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Abstract The study aimed to develop and validate a preoperative scoring system to predict the risk of lymph node metastasis (LNM) in cervical cancer (CC). A total of 426 stage IB1–IIA1 CC patients were randomly divided into two sets. A logistic regression model was used to determine independent factors that contribute to LNM. A preoperative scoring system was developed based on beta (β) coefficients. An area under the receiver operating curve (AUC) was used to test for model discrimination. Five-year overall survival (OS) rate was 91.7%. Multivariable logistic regression analysis showed that FIGO stage, tumor size, depth of invasion on MRI, and squamous cell carcinoma antigen levels were independent risk factors in the development set (all P

Abstract The clinical heterogeneity of early-stage endometrial cancer (EC) is worthy of further study to identify high-quality prognostic markers and their potential role in aggressive tumor behavior. Mutation of TP53 was considered as an important primary triage in modified molecular typing for EC, it still cannot precisely predict the prognosis of EC. After proteomic analysis of cancer and para-cancerous tissues from 24 early-stage endometrioid EC patients with different survival outcomes, 13 differentially expressed proteins were screen out while 2 proteins enriched in p53 signaling pathway were further identified by single-cell transcriptome (scRNA-seq). Interestingly, tumor necrosis factor type-1 receptor-associated protein (TRAP1) and calmodulin-regulated spectrin-associated protein family member 3 (CAMSAP3) were found to be significantly downregulated in the specific cell cluster. Expectedly, the signature genes of TRAP1low/CAMSAP3low cluster included classical oncogenes. Moreover, close cellular interactions were observed between myeloid cells and the TRAP1low/CAMSAP3low cluster after systematically elucidating their relationship with tumor microenvironment (TME). The expression of TRAP1 and CAMSAP3 was verified by immunohistochemistry. Thus, a novel prediction model combining TRAP1, CAMSAP3 and TP53 was construct by multi-omics. Compared with the area under the curve, it demonstrated a significantly improvemrnt in the diagnostic efficacy in EC patients from TCGA bank. In conclusion, this work improved the current knowledge regarding the prognosis of early-stage EC through proteomics and scRNA-seq. These findings may lead to improvements in precise risk stratification of early-stage EC patients.

PurposeCurrently, there are no reliable indicators for the early identification of patients with low-risk gestational trophoblastic neoplasia (GTN) who develop resistance to monotherapy. This study aimed to evaluate the effectiveness of combining the Systemic Immune-Inflammation Index (SII) and Prognostic Nutritional Index (PNI) in detecting early resistance to monotherapy in patients with low-risk GTN.MethodsThis retrospective study included 91 patients with low-risk GTN who received initial monotherapy at Fujian Maternal and Child Health Hospital between 2013 and 2021. The SII and PNI before chemotherapy were calculated from prechemotherapy peripheral blood samples, with cut-off values determined by receiver operating characteristic (ROC) curves. The SII-PNI score ranged from 0 to 2 points and was categorized as follows: a score of 2 points indicated a high SII (≥467.02) and a low PNI (≤51.35); a score of 1 point indicated either a high SII or a low PNI; and a score of 0 points indicated neither a high SII nor a low PNI.ResultsNinety-one patients with low-risk GTN underwent monotherapy, 19 of whom developed resistance, whereas the remaining 72 did not. The SII was significantly greater in chemotherapy-resistant patients than in non-resistant patients (P=0.04), whereas the PNI was markedly lower in chemotherapy-resistant patients (P=0.002). Univariate analysis revealed that cut-off values of 467.02 for the SII (P=0.04) and 51.35 for the PNI (P=0.024) were associated with chemotherapy resistance in patients with low-risk GTN. As the SII-PNI score increased, the proportion of chemotherapy-resistant patients increased (P

Trichomoniasis and HPV infection are common non-viral and viral sexually transmitted diseases worldwide. Emerging evidence shows that the female genital tract and its microbiota are greatly affected by these pathogens. However, the relationship between Trichomonas vaginalis, the vaginal microbiome, and High-risk (HR)-HPV infection is complex and multifaceted. Studies have proven that concurrent infections of HIV and HPV increase the risk of cervical cancer. With this basis, a question arises: How does the concurrent infection of trichomonas vaginalis and HPV affect genital tract health? Does this concurrent infection enhance or inhibit the development of cervical lesions? This review aims to bring light to these questions. This review also covers the association of trichomonas vaginalis and HPV with the microbiota of the genital tract.

Abstract Background Tumor cells can resist chemotherapy-induced pyroptosis through glycolytic reprogramming. Estrogen-related receptor alpha (ERRα) is a central regulator of cellular energy metabolism associated with poor cancer prognosis. Herein, we refine the oncogenic role of ERRα in the pyroptosis pathway and glycolytic metabolism. Methods The interaction between ERRα and HIF-1α was verified using co-immunoprecipitation. The transcriptional binding sites of ERRα and NLRP3 were confirmed using dual-luciferase reporter assay and cleavage under targets and tagmentation (CUT&Tag). Flow cytometry, transmission electron microscopy, scanning electron microscopy, cell mito stress test, and extracellular acidification rate analysis were performed to investigate the effects of ERRα on the pyroptosis pathway and glycolytic metabolism. The results of these experiments were further confirmed in endometrial cancer (EC)-derived organoids and nude mice. In addition, the expression of ERRα-related pyroptosis genes was analyzed using The Cancer Genome Atlas and Gene Expression Omnibus database. Results Triggered by a hypoxic microenvironment, highly expressed ERRα could bind to the promoter of NLRP3 and inhibit caspase-1/GSDMD signaling, which reduced inflammasome activation and increased pyroptosis resistance, thereby resulting in the resistance of cancer cells to cisplatin. Moreover, ERRα activated glycolytic rate-limiting enzyme to bridge glycolytic metabolism and pyroptosis in EC. This phenomenon was further confirmed in EC-derived organoids and nude mice. CUT & Tag sequencing and The Cancer Genome Atlas database analysis showed that ERRα participated in glycolysis and programmed cell death, which resulted in EC progression. Conclusions ERRα inhibits pyroptosis in an NLRP3-dependent manner and induces glycolytic metabolism, resulting in cisplatin resistance in EC cells.

