Associations of Single Versus Multiple Human Papillomavirus Infections With the Prevalence of Cervical Intraepithelial Neoplasia 2/3 and Squamous Cell Carcinoma Lesions: Human Papillomavirus Type-Specific Attribution.

The risk of developing cervical squamous lesions in women with multiple high-risk human papillomavirus (hrHPV) infections is uncertain. The aim of this retrospective study was to investigate the type-specific attribution and phylogenetic effects of single and multiple hrHPV subtypes in cervical squamous lesions. All cases with cervical histopathologic diagnosis and human papillomavirus (HPV) genotyping results in the 6 months preceding biopsy from October 2018 to December 2022 were studied and analyzed. Over the study period, 70,361 cases with histopathologic follow-up and prior HPV genotyping were identified. The hrHPV-positive rate was 55.6% (39,104/70,361), including single hrHPV detected in 27,182 (38.6%), 2 types of hrHPV detected in 8158 (11.6%), and 3 types of hrHPV detected in 2486 (3.5%). Among 16,457 cases with a histologically diagnosed squamous lesion (cervical intraepithelial neoplasia 1: 11411; cervical intraepithelial neoplasia 2/3: 4192; squamous cell carcinoma: 854 cases), the prevalence of single hrHPV infection increased, but the rate of multiple concomitant hrHPV infections showed negative association as the degree of squamous lesions increased. Among women with a single HPV16 infection, cervical intraepithelial neoplasia 2/3 and squamous cell carcinoma (CIN2+) diagnostic rate was 30.6%, and it increased to 47.6% when coinfected with HPV33 (P < .001) but significantly decreased when coinfected with all other hrHPV types (P < .05). By comparing CIN2+ diagnostic rates in 40 most common 2 types of hrHPV infections with related single hrHPV infection, CIN2+ rates were decreased in 12 combinations (30.0%), equivalent in 26 combinations (65.0%), and increased in 2 combinations (5.0%). The cases with 3 types of HPV infections reduced the risk for CIN2+ compared with related single HPV infections. HPV16+52+53, HPV16+52+68, HPV16+52+51, HPV16+39+52, and HPV16+58+53 significantly decreased the risk of CIN2+ compared with HPV16 single infection (P < .05). This study demonstrates that multiple hrHPV infections are not associated with cumulatively higher risk for CIN2+ development, suggesting that oncogenic progression of multiple hrHPV-associated cervical squamous lesions is neither synergistic nor a cumulative effect at the phylogenetic level, possibly a way of competitive interference.

Cervical Septum Incision Adversely Impacts Clinical Outcomes in Women with Complete Uterine Septum and Duplicated Cervix.

STUDY OBJECTIVE: To investigate the reproductive outcomes of women with complete septate uterus and duplicated cervix who either did or did not receive cervical septum incision during hysteroscopic transcervical incision of the uterine septum. DESIGN: Retrospective study approved by the hospital ethics committee. SETTING: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. PATIENTS: Women with complete septate uterus and duplicated cervix who underwent hysteroscopic transcervical incision of the uterine septum in Obstetrics and Gynecology Hospital of Fudan University between January 2008 and December 2020 (n = 105). INTERVENTIONS: Hysteroscopic incision of the septum. MEASUREMENTS AND MAIN RESULTS: Included patients were grouped according to whether or not cervical septum incision was performed. Reproductive outcomes including gravidity, abortion rate, preterm birth rate, full-term birth rate, premature rupture of membranes, and cervical incompetence were assessed. In the no incision group, the abortion rate (7.4%) was significantly lower than that of the incision group (27.6%, p = .01); the preterm birth rate (4.6%) was significantly lower than that of the incision group (36.8%); and the full-term birth rate (95.5%) exceeded that of the incision group (63.2%, p <.01). Incidence of premature rupture of membranes and cervical incompetence during pregnancy was higher in the incision group (15.8% and 10.5%, p <.01 and p = .03). CONCLUSION: Significantly improved reproductive outcomes were observed among patients with complete septate uterus and duplicated cervix whose cervical septum was preserved during the hysteroscopic transcervical incision of the uterine septum procedure.

Vaccine escape challenges virus prevention: The example of two vaccine-preventable oncogenic viruses.

