Histological Subtype Of Cervical Cancer Research Articles

Features of the systemic influence of cervical cancer on peripheral blood and hemostasis according to the tumor histological subtype

Aim. To identify the features of the systemic effect on hematopoiesis and the blood coagulation system of different histological subtypes of cervical cancer (CC).Materials and methods. A single-center retrospective cohort study of 428 patients (61 patients with high grade squamous intraepithelial lesion (carcinoma in situ) and 367 patients with CC) examined from 1997 to 2022 in the Polyclinic of P. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiology Center, Ministry of Health of Russia. The age of patients was from 18 to 90 years (median age – 42 [34; 51] years). Patients were divided into 4 groups: group 1 – patients with high grade squamous intraepithelial lesion and 3 groups depending on tumor’s histological subtype (squamous cell, glandular squamous cell, adenocarcinoma). Demographic and clinical data were analyzed including laboratory tests (general blood count, biochemical blood test and iron metabolism and coagulograms (total 32 variables)) compared to clinical and surgical stages of CC.Results. High grade squamous intraepithelial lesion does not have a systemic effect on the parameters of general, biochemical blood tests and hemostasis (p >0.05). On the other hand, statistically significant changes were found in the parameters of routine laboratory blood tests, which correlate with the results of microinvasive analysis of CC, thus revealing the systemic effect of a malignant tumor: at p ≤0.001 for thrombin time, total protein, alkaline phosphatase levels; at p ≤0.05 for alanine aminotransferase, aspartate aminotransferase, C-reactive protein, serum iron and urea levels. Among patients with CC, statistically significant (p<0.001) correlations were obtained between hematological, hemostasiological and biochemical blood parameters. Of statistical significance, the presence of the glandular component in the tumor increases the systemic effect of CC on blood parameters, hemostasis, markers of inflammation and iron metabolism: leukocytosis and maximum erythrocyte sedimentation rate values compared to CC, high fibrinogen and the level of soluble fibrin-monomer complexes which increased activation of coagulation hemostasis along the common coagulation pathway (thrombin time) (p<0.001). It leads to an increase in the risk of venous thromboembolic complications in this category of patients.Conclusion. The identified changes in blood parameters made it possible to reveal the unique biological characteristics of each histological subtype of CC, including biochemical ones, which will help in developing an improved diagnosis of CC depending on the histological subtype and stage of the disease, along with developing preventive measures and treatment methods adapted to each specific case.

Distant organ metastasis patterns and prognosis of cervical adenocarcinoma: a population-based retrospective study.

Adenocarcinoma is a common histological subtype of cervical cancer, accounting for 10-15% of all cases. The prognosis of cervical adenocarcinoma with distant organ metastases remains unclear. Therefore, our study aimed to investigate the patterns and prognosis of distant organ metastasis in cervical adenocarcinoma. We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2010 to 2019. Cox regression, Kaplan-Meier, and log-rank analyses were conducted. We observed that adenocarcinoma (AC) of the cervix primarily metastasizes to single organs, with a rate of 73.3%. The lungs are the most common organs of metastasis, followed by the liver and bones. Patients with bone metastases have a median survival period of 12 months, which is slightly longer compared to metastasis in other organs. Distant organ metastasis, age, positive lymph nodes, higher AJCC stages, larger tumor diameter, and higher cell grades are related to poor prognosis (p < 0.001). Furthermore, we have observed that surgical intervention, radiotherapy, and chemotherapy can potentially provide benefits for patients with distant organ metastases. Metastasis is an independent prognostic factor for cervical adenocarcinoma patients. Surgery, radiotherapy, and chemotherapy can provide an overall survival advantage for patients with distant organ metastases.

State of the art of cervical cancer treatment in rare histologies.