During acute respiratory infections, women may concurrently receive human papillomavirus (HPV) and respiratory vaccines, as observed during the coronavirus disease 2019 (COVID-19) pandemic in China. However, few studies have assessed the safety of such concurrent administration, which could impact HPV vaccination schedules. This study analyzes the safety and optimal sequence of concurrent HPV and COVID-19 vaccinations. For this purpose, we surveyed women with both vaccines from January to October 2023 in Fujian Province, China. During this process, we collected vaccination history and adverse event (AE) data via telephone or interviews. Participants were grouped as Before, Concurrent, or After based on their vaccination sequence. A Chi-squared test, exact Fisher tests, and logistic regression were used to analyze the incidence of AEs and factors influencing vaccine safety. Overall, 1416 eligible participants were included. Although overall AE risk with the HPV vaccine was unaffected by vaccination sequence, individual AEs varied statistically between groups, including pain at the vaccination site (p < 0.001) and prolonged menstruation duration (p = 0.003). Based on the results, the optimal sequence would be to receive the HPV vaccine after the COVID-19 vaccine (After group). This insight may guide future emergency vaccination sequences for HPV and other respiratory infectious diseases.

Abstract Background There is a close correlation between HPV infection and systemic immune status. The purpose of this study was to determine which lymphocytes in peripheral blood influence human papillomavirus (HPV) infection and to identify whether peripheral blood lymphocyte (PBL) subsets could be used as biomarkers to predict HPV clearance in the short term. Methods This study involved 716 women undergoing colposcopy from 2019 to 2021. Logistic and Cox regression were used to analyze the association of PBLs with HPV infection and clearance. Using Cox regression, bidirectional stepwise regression and the Akaike information criterion (AIC), lymphocyte prediction models were developed, with the C-index assessing performance. ROC analysis determined optimal cutoff values, and their accuracy for HPV clearance risk stratification was evaluated via Kaplan‒Meier and time-dependent ROC. Bootstrap resampling validated the model and cutoff values. Results Lower CD4 + T cells were associated with a higher risk of HPV, high-risk HPV, HPV18 and HPV52 infections, with corresponding ORs (95% CI) of 1.58 (1.16–2.15), 1.71 (1.23–2.36), 2.37 (1.12–5.02), and 3.67 (1.78–7.54), respectively. PBL subsets mainly affect the natural clearance of HPV, but their impact on postoperative HPV outcomes is not significant (P > 0.05). Lower T-cell and CD8 + T-cell counts, as well as a higher NK cell count, are unfavorable factors for natural HPV clearance (P

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant health issue closely associated with multiple extrahepatic cancers. The association between MAFLD and clinical outcomes of endometrial cancer (EC) remains unknown. Methods: We retrospectively included 725 EC patients between January 2012 and December 2020. The odds ratios (ORs) were calculated using logistic regression analyses. Kaplan–Meier survival curves were used for survival analysis. Results: Among EC patients, the prevalence of MAFLD was 27.7% (201/725, 95% confidence interval (Cl) = 0.245–0.311). MAFLD was significantly associated with cervical stromal involvement (CSI) (OR = 1.974, 95% confidence interval (Cl) = 1.065–3.659, p = 0.031). There was a significant correlation between overall survival (OS) and CSI (HR = 0.31; 95%CI: 0.12–0.83; p = 0.020), while patients with MAFLD had a similar OS to those without MAFLD (p = 0.952). Moreover, MAFLD was significantly associated with CSI in the type I EC subgroup (OR = 2.092, 95% confidence interval (Cl) = 1.060–4.129, p = 0.033), but not in the type II EC subgroup (p = 0.838). Further logistic regression analysis suggested that the hepatic steatosis index (HSI) was significantly associated with CSI among type I EC patients without type 2 diabetes mellitus (T2DM) (OR = 1.079, 95% confidence interval (Cl) = 1.020–1.139, p = 0.012). Conclusions: About one-quarter of our cohort had MAFLD. MAFLD was associated with the risk of CSI in EC patients, and this association existed in type I EC patients but not in type II EC patients. Furthermore, the HSI can help predict CSI in type I EC patients without T2DM.

Persistent infections with specific high-risk human papillomavirus (HR-HPV) strains are the leading cause of cervical cancer and precancerous lesions. HPV-16 and HPV-18 are associated with more than 70% of cervical cancer. However, with recent widespread vaccination efforts against cervical cancer, the infection rates of HPV-16 and HPV-18 have decreased across all age groups, while the infection rates of other HR-HPV strains have increased. The non-16/18 HR-HPV strains play an important role in cervical lesions. These strains can be identified with extended genotyping, and the 2019 American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines recommended an HPV-based testing to assess the risk of cervical disease in patients. We reviewed and analyzed the clinical benefits of applying extended HR-HPV genotyping, which was published by the International Agency for Research on Cancer (HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), to cervical cancer screening. This review concluded that cervical cancer screening needs to include extended HR-HPV genotyping. The examination of extended HR-HPV genotyping in cervical intraepithelial lesions and cervical cancers can help guide clinical practices.