Over the years, the pace of developing vaccines for HBV and HPV has never stopped. After more than 30 years of application, the HBV vaccine has reduced 80% of hepatocellular carcinoma (HCC). However, vaccine escape variants occur under selective pressure induced by widespread vaccination and antiviral therapy, which results in fulminant infection and horizontal transmission. Several mechanisms have been studied to explain HBV vaccine escape, including vaccine escape mutations (VEMs) in the major hydrophilic region, which leads to a decrease in the binding ability to neutralize antibodies and is the primary escape mechanism, protein conformational and N-linked glycosylation sites changes caused by VEMs, differences in genotype distribution, gene recombination, and some temporarily unknown reasons. However, effective solutions are still being explored. The HPV vaccine has also been proven to prevent 70%-90% of cervical cancer worldwide. Cases of HPV infection after being vaccinated have been observed in clinical practice. However, few researchers have paid attention to the mechanism of HPV vaccine escape. Thus, we reviewed the literature on vaccine escape of both HBV and HPV to discuss the mechanism of the virus escaping from vaccine protection and possible solutions to this problem. We analyzed the gap between studies of HPV and HBV and made prospects for further research in HPV vaccine escape.

25-hydroxycholesterol inhibits human papillomavirus infection in cervical epithelial cells by perturbing cytoskeletal remodeling.

Persistent high-risk human papilloma virus (HR-HPV) infection is the main risk factor for cervical cancer, threatening women's health. Despite growing prophylactic vaccination, annual cervical cancer cases are still increasing and show a trend of younger onset age. However, therapeutic approaches towards HPV infection are still limited. 25-hydrocholesterol (25HC) has a wide-spectrum inhibitory effect on a variety of viruses. To explore efficient interventions to restrict HPV infection at an early time, we applied different pseudoviruses (PsV) to evaluate anti-HPV efficacy of 25HC. We tested PsV inhibition by 25HC in cervical epithelial-derived HeLa and C-33A cells, using high-risk (HPV16, HPV18, HPV59), possibly carcinogenic (HPV73), and low-risk (HPV6) HPV PsVs. Then we established murine genital HPV PsV infection models and applied IVIS to evaluate anti-HPV efficacy of 25HC in vivo. Next, with the help of confocal imaging, we targeted 25HC activity at filopodia upon HPV exposure. After that, we used RNA-seq and Western blot analysis to investigate (1) how 25HC disturbs actin cytoskeleton remodeling during HPV infection and (2) how prenylation regulates the cytoskeletal remodeling signaling pathway. Our findings suggest that 25HC perturbs F-actin rearrangement by reducing small GTPase prenylation. In this way, the phenomenon of HPV virion surfing was restricted, leading to failed infection.

Construction and evaluation of intrauterine adhesion model in rats by different methods of mechanical injury.

PURPOSE: The study aimed to establish a stable and effective animal model for the experimental study of intrauterine adhesion (IUA) by evaluating various mechanical injury methods. METHODS: A total of 140 female rats were divided into four groups according to the extent and area of endometrial injury: group A (excision area: 2.0 × 0.5 cm2), group B (excision area: 2.0 × 0.25 cm2), group C (endometrial curettage) and group D (sham operation). On the 3rd, 7th, 15th and 30th day after the operation, the tissue samples of each group were collected, and the uterine cavity stenosis and histological changes were recorded by HE and Masson staining. Immunohistochemistry of CD31 was applied to visualize microvessel density (MVD). The pregnancy rate and the number of gestational sacs were used to evaluate the reproductive outcome. RESULTS: The results showed that endometrium injured by small-area endometrial excision or simple curettage could be repaired. The ratio of fibrosis in groups A and B was higher than that in groups C and group D 30 days after modeling (P < 0.001). The number of endometrial glands and MVD in group A was significantly lower than those in groups B, C and D (P < 0.05). The pregnancy rate in group A was 20%, which was lower than that in groups B (33.3%), C (89%) and D (100%) (P < 0.05). CONCLUSION: Full-thickness endometrial excision has a high rate of success in constructing stable and effective IUA models in rats.

Clinical Diagnostic Value of Atypical Glandular Cells in Cervical Cytology: A Single Center Experience From China.