The objective of this review is to summarize the current scientific evidence to formulate clinical recommendations regarding the classification, diagnostic approach, and treatment of rare histological subtypes of cervical cancer; neuroendocrine carcinoma, gastric-type mucinous adenocarcinoma, and glassy cell adenocarcinoma. These histological subtypes are generally characterized by their low frequency, aggressive biological behavior, certain chemoradioresistance, and consequently, high recurrence rates with a deleterious impact on survival. Molecular studies have identified several associated mutations in neuroendocrine carcinoma (PIK3CA, MYC, TP53, PTEN, ARID1A, KRAS, BRCA2) and gastric-type adenocarcinoma (KRAS, ARID1A, PTEN) that may serve as molecular targets. While adenocarcinomas are typically treated and classified based on squamous histology across early, locally advanced, and advanced stages, the treatment strategies for neuroendocrine carcinomas in early stages or locally advanced cases differ, particularly in the sequencing of administering chemotherapy, chemoradiotherapy, or surgery. The chemotherapy regimen is based on etoposide plus cisplatin (EP). Unlike squamous cell carcinomas, immune checkpoint inhibitors are yet to establish a standard role in the treatment of recurrent neuroendocrine carcinomas due to the absence of clinical trials. Regarding glassy cell adenocarcinomas and gastric-type adenocarcinoma, the potential use of immunotherapy in advanced stages/disease requires further evaluation through international collaborations, given the limited number of cases.

Twenty-five-year mortality trends of four major histological subtypes of cervical cancer: a population-based study using the Osaka cancer registry data

ObjectiveTo assess the mortality trends of four major histological subtypes of cervical cancer diagnosed between 1994 and 2018.MethodsThis population-based retrospective cohort study was conducted using the Osaka Cancer Registry data from 1994 to 2018. A total of 12,003 patients with cervical cancer, squamous cell carcinoma (SCC), adenocarcinoma (A), adenosquamous cell carcinoma (AS), or small cell neuroendocrine carcinoma (SCNEC) were identified. Patients were classified into groups according to the extent of disease (localized, regional, or distant), year of diagnosis (1994–2002, 2003–2010, or 2011–2018), and histological subtype (SCC, A/AS, or SCNEC). Then, their survival rates were assessed using univariate and multivariate analyses.ResultsOverall, improved survival rates were observed according to the year of diagnosis in patients with local, regional, and distant cervical cancers. When examined according to the histological subtypes, improved survival rates according to the year of diagnosis were observed in patients with local, regional, and distant SCCs and in those with local and regional A/AS. In patients with distant A/AS, the survival rates did not improve since 2003. In patients with cervical cancer with SCNEC, the survival rates did not improve since 1994 irrespective of the extent of the disease. In the multivariate analysis, non-SCC histology was found to be an independent prognostic factor for OS.ConclusionIn contrast to SCC histology associated with improved survival between 1994 and 2018, SCNEC histology and advanced (stage IVB) A/AS remain to be the unmet medical needs for the management of cervical cancer.

Population-Based Survival Analysis of Stage IVB Small-Cell Neuroendocrine Carcinoma in Comparison to Major Histological Subtypes of Cervical Cancer.

The aim of the current study is to investigate the survival outcome of stage IVB SCNEC of the uterine cervix in comparison to major histological subtypes of cervical cancer. A population-based retrospective cohort study was conducted using the Osaka Cancer Registry data from 1994 to 2018. All FIGO 2009 stage IVB cervical cancer patients who displayed squamous cell carcinoma (SCC), adenocarcinoma (A), adenosquamous cell carcinoma (AS), or small-cell neuroendocrine carcinoma (SCNEC) were first identified. The patients were classified into groups according to the types of primary treatment. Then, their survival rates were examined using the Kaplan-Meier method. Overall, in a total of 1158 patients, clearly differential survival rates were observed according to the histological subtypes, and SCNEC was associated with shortest survival. When examined according to the types of primary treatments, SCNEC was associated with significantly decreased survival when compared to SCC or A/AS, except for those treated with surgery. In patients with FIGO 2009 stage IVB cervical cancer, SCNEC was associated with decreased survival when compared to SCC or A/AS. Although current treatments with either surgery, chemotherapy or radiotherapy have some therapeutic efficacies, to improve the prognosis, novel effective treatments specifically targeting cervical SCNEC need to be developed.