Oridonin is the primary active component in the traditional Chinese medicine Rabdosia rubescens, displaying anti-inflammatory, anti-tumor, and antibacterial effects. It is widely employed in clinical therapy for acute and chronic pharyngitis, tonsillitis, as well as bronchitis. Nevertheless, the clinical application of oridonin is significantly restricted due to its reproductive toxicity, with the exact mechanism remaining unclear. The aim of this study was to investigate the mechanism of oridonin-induced damage to HTR-8/SVneo cells. Through the integration of epigenetics, proteomics, and metabolomics methodologies, the mechanisms of oridonin-induced reproductive toxicity were discovered and confirmed through fluorescence imaging, RT-qPCR, and Western blotting. Experimental findings indicated that oridonin altered m6A levels, gene and protein expression levels, along with metabolite levels within the cells. Additionally, oridonin triggered oxidative stress and mitochondrial damage, leading to a notable decrease in WNT6, β-catenin, CLDN1, CCND1, and ZO-1 protein levels. This implied that the inhibition of the Wnt/β-catenin signaling pathway and disruption of tight junction might be attributed to the cytotoxicity induced by oridonin and mitochondrial dysfunction, ultimately resulting in damage to HTR-8/SVneo cells.

Abstract Introduction Myometrial invasion is a prognostic factor for lymph node metastases and decreased survival in non-endometrioid endometrial carcinoma patients. Herein, we explored the mode of myometrial invasion diagnosis in FIGO stage I non-endometrioid carcinoma and evaluated the differences in diagnostic efficiency among intraoperative frozen section (IFS), intraoperative gross examination (IGE), magnetic resonance imaging (MRI), and computed tomography (CT) in clinical practice. Finally, we suggested which test should be routinely performed. Method This was a historical cohort study nationwide with 30 centers in China between January 2000 and December 2019. Clinical data, including age, histology, method of myometrial invasion evaluation (MRI, CT, IGE, and IFS), and final diagnosis of postoperative paraffin sections, were collected from 490 non-endometrioid endometrial carcinoma (serous, clear cell, undifferentiated, mixed carcinoma, and carcinosarcoma) women in FIGO stage I. Results Among the 490 patients, 89.59% presented myometrial invasion. The methods reported for myometrial invasion assessment were IFS in 23.47%, IGE in 69.59%, MRI in 37.96%, and CT in 10.20% of cases. The highest concordance was detected between IFS and postoperative paraffin sections (Kappa = 0.631, accuracy = 93.04%), followed by IGE (Kappa = 0.303, accuracy = 82.40%), MRI (Kappa = 0.131, accuracy = 69.35%), and CT (Kappa = 0.118, accuracy = 50.00%). A stable diagnostic agreement between IFS and the final results was also found through the years (2000–2012: Kappa = 0.776; 2013–2014: Kappa = 0.625; 2015–2016: Kappa = 0.545; 2017–2019: Kappa = 0.652). Conclusion In China, the assessment of myometrial invasion in non-endometrioid endometrial carcinoma is often performed via IGE, but the reliability is relatively low in contrast to IFS. In clinical practice, IFS is a reliable method that can help accurately assess myometrial invasion and intraoperative decision-making (lymph node dissection or not). Hence, it should be routinely performed in non-endometrioid endometrial carcinoma patients.

Abstract This study aimed to explore the changes of the vaginal microbiota and enzymes in the women with high-risk human papillomavirus (HR-HPV) infection and cervical lesions. A total of 448 participants were carried out HPV genotyping, cytology tests, and microecology tests, and 28 participants were treated as sub-samples, in which vaginal samples were characterized by sequencing the bacterial 16S V4 ribosomal RNA (rRNA) gene region. The study found the prevalence of HR-HPV was higher in patients with BV (P = 0.036). The HR-HPV infection rate was 72.73% in G. vaginalis women, which was significantly higher than that of women with lactobacillus as the dominant microbiota (44.72%) (P = 0.04). The positive rate of sialidase (SNA) was higher in women with HR-HPV infection (P = 0.004) and women diagnosed with cervical intraepithelial neoplasia (CIN) (P = 0.041). In HPV (+) women, the α-diversity was significantly higher than that in HPV (−) women. The 16S rRNA gene-based amplicon sequencing results showed that Lactobacillus was the dominant bacteria in the normal vaginal microbiota. However, the proportion of Gardnerella and Prevotella were markedly increased in HPV (+) patients. Gardnerella and Prevotella are the most high-risk combination for the development of HPV (+) women. The SNA secreted by Gardnerella and Prevotella may play a significant role in HPV infection progress to cervical lesions.

Abstract Background Estrogen-related receptor α (ERRα) has been reported to play a critical role in endometrial cancer (EC) progression. However, the underlying mechanism of ERRα-mediated lipid reprogramming in EC remains elusive. The transcription factor EB (TFEB)-ERRα axis induces lipid reprogramming to promote progression of EC was explored in this study. Methods TFEB and ERRα were analyzed and validated by RNA-sequencing data from the Cancer Genome Atlas (TCGA). The TFEB-ERRα axis was assessed by dual-luciferase reporter and chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR). The mechanism was investigated using loss-of-function and gain-of-function assays in vitro. Lipidomics and proteomics were performed to identify the TFEB-ERRα-related lipid metabolism pathway. Pseudopods were observed by scanning electron microscope. Furthermore, immunohistochemistry and lipidomics were performed in clinical tissue samples to validate the ERRα-related lipids. Results TFEB and ERRα were highly expressed in EC patients and correlated to EC progression. ERRα is the direct target of TFEB to mediate EC lipid metabolism. TFEB-ERRα axis mainly affected glycerophospholipids (GPs) and significantly elevated the ratio of phosphatidylcholine (PC)/sphingomyelin (SM), which indicated the enhanced membrane fluidity. TFEB-ERRα axis induced the mitochondria specific phosphatidylglycerol (PG) (18:1/22:6) + H increasing. The lipid reprogramming was mainly related to mitochondrial function though combining lipidomics and proteomics. The maximum oxygen consumption rate (OCR), ATP and lipid-related genes acc, fasn, and acadm were found to be positively correlated with TFEB/ERRα. TFEB-ERRα axis enhanced generation of pseudopodia to increase the invasiveness. Mechanistically, our functional assays indicated that TFEB promoted EC cell migration in an ERRα-dependent manner via EMT signaling. Consistent with the in vitro, higher PC (18:1/18:2) + HCOO was found in EC patients, and those with higher TFEB/ERRα had deeper myometrial invasion and lower serum HDL levels. Importantly, PC (18:1/18:2) + HCOO was an independent risk factor positively related to ERRα for lymph node metastasis. Conclusion Lipid reprogramming induced by the TFEB-ERRα axis increases unsaturated fatty acid (UFA)-containing PCs, PG, PC/SM and pseudopodia, which enhance membrane fluidity via EMT signaling to promote EC progression. PG (18:1/22:6) + H induced by TFEB-ERRα axis was involved in tumorigenesis and PC (18:1/18:2) + HCOO was the ERRα-dependent lipid to mediate EC metastasis.

