Factor For Cervical Cancer Research Articles

The mutual interplay between NTRK fusion genes and human papillomavirus infection in cervical cancer progression (Review).

Cervical cancer is a significant global health concern, with a substantial portion of cases attributed to human papillomavirus (HPV) infection. Recent advancements in molecular profiling have identified distinct subtypes of cervical cancer based on their genomic alterations. One such subgroup is neurotrophic tropomyosin receptor kinase (NTRK) fusion-positive cervical cancers, characterized by gene fusions involving the NTRK genes. Although both NTRK fusion genes and HPV infections are independently recognized as significant risk factors in cervical cancer, their interplay and mutual effects on cancer progression are not yet fully understood. The present review is the first of its kind to explore the potential interplay between NTRK fusion genes and HPV infections. It surveys in detail how their combined effect can influence the signaling pathways during cervical cancer development and progression. Moreover, the present study discussed the clinical features, histopathological examinations, treatment procedures and follow-up outcomes of NTRK-fusion gene-positive cervical cancer. The present review may help in the understanding of the management and treatment of such rare, lethal and resistant cervical cancers.

Socio-demographic and Risk Factors Study of Cervical Cancer among Women in South India

Cervical cancer is the second most common cancer among women in the world. Despite the good achievements in this type of cancer prevention and treatment in developed countries, developing countries are still reporting high rates of new cases and mortalities, India as an example. In the current study, we aimed to study the most associated risk factors with cervical cancer in Coimbatore City, India. The study was first approved by the institutional Human Ethics Committee and then by the Sri Ramakrishna Hospital Human Ethics Committee. Then the data collected from cervical cancer patients after getting their informed consent. The collected data then analyzed statistically based on age, age at marriage, parity, smoking, and alcohol, level of education, and place of living. The study results showed that cervical cancer risk increases with age especially between 50 and 59 years old. The age of marriage data analysis revealed that 44% of the women married before 18 years old. The study found 51% of the patients have three or more children. The majority of the cases were women who had no education (64%) and the incidence decreased in the educated women (19% of 10th class, 9% 12th class, 8% degree or higher).75% of the cases are living in the rural areas. The study clearly showed the risky age (50 -59) and the importance of screening before this age as well as the role of education level, age of marriage, parity, and living place as key factors in cervical cancer.

Identification and Impact of Risk Factors in Cervical Cancer: an Integrative Approach

Identification and Impact of Risk Factors in Cervical Cancer: an Integrative Approach

Pan-cancer analysis of super-enhancer-induced LINC00862 and validation as a SIRT1-promoting factor in cervical cancer and gastric cancer

Immune checkpoints inhibitors are effective but it needs more precise biomarkers for patient selection. We explored the biological significance of LINC00862 in pan-cancer by bioinformatics. And we studied its regulatory mechanisms using chromatin immunoprecipitation and RNA immunoprecipitation assays etc. TCGA and single-cell sequencing data analysis indicated that LINC00862 was overexpressed in the majority of tumor and stromal cells, which was related with poor prognosis. LINC00862 expression was related with immune cell infiltration and immune checkpoints expression, and had a high predictive value for immunotherapy efficacy. Mechanistically, LINC00862 competitively bound to miR-29c-3p to unleash SIRT1’s tumor-promoting function. SIRT1 inhibitor-EX527 were screened by virtual screening and verified by in vitro and vivo assays. Notably, acetyltransferase P300-mediated super-enhancer activity stimulated LINC00862 transcription. Collectively, LINC00862 could be a diagnostic and prognostic biomarker. LINC00862 could also be a predictive biomarker for immunotherapy efficacy. Super-enhancer activity is the driver for LINC00862 overexpression in cervical cancer and gastric cancer.

The causal effects of genetically determined immune cells on gynecologic malignancies: a Mendelian randomization study.

