), 113 patients with cervical intraepithelial neoplasia (CIN Ⅰ, n=45; CINⅡ/Ⅲ, n=68) and 60 women with normal cervix (NC) were included in the study. Real time PCR and Western blot were performed to detect the expression levels of mRNA and protein about FHIT and MeCP2, respectively. The methylation status of FHIT gene CpG island was tested by methylation-specifc PCR (MSP). Kruskal-Wallis H test, χ(2) test, trend χ(2) test and Spearman correlation analysis were conducted with software SPSS 20.0. The interaction was evaluated by generalized multifactor dimensionality reduction (GMDR) model. Results: With the deterioration of cervical lesion, the methylation rates of FHIT gene CpG island (χ(2)=18.64, P<0.001; trend χ(2)=18.08, P<0.001) increased gradually, while the expression levels of FHIT mRNA (H=27.32, P<0.001; trend χ(2)=12.65, P<0.001) and protein (H=47.10, P<0.001; trend χ(2)=29.79, P<0.001) decreased gradually. There was a negative correlation between the methylation rates of FHIT gene CpG island and the expression level of FHIT protein (r=-0.226, P<0.001). The levels of MeCP2 mRNA (H=26.19, P<0.001; trend χ(2)=11.81, P=0.001) and protein (H=69.02, P<0.001; trend χ(2)=47.44, P<0.001) increased gradually with the aggravation of cervical lesions. There was a positive correlation between the expression level of MeCP2 protein and the FHIT mRNA Ct ratio (r=0.254, P<0.001). Expression of proteins were negatively correlated between MeCP2 and FHIT (r=-0.213, P=0.001). The results analyzed by GMDR model showed that there were interactions among high MeCP2 protein expression, the CpG island methylation of FHIT and mRNA and protein expression in CINⅡ/Ⅲ group, and among high MeCP2 mRNA and protein expression, the CpG island methylation of FHIT and low mRNA and protein expression in SCC group. Conclusion: High expression of MeCP2 mRNA and protein, the CpG island methylation and low mRNA and protein expression of FHIT could increase the risk of cervical carcinogenesis, and there might be a synergistic effect on cervical carcinogenesis.
Acid Anhydride Hydrolases/metabolism* ; Carcinoma, Squamous Cell/pathology* ; DNA Methylation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Methyl-CpG-Binding Protein 2/metabolism* ; Neoplasm Proteins/metabolism* ; Polymerase Chain Reaction/methods* ; RNA, Messenger ; Uterine Cervical Neoplasms/pathology* ; Uterine Cervical Dysplasia/pathology*

The aim of this study was to evaluate the occurrence of genital mycoplasmas, especially Ureaplasma parvum and Ureaplasma urealyticum, in women with atypical squamous cells of undetermined significance (ASCUS), low grade squamous intraepithelial lesions (LSIL) and high grade squamous intraepithelial lesions (HSIL), compared to women with normal cytology living in Katowice, Poland. Two sterile swabs were used to obtain material from the posterior vaginal fornix of 143 women with squamous intraepithelial lesions and 39 healthy women: first for general bacteriology, second for detection of urogenital mycoplasmas using Mycoplasma IST2 kit. From each positive Mycoplasma IST2 culture DNA was isolated and PCR was performed for identification of U. parvum and U. urealyticum. Mycoplasma IST was positive in 34.1% cases. Urogenital mycoplasmas were demonstrated in women with HSIL significantly more often compared to women with LSIL, ASCUS, and with normal cytology. DNA of U. parvum was demonstrated in majority of Mycoplasma IST2-positive cases, U. urealyticum DNA-only in 9 (4.9%). Predominance of 3/14 serovars of U. parvum was demonstrated. U. urealyticum biovar 2 was present more often in women with squamous intraepithelial lesions.
Adult ; Animals ; Female ; Humans ; Male ; Poland/epidemiology ; Pregnancy ; Ureaplasma/*genetics ; Ureaplasma Infections/epidemiology/*microbiology ; Ureaplasma urealyticum/*genetics ; Uterine Cervical Dysplasia/*microbiology/pathology

OBJECTIVETo investigate the clinical significance of atypical squamous cells of unknown significance (ASCUS) with abnormal DNA ploidy in the early diagnosis of cervical lesions.

METHODSEight thousand four hundred and forty-eight patients were included in this study and all had DNA quantitative analysis and cervical liquid-based cytology. Among 1041 cases with DNA aneuploidy and/or abnormal cervical liquid-based cytology and additional cervical biopsy, histological review was performed in 247 ASCUS cases with abnormal DNA ploidy.

