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Background and Objectives: This study aimed to evaluate the tumor response relating to and survival benefit of transarterial chemoperfusion (TACP) and transarterial chemoembolization (TACE) in the treatment of patients with unresectable gynecologic tumors who are intolerant of or have a suboptimal response to chemotherapy and radiotherapy. Materials and Methods: Between January 2000 and October 2023, 75 patients diagnosed with gynecologic tumors underwent 213 TACP and 154 TACE procedures. Of these, 33 patients were treated with TACP, 20 were treated with TACE, and 22 received a combination of both therapies. A retrospective evaluation of local tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) was conducted, and survival rates were determined using the Kaplan–Meier estimator. Results: Of the total 75 patients, 50 (67%) maintained a stable course of disease until the completion of therapy, 10 (13%) had a partial response, 2 (3%) had a complete response following thermal ablation, and 13 (17%) experienced progression. Furthermore, a 6% reduction in the sum of the longest diameters and an 8% reduction in tumor volume were observed. The median overall survival was 16.15 months, while the median progression-free survival was 13.19 months. Conclusions: TACP and TACE are potential treatment options for local tumor control in patients with unresectable gynecologic tumors who are intolerant of or show a poor response to chemotherapy and radiotherapy. However, further investigation and adjustment of treatment protocols are required to improve therapy response and survival outcomes. [ABSTRACT FROM AUTHOR]

Abstract Objective miR-497/195, located at 17p13.1, is a highly conserved miRNA cluster whose abnormal expression is a key regulator of carcinogenesis. We performed a comprehensive analysis of the miR-497/195 cluster to determine its prognostic utility and role in cervical cancer (CC) using publicly available datasets. Results In silico analysis and validation revealed that this cluster is downregulated in CC. A total of 60 target genes of miR-497/195 cluster were identified as differentially expressed between normal and CC samples. ShinyGO, STRING, CytoHubba, Timer 2.0, HPA, and HCMBD were used for functional enrichment, PPIN network construction, hub gene identification, immune infiltration correlation, histopathological expression, and determination of the metastatic potential of miR-497/195 cluster and their target genes. PPIN analysis identified CCNE1, CCNE2, ANLN, RACGAP1, KIF23, CHEK1, CDC25A, E2F7, CDK1, and CEP55 as the top 10 hub genes (HGs). Furthermore, the upregulation of RECK, ATD5, and BCL2, downregulation of OSBPL3, RCAN3, and HIST1H3H effected overall survival of CC patients. We identified 6 targets (TFAP2A, CLSPN, RASEF, HIST1H3H, AKT3, and ITPR1) of miR-497/195 cluster to influence metastasis. In addition, 8 druggable genes and 38 potential drugs were also identified. Our study identified miR-497/195 cluster target genes and pathways that could be used for prognostic and therapeutic applications in CC.

Objective: miR-497/195, located at 17p13.1, is a highly conserved miRNA cluster whose abnormal expression is a key regulator of carcinogenesis. We performed a comprehensive analysis of the miR-497/195 cluster to determine its prognostic utility and role in cervical cancer (CC) using publicly available datasets. Results: In silico analysis and validation revealed that this cluster is downregulated in CC. A total of 60 target genes of miR-497/195 cluster were identified as differentially expressed between normal and CC samples. ShinyGO, STRING, CytoHubba, Timer 2.0, HPA, and HCMBD were used for functional enrichment, PPIN network construction, hub gene identification, immune infiltration correlation, histopathological expression, and determination of the metastatic potential of miR-497/195 cluster and their target genes. PPIN analysis identified CCNE1, CCNE2, ANLN, RACGAP1, KIF23, CHEK1, CDC25A, E2F7, CDK1, and CEP55 as the top 10 hub genes (HGs). Furthermore, the upregulation of RECK, ATD5, and BCL2, downregulation of OSBPL3, RCAN3, and HIST1H3H effected overall survival of CC patients. We identified 6 targets (TFAP2A, CLSPN, RASEF, HIST1H3H, AKT3, and ITPR1) of miR-497/195 cluster to influence metastasis. In addition, 8 druggable genes and 38 potential drugs were also identified. Our study identified miR-497/195 cluster target genes and pathways that could be used for prognostic and therapeutic applications in CC. [ABSTRACT FROM AUTHOR]

The ectopic expression of cellular retinoic acid binding protein 2 (CRABP2) is associated with various tumorigenesis. However, the effects of CRABP2 on the progression of cervical cancer are still unclear. The current study aimed to investigate the role of CRABP2 in the malignant phenotypes of cervical cancer cells. CRABP2 was artificially regulated in CaSki, SiHa, and C-33A cells. CCK-8 assay and flow cytometry were used to assess the cell proliferation and apoptosis abilities, respectively. Wound healing assay and transwell assay were employed to measure the cell migration and invasion abilities, respectively. The results showed that CRABP2 was highly expressed in cervical carcinoma tissues and cell lines, and its high expression was associated with poor overall survival. Knockdown of CRABP2 promoted the cell apoptosis and inhibited cell proliferation, migration, and invasion in cervical carcinoma cells, whereas CRABP2 overexpression exhibited the opposite results. Mechanically, CRABP2 silencing suppressed the Integrin β1/FAK/ERK signaling via HuR. Treatment with siITGB1 or a FAK inhibitor PF-562271 or an ERK inhibitor FR180204 reversed the promoting effects of CRABP2 on cell proliferation, migration, and invasion. Moreover, the overexpression of CRABP2 reverted the HPV16 E6/E7 knockdown-induced inhibition of cell proliferation, migration, and invasion in cervical cancer cells. These results suggested that HPV16 E6/E7 promoted the malignant phenotypes of cervical cancer by upregulating the expression of CRABP2. In conclusion, CRABP2, upregulated by HPV E6/E7, promoted the progression of cervical cancer through activating the Integrin β1/FAK/ERK signaling pathway via HuR. [ABSTRACT FROM AUTHOR]

Introduction: Cervical carcinoma is the second commonest malignancy among females worldwide. In India, about 365.71 million women aged over 15 years are more vulnerable to cervical carcinoma. Risk factors may include immunodeficiency diseases, herpes, smoking and oral contraceptives. Scientific literature has documented that type 2 diabetes mellitus (T2DM) could aggravate the risk of some malignancies (hepatic, pancreatic, endometrial). This study aimed to evaluate the potential association between cervical carcinoma and diabetes mellitus in women. Material and Methods: Patients with cervical carcinoma, with or without diabetes, were assigned to two groups based on attainment of menopause. SPSS version 11.5 was used for data analysis. Odds ratios were calculated, and the chi-square test was used. P-values ≤ 0.05 were considered statistically significant. Results: It was observed that 29% of patients with cervical cancer were sixty to seventy years old, with a majority (40%) of them being multiparous. Though the association of body mass index as a risk factor for diabetic patients with cervical carcinoma was not significant in pre-and post-menopausal age groups, T2DM in cervical carcinoma is a useful prognostic indicator. Conclusions: Diabetic females after attaining menopause have a higher risk of developing cervical carcinoma and therefore should mandatorily receive routine screening. Future research with a longer timeframe is needed in order to generalize the results. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between the DNA methylation state of NRG1 promoter and its expression changes, and to analyze the clinical significance of its regulatory mechanism of DNA methylation in cervical carcinoma. Methods: This was a retrospective study. One-hundred and twenty patients from the Department of Gynecology of Cangzhou People's Hospital from September 2017 to September 2019 were selected, including 40 cases of cervical SCC, 40 cases of high grade squamous intraepithelial lesions (HSIL) and 40 cases of control cervical tissues. RT-qPCR, immunohistochemistry and DNA methylation-specific PCR (MSP) were used to detect the mRNA and protein expression of NRG1 and DNA methylation status in different tissue types. Results: Immunohistochemical results showed that the positive protein expression rate of NRG1 gene in the SCC group was lower than that in both HSIL and Control groups. RT-qPCR results showed that the mRNA gene of NRG1 gradually decreased in expression with the increase of cervical tissue lesions, with a statistically significant difference. Similarly, it also found that the mRNA expression level of NRG1 in the SCC group was independent of patients' age (p>0.05), but significantly correlated with tumor pathological staging, surgical pathology staging and lymphatic metastasis (p<0.05). Furthermore, methylation-specific PCR results revealed a significantly higher DNA methylation rate of NRG1 gene in the SCC group than in both HSIL and Control groups, with a statistically significant difference. Moreover, the methylation degree of NRG1 gene in SCC tissues was negatively correlated with its mRNA expression (p<0.05). Conclusions: Abnormal DNA hypermethylation of NRG1 gene inhibits the expression of mRNA and protein in the progression of cervical tissue from normal to cancerous state, which is involved in the occurrence and development of cervical carcinoma. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization states that cervical carcinoma is the fourth most common cancer among women worldwide. Pap smear is the simplest and easiest test to detect this prevalent cancer at its nascent stages. Aims and Objectives: This study aims to evaluate Pap smears using the conventional method (Bethesda 2014) and correlate the abnormal smears with cervical biopsy. Materials and Methods: The study is a combined retrospective and prospective study, from January 2021 to August 2023. Pap smears received were evaluated according to Bethesda 2014. Those cases categorized as Epithelial Cell Abnormality (ECA), were correlated with corresponding histopathology on cervical biopsy. Results: Out of the 615 pap smears in this study, 525 cases (91%) were categorized as Negative for Intraepithelial Lesion or Malignancy, 53 cases (9%) as Epithelial Cell Abnormality, and 37 cases (6%) as unsatisfactory. In the Negative for Intraepithelial Lesion or Malignancy category, 353 cases (67.2%) were reactive cellular changes including inflammation, four cases (0.7%) were squamous metaplasia, and 24 cases (4.6%) were atrophic smears. In the ECA category–21 cases (39.6%) were Atypical squamous cells of undetermined significance, two cases (3.8%) were Low-grade squamous intraepithelial lesion, five cases (9.4%) were Atypical squamous cells-cannot exclude HSIL(ASC-H), 14 cases (26.4%) were High grade squamous intraepithelial lesion (HSIL) and 3 cases (5.6%) were squamous cell carcinoma (SCC) cervix, seven cases were of ECA-glandular type (13.2%). On histopathological correlation, the maximum correlation was found for HSIL and SCC cases, 71% and 100%, respectively. Conclusion: Pap smear is a crucial screening tool to diagnose cervical carcinoma at its nascent stage. This study showed a positive correlation for high-grade lesions on Pap smears.