Evidence from observational studies suggested a connection between immune cells and gynecologic malignancies. To investigate potential causative associations between immunophenotype traits and gynecologic malignancies, we used a two-sample Mendelian randomization analysis. The genetic instrumental variables of 731 immunophenotypes of peripheral blood were obtained by the GWAS database; the GWAS data of common gynecologic cancers were obtained from FinnGen study. The main statistic method was the inverse-variance weighted method. We also used the weighted mode, weighted median, and MR Egger for evaluations. The MR Steiger directionality test was further used to ascertain the reverse causal relationship between immune cells and gynecologic cancers. We identified 50 highly probable immunophenotypes and 65 possible ones associated with gynecologic malignancies. The majority of the B cell panel was protective factors in cervical cancer. However, there was a correlation found in the B cells panel with a probable factor associated with an elevated risk of endometrial cancer. Immunophenotypes in the monocyte panel were linked to a lower probability of ovarian cancer and vulvar cancer. All of the gynecologic cancers in our study had no statistically significant impact on immune cells, according to reverse MR analysis. Our study firstly emphasized the genetically predicted causality between immune cells and gynecologic malignancies. This knowledge will be critical to formulating the measures to prevent malignancies in female at risk in future clinical practice.

Peritumoral stroma and systemic inflammatory response in cervical cancer.

To compare cervical stroma in advanced cervical cancer with the control group; to compare, in the pre-treatment period, hemogram parameters in patients with advanced cervical cancer with the same parameters as the control group; and to verify if there is an association of stromal markers with prognostic factors in cervical cancer. We prospectively evaluated 16 patients diagnosed with advanced invasive cervical cancer. A control group of 22 patients was used (uterine leiomyoma). Immunohistochemistry was performed to verify the stromal immunostaining of alpha-smooth muscle actin (SMA) and fibroblast activation protein alpha (FAP). Immunostainings and hemogram parameters were compared using Fisher's exact and Mann-Whitney Test, respectively. Strong FAP immunostaining was more frequent in patients with cervical cancer when compared with patients with leiomyoma (P = 0.0002). Regarding SMA, strong immunostaining was also found more in the group of cancer patients compared to the control group (P < 0.00001). The neutrophil-lymphocyte ratio (NLR) values were higher in the cancer patient group compared to the control group (P = 0.0019). There was no association of the parameters studied with prognostic factors. Strong FAP and SMA immunostaining was found more in patients with cervical cancer when compared to the control group. NLR values were also higher in cervical cancer.

Prevalence of human papillomavirus infection and associated factors among women attending cervical cancer screening in setting of Addis Ababa, Ethiopia

Human papillomaviruses (HPVs) are circular, nonenveloped small double-stranded DNA viruses that infect stratified epithelium and can cause a number of life-threatening diseases. HPV is the central risk factor for developing cervical cancer and is estimated that approximately 98% of this disease is associated with oncogenic types of HPV. HPV infection leads to an estimated 266,000 cervical cancer deaths annually. Therefore, the objective of this study was to determine the prevalence of HPV infection and risk factors associated with cervical lesion among women attending the cervical cancer screening clinic at the Ethiopian Family Guidance Association, Addis Ababa. A cross-sectional study was conducted to determine the prevalence of HPV infection. Data were collected using a questionnaire and samples leftover from cervical screening were taken. The leftover swab was air dried and DNA was extracted and amplified by using a PCR. A total of 247 women were included in the study. The prevalence of HPV was 9.72% among the population studied. Of all participants, 27.13% were positive for cervical intraepithelial neoplasia-1 (CIN1). CIN1 positivity was found in half of HPV positive women. Among HPV positive women, half of them had started sexual intercourse at ages 12–17 years and 41.66% were women who gave birth at ages 12–17 years. The high prevalence of HPV and the CIN1 positive group were ages 36–57 and women with multiple sexual partners. The other groups with the highest CIN1 positive were 22.39% grade (9–12) and 20.9% primary (1–8) and uneducated women. Among HPV positive women, 83.33% had an abortion history and 80% miscarried in the first trimester. Among the CIN1 positives, 53.73% had more than two sexual partners. Among HPV positive women, half of them were users of contraception methods. In conclusion, the highest prevalence of HPV is among women who began sexual intercourse earlier and who gave birth at 12–17 years of age, have an abortion history, with MSP and oral contraceptive methods users. In addition to HPV, early pregnancy and sexual intercourse at 12–17 years of age, abortion, MSP, and oral hormonal contraceptives are factors in cervical cancer. Finally, most women do not have enough knowledge and awareness about cervical cancer and the risk factor.

