Uterine Cervical Cancer Research Articles

Bone morphogenetic protein signaling is a possible therapeutic target in gynecologic cancer.

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor β (TGFβ) superfamily. BMPs play crucial roles in embryogenesis and bone remodeling. Recently, BMP signaling has been found to have diverse effects on different types of tumors. In this review, we summarized the effects of BMP signaling on gynecologic cancer. BMP signaling has tumor-promoting effects on ovarian cancer (OC) and endometrial cancer (EC), whereas it has tumor-suppressing effects on uterine cervical cancer (UCC). Interestingly, EC has frequent gain-of-function mutations in ACVR1, encoding one of the type I BMP receptors, which are also observed in fibrodysplasia ossificans progressiva and diffuse intrinsic pontine glioma. Little is known about the relationship between BMP signaling and other gynecologic cancers. Tumor-promoting effects of BMP signaling in OC and EC are dependent on the promotion of cancer stemness and epithelial-mesenchymal transition (EMT). In accordance, BMP receptor kinase inhibitors suppress the cell growth and migration of OC and EC. Since both cancer stemness and EMT are associated with chemoresistance, BMP signaling activation might also be an important mechanism by which OC and EC patients acquire chemoresistance. Therefore, BMP inhibitors are promising for OC and EC patients even if they become resistant to standard chemotherapy. In contrast, BMP signaling inhibits UCC growth in vitro. However, the in vivo effects of BMP signaling have not been elucidated in UCC. In conclusion, BMP signaling has a variety of functions, depending on the types of gynecologic cancer. Therefore, targeting BMP signaling should improve the treatment of patients with gynecologic cancer.

Evaluation of HE4 as a prognostic biomarker in uterine cervical cancer,

IntroductionUterine cervical cancer (UCC) is the fourth most common health problem worldwide among women. Currently available biomarkers CA125, CA199, and CEA for diagnosis or prognostic evaluation of UCC have not got widespread acceptance. MethodWhole blood samples of 64 patients with UCC were collected along with 63 healthy females and tested for serum levels of HE4 (sHE4). A cut-off value for positive result 64.0 pmol/L was set. Statistical analysis of different clinical variables was done. ResultSerum level of HE4 has a significant role in the diagnosis of uterine cervical cancer. Its level increases with age, higher parity (P < 0.05), stage (P < 0.16), tumor size, and parametrial invasion. Negative result was seen with vaginal invasion, lymph node involvement & cases which had recurrence. Various histological types showed variable results. So the serum level of HE4 (sHE) level may play a role in the diagnosis & therapeutic monitoring of UCC. But the prognostic evaluation needs further studies. ConclusionsHE4 is useful in the diagnosis of cervical cancer, but its prognostic significance is under the question marks. It may be associated with higher values in higher stages. Higher parity of the patient is associated with higher level of HE4 in UCC.

Plasma Cell-Free DNA in Uterine Cervical Cancer: Therapeutic Monitoring and Prognostic Values after Radical Radiotherapy.

In the present study, we aimed to establish a liquid biopsy-based monitoring method using peripheral blood cell-free DNA (cfDNA) for patients with cervical cancer who underwent radical radiotherapy (RT). Twenty-five patients with cervical cancer were prospectively recruited and treated with external beam RT and brachytherapy. In all patients, except one, chemotherapy was administered concurrently during RT. Whole peripheral blood samples were obtained at least twice from each patient. We performed next-generation sequencing (NGS) for the target-captured libraries (67 oncogenes and human papillomavirus [HPV] type 16/18) using 64 plasma cfDNA samples from the 25 participants. The ratio of HPV cfDNA and the variant allele frequency (VAF) in cfDNA was calculated, and their dynamic changes were monitored. The median follow-up duration was 25.4 months. In total, we identified 21,866 cfDNA variants. ARID1A and frameshift variants occupied the largest portion of altered genes and HIGH-grade variant types, respectively. In most cases, tumor shrinkage was followed by a decrease in the HPV ratio; however, an increase in HPV ratio indicated distant metastasis, despite the reduced tumor size. The initial HPV ratio reflecting the tumor burden was likely associated with treatment outcomes (p = 0.16). We did not determine a role for serial changes in the VAF in cfDNA. Our findings suggest that the HPV cfDNA ratio, calculated after targeted NGS, may be valuable for monitoring and predicting treatment responses. Accordingly, further validation of these findings is warranted.