Background: Angiogenesis is necessary for invasion and metastasis of cervical carcinoma and is a crucial stage in controlling the course of malignancy. Microvasculature may be quantified by calculating Mean Microvessel Density (MVD) using CD31 Immunohistochemical (IHC) labeling of endothelial cells. E6 and E7 oncogenes of Human Papillomavirus (HPV) will inactivate p53 and pRb, respectively. This has been discovered to encourage angiogenesis by up-regulating vascular endothelial growth factor and down-regulating thrombospondin-1 during the early stages of carcinogenesis. Aim and Objectives: To assess the IHC expression of CD31 in cervical dysplasia and carcinomas and link these expressions with the IHC expression of HPV (16E6 + 18E6) and specific clinicopathological criteria, such as stage and grade of cervical carcinoma. Material and Methods: In a cross-sectional investigation, 52 cervical tissue samples were formalin-fixed and paraffin-embedded. On hematoxylin and eosin slides, the histological diagnoses were obtained. Samples were then stained immunohistochemically with monoclonal mouse antibodies, including anti-CD31 antibody and Anti-HPV (16E6 + 18E8) antibody. Results: Mean MVD rose significantly with increasing cervical lesion severity. In 78.1% of patients with invasive cervical carcinomas, HPV expression was detected, compared to 41.7% of cases with high-grade squamous intra-epithelial lesion and 37.5% of cases with low-grade squamous intra-epithelial lesion. Conclusion: HPV plays a crucial role in malignant transformation of the cervix, with a substantial positive association between a rise in MVD and expression of high-risk HPV types (16 and 18) in malignant and premalignant instances.

Background: Immune checkpoint inhibitors (ICIs), especially anti-PD-1/PD-L1 antibodies, have emerged as promising therapeutic options for cervical cancer. However, the efficacy of anti-PD-1 antibody monotherapy is limited. Cryoablation could elicit an anti-tumor immune response, thereby presenting itself as a potential approach to augment the response of ICIs. The aim of our study was to investigate the systemic immunological effects of cryoablation and the potential synergistic anti-tumor effects of cryoablation and anti-PD-1 antibody in cervical cancer. Methods: We established U14 murine bilateral subcutaneous cervical cancer model, wherein the primary tumors were treated with cryoablation. Flow cytometry, immunohistochemistry and RNA-seq were used to analyze the immune cell infiltration and immune-associated pathways in the secondary tumor. Results: Our study revealed that cryoablation reprogrammed the immune landscape, leading to an enhanced infiltration of CD8+ T cell in distant tumors. Cryoablation created a conducive environment for increasing the efficacy of anti-PD-1 immunotherapy. Cryoablation in combination with anti-PD-1 antibody inhibited distant tumors growth and improved mouse survival. Mechanistically, this combination therapy could augment the infiltration of CD8+ T cells, CD4+ T cells, dendritic cells and M1-like tumor-associated macrophages, enhance multiple aspects of antitumor immune response, and reduce immunosuppressive cells such as M2-like tumor-associated macrophages and myeloid-derived suppressor cells in distant tumors. Conclusions: Combination therapy with cryoablation and anti-PD-1 antibody induces an effective abscopal effect in murine model of cervical cancer and may be a novel therapeutic approach for patients with advanced/recurrent cervical cancer.

Background: The World Health Organization states that cervical carcinoma is the fourth most common cancer among women worldwide. Pap smear is the simplest and easiest test to detect this prevalent cancer at its nascent stages. Aims and Objectives: This study aims to evaluate Pap smears using the conventional method (Bethesda 2014) and correlate the abnormal smears with cervical biopsy. Materials and Methods: The study is a combined retrospective and prospective study, from January 2021 to August 2023. Pap smears received were evaluated according to Bethesda 2014. Those cases categorized as Epithelial Cell Abnormality (ECA), were correlated with corresponding histopathology on cervical biopsy. Results: Out of the 615 pap smears in this study, 525 cases (91%) were categorized as Negative for Intraepithelial Lesion or Malignancy, 53 cases (9%) as Epithelial Cell Abnormality, and 37 cases (6%) as unsatisfactory. In the Negative for Intraepithelial Lesion or Malignancy category, 353 cases (67.2%) were reactive cellular changes including inflammation, four cases (0.7%) were squamous metaplasia, and 24 cases (4.6%) were atrophic smears. In the ECA category-21 cases (39.6%) were Atypical squamous cells of undetermined significance, two cases (3.8%) were Low-grade squamous intraepithelial lesion, five cases (9.4%) were Atypical squamous cells-cannot exclude HSIL(ASC-H), 14 cases (26.4%) were High grade squamous intraepithelial lesion (HSIL) and 3 cases (5.6%) were squamous cell carcinoma (SCC) cervix, seven cases were of ECA-glandular type (13.2%). On histopathological correlation, the maximum correlation was found for HSIL and SCC cases, 71% and 100%, respectively. Conclusion: Pap smear is a crucial screening tool to diagnose cervical carcinoma at its nascent stage. This study showed a positive correlation for high-grade lesions on Pap smears. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis is necessary for invasion and metastasis of cervical carcinoma and is a crucial stage in controlling the course of malignancy. Microvasculature may be quantified by calculating Mean Microvessel Density (MVD) using CD31 Immunohistochemical (IHC) labeling of endothelial cells. E6 and E7 oncogenes of Human Papillomavirus (HPV) will inactivate p53 and pRb, respectively. This has been discovered to encourage angiogenesis by up-regulating vascular endothelial growth factor and down-regulating thrombospondin-1 during the early stages of carcinogenesis. Aim and Objectives: To assess the IHC expression of CD31 in cervical dysplasia and carcinomas and link these expressions with the IHC expression of HPV (16E6 + 18E6) and specific clinicopathological criteria, such as stage and grade of cervical carcinoma. Material and Methods: In a cross-sectional investigation, 52 cervical tissue samples were formalin-fixed and paraffin-embedded. On hematoxylin and eosin slides, the histological diagnoses were obtained. Samples were then stained immunohistochemically with monoclonal mouse antibodies, including anti-CD31 antibody and Anti-HPV (16E6 + 18E8) antibody. Results: Mean MVD rose significantly with increasing cervical lesion severity. In 78.1% of patients with invasive cervical carcinomas, HPV expression was detected, compared to 41.7% of cases with high-grade squamous intra-epithelial lesion and 37.5% of cases with low-grade squamous intra-epithelial lesion. Conclusion: HPV plays a crucial role in malignant transformation of the cervix, with a substantial positive association between a rise in MVD and expression of high-risk HPV types (16 and 18) in malignant and premalignant instances. [ABSTRACT FROM AUTHOR]

Background: To explore the role of vaginal microbiota and metabolomics in the progression of cervical dysplasia. Methods: The patient group consists of female patients with low-grade, high-grade cervical dysplasia, and cervical cancer. Normal cervix samples from health volunteers were used as controls. The metabolic fingerprints of cervicovaginal lavage were analyzed using liquid chromatography-mass spectrometry, while the vaginal microbiota was examined through 16S rRNA sequencing. Bioinformatic analysis was adopted to investigate the interplay between hosts and microbes. The vaginal metabolic and microbiota profiles of 90 female patients with cervical dysplasia and 10 controls were analyzed to discover the biological characteristics underlying the progression of cervical cancer. Results: We found that Valyl-Glutamate, N, N′-Diacetylbenzidine, and Oxidized glutathione, which were involved in oxidative stress response, were discriminators to distinguish the normal cervix, invasive cervical carcinomas, and CIN3 from others. Cervical carcinoma was characterized by a large variety of vaginal microbes (dominated by non-Lactobacillus communities) compared to the control. These microbes affected amino acid and nucleotide metabolism, producing metabolites with cervical carcinoma and genital inflammation compared to the control group. Conclusions: This study revealed that cervicovaginal metabolic profiles were determined by cervical cancer, vaginal microbiota, and their interplays. ROS metabolism can be used to discriminate normal cervix, CIN3, and invasive cervical carcinoma.