Delta radiomics analysis for prediction of intermediary- and high-risk factors for patients with locally advanced cervical cancer receiving neoadjuvant therapy

This study aimed to assess the feasibility of using magnetic resonance imaging (MRI)-based Delta radiomics characteristics extrapolated from the Ax LAVA + C series to identify intermediary- and high-risk factors in patients with cervical cancer undergoing surgery following neoadjuvant chemoradiotherapy. A total of 157 patients were divided into two groups: those without any intermediary- or high-risk factors and those with one intermediary-risk factor (negative group; n = 75). Those with any high-risk factor or more than one intermediary-risk factor (positive group; n = 82). Radiomics characteristics were extracted using Ax-LAVA + C MRI sequences. The data was divided into training (n = 126) and test (n = 31) sets in an 8:2 ratio. The training set data features were selected using the Mann–Whitney U test and the Least Absolute Shrinkage and Selection Operator (LASSO) test. The best radiomics features were then analyzed to build a preoperative predictive radiomics model for predicting intermediary- and high-risk factors in cervical cancer. Three models—the clinical model, the radiomics model, and the combined clinic and radiomics model—were developed in this study utilizing the random forest Algorithm. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), accuracy, sensitivity, and specificity were used to assess the predictive efficacy and clinical benefits of each model. Three models were developed in this study to predict intermediary- and high-risk variables associated with postoperative pathology for patients who underwent surgery after receiving neoadjuvant radiation. In the training and test sets, the AUC values assessed using the clinical model, radiomics model, and combined clinical and radiomics models were 0.76 and 0.70, 0.88 and 0.86, and 0.91 and 0.89, respectively. The use of machine learning algorithms to analyze Delta Ax LAVA + C MRI radiomics features can aid in the prediction of intermediary- and high-risk factors in patients with cervical cancer receiving neoadjuvant therapy.

Dedifferentiated Schwann cells promote perineural invasion mediated by the PACAP paracrine signalling in cervical cancer.

Perineural invasion (PNI) has emerged as a key pathological feature and be considered as a poor prognostic factor in cervical cancer. However, the underlying molecular mechanisms are largely unknown. Here, PNI status of 269 cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) samples were quantified by using whole-slide diagnostic images obtained from The Cancer Genome Atlas. Integrated analyses revealed that PNI was an indicative marker of poorer disease-free survival for CESC patients. Among the differentially expressed genes, ADCYAP1 were identified. Clinical specimens supported that high expression of PACAP (encoded by ADCYAP1) contributed to PNI in CESC. Mechanistically, PACAP, secreted from cervical cancer cells, reversed myelin differentiation of Schwann cells (SCs). Then, dedifferentiated SCs promoted PNI by producing chemokine FGF17 and by degrading extracellular matrix through secretion of Cathepsin S and MMP-12. In conclusion, this study identified PACAP was associated with PNI in cervical cancer and suggested that tumour-derived PACAP reversed myelin differentiation of SCs to aid PNI.

Multi-omics Analysis Identifies Hypoxia Subtypes and S100A2 as an Immunosuppressive Factor in Cervical Cancer.

Cervical cancer is a common gynecological oncology. Growing evidence indicates hypoxia plays an important role in tumor progression and immunity. However, no study has examined the hypoxia landscape in cervical cancer. In this study, using hierarchical clustering, we identified three hypoxia subtypes in cervical cancer samples from The Cancer Genome Atlas dataset according to formerly described hypoxia-related genes. The overall survival time, hypoxic features, genomics, and immunological characteristics of these subtypes existed distinct differences. We also created a hypoxia score by principle component analysis for dimension reduction. The hypoxiaScore was an effective prognostic biomarker validated by GSE44001 and was associated with immunotherapy response. Furthermore, combined with single-cell RNA-sequence (scRNA-seq) and experiments, S100A2 was identified as an immunosuppressive factor induced by hypoxia and regulated expression of PD-L1. S100A2 also served as an oncogene promoting the proliferation and migration of cervical cancer cells. These findings depicted a new hypoxia-based classification and identified S100A2 as a potential therapeutic target for cervical cancer, thereby advancing the understanding of immunotherapy resistance mechanisms and cervical cancer genetic markers.