Exploratory analysis of radiomic as prognostic biomarkers in 18F-FDG PET/CT scan in uterine cervical cancer.

To evaluate the performance of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) radiomic features to predict overall survival (OS) in patients with locally advanced uterine cervical carcinoma. Longitudinal and retrospective study that evaluated 50 patients with cervical epidermoid carcinoma (clinical stage IB2 to IVA according to FIGO). Segmentation of the 18F-FDG PET/CT tumors was performed using the LIFEx software, generating the radiomic features. We used the Mann-Whitney test to select radiomic features associated with the clinical outcome (death), excluding the features highly correlated with each other with Spearman correlation. Subsequently, ROC curves and a Kaplan-Meier analysis were performed. A p-value < 0.05 were considered significant. The median follow-up was 23.5 months and longer than 24 months in all surviving patients. Independent predictors for OS were found-SUVpeak with an AUC of 0.74, sensitivity of 77.8%, and specificity of 72.7% (p = 0.006); and the textural feature gray-level run-length matrix GLRLM_LRLGE, with AUC of 0.74, sensitivity of 72.2%, and specificity of 81.8% (p = 0.005). When we used the derived cut-off points from these ROC curves (12.76 for SUVpeak and 0.001 for GLRLM_LRLGE) in a Kaplan-Meier analysis, we can see two different groups (one with an overall survival probability of approximately 90% and the other with 30%). These biomarkers are independent of FIGO staging. By radiomic 18F-FDG PET/CT data analysis, SUVpeak and GLRLM_LRLGE textural feature presented the best performance to predict OS in patients with cervical cancer undergoing chemo-radiotherapy and brachytherapy.

Integration of Consolidation Chemotherapy After Concurrent Chemoradiation in the Treatment of Locally Advanced Uterine Cervical Cancer.

Despite the current standard of concurrent chemoradiation (CCRT), around 30-40% are still dying from locally advanced cervical cancer. Increasing the radiation dose further was not a feasible option, but addition of chemotherapy further was tried due to the different toxicity profiles of it. So, the use of consolidation chemotherapy beyond CCRT has been studied. To evaluate the efficacy, toxicity, tumour response and loco-regional control following consolidation chemotherapy after concurrent chemoradiation in locally advanced carcinoma cervix (LACC). The patients were randomized into two arms: the conventional arm (control arm, n = 30) patients received conventional treatment with weekly injection cisplatin (35mg/m2) concurrently with pelvic external beam radiation (50Gy/25 fraction, 2Gy/fraction, 5 fraction weekly) followed by intracavitary radiotherapy of 21Gy in 3 fractions of 7Gy each by HDR brachytherapy. In the interventional arm (study arm, n = 30), patients received the standard treatment followed by 3 cycles of consolidation chemotherapy (paclitaxel + carboplatin) every three weekly. Haematological toxicity (grade 3 anaemia and grade 1 leucopenia, grade 1 and 2 thrombocytopenia) was higher in the study group. Renal, hepatic and gastrointestinal toxicity was more in the study arm. Peripheral neuropathy was mostly seen in the study arm. Median follow-up was 9months. Treatment response was better, and the rate of recurrence was less in the study arm. Addition of few cycles of consolidation chemotherapy after standard treatment is beneficial in patients with LACC with manageable toxicity and good compliance.

Is it time to modify the Japanese Uterine Cervical Cancer Guidelines to recommend a higher dose for radio-resistant tumors?