Lymphoepithelioma-like carcinoma of the cervix (LELC) is a rare subtype of squamous cell carcinoma. This is a case report of a 40-year-old female patient diagnosed with LELC. The tumor is clinically presented as an exophytic mass on the front lip of the cervix. Magnetic resonance imaging (MRI) of the pelvis revealed a cervical tumor mass with a diameter of 21 mm. The findings of the preoperative pathohistological analysis of the biopsy tissue indicated LELC. The disease was clinically and radiologically staged as IB1 stage according to the 2009 FIGO classification, and the patient underwent surgical treatment. A total radical hysterectomy with pelvic lymphadenectomy was performed, followed by external beam radiotherapy. The patient was regularly monitored with the last check-up on February 2024 (36 months) and MRI control of the pelvis and abdomen without signs of recurrence of the underlying disease. The patient is in good general condition, without subjective complaints and side effects of the applied therapy.

Background: Treatment of metastatic cervical cancer is a tricky issue. Currently, the National Comprehensive Cancer Network (NCCN) guideline recommends chemotherapy combined with bevacizumab for recurrent or metastatic cervical cancer. Still, the recurrence rate is high and the survival rate is low after standard treatment. We urgently need to achieve a multimodal therapy approach for recurrent or metastatic cervical cancer. Case description: We report the case of a patient with stage IB2 cervical squamous carcinoma who developed multiple metastases within a short term after receiving first-line standard treatment, and she underwent interstitial brachytherapy after systemic therapy with an encouraging outcome. The patient developed suspected inguinal lymph node metastases after 9 months at the end of first-line therapy and multiple metastases in the inguinal lymph nodes, anterior abdominal wall, and right lung after 17 months. As the patient had residual inguinal lymph nodes after systemic therapy, she received 3D-printed template-guided interstitial brachytherapy to the inguinal lymph nodes and maintenance therapy. By Sep 2023, she had achieved a good treatment outcome with a progression-free survival (PFS) of 36 months. Conclusion: Based on our patient response, when multiple metastases develop in the short term in early-stage cervical squamous carcinoma after first-line therapy, we may consider implementing local therapy combined with systemic therapy. [ABSTRACT FROM AUTHOR]

Background: Cervical carcinoma is a type of malignant tumor that primarily develops in the cervix, the lower part of the uterus. In recent years, Despite the considerable progress made in immunotherapy research for cervical carcinoma, an important aspect has been largely overlooked - the absence of a comprehensive bibliometric analysis in this field. By employing bibliometric techniques, this study aims to fill this gap and provide a comprehensive overview of the knowledge structure and research hotspots within the realm of immunotherapy in cervical carcinoma. Method: A comprehensive search was conducted on the web of science core collection(WoSCC) database to identify publications related to immunotherapy specifically for the treatment of cervical carcinoma. The search spanned the period from the year 2000 to 2023. Several analytical tools were employed. These included VOSviewers, CiteSpace, and the R package "bibliometrix". Results: A total of 654 research articles from 66 different countries have been included in the analysis. The United States and China have emerged as the leading countries in publishing research on immunotherapy in cervical carcinoma. Leiden University and Memorial Sloan-Kettering Cancer Center from the Netherlands and the United States respectively have a close cooperation. Fudan University from China and the German Cancer Research Center are also among the key institutions leading research in this area. Frontiers in Oncology has emerged as the most popular and widely recognized publication in the field of immunotherapy in cervical carcinoma. Journal of Clinical Oncology is frequently cited by researchers in this area. Van Der Burg, Sjoerd H has published the highest number of papers. Tewari, Krishnansu S has been the most co-cited author. Keywords such as PD-L1, chemotherapy, and immune checkpoint inhibitors have gained significant attention in recent years. Conclusion: This is the first bibliometric study that comprehensively summarizes the research trends and developments of immunotherapy in cervical carcinoma. This groundbreaking study not only summarizes the current research trends and developments in immunotherapy for cervical carcinoma but also provides a reference for scholars studying the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

Abstract Background The roles of low molecular mass polypeptide 2 (LMP2) and transporter-associated with antigen processing (TAP2) in tumorigenesis are controversial. Here we aimed to explore the effect of LMP2 and TAP2 on the oncogenesis and metastasis of cervical cancer cells. Methods The expressions of LMP2 and TAP2 in cervical cancer and normal tissues were determined by qPCR. Plate colony formation, cell counting kit-8 analysis and in vivo tumor xenograft assays were used to detect the tumor growth. Wound healing and transwell assays were used to detect the metastasis of cervical cancer. Gelatin zymography and western blotting assays were used to detect the effect of LMP2 and TAP2 on the EMT and Wnt/β-catenin pathway in cervical cancer cells. Results In the present study, we reported that LMP2 and TAP2 levels were overexpressed in cervical cancer. Overexpression of LMP2 and TAP2 impaired the proliferation of Hela cells. In vivo studies substantiated that LMP2 and TAP2 antagonized tumor growth. Likewise, LMP2 and TAP2 overexpression decreased the migration and invasion ability of Hela cells by regulating the process of epithelial-mesenchymal transition (EMT). Mechanically, LMP2 and TAP2 subverted the protein abundance of Wnt1 and β-catenin, thereby downregulating their downstream targets Cyclin D1 and c-Myc. In addition, Wnt1 overexpression partially rescued the observed consequences of ectopic expression of LMP2 and TAP2 in cervical cancer cells. Taken together, our study revealed that LMP2 and TAP2 suppress the oncogenesis and metastasis of cervical cancer cells by Wnt/β-catenin pathway and altering EMT. Conclusion LMP2 and TAP2 may inhibit the oncogenesis and metastasis of cervical cancer cells by inhibiting the process of EMT and the Wnt/β-catenin signaling pathway, which may provide important insight into prospective targets for the treatment of cervical cancer.

Jie Dai,1,&ast; Shao Zhang,2,&ast; Yuhan Shi,3 Jinmei Xu,2 Weipeng Liu,1 Jia Yang,1 Li Shi,1 Zhiling Yan,2,4 Chuanyin Li1 1Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, 650118, People’s Republic of China; 2Department of Gynaecologic Oncology, The No. 3 Affiliated Hospital of Kunming Medical University, Kunming, 650118, People’s Republic of China; 3College of Agronomy and Biotechnology, Yunnan Agricultural University, Kunming, 650041, People’s Republic of China; 4Department of Gynaecologic Oncology, The Hospital of Yuanmou, Yuanmou, 651300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiling Yan, Department of Gynaecologic Oncology, The No. 3 Affiliated Hospital of Kunming Medical University, Kunming, 650118, People’s Republic of China, Email yanzhiling2021@126.com Chuanyin Li, Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, 650118, People’s Republic of China, Email chuanyinli@imbcams.com.cnBackground: Long noncoding RNAs (LncRNAs) have been revealed to involve in cervical cancer (CC) developing. The current study was designed to explore the association of SNPs (rs217727, rs2366152, rs1859168, rs10505477) located in the lncRNA H19, HOTAIR, HOTTIP and CASC8 genes with the risk of CC in a Chinese Han population.Methods: Four SNPs were selected and genotyped in 1426 participants (274 CIN patients, 448 CC patients, and 704 healthy control individuals) using MassArray. The association of these SNPs with susceptibility to CC was evaluated.Results: Significant differences in allelic distribution of rs217727 were observed in the comparison of CC with control (P = 0.001), indicating the risk of rs217727-A allele in CC (OR = 1.33; 95% CI: 1.12– 1.58). The inheritance model analysis revealed that 2AA+GA genotype represented a certain risk of CC (P = 0.001, OR = 1.35; 95% CI: 1.13– 1.62). The stratified analysis revealed a risk of the rs217727-A allele for cervical squamous cell carcinoma (SCC) (P = 0.002, OR = 1.33; 95% CI: 1.11– 1.60).Conclusion: rs217727 in lncRNA H19 exhibited a significant correlation with CC susceptibility, particularly SCC, and A/A genotype of this SNP might present as a risk in CC.Keywords: cervical cancer, lncRNA, H19, association, SNPs, CC, long noncoding RNAs