OBJECTIVE: This study aimed to investigate the diagnostic value of atypical glandular cells (AGCs) by analyzing the prevalence and histopathology of AGCs according to cervical cytology. METHODS: The authors retrospectively reviewed and analyzed the demographic characteristics and histopathological outcomes including pathological diagnosis, pathological site, and epithelial distribution of the AGC cases that were diagnosed by cervical cytology. RESULTS: A total of 387 AGC patients with follow-up records were included. Among them, the prevalence of AGC-not otherwise specified (NOS) and AGC-favor neoplastic (FN) was 73.39% (284/387) and 26.62% (103/387), respectively. The high-risk human papillomavirus (hr-HPV)-positive rate was higher in AGC-FN than in AGC-NOS ( p = .002). The difference in pathological severity was statistically significant between hr-HPV-positive and negative AGC patients ( p = .010). Hr-HPV-positive AGC mainly occurs in cervical diseases, whereas hr-HPV-negative AGC is mainly related to endometrial lesions. Precancerous or malignant lesions were found in 36.43% (141/387) of AGC cases and were more commonly seen in AGC-FN than AGC-NOS ( p < .001). The histopathological severity and the incidence of uterine disease were higher among AGC women aged 40 years and older than those younger than 40 years ( p < .05). The possibility of the abnormal origin of glandular epithelial was higher than that of squamous epithelial in AGC patients aged 40 years and older ( p = .0003). CONCLUSIONS: The management of AGC women by age triage is reasonable because the incidence of the glandular epithelial lesion and uterine disease increases in AGC patients 40 years or older. Standardized clinical diagnosis and regular follow-up are recommended for all AGC patients.

Visual appearance of the uterine cervix differs on the basis of HPV type status in high-grade squamous intraepithelial lesion: the results of a reliable method.

BACKGROUND: This study aimed to evaluate the differences in cervical appearance among different human papillomavirus (HPV) genotypes in patients with high-grade squamous intraepithelial lesions (HSILs). METHODS: A total of 239 histopathological HSIL patients were included and divided into eight groups on the basis of HPV genotype in this prospective study. We present a reliable imaging method that provides reproducible, sensitive and unbiased assessments of cervical appearance characteristics. Colorimetric and morphometric data of colposcopic patterns after the application of acetic acid and iodine were acquired using ImageJ software and the surrounding normal regions were used as controls. RESULTS: The differences in red, green, blue and mean greyscale values in acetowhite epithelium obtained from ImageJ were not significant between the HPV16 and HPV18 groups (P < 0.05). The differences in red, green, and mean greyscale values in iodine staining were significant between the HPV18 and the other groups (P < 0.05). The frequency of the occurrence of the coarse mosaic patterns was significantly different among groups (P < 0.05), reducing in sequence were the HPV16, HPV-negative, HPV18, HPV31/33 and HPV52/58 groups. For the lesion area of HSILs, the HPV-negative group was the largest. The sensitivity of colposcopic impression varied among HPV genotypes (P < 0.01), being lowest in the HPV52 group. CONCLUSIONS: Although being nonspecific, iodine negativity should be concerned in HPV18-positive lesions which is closely related to glandular epithelium. Vascular patterns in HPV52/58-positive HSIL are quite occult and tend to be missed by colposcopists. HPV-negative lesions are prone to be large and present typical vascular patterns despite being rare.

Precise Measurement of the Thickness of Vaginal Intraepithelial Neoplasia.

OBJECTIVES: Although carbon dioxide laser vaporization is frequently used for treating vaginal intraepithelial neoplasia (VaIN), the optimal depth of epithelial destruction with laser vaporization requires elucidation. We aimed to evaluate VaIN depth and better illustrate epithelial destruction during laser vaporization. MATERIALS AND METHODS: We included 246 women diagnosed with VaIN (low-grade VaIN [VaIN 1], 123 women; high-grade VaIN [VaIN 2/3], 123 women) using colposcopy-directed biopsy at our hospital from January 1, 2019, to April 30, 2020. The thickness of the noninvolved epithelium, if available, was determined. All available data, including cytology and histological information, were recorded. The t test and Pearson χ 2 test were used for statistical analysis. Statistical significance was set at p < .05. RESULTS: The involved epithelial thicknesses in VaIN 2/3 and VaIN 1 were 0.41 ± 0.21 and 0.40 ± 0.19 mm, respectively, which were both greater than their noninvolved epithelial thickness values (0.17 ± 0.10 and 0.17 ± 0.08 mm, p < .01 and p < .01, respectively). In subgroup comparisons between the VaIN 2/3 and VaIN 1 groups, the involved epithelial thickness did not differ between premenopausal patients, postmenopausal women receiving estrogen, and postmenopausal women who did not receive estrogen ( p > .05). In the VaIN 2/3 group, the lesion thickness in premenopausal was greater than that in postmenopausal women receiving estrogen ( p = .016) and those who were not receiving estrogen ( p = .017). CONCLUSIONS: The thickness of VaIN is generally less than 1 mm for women of all ages, except in rare cases of visible lesions with papillary hyperplasia.