Abstract Background The natural history of human papillomavirus (HPV) is influenced by vaginal microenvironment disorders, such as bacterial vaginosis (BV). The objective of this study was to assess the epidemiology of HPV combined with BV prevalence among Chinese women aged 20–35 years. Methods A total of 2000 sexually active women aged 20–35 years voluntarily enrolled in this study and underwent a ThinPrep cytologic test and PCR-reverse dot blot human papillomavirus genotyping (PCR-RDB HPV test). BV was diagnosed if clue cells were observed (20% more than epithelial cells). Results The overall HPV infection rate in this population was 16.2% (324/2000). Compared with HPV-negative individuals, BV prevalence was higher in the High-risk human papillomavirus (HR-HPV) (5.9% vs. 3.1%, P

BackgroundRelated studies have shown that it is safe for cancer patients to undergo assisted reproduction. However, studies on whether a history of cancer affects long-term reproductive outcomes in women who undergo assisted reproductive technology (ART) are scarce. In this study, we evaluated the long-term reproductive outcomes of patients with malignant tumors undergoing ART treatment and explored the impact of malignancy history on ART outcomes.MethodsThis retrospective study analyzed the clinical outcomes of patients with malignant tumors undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles compared with those of age-matched healthy infertile women at Fujian Maternity and Child Health Hospital between January 2003 and October 2020. We evaluated ovarian stimulation outcome, the pregnancy rate, the live birth rate, the risk of adverse obstetric outcomes and birth outcomes.ResultsThis study included 59 patients in the cancer group for data analysis who had a history of malignancy. By matching, a total of 118 healthy infertile women were included in the control group. No statistically significant association was found in terms of age, duration of infertility, BMI, or insemination type between the two groups of patients. Thyroid cancer(45.8%) and gynecologic malignancies (44.07%) were the major cancer types in this study. There were statistically significant differences in the antral follicle count (AFC) (12.00 ± 7.86 vs. 14.90 ± 8.71, P=0.033), length of ovarian stimulation (9.98 ± 2.68 vs. 11.42 ± 2.43, P=0.033) and endometrial thickness on the trigger day (10.16 ± 3.11 vs. 10.84 ± 2.17, P0.05). There were no significant differences in the clinical pregnancy rate per ET cycle (32% vs. 40.39%, P=0.156), live birth rate per ET cycle (27% vs. 35.96%, P=0.119), miscarriage rate per ET cycle (5% vs. 4.43%, P=0.779), or preterm delivery rate per ET cycle (11.11% vs. 17.80%, P=0.547) between the two groups. Additionally, regression analysis showed that a history of malignancy was not a risk factor for reproductive outcomes.ConclusionsOverall, it is feasible for women with a history of cancer to conceive using ART is feasible and their long-term reproductive outcomes are similar to these of healthy infertile women. A history of cancer does not decrease the number of retrieved oocytes, increase the risk of adverse obstetric outcomes or affect birth outcomes.

Oxygen is critical to energy metabolism, and tumors are often characterized by a hypoxic microenvironment. Owing to the high metabolic energy demand of malignant tumor cells, their survival is promoted by metabolic reprogramming in the hypoxic microenvironment, which can confer tumor cell resistance to pyroptosis. Pyroptosis resistance can inhibit anti-tumor immunity and promote the development of malignant tumors. Hypoxia inducible factor-1α (HIF-1α) is a key regulator of metabolic reprogramming in tumor cells, and estrogen-related receptor α (ERRα) plays a key role in regulating cellular energy metabolism. Therefore, the close interaction between HIF-1α and ERRα influences the metabolic and functional changes in cancer cells. In this review, we summarize the reprogramming of tumor metabolism involving HIF-1α/ERRα. We review our understanding of the role of HIF-1α/ERRα in promoting tumor growth adaptation and pyroptosis resistance, emphasize its key role in energy homeostasis, and explore the regulation of HIF-1α/ERRα in preventing and/or treating endometrial carcinoma patients. This review provides a new perspective for the study of the molecular mechanisms of metabolic changes in tumor progression.

The effect of cervical cancer immunotherapy is limited. Combination therapy will be a new direction for cervical cancer. Thus, it is essential to discover a novel and available predictive biomarker to stratify patients who may benefit from immunotherapy for cervical cancer. In this study, 563 participants were enrolled. Adenylate cyclase 7 (ADCY7) mRNA was detected by real-time quantitative PCR (qPCR) with cervical cytology specimens. The relationship between ADCY7 and cervical intraepithelial neoplasia in grade 2 and higher (CIN2+) was analyzed, and the optimal cut-off values of the relative expression of ADCY7 mRNA to predict CIN2+ were calculated. In addition, the clinical significance of ADCY7 in cervical cancer was determined by the Kaplan–Meier Cox regression based on the TCGA database. The mean ADCY7 mRNA expression increased significantly with cervical lesion development, especially compared with CIN2+ (p < 0.05). Moreover, the expression of ADCY7 increased significantly in high-risk human papillomavirus (HR-HPV) infection but not in HPV-A5/6 species. The area under the receiver operating characteristic curve (AUC) of ADCY7 was 0.897, and an optimal cut-off was 0.435. Furthermore, ADCY7 had the highest OR (OR= 8.589; 95% CI (2.281–22.339)) for detecting CIN 2+, followed by HPV genotyping, TCT, and age (OR = 4.487, OR = 2.071, and OR = 1.345; 95% CI (1.156–10.518), (0.370–8.137), and (0.171–4.694), respectively). Moreover, this study indicated that higher ADCY7 levels could be a suitable predictor for poor prognosis in cervical cancer due to immune cell infiltration. A new auxiliary predictor of CIN2+ in cervical cytology specimens is ADCY7 ≥ 0.435. Furthermore, it may be a promising prognosis predictor and potential immunotherapy target for the combined treatment of cervical cancer and possibly further block HR-HPV persistent infection.