Background and Objectives: This study aimed to evaluate the tumor response relating to and survival benefit of transarterial chemoperfusion (TACP) and transarterial chemoembolization (TACE) in the treatment of patients with unresectable gynecologic tumors who are intolerant of or have a suboptimal response to chemotherapy and radiotherapy. Materials and Methods: Between January 2000 and October 2023, 75 patients diagnosed with gynecologic tumors underwent 213 TACP and 154 TACE procedures. Of these, 33 patients were treated with TACP, 20 were treated with TACE, and 22 received a combination of both therapies. A retrospective evaluation of local tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) was conducted, and survival rates were determined using the Kaplan–Meier estimator. Results: Of the total 75 patients, 50 (67%) maintained a stable course of disease until the completion of therapy, 10 (13%) had a partial response, 2 (3%) had a complete response following thermal ablation, and 13 (17%) experienced progression. Furthermore, a 6% reduction in the sum of the longest diameters and an 8% reduction in tumor volume were observed. The median overall survival was 16.15 months, while the median progression-free survival was 13.19 months. Conclusions: TACP and TACE are potential treatment options for local tumor control in patients with unresectable gynecologic tumors who are intolerant of or show a poor response to chemotherapy and radiotherapy. However, further investigation and adjustment of treatment protocols are required to improve therapy response and survival outcomes.

Background: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are becoming more common in younger women. Solute carrier family 39 member 4 (SLC39A4) produces a zinc ion transporter involved in metastasis and invasion of tumors. Methods: The Cancer Genome Atlas RNA-seq data was used to investigate the expression of SLC39A4 and its prognostic potential. The assessment of the effect of SLC39A4 on cell growth and migration in CESC was conducted using MTT, colony formation, and Transwell assays. SLC39A4 was studied in vivo using a xenograft mouse model, and its functional involvement in oncogenesis was investigated by identifying the associated differentially expressed genes (DEGs). We evaluated the relationships among SLC39A4 levels, chemosensitivity, radiosensitivity and immune infiltration. Results: SLC39A4 was upregulated in CESC samples, and individuals with greater SLC39A4 mRNA expression had shorter overall survival. SLC39A4 has been identified to be a regulator of tumor cell metastasis and proliferation in vivo and in vitro, with an area under the curve of 0.874 for diagnosing CESC. In total, 948 DEGs were discovered to be enriched in key CESC progression-related signaling pathways. Additionally, intratumoral immune checkpoint and infiltration activity were associated with SLC39A4 expression. High SLC39A4 expression exhibited poor chemosensitivity and radiosensitivity profiles. Conclusion: In conclusion, SLC39A4 is a key regulator of CESC development, prognosis, and the composition of the tumor immune microenvironment. SLC39A4 could be used as a prognostic or diagnostic screening tool and as a potential target for CESC treatment.

Background: Cervical cancer (CC) is currently the most common malignant tumour in the female reproductive tract, and paclitaxel (PTX) is a commonly used chemotherapeutic agent, but tumour cell resistance will seriously affect the therapeutic efficacy of PTX. Nanoparticle human serum albumin-bound paclitaxel (Nano-HSA-PTX) is a novel drug delivery modality that may have superior effects to PTX alone. Objective: To clarify the effect of Nano-HSA-PTX on cervical carcinoma (CC) cells and the underlying mechanisms. Methods: After the preparation of Nano-HSA-PTX, its morphology was observed by electron transmission microscope (TEM), and its entrapment efficiency (EE%) and drug loading rate (DL%) were detected. Nano-HSA-PTX was compared with conventional PTX for drug metabolism. Additionally, CC HeLa and SiHa cells were purchased and divided into three groups to treat with Nano-HSA-PTX, PTX and normal saline, respectively. MTT, cell cloning, Transwell and cell scratch assays were carried out to determine cell proliferation, invasion and migration, flow cytometry and Western blotting were performed to detect apoptosis rate and apoptosis-related protein expression, and PCR was conducted to quantify oxidative damage indicators. Further, CYP3A4 and CYP2C8 expression patterns in CC cells (HeLa and SiHa) and human normal cervical epithelia (End1/E6E7) and the changes of their levels under the intervention of Nano-HSA-PTX were measured. Subsequently, C57BL/6mice were purchased for subcutaneous tumorigenesis experiment to observe the impact of Nano-HSA-PTX on tumor growth. Results: Under TEM, Nano-HSA-PTX was complete and arranged compactly, with a stable structure and markedly higher EE% and DL% than PTX (P

Background: Posterior reversible encephalopathy syndrome (PRES), a neurological disorder with an unknown aetiology, is characterised by visual impairment, headache, vomiting, seizures, and transient alterations in consciousness. Case report: We present the case of a 49-year-old woman with advanced cervical carcinoma who received second-line therapy with oral anlotinib (12 mg, days 1-14, every 21 days) and injectable tislelizumab (200 mg, day 1, every 21 days). After 7 days of anlotinib administration, she began experiencing symptoms suggestive of PRES and was diagnosed on day 11. Interruption of anlotinib and supportive treatment led to recovery of her binocular vision. The Naranjo score (+5) graded the causality of this reaction as probable, suggesting the possibility that the event may have been an adverse reaction to anlotinib. Ethics: This case report was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine (Reference no. K-2023-068, 2023/06/09). Informed consent was obtained from the patient and her family. [ABSTRACT FROM AUTHOR]

The incidence of cervical cancer ranks third among all female tumours globally and second in developing countries. However, the role of eukaryotic translation initiation factor 3 subunit D (EIF3D) in cervical carcinoma is unknown. This study investigated the effects of EIF3D on cell progression of cervical carcinoma and its underlying mechanism in vivo and vitro models. There were increases of EIF3D expression mRNA and protein expression levels in patients with cervical carcinoma. Disease-free survival (DFS) and overall surviva (OS) of EIF3D lower expression in patients with cervical carcinoma was higher than those of EIF3D higher expression. EIF3D mRNA expression levels in cervical carcinoma cell lines (AV3, Hela229, CaSki and Hela cells) were up-regulated, compared with cervical normal cell line (UVECs). EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma. EIF3D interacting with GRP78 to reduce the activity of GRP78 in vitro model of cervical carcinoma. The inhibition of GRP78 reduced the effects of EIF3D on Warburg effect in vitro model of cervical carcinoma. Our work identifies EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma and the inhibition of EIF3D represents a potential therapeutic strategy for the treatment of cervical carcinoma. What is already known on this subject? The incidence of cervical cancer ranks third among all female tumours globally and second in developing countries. What do the results of this study add? This study investigated the effects of EIF3D on cell progression of cervical carcinoma and its underlying mechanism in vivo and vitro models. What are the implications of these findings for clinical practice and/or further research? EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma and the inhibition of EIF3D represents a potential therapeutic strategy for the treatment of cervical carcinoma. [ABSTRACT FROM AUTHOR]

Lipase G, endothelial type (LIPG) is expressed abundantly in tissues with a high metabolic rate and vascularisation. Research on LIPG has focussed on metabolic syndromes. However, the role of LIPG in providing lipid precursors suggests that it might function in the metabolism of carcinoma cells. Analysis in The Cancer Genome Atlas indicated that patients with cervical carcinoma with high LIPG expression had a lower survival prognosis compared with patients with low LIPG expression. The mechanism underlying the effects of LIPG in cervical carcinoma is unclear. The present study aimed to determine the role of LIPG in cervical carcinoma and its mechanism. The results showed that the LIPG expression level was higher in cervical cancer. Downregulation of LIPG expression inhibited cell migration, invasion, proliferation, and the formation of cell colonies, but increased the rate of apoptosis. The Human papillomavirus E6 protein might reduce the expression of miR-148a-3p, relieve the inhibitory effect of miR-148a-3p on LIPG expression, and promote the progression of cervical cancer through the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B/mechanistic target of rapamycin kinase signalling pathway. What is already known on this subject? LIPG provides lipid precursors, suggesting that it might function in the metabolism of carcinoma cells What do the results of this study add? LIPG might be regulated by HPV16 E6/miR-148a-3p and promote cervical carcinoma progression via the PI3K/AKT/mTOR signalling pathway. What are the implications of these finding for clinical practice and/or further research? The results indicated that novel treatment and diagnosis strategies for cervical carcinoma could be developed related to LIPG. However, the detailed relationship between LIPG and cervical carcinoma remains to be fully determined. [ABSTRACT FROM AUTHOR]