Compared with the European or the United States' uterine cervical cancer management guidelines, which aim to deliver >85Gy EQD2 (the equivalent effective dose in 2Gy per fraction) to the high-risk clinical target volume (CTVHR) D90 (minimal dose of 90% of the CTVHR), the dose goal of the corresponding Japanese guidelines does not recommend delivering such a high dose to the CTVHR D90. Subsequently, while the rate of late radiation-induced toxicities is reported to be much lower in the Japanese schedule, the local control rate is relatively inferior to that of clinical results reported by the IntErnational study on MRI-guided BRAchytherapy in CErvical cancer study (EMBRACE-I) in which the dose goal for CTVHR D90 was >85Gy and showed >90% local control regardless of tumor stage. In daily clinical practice, patients with residual disease supposedly due to insufficient total dose delivery are occasionally referred to our hospital for the possibility of re-irradiation, which is not usually recommended because the risk of late severe radiation-induced toxicity is high. In this report, the authors hope to raise a discussion in our community about modifying our treatment guidelines to recommend a higher dose at least for patients with poor response.

Prognostic Impact of Caspase-8, CDK9 and Phospho-CDK9 (Thr 186) Expression in Patients with Uterine Cervical Cancer Treated with Definitive Chemoradiation and Brachytherapy.

Introduction: After primary platinum-based chemoradiation of locally advanced uterine cervical cancer, a substantial proportion of women present with persistent, recurrent or metastatic disease, indicating an unmet need for biomarker development. Methods: We evaluated the clinical records of 69 cervical cancer patients (Federation of Gynecology and Obstetrics, FIGO Stage &gt; IB3) who were subjected to definitive CRT. Immunohistochemical scoring of caspase-8, cyclin dependent kinase 9 (CDK9) and phosphorylated (phospho-)CDK9 (threonine (Thr) 186) was performed on pretreatment samples and correlated with the histopathological and clinical endpoints, including relapse-free survival (RFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS) and overall survival (OS). Results: Lower levels of caspase-8 were more prevalent in patients with a higher T-stage (p = 0.002) and a higher FIGO stage (p = 0.003), and were significantly correlated with CDK9 expression (p = 0.018) and inversely with pCDK9 detection (p = 0.014). Increased caspase-8 levels corresponded to improved RFS (p = 0.005), DMFS (p = 0.038) and CSS (p = 0.017) in the univariate analyses. Low CDK9 expression was associated with worse RFS (p = 0.008), CSS (p = 0.015) and OS (p = 0.007), but not DMFS (p = 0.083), and remained a significant prognosticator for RFS (p = 0.003) and CSS (p = 0.009) in the multivariate analyses. Furthermore, low pCDK9 staining was significantly associated with superior RFS (p = 0.004) and DMFS (p = 0.001), and increased CSS (p = 0.022), and remained significant for these endpoints in the multivariate analyses. Conclusion: Increased caspase-8 and CDK9 levels correlate with improved disease-related outcomes in cervical cancer patients treated with CRT, whereas elevated pCDK9 levels predict worse survival in this patient population.

GSOR22 Presentation Time: 12:15 PM: A Novel Radiosensitizer Kortuc Enhanced Brachytherapy for Unresectable Recurrent Uterine Cervical Cancer

<h3>Purpose</h3> To evaluate the tolerability, safety and efficacy of KORTUC Intratumoral injection with brachytherapy in unresectable recurrent cervical cancer. <h3>Materials and Methods</h3> A novel radiosensitizer KORTUC (Kochi Oxydol Radiation Therapy for Unresectable Carcinoma) was invested by Dr. Yasuhiro Ogawa at Kochi University (Japan) in 2006 and was developed for the treatment of malignant solid tumours that contain numerous hypoxic cancer cells and/or large quantities of antioxidative enzymes. Hydrogen peroxide is the only agent known to be capable of inactivating antioxidative enzymes and producing oxygen simultaneously when applied to tumour tissues. KORTUC is a solution that contains 3% hydrogen peroxide with 1% sodium hyaluronate. Hydrogen peroxide is the active ingredient for this radiosensitizer. Sodium hyaluronate viscosity sustains the hydrogen peroxide in the tumour as well as delays decomposition of hydrogen peroxide and maintains a high concentration of oxygen in the tumour. Injecting the two components together at a particular ratio is the key feature of this product. Currently Phase 2 clinical trial for locally advanced and recurrent breast cancer has been conducted in the United Kingdom and India. Our institution, (Osaka Medical and Pharmaceutical University, Japan) has conducted single-arm clinical research of KORTUC since May 2010, we dosed KORTUC more than 250 patients of various solid cancers including more than 40 patients of the gynecological tumors treated with brachytherapy as of today. In this study we report our experiences of KORTUC with brachytherapy in recurrent local advanced cervical cancer patients who are likely the high risk of poor prognosis.From April 2012 to January 2020, 15 female patients with recurrent cervical cancer received KORTUC with brachytherapy. Previous treatments of 15 recurrent patients were surgery (n=4), radiation therapy (n=8), surgery + radiation therapy (n=3). The primary lesion of these 15 patients were vaginal stump (n=5), pelvic wall (n=3), cervix (n=3), vaginal wall (n=2), and lymph node (n=2). KORTUC was injected intratumorally under direct vision of colposcopy prior to radiation therapy. The dose of KORTUC ranged from 4 to 12 mL adjusted by tumor size. For patients who had the Interstitial brachytherapy, KORTUC was administered before and after the applicator insertion prior to irradiation. <h3>Results</h3> Intratumoral injection of KORTUC was completed without any technical and safety issues in all 15 patients. KORTUC was well tolerated and no adverse events judged to be related to KORTUC injection were observed, except the transient local pain at the injection site in some patients. KORTUC also showed efficacy in local control in recurrent patients. <h3>Conclusion</h3> Based on this result, we would like to confirm in a future study, KORTUC's efficacy with external irradiation as well as brachytherapy for the newly diagnosed unresectable locally advanced cervical cancer with high risk factors of poor prognosis. KORTUC may have potential as an effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor.