ObjectivesTo assess the risk factors of lymph node metastasis (LNM) in patients with FIGO stage (2009) IB1 cervical cancer (CC).MethodsPatients with FIGO stage IB1 CC who underwent radical resection between 2012 and 2018 were recruited. The risk factors for LNM were analysed. A recursive partitioning analysis (RPA) was used to divide the patients into risk groups and assess their risk of LNM.ResultsThe 5-year overall survival rate was 91.72%, while 80.0% and 93.5% for patients with or without LNM (P

Abstract Background New screening techniques may affect the optimal approaches for the prevention of cervical cancer. We evaluated the cost-effectiveness and accuracy of alternative screening strategies to provide evidence for cervical cancer screening guidelines in China. Methods In total, 32,306 women were enrolled. The current screening with Cervista® high-risk human papillomavirus (HR-HPV) nongenotyping and cytology cotesting (Cervista® cotesting) was compared with PCR-reverse dot blot HR-HPV genotyping and cytology cotesting (PCR-RDB cotesting). All eligible participants were divided into Arm 1, in which both HR-HPV assays were performed, and Arms 2 and 3, in which the PCR-RDB HPV or Cervista® HR-HPV assay, respectively, was performed. Outcome indicators included the cases, sensitivity, negative predictive value (NPV), colposcopy referral rate and cost of identifying cervical intraepithelial neoplasia of grade 2/3 or worse (CIN2+/CIN3+). Results Among the eligible participants, 18.4% were PCR-RDB HR-HPV-positive, while 16.9% were Cervista® HR-HPV-positive, which reflects good agreement (k = 0.73). PCR-RDB cotesting identified more CIN3+ cases than Cervista® cotesting in the first round of screening in Arm 1 (37 vs 32) and Arms 2/3 (252 vs 165). The sensitivity and NPV of PCR-RDB cotesting for identifying CIN3+ in Arm 1 (sensitivity: 94.9% vs 86.5%; NPV: 99.9% vs 99.7%) and Arms 2/3 (sensitivity: 95.1% vs 80.9%; NPV: 99.9% vs 99.6%) were higher than those of Cervista® cotesting, but the cost was similar. Conclusions The PCR-RDB HR-HPV genotyping and Cervista® HR-HPV assay results were consistent. PCR-RDB cotesting possesses optimal cost-effectiveness for cervical cancer screening in China, which has the highest number of cases globally but low screening coverage.

Colposcopy is an essential medical examination that mainly through visual inspection for cervical epithelial tissue to preventing cervical cancer. However, screening by artificial vision has the problems of missed diagnosis, low efficiency, and diversity. This paper proposes a deep learning-based method using multi-CNN decision feature integration for classification and diagnosis of cervical lesions. The proposed method first uses the k-means algorithm to aggregate training data into specific classes in data preprocessing and then trained in cross-validation to improve the generalization ability of the model. Subsequently, two kinds of CNN are separately fine-tuned based on the transfer learning, and then XGBoost algorithm is used to integrate the different CNN decision results for optimizing the final prediction. Two integration ways for decision features (named inner-model integration and outer-model integration) are proposed to embody multi-feature integration from the data level and the model structural level. Simultaneously, two specific integration strategies (inner-to-outer and outer-to-inner) are designed for as the final output based on the combination of the two ways. Experimental results show that the K-means data preprocessing method can improve the training of neural networks, and the proposed multi-decision feature fusion strategy can better obtain the results of computer-aided diagnosis that meet the needs of clinical diagnosis.

Background: Upregulating tumor cell targeting antigens and improving the cytotoxicity of chimeric antigen receptor T cell (CAR-T) are expected to facilitate better treatment efficacy for solid cancers represented by ovarian cancer. Methods: Killer cell lectin-like receptor subfamily K member 1 ligands (NKG2DL) are the target antigens for ovarian cancer. NKG2D-CAR-T cells were constructed for NKG2D ligand on the ovarian cancer cell surface. We used flow cytometry to evaluate the expression of NKG2DL on SKOV3 (a human ovarian cancer adenocarcinoma cell line). Innovatively, when combined with romidepsin to treat ovarian cancer cell SKOV3, to evaluate the killing ability of the combined strategy, we verified the cytotoxicity of CAR-T cells by lactate dehydrogenase (LDH) release test and determined the secretion of cytokines by enzyme-linked immuno sorbent assay (ELISA). Results: The results of flow cytometry showed effective activation of the NKG2D-CAR-T cells, and romidepsin treatment resulted in increased expression of NKG2DL on the surface of SKOV3. Cytotoxicity test showed that romidepsin could enhance the killing ability of NKG2D-CAR-T cells against ovarian cancer cells by regulating their NKG2DL expression (p < 0.05). The killing effects and secretion of interferon-γ (IFN-γ) increased synchronously (p < 0.05). Levels of interleukin-2 (IL-2) and Pore-forming protein (PFP) were statistically significant at a low target ratio but programmed cell death protein 1 (PD-1) remained unaffected (p ≥ 0.05). Conclusions: Enhancing the expression of tumor target antigen is a solution to improve the limited application of CAR-T cells in solid cancers.