Background: The roles of low molecular mass polypeptide 2 (LMP2) and transporter-associated with antigen processing (TAP2) in tumorigenesis are controversial. Here we aimed to explore the effect of LMP2 and TAP2 on the oncogenesis and metastasis of cervical cancer cells. Methods: The expressions of LMP2 and TAP2 in cervical cancer and normal tissues were determined by qPCR. Plate colony formation, cell counting kit-8 analysis and in vivo tumor xenograft assays were used to detect the tumor growth. Wound healing and transwell assays were used to detect the metastasis of cervical cancer. Gelatin zymography and western blotting assays were used to detect the effect of LMP2 and TAP2 on the EMT and Wnt/β-catenin pathway in cervical cancer cells. Results: In the present study, we reported that LMP2 and TAP2 levels were overexpressed in cervical cancer. Overexpression of LMP2 and TAP2 impaired the proliferation of Hela cells. In vivo studies substantiated that LMP2 and TAP2 antagonized tumor growth. Likewise, LMP2 and TAP2 overexpression decreased the migration and invasion ability of Hela cells by regulating the process of epithelial-mesenchymal transition (EMT). Mechanically, LMP2 and TAP2 subverted the protein abundance of Wnt1 and β-catenin, thereby downregulating their downstream targets Cyclin D1 and c-Myc. In addition, Wnt1 overexpression partially rescued the observed consequences of ectopic expression of LMP2 and TAP2 in cervical cancer cells. Taken together, our study revealed that LMP2 and TAP2 suppress the oncogenesis and metastasis of cervical cancer cells by Wnt/β-catenin pathway and altering EMT. Conclusion: LMP2 and TAP2 may inhibit the oncogenesis and metastasis of cervical cancer cells by inhibiting the process of EMT and the Wnt/β-catenin signaling pathway, which may provide important insight into prospective targets for the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Cervical cancer is the fourth most common cancer in the world and the fourth leading cause of cancer death in women. In 2020, there were 604,000 new cases and 342,000 deaths from cervical cancer worldwide. Among these, non-squamous cell carcinoma accounts for about 20% of all cervical cancers and is increasing. It has long been known that non-squamous cervical cancer has a poorer prognosis than squamous cervical cancer. Reasons for this include relatively early lymph node metastasis and low sensitivity to radiotherapy. Therefore, chemotherapy is more likely to improve prognosis than radiotherapy. However, there are few studies on adenocarcinoma and a high level of evidence is not yet available. We have previously reported the efficacy of SOX (S-1+oxaliplatin) therapy for cervical adenocarcinoma in a pilot study. We report on a phase II trial of SOX therapy to evaluate its efficacy and safety. Recurrent non-squamous cell carcinoma (non-SCC) of the uterine cervix is resistant to treatment and has a poor prognosis. The efficacy and safety of S-1/oxaliplatin (SOX) therapy in patients with recurrent non-SCC was examined in a phase II study. Fifteen patients were enrolled between August 2013 and March 2023. S-1 was administered orally at a daily dose of 80–120 mg for 14 days, and oxaliplatin was administered intravenously at a dose of 100 mg/m2 on day 1. Each treatment cycle lasted 21 days. The anti-tumor effects, adverse events, progression-free survival (PFS), and overall survival (OS) were investigated. The median patient age was 54 (41–74) years. The anti-tumor effect was rated as a partial response in five patients, stable disease in four, and progressive disease in 6. The overall response rate was 33% and the disease control rate was 60%. Regarding hematologic toxicities of grade 3 or more severity, leukopenia, neutropenia, anemia, and thrombocytopenia occurred in 26.6–40.0%. None of the patients discontinued the treatment because of adverse events. The median PFS and OS were 6 months (95% confidence interval [CI]: 2–11 months) and 22 months (95% CI: 11–23 months), respectively. No treatment-related deaths occurred. These results suggest that SOX therapy is useful for the treatment of recurrent non-SCC with promising anti-tumor effects and minimal adverse events. [ABSTRACT FROM AUTHOR]

Background: Our aim was to assess the p16 expression in normal cervical epithelium and cervical lesions and how it correlated with HPV oncoprotein E7 and other etiological parameters of cervical cancer. Methods: For this purpose, we analyzed protein expression of p16 and E7 oncoprotein in total 20 normal cervical epithelium tissue (as control) and 62 cervical lesions. Next, the result was correlated with different clinico-pathological parameters. Results: Out of 62 cases of cervical lesions, we found around 75%–100% of the cervical lesion samples exhibited E7 nuclear protein expression, whereas around 33.33%–75% samples were p16 positive. On the other hand, p16 expression showed strong association with E7 oncoprotein and other clinico-pathological parameters (like high parity, early age of sextual debut) in the same set of samples of our study. Conclusion: We concluded that overexpression of p16 is very practical and can be readily implemented in most diagnostic pathology laboratories. [ABSTRACT FROM AUTHOR]

Abstract Cervical cancer, the fourth most common cancer among females in the world, ranks the second in China. In advanced disease, metastases may be commonly present in the lungs, bones, liver and lymph nodes or elsewhere, but uncommon to the skin. In this report, a 63‐year‐old woman was diagnosed as stage IVB cervical squamous cell cancer in January 2021. The patient was scheduled for concurrent chemoradiotherapy; however, a metastatic lesion of skin was proved by biopsy during the process of treatment. She died 1 month after confirmed skin metastases. Cutaneous metastasis of cervical cancer may predict the mix of lymphatic and hematogenous metastasis and the rapid fatal termination.

Background Untreated lymphedema of an extremity leads to an increase in volume. The therapy of this condition can be conservative or surgical. Methods “Lymphological liposculpture” is a two-part procedure consisting of resection and conservative follow-up treatment to achieve curative volume adjustment of the extremities in secondary lymphedema. This treatment significantly reduces the need for complex decongestive therapy (CDT). From 2005 to 2020, 3,184 patients with secondary lymphedema after breast cancer and gynecological tumors were treated in our practice and clinic. “Lymphological liposculpture” was applied to 65 patients, and the data were recorded and evaluated by means of perometry and questionnaires. Results The alignment of the sick to the healthy side was achieved in all patients. In 58.42% (n = 38), the CDT treatment could be completely stopped postoperatively; in another 33.82% (n = 22) of the patients, a permanent reduction of the CDT was achieved. In 7.69% (n = 5) patients, the postoperative CDT could not be reduced. A total of 92.30% (n = 60) of the patients described a lasting significant improvement in their quality of life. Conclusion “Lymphological liposculpture” is a standardized curative sustainable procedure for secondary lymphedema for volume adjustment of the extremities and reduction of postoperative CDT with eminent improvement of the quality of life.

Cervical cancer is a typical cancer characterized by abnormal cell growth in the cervical area. Ginkgo biloba L. is a deciduous tree of the genus Ginkgo, possessing anti-cancer effects. The aim of this study was to explore the effect of strain J1 from Ginkgo biloba L. on apoptosis of cervical cancer cells. Bacteriostatic activity test, MTT assay and Flow cytometry were used in this study. Crude extract of J1 fermentation reduced cell growth in cervical cancer. The crude extract of the fermentation broth of strain J1 had a good inhibitory effect on Staphylococcus aureus. The crude extract of the J1 fermentation had no toxic effect on normal WISH cells in the range of anti-cervical cancer concentration. Crude extract of J1 fermentation induced apoptosis and regulated cell cycle in cervical cancer. The active compounds were separated and identified by preparative chromatography, and more than ten compounds were obtained. Our study suggests that the crude extract of J1 fermentation from Endophytic fungi of Ginkgo biloba reduced cell growth, and promoted apoptosis of cervical cancer, and is a potential therapeutic strategy for the treatment of cervical carcinoma.

The incidence of cervical cancer ranks third among all female tumours globally and second in developing countries. However, the role of eukaryotic translation initiation factor 3 subunit D (EIF3D) in cervical carcinoma is unknown. This study investigated the effects of EIF3D on cell progression of cervical carcinoma and its underlying mechanism in vivo and vitro models. There were increases of EIF3D expression mRNA and protein expression levels in patients with cervical carcinoma. Disease-free survival (DFS) and overall surviva (OS) of EIF3D lower expression in patients with cervical carcinoma was higher than those of EIF3D higher expression. EIF3D mRNA expression levels in cervical carcinoma cell lines (AV3, Hela229, CaSki and Hela cells) were up-regulated, compared with cervical normal cell line (UVECs). EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma. EIF3D interacting with GRP78 to reduce the activity of GRP78 in vitro model of cervical carcinoma. The inhibition of GRP78 reduced the effects of EIF3D on Warburg effect in vitro model of cervical carcinoma. Our work identifies EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma and the inhibition of EIF3D represents a potential therapeutic strategy for the treatment of cervical carcinoma.IMPACT STATEMENT What is already known on this subject? The incidence of cervical cancer ranks third among all female tumours globally and second in developing countries. What do the results of this study add? This study investigated the effects of EIF3D on cell progression of cervical carcinoma and its underlying mechanism in vivo and vitro models. What are the implications of these findings for clinical practice and/or further research? EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma and the inhibition of EIF3D represents a potential therapeutic strategy for the treatment of cervical carcinoma.