197P The risk of uterine cervical cancer in inflammatory bowel disease: An updated systematic review and meta-analysis

There is few information on association between incidence of uterine cervical cancer in patients with inflammatory bowel disease (IBD). The aim of this systematic review and meta-analysis was to assess risk of uterine cervical cancer in patients with IBD.

Measuring tumour hypoxia using oxygen-enhanced MRI in uterine cervical cancer patients

Category: Gynaecological radiology

Deep Learning-Based Classification of Uterine Cervical and Endometrial Cancer Subtypes from Whole-Slide Histopathology Images.

Uterine cervical and endometrial cancers have different subtypes with different clinical outcomes. Therefore, cancer subtyping is essential for proper treatment decisions. Furthermore, an endometrial and endocervical origin for an adenocarcinoma should also be distinguished. Although the discrimination can be helped with various immunohistochemical markers, there is no definitive marker. Therefore, we tested the feasibility of deep learning (DL)-based classification for the subtypes of cervical and endometrial cancers and the site of origin of adenocarcinomas from whole slide images (WSIs) of tissue slides. WSIs were split into 360 × 360-pixel image patches at 20× magnification for classification. Then, the average of patch classification results was used for the final classification. The area under the receiver operating characteristic curves (AUROCs) for the cervical and endometrial cancer classifiers were 0.977 and 0.944, respectively. The classifier for the origin of an adenocarcinoma yielded an AUROC of 0.939. These results clearly demonstrated the feasibility of DL-based classifiers for the discrimination of cancers from the cervix and uterus. We expect that the performance of the classifiers will be much enhanced with an accumulation of WSI data. Then, the information from the classifiers can be integrated with other data for more precise discrimination of cervical and endometrial cancers.

Improved stratification of stage-specific survival for cervical uterine cancer by integrating FDG-PET/CT and MRI for lymph node staging in 2018 FIGO classification

ObjectiveStaging carcinoma of the uterine cervix (CCU) by FIGO-2018 suggests stage migration of FIGO-2009 stage I-III patients with lymph node metastasis into FIGO-2018 stage IIIC. We aimed to investigate the prognostic value of lymph node metastases identified by imaging. MethodsWe enrolled all patients with biopsy-verified CCU from 2007 to 2016 at Odense University Hospital, Denmark. FDG-PET/CT and MRI were performed before clinical examination in general anesthesia. Disease-specific mortality was compared between women with lymph node-positive and lymph node-negative imaging. ResultsIn total, 488 patients underwent clinical staging according to FIGO-2009. Lymph node-positive imaging was identified in 146 (30%) patients: 0/36 (0%) in stage IA, 22/195 (11%) in IBI, 14/30 (47%) in IB2, 70/164 (43%) in II and 40/63 (63%) in III. The 5-year cumulative incidence of death due to CCU lymph node-negative vs. lymph node-positive patients was 0.8% vs. 7.1% (p = 0.034) in stage IBI, 0% vs. 34.5% (p = 0.003) in stage IB2, 15.1% vs. 41.4% (p < 0.0001) in stage II, and 33.3% vs. 46.6% (p = 0.28) in stage III by FIGO-2009. ConclusionsOne of three women with FIGO-2009 stage I-III CCU had suspected lymph node metastasis on imaging and is upstaged to stage IIIC according to FIGO-2018. The cancer-specific mortality by CCU was significantly lower in the lymph node-negative women stages IBI-II, thus supporting stage migration due to suspected lymph node metastasis. However, the exact prognostic value within stage IIIC is challenged, and future revision of FIGO stages may include new sub-stages.