Prevalence and Landscape of Pathogenic or Likely Pathogenic Germline Variants and Their Association With Somatic Phenotype in Unselected Chinese Patients With Gynecologic Cancers

Understanding germline and somatic status in patients with gynecologic cancers could improve risk assessment and guide therapeutic decision-making. To evaluate the prevalence and landscape of germline pathogenic or likely pathogenic (P/LP) variants and explore whether these variants are associated with somatic phenotypes and cancer risk in unselected patients with gynecologic cancers. This cross-sectional study retrospectively enrolled unselected patients in China with a gynecologic cancer, including ovarian, cervical, and endometrial, who underwent tumor-normal sequencing using a 520-gene panel from October 1, 2017, through May 31, 2021. Germline variants in gynecologic cancers. The P/LP germline variant rates in 62 cancer predisposition genes were assessed using descriptive statistics. The associations of P/LP variant status with age, somatic profiles, and cancer risk were also investigated using the Fisher exact test or Student t test. A total of 1610 women (median [IQR] age, 54 [47-62] years; 1201 [74.6%] with stage III-IV disease) were included (945 with ovarian cancer, 307 with endometrial cancer, and 358 with cervical cancer). The prevalence of patients with P/LP variants was 20.5% (194 of 945) for ovarian cancer, 13.4% (41 of 307) for endometrial cancer, and 6.4% (23 of 358) for cervical cancer; 95.1% of the germline findings (n = 252) were potentially actionable, mainly in homologous recombination repair (HRR) and mismatch repair genes. Chinese patients with endometrial cancer had a higher rate of P/LP variants than a White population from The Cancer Genome Atlas (42 of 307 [13.7%] vs 24 of 367 [6.5%]; P = .003). In endometrial and cervical cancers, the prevalence of P/LP variants was 12.7% (30 of 237) and 4.8% (13 of 270), respectively, in patients diagnosed at age 45 years or older and increased to 25.0% (9 of 36; P = .09) and 12.0% (10 of 83; P = .04), respectively, for those with an onset age of less than 45 years. Mismatch repair P/LP variants were associated with a younger age at onset for ovarian cancer (46 vs 54 years; P = .02) and endometrial cancer (48 vs 57 years; P < .001), while HRR P/LP variants were associated with a younger age at onset for cervical cancer (46 vs 52 years; P = .04). Carriers of HRR P/LP variants had more prevalent somatic TP53 variants and less common somatic variants in oncogenic driver genes vs noncarriers. BRCA1/2 P/LP variants were also associated with moderate risks for endometrial and cervical cancer. This study delineates the landscape of germline P/LP variants in Chinese women with gynecologic cancers. The findings highlight the hereditary factor in cervical cancer that has long been neglected and suggest the importance of next-generation sequencing-based genetic testing with a large gene panel for gynecologic cancers.

Association of dietary intake and cervical cancer: a prevention strategy

IntroductionCervical cancer is one of lethal cancers in women. As a global concern, identifying important factors of cancer is a useful strategy for prevention. Due to the role of diet/nutrition factors for cancer, the purpose of our study was to determine the impact of 150 nutrition/vitamin factors and 50 non-nutritional factor in cervical cancer and phase.MethodsPopulation samples of 2088 healthy subjects and patients with cervical cancer were investigated. 200 factors such as vitamin E, B1, B6, fruits, HPV, and age were gathered. Deep learning, Decision tree, and correlation matrix were used for modeling and identifying important factors. SPSS 26, R4.0.3, and Rapid miner were utilized for implementation.ResultsOur findings indicated that zinc, Iron, Niacin, Potassium, Phosphorous, and Cooper have a beneficial impact in reducing the risk of cervical cancer and progression of phase in Iranian women, as well as Salt, snacks and milk Were identified as high-risk food factors (P value < 0.05 and coefficient correlation > 0.6). Also, alcohol, and sex patient with two groups, HPV positive have an impact on cervical cancer incidence. Phosphorus and selenium in the Micronutrients category (R2 = 0.85, AUC = 0.993) and polyunsaturated fatty acid and salt in the Macronutrients category and other categories of nutrients were identified as the most effective factors in cervical cancer using deep learning (R2 = 0.93, AUC = 0.999).ConclusionsA diet and rich nutrition can be helpful for the prevention of cervix cancer and may reduce the risk of disease. Additional research is necessary for different countries.