Background: China’s Fujian Cervical Pilot Project (FCPP) transitioned cervical cancer screening from high-risk human papillomavirus (HR-HPV) nongenotyping to genotyping. We investigated the clinical impact of this introduction, comparing performance indicators between HR-HPV genotyping combined with cytology screening (HR-HPV genotyping period) and the previous HR-HPV nongenotyping combined with cytology screening (HR-HPV nongenotyping period). Methods: A retrospective population-based cohort study was performed using data from the FCPP for China. We obtained data for the HR-HPV nongenotyping period from 1 January 2012 to 31 December 2013, and for the HR-HPV genotyping period from 1 January 2014 to 31 December 2016. Propensity score matching was used to match women from the two periods. Multivariable Cox regression was used to assess factors associated with cervical intraepithelial neoplasia of grade 2 or worse (CIN2+). The primary outcome was the incidence of CIN2+ in women aged ⩾25 years. Performance was assessed and included consistency, reach, effectiveness, adoption, implementation and cost. Results: Compared with HR-HPV nongenotyping period, in the HR-HPV genotyping period, more CIN2+ cases were identified at the initial screening (3.06% versus 2.32%; p

Aggressive angiomyxoma is an interstitial tumour that is often misdiagnosed and is likely to recur. There have been few reported cases of angiomyxoma in pregnant women. We report a case of a woman who was previously diagnosed with a tumour in her vulva that increased in size during both of her pregnancies and spontaneously decreased postpartum. Local excision was performed and a gonadotropin-releasing hormone agonist was administered. According to a literature review, aggressive angiomyxoma is associated with good maternal and child outcomes. Caesarean section is not the delivery method of choice, but it is indicated if the tumour is preventing vaginal birth. Treatment for angiomyxoma is mainly postpartum local resection supplemented by hormone therapy. This tumour frequently recurs and patients should undergo long-term follow-up.

Purpose. This study investigated the infection status and relationship between other common lower genital tract infectious pathogens and high-risk human papillomavirus (HR-HPV) in the high-grade cervical lesions. Methods. Overall, 882 patients were enrolled in this retrospective study, of which 339 patients (≥HSIL group) were confirmed with high-grade squamous intraepithelial lesions (HSIL) or cervical squamous cell carcinoma (SCC), while 543 patients (≤LSIL group) were diagnosed with low-grade squamous intraepithelial lesions (LSIL) or normal cervical pathology diagnosis. Cervical swab specimens were tested for HPV, pathogenic bacteria (PB), U. urealyticum (UU), M. hominis (MH), and C. trachomatis (CT) in both groups. Results. The infection rates of HR-HPV, PB, UU (at high density), and CT were higher in the ≥HSIL group than in the ≤LSIL group (P0.05). PB, UU, and CT were associated with HR-HPV infection (P0.05). Furthermore, 259 pathogenic bacterial strains were detected in 882 cases. The difference in the distribution of pathogenic bacterial flora in the different grades of cervical lesions had no statistical significance, which was prioritized over Escherichia coli (P>0.05). Conclusion. PB, UU, and CT infection is associated with susceptibility to HR-HPV, HR-HPV coinfection with these pathogens might increase the risk of high-grade cervical lesions, and PB and UU might be independent risk factors for cervical lesions.

Abstract Few studies have examined the potential transcription factor (TF) simultaneously associated with cisplatin resistance and metastasis in ovarian cancer. To assess a related mechanism, a 345-channel protein/DNA array and transcriptional activity ELISA were performed to compare the TF activities in the cisplatin-sensitive SKOV3 and cisplatin-resistant SKOV3-DDP cells and in HO-8910 and the homologous highly metastatic HO-8910PM cells. In SKOV3-DDP vs. SKOV3 cells, 43 TFs were up-regulated, while 31 were down-regulated. In HO-8910PM vs. HO-8910 cells, 13 TFs were up-regulated, while 18 were down-regulated. In these two models, 4 TFs (HOXD8(1), HOXD8(2), RB, RFX1/2/3) were simultaneously up-regulated, and 9 TFs (SRE, FKHR, Angiotensinogen ANG-IRE, Pax2, CD28RC/NF-IL2B, HLF, CPE, CBFB and c-Ets-1) were down-regulated. HOXD8 mRNA and protein expression levels measured by reverse transcription polymerase chain reaction and ELISA, respectively, were significantly higher in SKOV3-DDP and HO-8910PM than in their corresponding cell lines (both p

Purpose: Currently, there are no reliable indicators for the early identification of patients with low-risk gestational trophoblastic neoplasia (GTN) who develop resistance to monotherapy. This study aimed to evaluate the effectiveness of combining the Systemic Immune-Inflammation Index (SII) and Prognostic Nutritional Index (PNI) in detecting early resistance to monotherapy in patients with low-risk GTN. Methods: This retrospective study included 91 patients with low-risk GTN who received initial monotherapy at Fujian Maternal and Child Health Hospital between 2013 and 2021. The SII and PNI before chemotherapy were calculated from prechemotherapy peripheral blood samples, with cut-off values determined by receiver operating characteristic (ROC) curves. The SII-PNI score ranged from 0 to 2 points and was categorized as follows: a score of 2 points indicated a high SII (=467.02) and a low PNI (=51.35); a score of 1 point indicated either a high SII or a low PNI; and a score of 0 points indicated neither a high SII nor a low PNI. Results: Ninety-one patients with low-risk GTN underwent monotherapy, 19 of whom developed resistance, whereas the remaining 72 did not. The SII was significantly greater in chemotherapy-resistant patients than in non-resistant patients (P=0.04), whereas the PNI was markedly lower in chemotherapyresistant patients (P=0.002). Univariate analysis revealed that cut-off values of 467.02 for the SII (P=0.04) and 51.35 for the PNI (P=0.024) were associated with chemotherapy resistance in patients with low-risk GTN. As the SII-PNI score increased, the proportion of chemotherapy-resistant patients increased (P<0.001), and the time for human chorionic gonadotropin (hCG) normalization correspondingly increased (P<0.001). Multivariate logistic regression analysis indicated that a high SII-PNI score is an independent risk factor for chemotherapy resistance in patients with low-risk GTN (P=0.001). Conclusion: A high SII and low PNI are linked to chemotherapy resistance in patients with low-risk GTN. The pretreatment SII-PNI score is a key indicator for predicting the sensitivity of patients with low-risk GTN to single-agent chemotherapy, aiding in the early identification of individuals at high risk of resistance. [ABSTRACT FROM AUTHOR]