Preparation and characterization of boron-doped corn straw biochar: Fe (â ¡) removal equilibrium and kinetics.

Nowadays, iron ions as a ubiquitous heavy metal pollutant are gradually concerned and the convenient and quick removal of excessive iron ions in groundwater has become a major challenge for the safety of drinking water. In this study, boron-doped biochar (B-BC) was successfully prepared at various preparation conditions with the addition of boric acid. The as-prepared material has a more developed pore structure and a larger specific surface area (up to 897.97 m²/g). A series of characterization results shows that boric acid effectively activates biochar, and boron atoms are successfully doped on biochar. Compared with the ratio of raw materials, the pyrolysis temperature has a greater influence on the amount of boron doping. Based on Langmuir model, the maximum adsorption capacity of 800B-BC1:2 at 25 °C, 40 °C, 55 °C are 50.02 mg/g, 95.09 mg/g, 132.78 mg/g, respectively. Pseudo-second-order kinetic model can better describe the adsorption process, the adsorption process is mainly chemical adsorption. Chemical complexation, ions exchange, and co-precipitation may be the main mechanisms for Fe2+ removal.

Risk of High-Grade Histopathology Diagnosed by Cervical Conization in Endocervical Curettage Cervical Intraepithelial Neoplasia 1: A Case-Control Study.

OBJECTIVE: The aim of the study was to estimate risks of cervical intraepithelial neoplasia 2+ (CIN 2+) on loop electrosurgical excisional procedure (LEEP) specimens with the diagnosis of endocervical curettage (ECC) CIN 1 compared with biopsy CIN 1. MATERIALS AND METHODS: We performed a retrospective computer-based search for subjects enrolled in the Obstetrics and Gynecology Hospital of Fudan University. The case group comprised women with an ECC CIN 1 (ECC results of CIN 1 with colposcopy-directed biopsy results ≤CIN 1), and the control group comprised women with a biopsy CIN 1 (colposcopy-directed biopsy results of CIN 1 with negative ECC findings) diagnosis. Variables, including age, cytology, high-risk human papillomavirus, and ECC results, were included in univariate and multivariate logistic regression analyses. p < .05 was defined statistically significant. RESULTS: Overall, 1,195 women with ECC CIN 1 and/or biopsy CIN 1 diagnosis who underwent LEEP participated in the study. ECC CIN 1 comprised 400 women, with LEEP histopathology results revealing 104 (26.00%) CIN 2+. Biopsy CIN 1 comprised 795 women, with LEEP histopathology results showing 150 (18.87%) CIN 2+. Univariate logistic regression showed that cytology (p < .001) and ECC (p = .005) results differ significantly between less than CIN 2+ and CIN 2+. Multivariate logistic regression revealed that the cytology of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (OR = 4.73, 95% CI = 2.78-8.05, p < .001) and high-grade squamous intraepithelial lesions or worse (HSIL+, OR = 4.88, 95% CI = 3.00-7.94, p < .001), and ECC CIN 1 (OR = 1.80, 95% CI = 1.33-2.44, p < .001) were risk factors for CIN 2 + . CONCLUSIONS: Endocervical curettage CIN 1 has a greater risk of CIN 2+ diagnosis than biopsy CIN 1, but high-grade cytology has a higher risk than ECC CIN 1.

Importance of Colposcopy Impression in the Early Diagnosis of Posthysterectomy Vaginal Cancer.

OBJECTIVE: The aim of the study was to investigate the value of cytology, high-risk human papillomavirus (hrHPV) status and colposcopy in the early diagnosis of vaginal cancer after hysterectomy. MATERIALS AND METHODS: A retrospective study was performed in the Obstetrics and Gynecology Hospital of Fudan University. Posthysterectomy patients who were diagnosed with vaginal high-grade intraepithelial lesion (HSIL) by colposcopy-directed biopsy with colposcopy impression of extensive HSIL or suspicion of cancer and underwent upper or total vaginectomy from January 2009 to December 2017 were included. RESULTS: Eighty-six posthysterectomy vaginal HSIL patients were included. Available abnormal cytology and positive hrHPV were observed in 90.7% (49/54) and 96.2% (51/53) of the patients, respectively. A total of 18.6% (16/86) of the patients were diagnosed with squamous cell cancer by vaginectomy, and the average interval between hysterectomy and vaginectomy was 3.5 years. Among them, 62.5% (10/16) cancers occurred after hysterectomy for cervical cancer, 31.2% (5/16) after hysterectomy for cervical precancer, and 6.3% (1/16) after hysterectomy for myoma. An indication for hysterectomy (cervical cancer vs HSIL, odds ratio = 7.2, 95% CI = 1.9-28.0, p = .004) and colposcopy impression of vaginal cancer (vaginal cancer vs HSIL, odds ratio = 5.9, 95% CI = 1.3-26.8, p = .021) were high-risk factors of cancer confirmed by vaginectomy in colposcopy-directed biopsy vaginal intraepithelial neoplasia 2/3 posthysterectomy in multiple logistic regression analysis. CONCLUSIONS: Colposcopy is pivotal in the evaluation of abnormal cytology/hrHPV tests in follow-up of cervical cancer patients after hysterectomy and decision-making for vaginectomy in detecting early cancer.