Pretreatment Systemic Inflammatory Markers, Neutrophil Lymphocyte Ratio, and Platelet Lymphocyte Ratio as a Prognostic Factor in Cervical Cancer: A Retrospective Study

Inflammation has been recognized as a promoter of the neoplastic process initiation and progression. Neutrophilia, lymphocytopenia, and thrombocytosis are hallmarks of inflammatory reaction. The aim of this study is to find the correlation and prognostic value of pretreatment neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), with the recurrence in carcinoma cervix.Data of 208 biopsy-proven cases of squamous cell carcinoma cervix treated with definitive chemoradiotherapy were retrospectively analyzed. Neutrophil, lymphocyte, and platelet count at diagnosis were recorded and NLR and PLR were calculated. The cutoff value of NLR and PLR were calculated using receiver operator characteristics curve analysis. Correlation between locoregional recurrence (LRR) and NLR and PLR is evaluated. Median age of diagnosis is at 50 years. International Federation of Gynecology Obstetrics stage IIB was the most prevalent stage in this study. The NLR and PLR were statistically significantly affecting the LRR. The cutoff value of NLR was 2.45 with a sensitivity of 82.6% and specificity of 77.7%. The cutoff value for PLR was 140.6 with a sensitivity of 85.5% and specificity of 80.6%. On univariate regression analysis stage (p = 0.045), tumor grade (p = 0.001), addiction (p = 0.024), NLR (p &lt; 0.001), and PLR (p &lt; 0.001) were associated with LRR. Multivariate regression analysis showed that NLR (p = 0.005) risk group and PLR (p &lt; 0.001) risk group are independent risk factors associated with LRR. Conclusion High value of NLR and PLR correlate with poor prognosis in squamous cell carcinoma cervix. Hence, these biomarkers may be used as surrogates for tumor prognosis.

ADAR1 has an oncogenic function and can be a prognostic factor in cervical cancer

Adenosine deaminase acting on RNA 1 (ADAR1), a recently described epigenetic modifier, is believed to play a critical oncogenic role in human cancers. However, its functional role and clinical significance in cervical cancer (CC) remain unclear. ADAR1 knockdown was performed to investigate its oncogenic functions in SiHa (HPV16), HeLa (HPV18), and Yumoto (non-HPV) CC cell lines. Cytoplasmic and nuclear ADAR1 expression were examined to clarify their correlation with clinicopathological parameters and prognosis in patients with CC. This resulted in increased apoptosis and necroptosis in HPV16 -type SiHa, HPV18-type HeLa, and non-HPV-type Yumoto CC cell lines. Progression-free survival (PFS) rates of patients exhibiting high cytoplasmic and nuclear ADAR1 expression were poorer than those in the other groups (P = 0.016). Multivariate analysis indicated that the combination of higher cytoplasmic and nuclear ADAR1 expression was an independent predictor of prognosis in patients with CC (P = 0.017). ADAR1 could be a potential therapeutic target for HPV-positive or HPV-negative CC. The combination of cytoplasmic and nuclear ADAR1 comprises a better prognostic factor for CC.

An integrative pan-cancer analysis illustrating the key role of LRP11 in cervical cancer.

Low density lipoprotein receptor-related protein 11 (LRP11) was involved in the progression of several tumors. However, its role in cervical cancer still remains uncertain. The original tumor data was downloaded from the Cancer Genome Atlas and genotype-tissue expression databases. The expression of LRP11 in normal tissues, tumor tissues and adjacent tissues were evaluated. In addition, we also explored the genetic alteration, prognostic value, and gene function of LRP11. We deeply assessed the interaction between LRP11 and tumor immunity at the pan-cancer level. Finally, research on the association between LRP11 and the resistance of anti-tumor drugs was carried out. LRP11 was highly expressed and played a risk prognostic factor in cervical cancer and a variety of tumors. Enrichment analysis revealed that LRP11 was involved in multiple tumor malignant pathways. Our research also pointed out the unique role between LRP11 and tumor immune microenvironment. The tumor immune microenvironment of patients with high expression of LRP11 are lack of most immune cells, indicating a immune desert tumor microenvironment. The final drug resistant analysis suggested that patients with high expression of LRP11 may be related to the resistance of many anti-tumor drugs. LRP11 was a potential oncogene and prognostic marker in cervical cancer and pan-cancer. Patients with high LRP11 expression may have immune desert tumor microenvironment.