Objective: CD112 and CD112R were new immune checkpoints. They expressed in both programmed death-ligand 1-negtive and PD-L-positive tumor tissues. However, their expression pattern and biological significance in cervical cancer remain unknown. Methods: In this study, we obtained the expression of CD112/CD112R and clinical prognosis in cervical cancer via multiple databases. The results were further investigated using realtime quantitative polymerase chain reaction (RT-qPCR) in cytology specimens and immunohistochemical staining (IHC) in tissue microarray (TMA). Furthermore, receiver operating characteristics (ROC) analysis and Kaplan-Meier Cox regression were used to assess the clinical significance and prognosis of CD112/CD112R in cervical cancer patients. Results: CD112 and CD112R highly increased in almost all tumors, including cervical cancer. RT-qPCR and IHC results were consistent with the above. Also, CD112 mRNA expression increased with the development of cervical lesions. In addition, we found that CD112 mRNA expression had a highly area under the ROC curve with 0.849 and an optimal cut-off was 0.465 to predict the more than high grade cervical lesions (cervical intraepithelial neoplasia 2+). And, CD112 expression is an independent prognostic factor. Furthermore, high-expression of CD112 was significantly related to poor overall survival (OS) (hazard ratio [HR]=2.97; 95% confidence interval [CI]=1.05-8.44) and disease-free survival (DFS) (HR=3.15; 95% CI=1.15-8.61). However, high-expression of CD112R was associated with poor OS (HR=2.87; 95% CI=1.01-8.14), but not DFS. The results demonstrated that CD112 and CD112R expression were associated with immune cell infiltration in cervical cancer, but not other immune checkpoints. Conclusion: It demonstrated that CD112/CD112R expression increased in cervical cancer. Moreover, they can be novel and valuable predictors and prognostic biomarkers. Importantly, they may be promising and potential immunotherapy target for combination immunotherapy in. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the polymerase chain reaction (PCR)-reverse-dot-blot (RDB) human papillomavirus (HPV) genotyping test as a feasible assay for the cervical cancer primary screening. Methods: In a hospital-based cohort, a total of 21,568 women were voluntarily enrolled from March 2009 to November 2016 for evaluating the 3 current cervical cancer screening strategies: co-test, cytology primary and high-risk HPV (HR-HPV) primary by using PCRRDB HPV genotyping and liquid-based cytology (thinprep cytologic test [TCT]). Women with HR-HPV infection and/or abnormal cytology were referred for colposcopy, and the biopsy or conization was performed according to the American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines. Results: Overall, 18.20% (3,935/21,568) of the women were detected as HR-HPVpositive, 5.04% (1,088/21,568) were diagnosed with cervical intraepithelial neoplasia 2 or higher (CIN2+), and 3.43% (739/21,568) with CIN3+. The cumulative incidence rates for CIN2+/CIN3+ in patients with HPV-16/18-positive were 48.28%/37.20%, while they were 0.86%/0.38%, 0.30%/0.15% and 0.18%/0.09% in cytology-negative, HR-HPV-negative and co-test-negative population, respectively. Using CIN2+ and CIN3+ as the observed endpoints, the sensitivity and negative predictive value (NPV) of HR-HPV genotyping as a primary screening tool were 90.99%/99.49% and 91.57%/99.80%. Moreover, using HR-HPV genotyping primary screening could detect the same more CIN2+/CIN3+ cases in baselinedetection as co-testing (990/700 vs. 991/701) and far more than cytology primary screening (903/656, p<0.05). It also achieved the lowest misdiagnosis rate (8.01%/5.02%). Although HPV genotyping primary screening required an increased number of colposcopies (2.75/3.89 per CIN2+/CIN3+ case), it yielded an acceptable rate. Conclusions: The PCR-RDB HPV genotyping test is a cost-effective and beneficial cervical cancer primary screening for hospital-based opportunistic screening. [ABSTRACT FROM AUTHOR]

Objective: To determine the clinical significance of the polymerase chain reaction (PCR)- reverse dot blot (RDB) human papillomavirus (HPV) genotyping assay in cervical cancer screening. Methods: A total of 10,442 women attending the Fujian Provincial Maternity and Children's Health Hospital were evaluated using the liquid-based cytology (thinprep cytologic test [TCT]) and the PCR-RDB HPV test. Women with HPV infection and/or abnormal cytology were referred for colposcopy and biopsy. For HPV DNA sequencing, 120 specimens were randomly selected. Pathological diagnosis was used as the gold standard. Results: Using the PCR-RDB HPV test, overall HPV prevalence was 20.57% (2,148/10,442) and that of high-risk (HR)-HPV infection was 18.68% (1,951/10,442). There was 99.2% concordance between HPV PCR-RDB testing and sequencing. In this studied population, the most common HR-HPV types were HPV-16, -52, -58, -18, -53, -33, and -51, rank from high to low. HPV-16, -18, -58, -59, and -33 were the top 5 prevalent genotypes in cervical cancer but HPV-16, -18, -59, -45, and -33 were the top 5 highest risk factors for cancer (odds ratio [OR]=34.964, 7.278, 6.728, 6.101, and 3.658; all p<0.05, respectively). Among 10,442 cases, 1,278 had abnormal cytology results, of which, the HR-HPV positivity rate was 83.02% (1,061/1,278). To screen for cervical cancer by PCR-RDB HPV testing, when using CIN2+, CIN3+, and cancer as observed endpoints, the sensitivity was 90.43%, 92.61%, and 94.78% and the negative predictive value (NPV) was 99.06%, 99.42%, and 99.78%, respectively. PCRRDB HPV and TCT co-testing achieved the highest sensitivity and NPV. Conclusion: For cervical cancer screening, the PCR-RDB HPV test can provide a reliable and sensitive clinical reference. [ABSTRACT FROM AUTHOR]