Enhancing prognostic accuracy: a SEER-based analysis for overall and cancer-specific survival prediction in cervical adenocarcinoma patients

BackgroundCervical adenocarcinoma (CA) is the second most prevalent histological subtype of cervical cancer, following cervical squamous cell carcinoma (CSCC). As stated in the guidelines provided by the National Comprehensive Cancer Network, they are staged and treated similarly. However, compared with CSCC patients, CA patients are more prone to lymph node metastasis and recurrence with a poorer prognosis. The objective of this research was to discover prognostic indicators and develop nomograms that can be utilized to anticipate the overall survival (OS) and cancer-specific survival (CSS) of patients diagnosed with CA.MethodsUsing the Surveillance, Epidemiology, and End Result (SEER) database, individuals with CA who received their diagnosis between 2004 and 2015 were identified. A total cohort (n = 4485) was randomly classified into two separate groups in a 3:2 ratio, to form a training cohort (n = 2679) and a testing cohort (n = 1806). Overall survival (OS) was the primary outcome measure and cancer-specific survival (CSS) was the secondary outcome measure. Univariate and multivariate Cox analyses were employed to select significant independent factors and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis was utilized to develop predictive nomogram models. The predictive accuracy and discriminatory ability of the nomogram were assessed by employing metrics such as the calibration curve, receiver operating characteristic (ROC) curve, and the concordance index (C-index).ResultsAge, Tumor Node Metastasis stages (T, N, and M), SEER stage, grade, and tumor size were assessed as common independent predictors of both OS and CSS. The C-index value of the nomograms for predicting OS was 0.832 (95% CI 0.817–0.847) in the training cohort and 0.823 (95% CI 0.805–0.841) in the testing cohort.ConclusionWe developed and verified nomogram models for predicting 1-, 3- and 5-year OS and CSS among patients with cervical adenocarcinoma. These models exhibited excellent performance in prognostic prediction, providing support and assisting clinicians in assessing survival prognosis and devising personalized treatments for CA patients.

Paclitaxel-carboplatin plus bevacizumab therapy for advanced neuroendocrine carcinoma of the uterine cervix: A retrospective case series.

There is no conclusive data on the prognosis of patients who receive paclitaxel-carboplatin (TC) plus bevacizumab therapy for advanced neuroendocrine carcinoma (NEC) of the uterine cervix, a rare histological subtype of cervical cancer. Thus, the aim of this study was to determine the efficacy of TC chemotherapy plus bevacizumab and bevacizumab single maintenance therapy for advanced NEC of the cervix. This was a retrospective review of patients who received TC plus bevacizumab therapy for metastatic, recurrent, or persistent NEC of the cervix at seven institutions between 2015 and 2020. Relevant data were extracted from the patients' medical records and analyzed. Seven patients, including six with small-cell NEC and one with large-cell NEC, were included for analysis. Three patients received bevacizumab single maintenance therapy following TC plus bevacizumab therapy, whereas four patients did not receive bevacizumab single maintenance therapy. The median overall survival and progression-free survival of the patients who received bevacizumab single maintenance therapy were longer than those of the patients who did not receive the therapy (34 months vs. 10.5 months and 19 months vs. 5 months, respectively). However, the patients who received bevacizumab single maintenance therapy had received cisplatin-based chemotherapy previously. On the premise that cisplatin-based chemotherapy is administered as the first-line treatment for advanced NEC of the cervix, bevacizumab single maintenance therapy following TC plus bevacizumab may be considered the second- or third-line treatment. However, the risk of adverse events, such as intestinal perforation, should be discussed with patients.

Prognostic Model for Predicting Overall and Cancer-Specific Survival Among Patients With Cervical Squamous Cell Carcinoma: A SEER Based Study.