CT-based image-guided brachytherapy in uterine cervical cancer: Effect of tumor dose and volume on local control

To determine the optimal primary tumor dose for cervical cancer treatment using computed tomography (CT)-based image-guided brachytherapy (IGBT). We retrospectively reviewed 171 patients with cervical cancer who underwent both external beam radiation therapy (EBRT) and IGBT between May 2015 and December 2019. Majority of EBRT plan included central shielding technique. CT-based IGBT was performed weekly a median of three times. Magnetic resonance imaging preceded the first and third session of IGBT for target delineation. The median age of the patients was 64 years (range: 30-91 years). The median follow-up time for living patients was 43 months (range: 6-76 months). The 3-year local control rates according to the International Federation of Gynecology and Obstetrics (FIGO, 2008) stages were 89%, 100%, 92%, 89%, 78%, and 100% for stages IB, IIA, IIB, IIIA, IIIB, and IVA, respectively. The median EBRT dose to the central pelvis and parametrium/pelvic wall was 41.4 Gy and 50.4 Gy, respectively. Patients who received a cumulative 2 Gy equivalent dose (EQD2) (α/β = 10 Gy) of high-risk clinical target volume (HR CTV) D90% ≥ 75 Gy achieved a long-term local control rate of 93%, compared with 80% in those who received <75 Gy (p = 0.02). This is one of the largest CT-based IGBT series examining the treatment of cervical cancer based on the tumor dose-volume relationship. An HR CTV D90% ≥75 Gy was significantly associated with favorable local control in this study.

Direct Comparison of HPV16 Viral Genomic Integration, Copy Loss, and Structural Variants in Oropharyngeal and Uterine Cervical Cancers Reveal Distinct Relationships to E2 Disruption and Somatic Alteration.

Simple SummaryHPV16 causes approximately 60% of uterine cervical cancer and 95% of HPV-driven oropharynx cancers. Despite both being HPV-associated, these tumors are very different. We directly compare integration of the HPV16 genome into the human genome in these two diseases, finding that the viral gene E2 is frequently lost in cervical cancer, but usually maintained in oropharyngeal cancer. We also found that oropharyngeal cancers with integration have many more integration sites per tumor and these more frequently occur in genomic regions with a high density of genes.Squamous cell carcinoma of the oropharynx caused by HPV type 16 (HPV16+ OPSCC) is the most common HPV-associated malignancy in the USA and has many molecular differences from uterine cervical squamous cell carcinoma (UCSCC). Our understanding of HPV oncogenesis relied on studies of UCSCC revealing a consensus model reliant on HPV integration with a loss of E2. Here, we compare patterns of HPV integration in UCSCC and OPSCC by analysis of affinity capture sequencing of the HPV16 genome in 104 OPSCC and 44 UCSCC tumors. These cohorts were contemporaneously sequenced using an identical strategy. Integration was identified using discordant read pair clustering and assembly-based approaches. Viral integration sites, structural variants, and copy losses were examined. While large-scale deep losses of HPV16 genes were common in UCSCC and were associated with E2 loss, deep copy losses of the HPV16 genome were infrequent in HPV16+ OPSCC. Similarly, structural variants within HPV16 favored E2 loss in UCSCC but not OPSCC. HPV16 integration sites were non-random, with recurrent integration hot-spots identified. OPSCC tumors had many more integration sites per tumor when compared to UCSCC and had more integration sites in genomic regions with high gene density. These data show that viral integration and E2 disruption are distinct in UCSCC and OPSCC. Our findings also add to growing literature suggesting that HPV tumorigenesis in OPSCC does not follow the model developed based on UCSCC.