Gestational trophoblastic disease (GTD) is a group of conditions that originate from the abnormal proliferation of trophoblastic cells. GTDs encompass hydatidiform moles (HMs) and gestational trophoblastic neoplasia (GTN). GTNs are a group of malignant diseases that require chemotherapy, or more aggressive treatment. There is a requirement for more tumor markers to predict the development of GTN from HMs. The current study evaluated the expression of maspin and tumor protein p53 (p53) in GTD, and their role in predicting the development of GTN. Expression of maspin and mutant p53 (m-p53) was detected by immunohistochemistry in 48 normal first trimester placentas, matched for gestational age to 49 HMs that regressed, 39 malignant HMs and 11 invasive moles or choriocarcinomas. Spearman's rank correlation analysis and logistic regression were performed on the expression patterns of maspin and m-p53, and on the clinical prognostic factors in GTD. Compared with normal placenta levels, the expression levels of maspin were decreased, whereas the expression levels of m-p53 were increased in GTDs (P<0.05). The expression levels of maspin and m-p53 in complete and partial HMs were not significantly different (P>0.05). In HMs, maspin expression was inversely correlated with serum β human chorionic gonadotropin, uterine size and diameter of theca-lutein cysts however, m-p53 expression demonstrated a positive correlation with these factors (all P<0.05). Compared with the high-risk metastatic group (FIGO score ≥7), the low-risk group (FIGO score <7) exhibited a higher rate of positive maspin expression (P=0.041), and the frequency of positive m-p53 expression was significantly higher in patients with an advanced FIGO stages (FIGO stage ≥III) compared with patients in early stages (FIGO stage ≤II; 87.9 vs. 58.8%; P=0.019). The combination of maspin negative expression with m-p53 positive expression had an 84% specificity value, 76% positive predictive value and 70% negative predictive value for the development of GTN. In conclusion, maspin-negative and m-p53-positive expression is associated with the development of GTN in HMs. [ABSTRACT FROM AUTHOR]

Tumor invasion and metastasis are complex biological processes. Matriptase and its endogenous inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1) are involved in invasion and metastasis. To evaluate the ratio of matriptase/HAI-1 and their potential therapeutic value in ovarian cancer, HO-8910 human ovarian cancer cells and the homologous high-metastatic HO-8910PM cells were used as in vitro cellular models ovarian cancer. The invasive and metastatic abilities, and the expression of matriptase and HAI-1 in these cells were detected using scratch assays, Transwell chamber assays, reverse transcription-quantitative polymerase chain reaction, western blotting and fluorescent immunocytochemistry. Following infection with lentivirus-mediated matriptase-targeting small interfering RNA (siRNA), cell cycle progression and apoptosis were also analyzed. The migration distance and number of invading HO-8910PM cells were significantly increased compared with HO-8910 cells. HO-8910PM cells exhibited a significantly higher ratio of matriptase/HAI-1 mRNA levels compared with HO-8910 cells (0.51 vs. 0.24, ~2.2 fold increase). Compared with HO-8910 cells, the matriptase mRNA level was increased by ~3.6 fold in HO-8910PM cells, whereas the HAI-1 mRNA level was increased by ~1.7 fold. Similar increases in protein expression levels were also observed in HO-8910PM cells compared with HO-8910 cells. Migration and invasiveness were positively correlated with matriptase expression level (r=0.994, P<0.01) and the ratio of matriptase/HAI-1 (r=0.929, P<0.01). Downregulation of matriptase using siRNA resulted in inhibition of the invasive and metastatic abilities of HO-8910PM cells, cell cycle arrest in the G0/G1 phase and increased apoptosis. The present study demonstrated that ovarian cancer cell metastasis and invasion were more dependent on upregulation of matriptase levels than downregulation of HAI-1. Matriptase may be a potential adjuvant therapeutic target for inhibiting ovarian cancer invasion and metastasis. [ABSTRACT FROM AUTHOR]

A subfamily of orphan receptors, estrogen receptor-related receptors (ERRs), has been demonstrated to modulate the transcription of some estrogen responsive genes via variant estrogen response elements (EREs). This study was conducted to determine whether human ERRα, ERRβ, and ERRγ might be involved in the tumorigenesis of ovarian cancer. RT-PCR was performed to analyze the expression of hERRα, hERRβ, hERRβ-2, and hERRγ mRNA in five ovarian cancer cell lines as well as 33 samples of ovarian cancer and 12 samples of normal ovary. Serum CA-125 levels were also analyzed in all samples by ELISA. Progression-free survival and overall survival of patients with different expression of ERRs were analyzed by the Kaplan–Meier method. To analyze the subcellular localization of ERRα, a green fluorescent protein (GFP)-reporter plasmid of hERRα was constructed and transfected into the ovarian cancer cell line OVCAR-3. Expression of hERRα-GFP fusion protein was observed in the nucleus of OVCAR-3 ovarian cancer cell lines. We observed increased expression of hERRα mRNA ( P=0.020) and hERRγ mRNA ( P=0.045) in ovarian cancers compared to normal ovaries. In contrast, hERRβ was only observed in 9.1% of ovarian cancers. We found a positive correlation between the serum CA-125 levels and hERRα expression ( P=0.012), but not hERRβ and hERRγ expression. Survival analysis showed that the hERRα-positive group has a reduced overall survival ( P=0.015), and the ERRγ-positive group has a longer progression-free survival ( P=0.020). In multivariate analysis, expression of hERRα was an independent prognostic factor for poor survival (relative risk, 3.032; 95% CI, 1.27–6.06). Based on our results, ERRs may play an important role in ovarian cancer. hERRα may represent a biomarker of poor prognosis, and hERRγ may be a new therapeutic target in ovarian cancer. [ABSTRACT FROM AUTHOR]