Lipase G, endothelial type (LIPG) is expressed abundantly in tissues with a high metabolic rate and vascularisation. Research on LIPG has focussed on metabolic syndromes. However, the role of LIPG in providing lipid precursors suggests that it might function in the metabolism of carcinoma cells. Analysis in The Cancer Genome Atlas indicated that patients with cervical carcinoma with high LIPG expression had a lower survival prognosis compared with patients with low LIPG expression. The mechanism underlying the effects of LIPG in cervical carcinoma is unclear. The present study aimed to determine the role of LIPG in cervical carcinoma and its mechanism. The results showed that the LIPG expression level was higher in cervical cancer. Downregulation of LIPG expression inhibited cell migration, invasion, proliferation, and the formation of cell colonies, but increased the rate of apoptosis. The Human papillomavirus E6 protein might reduce the expression of miR-148a-3p, relieve the inhibitory effect of miR-148a-3p on LIPG expression, and promote the progression of cervical cancer through the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B/mechanistic target of rapamycin kinase signalling pathway.IMPACT STATEMENT What is already known on this subject? LIPG provides lipid precursors, suggesting that it might function in the metabolism of carcinoma cells What do the results of this study add? LIPG might be regulated by HPV16 E6/miR-148a-3p and promote cervical carcinoma progression via the PI3K/AKT/mTOR signalling pathway. What are the implications of these finding for clinical practice and/or further research? The results indicated that novel treatment and diagnosis strategies for cervical carcinoma could be developed related to LIPG. However, the detailed relationship between LIPG and cervical carcinoma remains to be fully determined.

Introduction: Cervical cancer (CC) is associated with high morbidity and mortality rates in women. Members of the receptor-interacting protein kinase (RIPK) family are important regulators of inflammation and cell death. However, the characteristics, molecular functions, and expression mechanisms of RIPK1 in CC remain unclear. Material and methods: To determine whether RIPK1 can be used for targeted therapy of CC, we assessed the clinical importance, biological function, and potential impact of RIPK1 in CC in 50 patients with CC. We utilized immunohistochemical staining, transfection, western blotting, cell counting kit-8 assay, colony formation assay, and wound healing assays among others, to elucidate the role of RIPK1 in CC. Results: RIPK1 expression was higher in tumor tissues than in paracancerous tissues. Poor prognosis of CC was linked to RIPK1 upregulation. Furthermore, silencing RIPK1 significantly inhibited the proliferation, migration, and invasion of CC cells in vitro. We also established that RIPK1 increased cell migration, invasion, and multiplication by regulating nuclear factor kappa-B (NF-κB) and tumor necrosis factor (TNF). Discussion: RIPK1 activates NF-κB and regulates TNF release to enhance the proliferation and spread of CC cells while suppressing their apoptosis. Therefore, RIPK1 plays a key role in the formation and progression of CC and is a potential target for CC treatment.

Background: Many acute toxicities are associated with concurrent chemoradiation in cervical carcinoma, which includes burning micturition, burning defecation, pain lower abdomen, increased frequency of stools along with Acute Hematological Toxicity (AHT). AHT is often an expected adverse effect, which can lead to treatment interruptions and decreased response rates. The purpose of this study is to analyze if there are any dosimetric constraints on the volume of bone marrow irradiated with AHT in cervical carcinoma patients treated with concurrent chemoradiation. Material and Methods: In this retrospective study of 215 patients, a total of 180 patients were eligible for analysis. Multiple parameters of bone marrow volumes (whole pelvis bone marrow and its sub-volumes––ilium, lower pelvis, and lumbosacral spine) which were contoured individually for all patients were assessed to have any statistically significant association with AHT. Results: The median age of the cohort was 57 years and majority of cases were locally advanced (stage IIB-IVA: 88.3%). Grade I, II, III leukopenia was seen in 44, 25, and 6 patients, respectively. A statistically significant correlation between grade 2+ and 3+ leukopenia was seen if bone marrow V10, V20, V30, and V40 were more than 95%, 82%, 62%, and 38%, respectively. In subvolume analysis, volumes of lumbosacral spine V20, V30, and V40 more than 95%, 90%, and 65%, respectively, were statistically significant for AHT. Conclusion: Bone marrow volumes should also be given a constraint and should be tried to be achieved so that it leads to minimal treatment breaks due to AHT. [ABSTRACT FROM AUTHOR]

Abstract Cervical carcinoma (CC) has been associated with high morbidity, poor prognosis, and high intratumor heterogeneity. Necroptosis is the significant cellular signal pathway in tumors which may overcome tumor cells’ apoptosis resistance. To investigate the relationship between CC and necroptosis, we established a prognostic model based on necroptosis-related genes for predicting the overall survival (OS) of CC patients. The gene expression data and clinical information of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients were obtained from The Cancer Genome Atlas (TCGA). We identified 43 differentially expressed necroptosis-related genes (NRGs) in CESC by examining differential gene expression between CESC tumors and normal tissues, and 159 NRGs from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Gene ontology (GO) and KEGG enrichment analysis illustrated that the genes identified were mainly related to cell necrosis, extrinsic apoptosis, Influenza A, I − kappaB kinase/NF − kappaB, NOD − like receptor, and other signaling pathways. Subsequently, least absolute shrinkage and selection operator (LASSO) regression and univariate and multivariate Cox regression analyses were used to screen for NRGs that were correlated with patient prognosis. A prognostic signature that includes CAMK2A, CYBB, IL1A, IL1B, SLC25A5, and TICAM2 was established. Based on the prognostic model, patients were stratified into either the high-risk or low-risk subgroups with distinct survival. Receiver operating characteristic (ROC) curve analysis was used to identify the predictive accuracy of the model. In relation to different clinical variables, stratification analyses were performed to demonstrate the associations between the expression levels of the six identified NRGs and the clinical variables in CESC. Immunohistochemical (IHC) validation experiments explored abnormal expressions of these six NRGs in CESC. We also explored the relationship between risk score of this necroptosis signature and expression levels of some driver genes in TCGA CESC database and Gene Expression Omnibus (GEO) datasets. Significant relationships between the six prognostic NRGs and immune-cell infiltration, chemokines, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoints in CESC were discovered. In conclusion, we successfully constructed and validated a novel NRG signature for predicting the prognosis of CC patients and might also play a crucial role in the progression and immune microenvironment in CC.

Simple Summary: Definitive chemoradiotherapy is the standard treatment for locally advanced cervical carcinoma. The risk of local recurrence is usually low for cervical carcinoma patients treated with radical radiotherapy (external beam radiotherapy and brachytherapy). However, some of the patients relapsed with metastatic recurrence. The purpose of this study was to investigate prognostic factors associated with metastatic recurrence in cervical carcinoma treated with definitive radiotherapy. In addition to stage, our study found that age and radioactive level of brachytherapy significantly affected cervical cancer. An important finding was the interaction between age and source activity. In specific terms, brachytherapy with a high activity of radioactive source significantly benefits cervical carcinoma patients no more than 53 years old by prolonging the metastatic recurrence-free survival time compared with that using a low activity of radioactive source. Brachytherapy with mild source activity is more suitable for elderly patients. Objectives: This study aims to identify prognostic factors associated with metastatic recurrence-free survival of cervical carcinoma (CC) patients treated with radical radiotherapy and assess the cure probability of radical radiotherapy from metastatic recurrence. Methods: Data were from 446 cervical carcinoma patients with radical radiotherapy for an average follow up of 3.96 years. We applied a mixture cure model to investigate the association between metastatic recurrence and prognostic factors and the association between noncure probability and factors, respectively. A nonparametric test of cure probability under the framework of a mixture cure model was used to examine the significance of cure probability of the definitive radiotherapy treatment. Propensity-score-matched (PSM) pairs were generated to reduce bias in subgroup analysis. Results: Patients in advanced stages (p = 0.005) and those with worse treatment responses in the 3rd month (p = 0.004) had higher metastatic recurrence rates. Nonparametric tests of the cure probability showed that 3-year cure probability from metastatic recurrence was significantly larger than 0, and 5-year cure probability was significantly larger than 0.7 but no larger than 0.8. The empirical cure probability by mixture cure model was 79.2% (95% CI: 78.6–79.9%) for the entire study population, and the overall median metastatic recurrence time for uncured patients (patients susceptible to metastatic recurrence) was 1.60 (95% CI: 1.51–1.69) years. Locally advanced/advanced stage was a risk factor but non-significant against the cure probability (OR = 1.078, p = 0.088). The interaction of age and activity of radioactive source were statistically significant in the incidence model (OR = 0.839, p = 0.025). In subgroup analysis, compared with high activity of radioactive source (HARS), low activity of radioactive source (LARS) significantly contributed to a 16.1% higher cure probability for patients greater than 53 years old, while cure probability was 12.2% lower for the younger patients. Conclusions: There was statistically significant evidence in the data showing the existence of a large amount of patients cured by the definitive radiotherapy treatment. HARS is a protective factor against metastatic recurrence for uncured patients, and young patients tend to benefit more than the elderly from the HARS treatment. [ABSTRACT FROM AUTHOR]