Combination treatment with cyclosporin A and arsenic trioxide induce synergistic cell death via non-apoptotic pathway in uterine cervical cancer cells

Cyclosporin A is an immunosuppressive drug with anti-cancer effect. Arsenic trioxide (As2O3), a well-known cancer-inhibiting drug, induced cytotoxicity via apoptosis and autophagy. The aim of this study is to evaluate the effect of combinational treatment with cyclosporin A and arsenic trioxide on cell viability inhibition in cervical cancer cells. Using MTT assay and combination index, combinational treatment with cyclosporin A and arsenic trioxide induced a synergistic cytotoxic effect in Caski and SiHa cells. Cyclosporin A and arsenic trioxide triggered cell death via non-apoptotic pathway by using annexin V/propidium iodide (PI) assay. Cyclosporin A and arsenic trioxide combined treatment decreased mitochondrial membrane potential and increase reactive oxygen species (ROS) generation. This co-treatment increased LC3B-II expression and autophagosome formation in cervical cancer cells. This study first demonstrated that combinational treatment with cyclosporin A and As2O3 trigger synergistic cytotoxic effect via autophagy in cervical cancer cells.

Papillomavirus Infection and Prevention: How Much Does the Sicilian Population Know? An Observational Study.

Highlights To date, incidence of HPV-related oral and oropharyngeal carcinoma is increased;Spread of HPV infection among youth is due to sexual precocity and promiscuity;Two HPV strains are primarily related to cancer onset: 16 and 18;There are different HPV vaccines but knowledge and adherence are still quite low;Not only young women must be aware on risk factors and vaccine. Human papillomavirus is a sexually transmitted virus that is responsible not only for uterine cervical cancer, but also for the oral and oropharyngeal cancers. In this latter case, the virus indiscriminately affects both sexes at any age. Vaccination plays a key role in preventing infection and its possible consequences. Therefore, this study aimed to assess the degree of awareness of papillomavirus infection and its possible prevention in the Sicilian population. A prospective observational study was carried out on the Sicilian population through a self-administered questionnaire, consisting of 10 multiple-choice questions. The survey lasted from June 2021 to December 2021. A total of 844 respondents were included: 60.90% were female and 53.55% were aged between 21 and 30 years. Most of the surveyed population knew about the virus and the existence of the vaccine, however, many of them did not know about virus’s effects on the oral and oropharyngeal sites (49.17%), or about the indication for vaccination for males (39.69%). Oral and oropharyngeal papillomavirus-related cancers are an increasingly frequent finding, especially in young adults. Therefore, it is necessary and quite mandatory to educate the population about the risks that certain voluptuous habits may cause, with the help of general practitioners, schools, social media, and social networks.

Fyn expression is associated with the response of patients with locally advanced uterine cervical squamous cell carcinoma to neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) followed by surgery is the current standard of treatment for locally advanced uterine cervical cancer; however, its value and outcomes remain contested. Identifying biomarkers that allow for the prediction of the effect of NAC efficacy before initiation of treatment is essential, in order to assist in choosing the optimum therapeutic regimen to maximize the beneficial outcomes of treatment. In the present retrospective study, 44 patients with locally advanced uterine cervical squamous cell carcinoma who underwent NAC were divided into two groups: A NAC successful group and a NAC failure group, depending on the efficacy of NAC. Subsequently, the association between Fyn expression, a non-receptor tyrosine kinase that is a member of the Src family kinases, and NAC efficacy was determined; Fyn expression was detected by immunohistochemistry and assessed using a weighted scoring method. Additionally, the effect of Fyn knockdown on the sensitivity of a uterine cervical cancer cell line to cisplatin was determined. Notably, there were no significant differences between the two groups of patients regarding their characteristics. Regarding overall survival, the NAC successful group had a significantly longer survival time than the NAC failure group (P=0.01). Furthermore, the expression levels of Fyn in tumor tissues were significantly lower in the NAC successful group compared with those in the NAC failure group (P=0.003). The patients were subsequently divided into two groups (high expression group and low expression group) according to a cutoff value of 3, which was determined by producing a receiver operating characteristic curve from the weighted scores. The low expression group was significantly more sensitive to NAC than the high expression group (P<0.001). In vitro experiments revealed that Fyn knockdown significantly enhanced the sensitivity of uterine cancer cells to cisplatin (P<0.05). In conclusion, Fyn expression may be a potentially useful biomarker for predicting the response to NAC in patients with locally advanced uterine cervical squamous cell carcinoma, and may also be a promising molecular target for the management of uterine cancer.