RESULTS(1) Among 8448 cases, 7877 were normal or benign, 426 were ASCUS, 45 were ASC-H, 55 were LSIL and 22 were HSIL by TBS diagnosis. The presence of 1-2 abnormal DNA ploidy cells was detected in 15.3% (65/426) of ASCUS, 11.1% (5/45) of ASC-H, 9.1% (5/55) of LSIL, and 0 (0/22) of HSIL. The presence of ≥ 3 abnormal DNA ploidy cells was detected in 39.0% (166/426) of ASCUS, 75.6% (34/45) of ASC-H, 76.4% (42/55) of LSIL, and 95.5% (21/22) of HSIL. (2) A total of 67 cases of CIN 2, CIN 3 or cancers were found in 247 patients with ASCUS by colposcopy biopsies, of which 13.9% (5/36) had 1-2 abnormal DNA ploidy cells, 45.5% (56/123) had ≥ 3 abnormal DNA ploidy cells and 6.8% (6/88) had normal DNA polidy. ASCUS with 1-2 abnormal DNA ploidy cells and with ≥ 3 abnormal DNA ploidy cells were compared. The difference was statistically significant (χ(2) = 11.79, P < 0.01). But the difference between ASCUS with 1-2 abnormal DNA ploidy cells and normal DNA ploidy had no statistical significance (P > 0.05).

CONCLUSIONSASCUS with ≥ 3 abnormal DNA ploidy cells has higher risk for developing CIN 2, CIN 3 or invasive carcinoma. The application of DNA quantitative analysis and cervical liquid-based cytology test can help in guiding clinical follow-up and treatment options in patients with ASCUS.

Adenocarcinoma ; diagnosis ; genetics ; pathology ; Adolescent ; Adult ; Aged ; Aneuploidy ; Carcinoma in Situ ; diagnosis ; genetics ; pathology ; Carcinoma, Squamous Cell ; diagnosis ; genetics ; pathology ; Cervical Intraepithelial Neoplasia ; diagnosis ; genetics ; pathology ; Colposcopy ; DNA, Neoplasm ; genetics ; Female ; Humans ; Middle Aged ; Uterine Cervical Dysplasia ; diagnosis ; genetics ; pathology ; Uterine Cervical Neoplasms ; diagnosis ; genetics ; pathology ; Young Adult

OBJECTIVETo investigate the value of computer-assisted slide-screening system (ThinPrep imaging system, TIS) in the diagnosis of cervical Thinprep smears.

METHODSA total of 19 600 ThinPrep smears were collected, including 9800 slides by TIS-assisted screening from September 2011 to March 2012 and 9800 slides by manual screening from September 2010 to April 2011 as control. The detection rates of abnormal cells and common microbial infection by the different screening methods were compared. With histopathological diagnosis of colposcopic biopsy as the gold standard, the screening efficiency and correlation of cytologic diagnosis among different screening methods were analyzed.

RESULTSCompared with manual screening, the detection rate of abnormal cells in 9800 cases by TIS-assisted screen was increased from 5.4% (525/9800) to 6.8% (665/9800), mainly in the categories of ASCUS and LSIL (P < 0.05). TIS had a higher accordance rate between cytologic diagnosis and histopathological diagnosis in the NILM and ASCUS than that by manual screening. False-negative rate of finding abnormal cells by TIS decreased from 8.5% (17/200) to 0.7% (2/289, P < 0.01) with an increased sensitivity compared to manual screening, although the specificity was similar. Both TIS and manual screening had advantages and disadvantages respectively in the detection of microbial organisms. TIS improved screening efficiency by 50%.

CONCLUSIONTIS improves not only the screening efficiency but also the detection of abnormal cells with a reduced false negativity, and it therefore has a broad application prospect.

Adenocarcinoma ; diagnosis ; pathology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Candida ; isolation & purification ; Carcinoma, Squamous Cell ; diagnosis ; pathology ; Cervical Intraepithelial Neoplasia ; diagnosis ; pathology ; Cytodiagnosis ; False Negative Reactions ; Female ; Humans ; Image Processing, Computer-Assisted ; instrumentation ; Mass Screening ; Middle Aged ; Sensitivity and Specificity ; Trichomonas vaginalis ; isolation & purification ; Uterine Cervical Dysplasia ; diagnosis ; pathology ; Uterine Cervical Neoplasms ; diagnosis ; pathology ; Vaginal Smears ; Young Adult