Risk Factor Analysis of Persistent High-Grade Squamous Intraepithelial Lesion After Loop Electrosurgical Excision Procedure Conization.

OBJECTIVE: The aim of the study was to analyze the clinical outcomes of high-grade squamous intraepithelial lesion (HSIL) 6 months after loop electrosurgical excision procedure (LEEP). We explored the risk factors of persistent cervical HSIL after LEEP and evaluated the methods of follow-up. PATIENTS AND METHODS: This retrospective study included women who underwent a LEEP and had a diagnosis of HSIL in their LEEP specimen during 2011 to 2015. The purpose was to determine the risk factors among these women for having persistent HSIL disease at their 6-month follow-up visit. At their follow-up visit, each woman underwent cervical cytology and high-risk human papilloma virus (hrHPV) testing, colposcopy-directed punch biopsy, and/or endocervical curettage. RESULTS: A total of 3582 women were enrolled. There were 9 cases invasive cervical cancer found and 101 women had persistent HSIL. The persistence rate was higher in women 50 years or older. The circumference, length, and width of LEEP specimens did not differ statistically between the persistent and nonpersistent group. The persistence rate among women with positive LEEP specimen margins was higher than among women with negative margins. Positive endocervical margins were associated with a higher rate of persistence than positive ectocervical margins. Multivariate logistic analysis showed that age, positive margins, abnormal cytology, and positive hrHPV during follow-up were all independent risk factors for persistent HSIL lesions. CONCLUSIONS: Being 50 years or older, positive margins, particularly endocervical margins, and having abnormal cytology and positive hrHPV testing during follow-up were risk factors for persistent HSIL lesions after LEEP conization. Colposcopy plays an indispensable role in the diagnosis of persistent HSIL and progression.

Distribution of human papilloma virus genotype prevalence in invasive cervical carcinomas and precancerous lesions in the Yangtze River Delta area, China.

BACKGROUND: This study aimed to provide more information for cancer prevention strategies by determining the distribution of human papilloma virus (HPV) genotype prevalence in invasive cervical carcinoma (ICC) and precancerous lesion patients in the Yangtze River Delta area in China. METHODS: This multi-centre descriptive cross-sectional study involves four university hospitals in the Jiangzhehu area. Women with histologically confirmed cervical intraepithelial neoplasia (CIN) 1, CIN2, CIN3 or ICC who were diagnosed and treated in the four selected hospitals between February 2012 and April 2014 were eligible for recruitment. The average age of the patients was 40.93 ± 11.87 years old, among whom the youngest was 17 years old and the oldest was 76 years old.Those with immunodeficiency diseases or a previous history of cancer or CIN were excluded. HPV genotyping was performed by a central laboratory. The distribution and age and disease specificity of the HPV genotype prevalence were analysed. RESULTS: Of the 2181 collected samples, 251 were ICC and 1930 were CIN. The mean age of cervical cancer and CIN patients was 40.93 ± 11.8 years (range, 17-76 years). The five most commonly identified HPV types in each lesion class were as follows: CIN1: 52, 58, 16, 33, and CP; CIN2: 16, 58, 52, 33, and 31; CIN3: 16, 58, 33, 52, and 31; and ICC: 16, 58, 18, 52, and 33. CIN1 had an earlier age of onset (30-40 years) than CIN2, CIN3, and cervical cancer. The age of onset of cervical cancer exhibited two peaks at 40-44 and 50-54 years of age. In all infected patients, the frequency of HPV infection with a single type was 62.9%, and with multiple types, it was 38.1%. There was no difference in the frequencies of multiple types amongst the different cervical lesions. CONCLUSIONS: The most prevalent genotypes in the investigated area (52, 58, 16 and 18) justify the necessity of anti-HPV vaccination in teenagers and young girls under 24 years old in the Yangtze River Delta area in China. Infection with multiple high-risk HPV types versus single infection does not increase the risk for ≥ CIN2 in ICC development.