Cervical cancer, the fourth most common cancer among females in the world, ranks the second in China. In advanced disease, metastases may be commonly present in the lungs, bones, liver and lymph nodes or elsewhere, but uncommon to the skin. In this report, a 63‐year‐old woman was diagnosed as stage IVB cervical squamous cell cancer in January 2021. The patient was scheduled for concurrent chemoradiotherapy; however, a metastatic lesion of skin was proved by biopsy during the process of treatment. She died 1 month after confirmed skin metastases. Cutaneous metastasis of cervical cancer may predict the mix of lymphatic and hematogenous metastasis and the rapid fatal termination. [ABSTRACT FROM AUTHOR]

Background Untreated lymphedema of an extremity leads to an increase in volume. The therapy of this condition can be conservative or surgical. Methods "Lymphological liposculpture" is a two-part procedure consisting of resection and conservative follow-up treatment to achieve curative volume adjustment of the extremities in secondary lymphedema. This treatment significantly reduces the need for complex decongestive therapy (CDT). From 2005 to 2020, 3,184 patients with secondary lymphedema after breast cancer and gynecological tumors were treated in our practice and clinic. "Lymphological liposculpture" was applied to 65 patients, and the data were recorded and evaluated by means of perometry and questionnaires. Results The alignment of the sick to the healthy side was achieved in all patients. In 58.42% (n = 38), the CDT treatment could be completely stopped postoperatively; in another 33.82% (n = 22) of the patients, a permanent reduction of the CDT was achieved. In 7.69% (n = 5) patients, the postoperative CDT could not be reduced. A total of 92.30% (n = 60) of the patients described a lasting significant improvement in their quality of life. Conclusion "Lymphological liposculpture" is a standardized curative sustainable procedure for secondary lymphedema for volume adjustment of the extremities and reduction of postoperative CDT with eminent improvement of the quality of life. [ABSTRACT FROM AUTHOR]

Background/Aim: A wide variety of answers can be found regarding the question of whether G-protein-coupled estrogen receptor 1 (GPER1) is tumor supportive or tumor suppressive. In cervical carcinoma (CC), the function of GPER1 is poorly understood. In this work, we aimed to clarify what role GPER1 plays in CC, tumor promoting of tumor suppressive. Materials and Methods: Transient GPER1 silencing was conducted using RNAi and approved by RTqPCR. Clonogenic potential was tested by colony and sphere formation. Expression of SERPINE1/PAI-1 was quantified by RT-qPCR and Western blot. Morphological changes were analyzed using Phalloidin staining. Localization of GPER1 in tumor spheres was examined by immunofluorescence. Results: After GPER1 knockdown, more colonies formed in HeLa and SiHa, and larger colonies formed in C33-A and SiHa CC cells. Size of HeLa and SiHa tumor spheres was also increased. In addition, number of HeLa tumor spheres was elevated, and larger secondary colonies were present. C33-A only formed tumor sphere-like clusters showing no differences in number and size. Phalloidin staining revealed greater cellular length-to-width ratio and increased average filopodia length. Expression of SERPINE1/PAI-1 was increased in HeLa and decreased in C33-A. In SiHa cells, SERPINE1 was slightly decreased, whereas the protein PAI-1 was increased. Strong expression of GPER1 was detectable in peripheral areas and in sprouts of tumor spheres. Conclusion: GPER1 appears to be tumor suppressive in CC, as GPER1 knockdown provoked increased stem cell properties and increased migration/invasion. EMT also appears to be enhanced. Of interest is the increase in SERPINE1/PAI-1 expression after GPER1 knockdown. [ABSTRACT FROM AUTHOR]

The Research Topic (RT) is a comprehensive and highly relevant subject matter for the section of Cell Adhesion and Migration of Frontiers in Cell and Developmental Biology. The RT includes outstanding, high-impact manuscripts that are of interest to more than one research discipline. The RT covers two original research articles (Zhou et al. Luo et al.) and three review articles (Melo et al. Mierke; Zhou et al.) One of the original research articles deals with cervical cancer and its malignant progression with a focus on epithelialmesenchymal transition (EMT) and autophagy (Zhou et al.) The other original research article comprises a pan-cancer approach to figure out whether splicing defects impacts cellular functions and cancer therapy outcome (Luo et al.) The first review article covers the impact of the tumor microenvironment on immunotherapies (Melo et al.) The second review article deals with posttranslational proteolytic cleavage induced by ADAM8 that alters directly or indirectly cancer cell behavior and characteristics (Mierke). The third review article emphasizes the role the α5β1 integrin, which binds the extracellular matrix protein fibronectin, in three specific cancer types: prostate cancer, renal cell carcinoma, and bladder cancer (Zhou et al.) These five articles show how broad the field of RT is and that molecular biological, biochemical, cell biological, medical and biophysical approaches, which belong to very different scientific disciplines, are expected to play a crucial role in understanding the complexity of cancer. Only the cooperation of these different areas and the analysis of different tumor types makes it possible to obtain a comprehensive picture of cancers and their malignant progression. In this way, similarities can be identified that would otherwise be lost or easily overlooked in the heterogeneity of tumors. In the following, the five outstanding articles will be described and their significance emphasized. Zhou et al. investigated cervical cancers in their original research article with a focus on malignant progression through invasion and metastasis. Thereby the switch of the cancer cells’ phenotype from epithelial to mesenchymal, the EMT, plays a crucial role. They highlighted that autophagy-related genes (ARGs) function in EMT, whereby the process of autophagy fulfills two major functions in the cancer disease initiation and advancement (Chavez-Dominguez et al., 2020; Lim et al., 2021; Russell and Guan, 2022). There is no doubt that autophagy is an integral process that is triggered and stringently controlled under diverse cellular stress circumstances with the aim of reacting accurately [ABSTRACT FROM AUTHOR]

Background: Carcinoma of the cervix is the most common gynecological malignancy, which ranks first among carcinomas in Indonesia. Lymph node metastasis is a risk of recurrence, affecting survival and therapy. The purpose of this study was to determine the clinicopathological characteristics of cervical carcinoma with pelvic lymph node metastasis that had undergone radical hysterectomy and lymphadenectomy at Dr. Hasan Sadikin General Hospital, Bandung. Methods: This study used a cross-sectional retrospective descriptive study. Data on the clinical stage I-II cervical cancer patients with pelvic lymph node metastasis were collected from the archives of the pathological anatomy laboratory during period from 2013 to 2021. Data were presented in percentage. Results: There were 64 data patients, and the most common age of cervical carcinoma ranged from 40 to 50 years old (52%), the most common stage was stage II (66%), and the most frequent histopathological type was squamous cell carcinoma (70%). The highest degree of differentiation was moderate differentiation (50%). There was no difference in tumor size between sizes

Background: The most frequent malignancy in Indian women is uterine cervix cancer. According to the clinical stage of the tumour and the surgical findings, surgery is the primary mode of treatment, coupled with radiation and chemotherapy. Despite the use of cisplatin-based combination treatment, patients with advanced or recurring illness have a poor prognosis. In order to replace or supplement the present therapy for these patients, it is becoming more and more important to identify novel therapeutic targets. The goal of the current investigation was to determine whether Her-2/neu expression was present. Methods: In this investigation, 81 cervical specimens were used. These cases included squamous cell carcinoma and adenocarcinoma diagnoses. BioGenex monoclonal mouse anti-human HER-2/neu Receptor IgG1 antibody was used for HER-2/neu immunostaining. Results: Malignant lesions showed higher expression of HER-2/neu compared to premalignant lesions. Additionally, there was a correlation between staining intensity and lymph node metastasis, clinical stage, and malignant tumour grade. Conclusion: Oncoprotein HER-2/neu overexpression has been linked to aggressive biological behaviour, a poor prognosis, and the propensity for metastatic spread.