Image processing techniques for the segmentation of cervical cancer

The most prevalent type of cancer in women worldwide is uterine cervical cancer. The majority of cervical cancer (CC) cases can be avoided by participating in screening programmes that look for precancerous lesions. Colposcopic cervigrams or images from digital colposcopy have been acquired in raw form. This study presents a novel framework that combines image enhancement, pre-processing, and image segmentation to identify cervical cancer. Three phases make up this framework: the Dual Tree Discrete Wavelet Transform (DTDWT) for pre-processing, the Curvelet transform and Contour Transform (CC) for image improvement, and the K-means clustering for segmentation.

Transcriptomic Immune Profiles Can Represent the Tumor Immune Microenvironment Related to the Tumor Budding Histology in Uterine Cervical Cancer.

Tumor budding (TB) histology has become a critical biomarker for several solid cancers. Despite the accumulating evidence for the association of TB histology with poor prognosis, the biological characteristics of TB are little known about in the context related to the tumor immune microenvironment (TIME) in uterine cervical cancer (CC). Therefore, this study aimed to identify the transcriptomic immune profiles related to TB status and further provide robust medical evidence for clinical application. In our study, total RNA was extracted and sequenced from 21 CC tissue specimens. As such, 1494 differentially expressed genes (DEGs) between the high- and low-TB groups were identified by DESeq2. After intersecting the list of DEGs and public immune genes, we selected 106 immune-related DEGs. Then, hub genes were obtained using Least Absolute Shrinkage and Selection Operator regression. Finally, the correlation between the hub genes and immune cell types was analyzed and four candidate genes were identified (one upregulated (FCGR3B) and three downregulated (ROBO2, OPRL1, and NR4A2) genes). These gene expression levels were highly accurate in predicting TB status (area under the curve >80%). Interestingly, FCGR3B is a hub gene of several innate immune pathways; its expression significantly differed in the overall survival analysis (p = 0.0016). In conclusion, FCGR3B, ROBO2, OPRL1, and NR4A2 expression can strongly interfere with TB growth and replace TB to stratify CC patients.

Postsurgical urodynamic study of total laparoscopic nerve-sparing radical hysterectomy for uterine cervical cancer.

To evaluate the impact on urodynamic results between the laparoscopic nerve-sparing radical hysterectomy (LRH) following a step-by-step procedure and abdominal nerve-sparing radical hysterectomy (ARH) for patients with uterine cervical cancer. This retrospective study enrolled 76 patients with cervical cancer: 35 in the LRH group and 41 in the ARH group. We analyzed their postoperative bladder function in a urodynamics study and examined the volume of resected pelvic nerves contained in parametrial sections using S-100 antibody staining. Estimated blood loss and hospital stay after operation for the LRH group were significantly better than those in the ARH group (p < 0.0001). As well, the number of harvested lymph nodes was significantly higher in the LRH group (p=0.044). There was no difference in perioperative complications between the two groups in this study. The 5-year disease-free survival rates and overall survival rates were 91.2% and 94.0% in the LRH group and 87.8% and 95.1% in the ARH group, both respectively. Although the median residual urine volume were no statistical differences between the LRH group and the ARH group, the recovery of postoperative bladder function (uroflowmetry) in the LRH group rapidly reached presurgery levels at 1month, and the LRH group had a smaller number of s-100 antibody stained nerves contained the parametrial sections. We demonstrated that LRH following a step-by-step procedure could achieve a higher level of prevention of damage to the bladder branch of the pelvic splanchnic nerve plexus and thus restore bladder function more rapidly.