Toll-like receptor 4 promotes proliferation and apoptosis resistance in human papillomavirus-related cervical cancer cells through the Toll-like receptor 4/nuclear factor-κB pathway.

Toll-like receptor 4 is overexpressed in various tumors, including cervical carcinoma. However, the role of Toll-like receptor 4 in cervical cancer remains controversial, and the underlying mechanisms are largely elusive. Therefore, Toll-like receptor 4 in cervical cancer and related mechanisms were investigated in this study. Quantitative reverse transcription polymerase chain reaction and western blot analyses were used to detect messenger RNA and protein levels in HeLa, Caski, and C33A cells with different treatments. Proliferation was quantified using Cell Counting Kit-8. Cell cycle distribution and apoptosis were assessed by flow cytometry. Higher levels of Toll-like receptor 4 expression were found in human papillomavirus-positive cells compared to human papillomavirus-negative cells. Proliferation of HeLa and Caski cells was promoted in lipopolysaccharide-stimulated groups but suppressed in short hairpin RNA-transfected groups. Apoptosis rates were lower in lipopolysaccharide-stimulated groups relative to short hairpin RNA-transfected groups. In addition, G2-phase distribution was enhanced when Toll-like receptor 4 was downregulated. Moreover, the pNF-κBp65 level was positively correlated with the Toll-like receptor 4 level in HeLa and Caski cells, though when an nuclear factor-κB inhibitor was applied to lipopolysaccharide-stimulated groups, the patterns of proliferation and apoptosis were opposite to those of the lipopolysaccharide-stimulated groups without inhibitor treatment. In conclusion, these data suggest that Toll-like receptor 4 promotes proliferation and apoptosis resistance in human papillomavirus-related cervical cancer cells at least in part through the Toll-like receptor 4/nuclear factor-κB pathway, which may be correlated with the occurrence and development of cervical carcinoma.

Reproductive Outcomes in Patients With Intrauterine Adhesions Following Hysteroscopic Adhesiolysis: Experience From the Largest Women's Hospital in China.

STUDY OBJECTIVE: To analyze the reproductive outcome of hysteroscopic adhesiolysis and assess the diagnostic accuracy of transvaginal ultrasonography (TVS) in infertile women resulting from intrauterine adhesions (IUAs). DESIGN: Retrospective, cross-sectional study (Canadian Task Force classification II-2). SETTING: University tertiary referral center. PATIENTS: Three hundred and fifty-seven patients with mild, moderate, and severe IUAs who underwent hysteroscopic adhesiolysis between January 2012 and December 2015. INTERVENTIONS: Hysteroscopic adhesiolysis in the outpatient analgesic setting for infertility and IUAs. MEASUREMENTS AND MAIN RESULTS: Among the 357 patients (135 with mild IUAs, 116 with moderate IUAs, and 106 with severe IUAs) who underwent hysteroscopic adhesiolysis, 334 (93.6%) experienced a completely restored uterine cavity. The reproductive outcomes of 332 women (93%) were followed for an average duration of 27 ± 9 months, and the overall conception rate after hysteroscopic adhesiolysis was 48.2%, which decreased with increased IUA severity (mild, 60.7%; moderate, 53.4%; severe, 25%). The mean time to conception following hysteroscopic adhesiolysis was 9.7 ± 3.7 months. The miscarriage rate was 9.4%, and the live birth rate was no lower than 85.6%. Eleven patients (7.9%) had postpartum hemorrhage, including 6 (4.3%) due to adherent placenta and 3 (2.1%) due to placenta accreta. CONCLUSION: Hysteroscopic adhesiolysis is a feasible and effective way to improve fertility in patients with Asherman's syndrome.

Factors that influence persistence or recurrence of high-grade squamous intraepithelial lesion with positive margins after the loop electrosurgical excision procedure: a retrospective study.