Determinants of Acquisition, Persistence, and Clearance of Oncogenic Cervical Human Papillomavirus Infection in the Philippines Using a Multi-Omics Approach: DEFEAT HPV Study Protocol

HPV infection is one of the most studied risk factors in cervical cancer-the second most common cancer site and cause of death due to cancer in the Philippines. However, there is a lack of population-based epidemiological data on cervical HPV infection in the Philippines. Local reports on co-infections with other lower genital tract pathogens, commonly reported globally, are also lacking, which emphasizes the need to increase efforts in targeting HPV prevalence, genotype, and distribution. Hence, we aim to determine the molecular epidemiology and natural history of HPV infection among reproductive-age Filipino women using a community-based prospective cohort design. Women from rural and urban centers will be screened until the target sample size of 110 HPV-positive women (55 from rural sites and 55 from urban sites) is reached. Cervical and vaginal swabs will be collected from all screened participants. For HPV-positive patients, HPV genotypes will be determined. One hundred ten healthy controls will be selected from previously screened volunteers. The cases and controls will comprise the multi-omics subset of participants and will be followed up after 6 and 12 months for repeat HPV screening. Metagenomic and metabolomic analyses of the vaginal swabs will also be performed at baseline, after 6 months, and after 12 months. The results of this study will update the prevalence and genotypic distribution of cervical HPV infection among Filipino women, determine whether the current vaccines used for HPV vaccination programs capture the most prevalent high-risk HPV genotypes in the country, and identify vaginal community state types and bacterial taxa associated with the natural history of cervical HPV infection. The results of this study will be used as the basis for developing a biomarker that can help predict the risk of developing persistent cervical HPV infection in Filipino women.

A Novel Immune-Related Signature to Predict Prognosis and Immune Infiltration of Cervical Cancer.

BACKGROUND Cervical cancer is one of the most common malignances among women globally. This study aimed to construct a novel immune-related signature to predict the prognosis and immune infiltration of cervical cancer. MATERIAL AND METHODS Transcriptomic profiles and corresponding clinical information of cervical cancer patients were obtained from The Cancer Genome Atlas (TCGA) database and GEO database. The hub immune-related genes were screened and selected using Cox regression analysis and LASSO regression analysis. A novel signature was established based on the expression levels and corresponding coefficients of the selected hub immune-related genes. Kaplan-Meier survival curve and ROC curve illustrated the prognostic value of this novel signature in cervical cancer. The predictive accuracy and stability of this novel signature were confirmed in the validation cohort, internal testing set and external testing set. Then, a nomogram was constructed to predict individual survival probability of cervical cancer patient. The association between the risk scores of novel signature and immune infiltration was investigated through single-sample gene set enrichment analysis (ssGSEA). RESULTS Ten hub immune-related genes (TFRC, SPP1, CAMP, CSF2, TUBB3, ZAP70, CHIT1, LEPR, DLL4, and DES) were selected to construct a novel signature. The risk score of this novel signature could be an independent prognostic factor in cervical cancer, which divided patients into high-risk and low-risk groups. The patients in high-risk groups showed significantly worse overall survival rates than those in low-risk groups in all training and validation cohorts (all P<0.05). A nomogram model was constructed based on the risk score of the novel signature and other clinical characteristics, which achieved the highest clinical net benefit across the entire range of reasonable threshold probabilities (concordance index=0.813). Furthermore, gene enrichment analysis revealed that the novel signature was closely related with immunology. The novel signature was negatively correlated with the infiltration of most immune cell types, especially T cell subsets (P<0.001). CONCLUSIONS The novel signature could comprehensively predict the prognosis and immune infiltration of cervical cancer. It may provide new insights for the precise treatment in cervical cancer.

Recent Advances in Cervical Cancer Management: A Review on Novel Prognostic Factors in Primary and Recurrent Tumors.