Introduction: Thrombocytosis is associated with progression of many diseases. There is increasing evidence that tumour cells, platelets, endothelial cells interact with each other leading to spread of tumour cells into the microvasculature which results in poor prognosis due to metastasis. Thrombocytosis is an indirect marker of occult advanced disease. Aim: To determine thrombocytosis in diagnosed carcinoma cervix patients and its association with stage of cancer cervix and prognosis. Materials and Methods: This was the retrospective study conducted at Sri Devaraj Urs Medical College, Kolar, Karnataka, India, from April 2021 to May 2022, on medical records of 52 patients who were diagnosed with cancer cervix. The data abstracted from each subject's medical record include the following: age, parity, clinical staging as per International Federation of Gynaecology and Obstetrics (FIGO), size of the lesion, complete blood count and length of the survival. Patients underwent surgery followed by appropriate chemo-radiotherapy or brachytherapy. They were followed-up after treatment every three months for the first two years and every six months for the next three years and annually thereafter. The five-year survival rate of these patients who were on complete followup was analysed. The normal platelet count was considered as 4.5×109/L. Results: The mean age of the study population was 50.28 years. Among the 52 patients, 47 (90.03%) were with advanced stages of cancer cervix (stages IIB-IVB) and 5 (9.6%) belonged to early stages of cancer cervix (stages 1B-IIA). Forty patients (76.92%) had a platelet count less than 4.5×109/L, out of which 2 patients were in early stage of cervical cancer and 16 patients were with tumor size less than 4 cm. A total of 12 patients had the platelet count more than 4.5 lac. All these 12 patients belonged to advanced stages of cancer cervix (stage IIB-IVB), p-value of 0.001. Among the 12, 11 patients had a tumour size of more than 4 cm, p-value 0.040. The mean five-year survival rate among patients with advanced stages of cancer cervix associated with thrombocytosis was 18%. Conclusion: The platelet count was found to have strong association with the tumour size, stage of the cervical cancer and five year survival rate thus making thrombocytosis to be a strong prognostic factor in cancer cervix. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the ability of the Venezia advanced multichannel tandem and ring applicator to consistently produce dosimetrically comparable plans utilizing a reduced number of needle channels, to reduce the risk of secondary complications when boosting cervical cancer treatments with high dose rate (HDR) brachytherapy. Methods: We evaluated 26 fractions from 13 patients who were treated with HDR brachytherapy using the Venezia (Elekta) applicator. The original plans included a full load of 12–16 needles, including both parallel and 30‐degree oblique needles. We replanned each original to nine new configurations, with a reduced number of two, three, four, or six needles. Comparisons included differences in percentage dose coverage to 90% of the high‐risk clinical target volume, and percentage dose to 2 cm3 of the bladder, rectum, sigmoid, and bowel. We considered new plans "passing" if they remained within our standards (D90 > 100%; D2 cm3 < 85% bladder, <65% rectum, sigmoid, bowel) or did not perform worse than original. Results: Removing only the two most anterior or the two most posterior needles from both sides showed 80.8% and 61.5% overall passing rate. Removal of the most anterior and posterior four needles together showed 65.4% overall passing rate. Removing all oblique needles showed 19.2% overall passing rate. Removing only left‐sided or only right‐sided oblique needles showed 46.2% and 23.1% overall passing, respectively. Removing only right‐sided or only left‐sided parallel needles separately showed 19.2% and 34.6% overall passing, respectively. Removing all parallel needles showed 11.5% overall passing rate. Conclusions: As only two replans required a full needle load to maintain dosimetric quality and 40 (76.9%), 36 (34.6%), 18 (69.2%), and 10 (19.2%) replans passed with 2, 3, 4, and 6 needles removed respectively, this indicates the potential for using a lesser number of interstitial needles during combined intracavitary and interstitial HDR brachytherapy while maintaining dosimetric quality. [ABSTRACT FROM AUTHOR]

Condensed abstract: No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving imageguided intensity-modulated radiation therapy (IG-IMRT). This is the first head-tohead propensity score-matched, nationwide population-based cohort study evaluating this survival effect. The results revealed that pretreatment 18FDGPET- CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving radiotherapy or concurrent chemoradiotherapy, especially in the IG-IMRT era. Purpose: No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving imageguided intensity-modulated radiation therapy (IG-IMRT). Therefore, in this propensity score-matched, population-based cohort study, we investigated these survival effects. Patients and methods: We included 4167 patients with stage IB-IVA cervical cancer receiving radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through the IG-IMRT technique. The patients were categorized into two 1:2 propensity score-matched groups depending on whether they underwent pretreatment 18FDG-PET-CT, and their outcomes were compared. Results: We included 2778 and 1389 patients with cervical cancer in the nonpretreatment and pretreatment PET-CT groups, respectively. Univariable and multivariable analyses revealed an association between pretreatment PET-CT and improved survival in the patients (in the adjusted model, the adjusted hazard ratio [aHR] was 0.88; 95% confidence interval [CI], 0.80-0.97: P = 0.010). Regardless of the cancer stage (early or advanced), pretreatment PET-CT was significantly superior to nonpretreatment PET-CT in terms of all-cause death (aHR, 0.78; 95% CI, 0.60-0.92; P = 0.013 and aHR, 0.90; 95% CI, 0.81-0.99; P = 0.039 for the early [IB-IIA] and advanced stages [IIB-IVA], respectively). Conclusions: Pretreatment 18FDG-PET-CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving RT or CCRT, especially in the era of IG-IMRT. [ABSTRACT FROM AUTHOR]

Abstract Purpose The current study aimed to construct a novel cancer artificial intelligence survival analysis system for predicting the individual mortality risk curves for cervical carcinoma patients receiving different treatments. Methods Study dataset (n = 14,946) was downloaded from Surveillance Epidemiology and End Results database. Accelerated failure time algorithm, multi-task logistic regression algorithm, and Cox proportional hazard regression algorithm were used to develop prognostic models for cancer specific survival of cervical carcinoma patients. Results Multivariate Cox regression identified stage, PM, chemotherapy, Age, PT, and radiation_surgery as independent influence factors for cervical carcinoma patients. The concordance indexes of Cox model were 0.860, 0.849, and 0.848 for 12-month, 36-month, and 60-month in model dataset, whereas it were 0.881, 0.845, and 0.841 in validation dataset. The concordance indexes of accelerated failure time model were 0.861, 0.852, and 0.851 for 12-month, 36-month, and 60-month in model dataset, whereas it were 0.882, 0.847, and 0.846 in validation dataset. The concordance indexes of multi-task logistic regression model were 0.860, 0.863, and 0.861 for 12-month, 36-month, and 60-month in model dataset, whereas it were 0.880, 0.860, and 0.861 in validation dataset. Brier score indicated that these three prognostic models have good diagnostic accuracy for cervical carcinoma patients. The current research lacked independent external validation study. Conclusion The current study developed a novel cancer artificial intelligence survival analysis system to provide individual mortality risk predictive curves for cervical carcinoma patients based on three different artificial intelligence algorithms. Cancer artificial intelligence survival analysis system could provide mortality percentage at specific time points and explore the actual treatment benefits under different treatments in four stages, which could help patient determine the best individualized treatment. Cancer artificial intelligence survival analysis system was available at: https://zhangzhiqiao15.shinyapps.io/Tumor_Artificial_Intelligence_Survival_Analysis_System/ .

Abstract Background Even with different histologic origins, squamous cell carcinoma (SCC) and adenocarcinoma (AC) are considered a single entity, and the first-line treatment is the same. Locally advanced disease at the diagnosis of cervical cancer is the most important prognostic factor, the recurrence rate is high, making it necessary to evaluate prognostic factors other than clinical or radiological staging; histology could be one of them but continues to be controversial. The aim of this study was to evaluate tumor histology as a prognostic factor in terms of treatment outcomes, disease-free survival (DFS) and overall survival (OS) in a retrospective cohort of patients with Locally Advanced Cervical Carcinoma (LACC). Methods The records of 1291patients with LACC were reviewed, all of them were treated with 45–50 Gy of external beam radiotherapy with concurrent chemotherapy and brachytherapy. A descriptive and comparative analysis was conducted. Treatment response was analyzed by the chi-square test; DFS and OS were calculated for each histology with the Kaplan–Meier method and compared with the log-rank test; and the Cox model was applied for the multivariate analysis. Results We included 1291 patients with LACC treated from 2005 to 2014, of which 1154 (89·4%) had SCC and 137 (10·6%) had AC. Complete response to treatment was achieved in 933 (80·8%) patients with SCC and 113 (82·5%) patients with AC. Recurrence of the disease was reported in 29·9% of SCC patients and 31·9% of AC patients. Five-year DFS was 70% for SCC and 62·2% for AC. The five-year OS rates were 74·3% and 60% for SCC and AC, respectively. The mean DFS was 48·8 months for SCC vs 46·10 for AC (p = 0·043), the mean OS was 50·8 for SCC and 47·0 for AC (p = 0·002). Conclusion Our findings support the hypothesis that SCC and AC are different clinical entities. Trial Registration NCT04537273 .