BACKGROUND: In 5-20 % of patients with cervical high-grade squamous intraepithelial lesion (HSIL), a positive margin after the loop electrosurgical excision procedure (LEEP) is associated with persistence/recurrence, but the prognostic value of other clinico-pathological factors is less clear. METHODS: Among 4336 patients with HSIL who underwent an initial LEEP, 275 (6 %) had HSIL-positive margins, 37 of whom were lost to follow-up. We evaluated the remaining 238 patients. Persistence/recurrence was defined as histopathological HSIL during follow-up. RESULTS: The age of the patients ranged from 21 to 69 years (median: 40). The median follow-up period was 25 months (range: 6-43). Of the 238 patients, 211 (88.7 %) patients remained free of persistence/recurrence, while 27 (11.3 %) experienced persistence/recurrence. According to a univariate analysis, age (P = 0.03) and maximum specimen diameter (P = 0.043) were associated with persistence/recurrence, but number/location of involved margin sections and the pathology of the endocervical curettage were not (P > 0.10). The relative risk of the subjects (greater than or equal to 35 years ages) was 4.6 times of the subject less than 35 years, the difference was statistically significant (14 % vs. 3 %, P < 0.05). A multivariate analysis indicated that an age of 35 years or older was the only independent risk factor (OR 4.97, 95 % CI 1.14-21.62, P = 0.03). CONCLUSION: In patients with HSIL and HSIL-involved margins after an initial LEEP, age is a strong independent predictor of persistence/recurrence. Follow-up with screening cytology and/or biopsy may be considered in younger patients, whereas a secondary LEEP/hysterectomy may be considered in older patients.

[Agreement between colposcopic diagnosis with 2011 international terminology of colposcopy and cervical pathology in cervical lesions].

OBJECTIVE: To evaluate the agreement between colposcopic diagnosis with 2011 colposcopic terminology of the International Federation for Cervical Pathology and Colposcopy (IFCPC) and cervical pathology in cervical lesions. METHODS: A retrospective cohort study was performed, which included 376 patients who underwent colposcopy with 2011 international terminology of colposcopy at Obstetrics and Gynecology Hospital of Fudan University from September 2014 to November 2014. With conization or cervical biopsy pathology as the gold standard, the agreement between colposcopic diagnosis and pathologic diagnosis was calculated and correlations between variables were analyzed. RESULTS: With 2011 international terminology of colposcopy, agreement of colposcopic diagnosis and cervical pathology was 60.9% (229/376) perfectly matched, and the strength of agreement with weighted Kappa statistic was 0.401 (P < 0.01), and agreement within one grade was 97.6% (367/376), which were improved compared with traditional methods. Colposcopic diagnosis were 19.9% (75/376) overestimated and 19.1% (72/376) underestimated. There were no significant difference between agreements in various grade lesions (χ(2) = 1.996, P = 0.573). Positive predictive value of high grade colposcopy or more was 84.4%, the negative predictive value of low grade colposcopy or less was 88.8%, whereas false positives were 3.5% and false negatives were 39.3%. A linear trend among three types of transformation zone and patient ages was found (χ(2) = 45.910, P < 0.01), whereas lesion sizes were not linearly correlated with lesion degrees (χ(2) = 0.690, P = 0.406). In grade 1, grade 2 and nonspecific findings, thin acetowhite epithelium, dense acetowhite epithelium and Lugol's non-staining were most frequent, the Youden indexes of each were 0.170, 0.373 and 0.145, 0.069 respectively. Positive predictive value of some other findings (such as fine mosaic) and two new signs (inner border sign and ridge sign) were 100.0%. There were no significant difference between agreements in examiners with different levels of experience (χ(2) = 1.197, P = 0.550). CONCLUSIONS: Compared to traditional methods (such as Reid index), 2011 international terminology of colposcopy could improve the agreement between colposcopic diagnosis and pathologic diagnosis, without significant differences by the severity of lesion and the level of examiners' experience. Common findings were classified reasonably, and some signs were highly reliable, which is important for guiding biopsy. However, the reproducibility of transformation zone types and the implication of lesion size need to be further discussed.

[Study on the expression and signification of TLR4/NO pathway in cervical tumorigenesis with high risk HPV infection].