Several pathological parameters, including tumor size, depth of stromal invasion, lympho-vascular space invasion and lymph node status, have been proposed as prognostic predictors in cervical cancer. However, given the high mortality and recurrence rate of cervical cancer, novel parameters that are able to provide additional prognostic information are needed in order to allow a better prognostic stratification of cervical cancer patients. A search was conducted on PubMed to identify relevant literature data regarding prognostic factors in cervical cancer. The key words "cervical cancer", "prognostic factors", "pathology", and "outcome" were used. The novel pathological grading system based on tumor budding and cell nest size appeared the most relevant prognostic factor in primary neoplasms. Moreover, other potentially useful prognostic factors were tumor size, depth of stromal invasion, lympho-vascular space invasion, perineural invasion, tumor-free distance and tumor-infiltrating lymphocytes. Prognostic factors related to advanced-stage cervical cancer, including lymph-nodes status, endometrial and cervical involvement as well as distant metastases, were also taken into consideration. According to our findings, tumor budding and cell nest size grading system, depth of stromal invasion, lympho-vascular space invasion, perineural invasion, tumor-free distance and tumor-infiltrating lymphocytes appeared the most relevant factors included in the pathology report.

Characterization of the microenvironment in different immune-metabolism subtypes of cervical cancer with prognostic significance.

Introduction: Immune cell infiltration and metabolic reprogramming may have great impact on the tumorigenesis and progression of malignancies. The interaction between these two factors in cervical cancer remains to be clarified. Here we constructed a gene set containing immune and metabolism related genes and we applied this gene set to molecular subtyping of cervical cancer. Methods: Bulk sequencing and single-cell sequencing data were downloaded from the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database respectively. Immune and metabolism related genes were collected from Immport and Kyoto encyclopedia of genes and genomes (KEGG) database respectively. Unsupervised consensus clustering was performed to identify the molecular subtypes. Cibersort was applied to evaluate the immune cells infiltration status. Differential expression analysis and Gene set enrichment analysis (GSEA) were performed to characterize the molecular pattern of different subtypes. Multivariate Cox regression analysis was used for prognosis prediction model construction and receiver operating characteristic (ROC) curve was used for performance evaluation. The hub genes in the model were verified in single-cell sequencing dataset and clinical specimens. In vitro experiments were performed to validate the findings in our research. Results: Three subtypes were identified with prognostic implications. C1 subgroup was in an immunosuppressive state with activation of mitochondrial cytochrome P450 metabolism, C2 had poor immune cells infiltration and was characterized by tRNA anabolism, and the C3 subgroup was in an inflammatory state with activation of aromatic amino acid synthesis. The area under the ROC curve of the constructed model was 0.8, which showed better performance than clinical features. IMPDH1 was found to be significantly upregulated in tumor tissue and it was demonstrated that IMPDH1 could be a novel therapeutic target in vitro. Discussion: In summary, our findings suggested novel molecular subtypes of cervical cancer with distinct immunometabolic profiles and uncovered a novel therapeutic target.

L1CAM Is Not a Predictive Factor in Early-stage Squamous-cell Cervical Cancer.

Our study aimed to assess expression of L1 cell adhesion molecule (L1CAM) in early-stage cervical squamous-cell cancer as a prognostic factor. This retrospective, single-institution study included 154 patients who underwent radical hysterectomy for early-stage squamous cell cervical cancer between 2007 and 2017. Tumor samples from 154 patients were available for L1CAM analysis by immunohistochemistry. Among all patients, radical abdominal hysterectomy was performed in 144 cases. L1CAM expression was positive in 24 tumors (15.6%) of the whole group. In relation to the grade of differentiation and the presence of lymphovascular invasion, L1CAM expression did not show an association (p=0.154 and p=0.306, respectively). The disease-free interval and overall survival also did not significantly differ between L1CAM-positive and L1CAM-negative cases (p=0.427 and p=0.240, respectively). For histopathological characteristics, L1CAM-positive cases had a significantly higher median tumor size (p=0.015). Even in the selected group of 115 cases without nodal infiltration, L1CAM status had no effect on the relapse rate during follow-up. Our study did not confirm the results of previous studies showing L1CAM expression to be a negative prognostic factor in cervical cancer. In our study, increased L1CAM expression in early-stage squamous-cell cervical cancer was not associated with adverse prognosis regarding disease recurrence, disease-free survival, nor overall survival. L1CAM expression was correlated only with the size of the tumor.