OBJECTIVE: To explore the role of toll-like receptor (TLR)/ nitric oxide (NO) pathway in cervical tumor with high risk human papillomavirus (hrHPV) infection. METHODS: (1)Study was based on 36 women with nonmalignantcervical tissue as control group and 36 women with squamous cell cervical cancer (SCC), all with hrHPV infection which were assessed by using 14 types hrHPV E6/E7 mRNA real-time PCR kit. The amount of NO was detected by Griess reaction, the expression of inducible nitric oxide synthase(iNOS) was detected by immunohistochemistry (IHC). The mRNA expression of TLR3, TLR4, TLR7, TLR8, TLR9, nuclear factor-κB (NF-κB) p65 and iNOS in control and SCC epithelium which was captured by laser capture microdissection (LCM) were determined.(2)The expressions of TLR4 in CaSki, HeLa and C33a were detected by cell immunofluorescence method. The mRNA and protein expression of TLR/NO pathway transduction molecules including TLR4,NF-κBp65 and iNOS in CaSki, HeLa and C33a cell lines were detected by real-time PCR and western blot. RESULTS: (1)The level of NO was much higher in SCC group than that in control group [(42.92±0.36)µmol/L vs(15.49±0.24)µmol/L; P < 0.05 ]. iNOS was detected in 75% (27 cases ) of patients with squamous cervical carcinoma, while only 6% (2 cases) of normal controls were confirmed with positve result (P < 0.05). TLR/NO pathway maybe activated in SCC, for the mRNA levels of TLR3, TLR4, TLR7, TLR8, NF-κBp65 and iNOS increased significantly when compared to control group (all P < 0.05), and the greatest change in the expression level of TLR in SCC was spotted on TLR4(7.41±0.39 vs 1.86±0.21). (2)The results of immunofluorescence showed that TLR4 was located at plasma membrance of hrHPV positive HeLa and CaSki cells, while the integral optical density of TLR4 in HeLa cells (3 599±427) or CaSki cells (2 080±456) were higher than that in C33a cells (730± 96; P < 0.05). The mRNA and protein level of TLR4, NF-κBp65 and iNOS in HeLa and CaSki cells were higher than those of C33a cells (P < 0.05). CONCLUSION: TLR4/NO pathway is highly expressed in cervical cancer with hrHPV infection, while the pathway may be involved in cervical tumorigenesis with hrHPV infection.

[Expression and significance of p63, aromatase P450 and steroidogenic factor-1 in endometrial polyp].

OBJECTIVE: To investigate the expression and signification of p63, aromatase P450 (P450 arom) and steroidogenic factor-1 (SF-1) in endometrial polyp, and to explore its role in the pathogenesis of endometrial polyp. METHODS: Specimen were collected from hysteroscopic resection, pathologically confirmed endometrial polyp specimens of 30 cases of endometrial polyp and the adjoining endometrium around endometrial polyp in 20 cases, endometrial tissue of normal control group of 25 patients. Immunohistochemistry SP method and real- time PCR technology were used to detect the three groups in the expression of p63, P450 arom and SF- 1 protein and gene. RESULTS: P450arom gene (0.274 ± 0.082) and protein (1.2 ± 1.1) expression in endometrial polyp was significantly higher than the adjoining endometrium and normal endometrium (P < 0.05); the expression of SF- 1 protein (1.1 ± 0.8) and p63 protein (0.8 ± 0.5) were also higher in the endometrial polyp than the other two control groups (P < 0.05); while the expression of SF-1 mRNA (0.105 ± 0.049 versus 0.053 ± 0.043) and p63 mRNA (0.261 ± 0.052 versus 0.180 ± 0.018) in endometrial polyp had no significant difference between endometrial polyp and the adjoining endometrial (P > 0.05). CONCLUSION: p63, P450 arom and SF-1 may play a role in the formation of endometrial polyp.

3D reconstruction of the uterus and automatic segmentation of the uterine cavity on 3D magnetic resonance imaging: A preliminary study.

Purpose: To determine the differences in 3D shape features between septate uterus (SU) and normal uterus and to train a network to automatically delineate uterine cavity on 3D magnetic resonance imaging (MRI). Methods: A total of 43 patients (22 cases of partial septate uterus and 21 cases of complete septate uterus) were included in the experimental group. Nine volunteers were recruited as a control group. The uterine cavity (UC), myometrium (UM), and cervical canal of the uterus were segmented manually using ITK-SNAP software. The three-dimensional shape features of the UC and UM were extracted by using PyRadiomics. The recurrent saliency transformation network (RSTN) method was used to segment the UC. Results: The values of four 3D shape features were significantly lower in the control group than in the partial septate group and the complete septate group, while the values of two features were significantly higher (p < 0.05). The UCs of the three groups were significantly different in terms of flatness and sphericity. The values of six features were significantly lower in the UMs of the control group than in those of the partial septate group and the complete septate group (p < 0.05). After the deep learning networks were trained, the Dice similarity coefficient (DSC) scores of the four folds for different thresholds were all over 80 %. The average volume ratio between predictions and manual segmentation was 101.2 %. Conclusions: Based on 3D reconstruction, 3D shape features can be used to comprehensively evaluate septate uterus and provide a reference for subsequent research. The UC can be automatically segmented on 3D MRI using the RSTN method.