BackgroundCervical squamous cell carcinoma (CSCC) is the most common histological subtype of cervical cancer. The purpose of this study was to assess prognostic factors and establish personalized risk assessment nomograms to predict overall survival (OS) and cancer-specific survival (CSS) in CSCC patients.MethodsCSCC patients diagnosed between 1988 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox proportional hazard regression models were applied to select meaningful independent predictors and construct predictive nomogram models for OS and CSS. The concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve were used to determine the predictive accuracy and discriminability of the nomogram.ResultsA total cohort (n=17962) was randomly divided into a training cohort (n=11974) and a validation cohort (n=5988). Age, race, histologic grade, clinical stage, tumor size, chemotherapy and historic stage were assessed as common independent predictors of OS and CSS. The C-index value of the nomograms for predicting OS and CSS was 0.771 (95% confidence interval 0.762-0.780) and 0.786 (95% confidence interval 0.777-0.795), respectively. Calibration curves of the nomograms indicated satisfactory consistency between nomogram prediction and actual survival for both 3-year and 5-year OS and CSS.ConclusionWe constructed nomograms that could predict 3- and 5-year OS and CSS of CSCC patients. These nomograms showed good performance in prognostic prediction and can be used as an effective tool to evaluate the prognosis of CSCC patients, thus contributing to clinical decision making and individualized treatment planning.

Adenosquamous Carcinoma of the Uterine Cervix – Impact of Histology on Clinical Management

IntroductionHistorically, the incidence rate of cervical cancer (CC) in Eastern Europe and particularly in Bulgaria has constantly been higher than that in the other European countries. Adenosquamous carcinoma (ASC) is a rare histological subtype of CC with incidence rate of less than 6 per 100,000. We aimed to analyze the epidemiology and prognosis of all Bulgarian patients with ASC, registered at the Bulgarian National Cancer Registry (BNCR), and to compare patients’ characteristics and outcomes with those of patients, treated at a large specialized institution – the Department of Gynecologic Oncology, University Hospital in Pleven, Bulgaria.Materials and MethodsThis is a retrospective study of all cases of ASC, registered at the BNCR for a 10-year period of time. The Kaplan–Meier analysis with Log rank test was used to estimate the significant differences.ResultsThe incidence rate of ASC was calculated as 3.2% of all CC registered in BNCR and 4.97% of all stage I patients, treated in our department. The 5-year overall survival (OS) rate of all patients with ASC tumors from the registry was 50.5%. A total of 171 (48.4%) of the patients had T1 tumors and a 5-year OS of 67.1%. Lymph node status was a significant prognostic factor for OS (p=0.001). Thirty-one patients with T1 tumors and ASC histology were treated in our department for the same period of time. Lymph node metastases were found in 10 of them (32.2%). The 5-year observed OS in ASC group was 74.19%.ConclusionThe histological subtype of cancer of the uterine cervix has an impact on prognosis and should not be simply considered as a descriptive characteristic but a poor prognostic feature and should be an integral part of the decision-making in clinical management of patients.

Trends in glassy cell cervical cancer in the United States from 1973-2015: Analysis based on SEER database.

e17502 Background: Glassy cell carcinoma of cervix (GCCC) is a rare histological subtype of cervical cancer which has historically been associated with rapidly progressive disease, early development of metastases and overall poor prognosis. We attempt to define real-world trends in GCCC in the United States based on data from SEER (Surveillance, Epidemiology and End Results) database. Methods: We extracted data from the US National Cancer Institute's SEER 2018 dataset using ICD-O code for ‘Cervix Uteri Glassy Cell Carcinoma’. All patients who were diagnosed between 1973-2015 were included. Statistical analysis was done using SPSS 26. Kaplan Meier curve was used for survival analysis. Results: Data for a total of 57 patients with GCCC was available from 1975 to 2017. Median age at diagnosis was 38 years (range 30.5-44.5). Increased frequency of cases was noted in white females (77.2%) as compared to black population (22.2%). Most cases initially presented with localized or regional spread (47.4% and 40.4% respectively) with distant metastasis seen in only 10.5% patients. Data analysis revealed that 63.2% patients had Grade III poorly differentiated carcinoma, 66.7% received radiation therapy, 57.9% underwent chemotherapy and 59.6% had cancer direceted surgery performed. Calculated mean overall survival was 121.9 months. We were unable to calculate 5 year and 10 year median overall survival due to small sample size and censored data. Conclusions: GCCC is a rare histologic type of cervical cancer that presents at a younger age, is more frequently seen in white females and is commonly associated with localized or regional spread at time of initial presentation.[Table: see text]

Multiparametric MRI-based radiomics analysis: differentiation of subtypes of cervical cancer in the early stage.

There are significant differences in outcomes for different histological subtypes of cervical cancer (CC). Yet, it is difficult to distinguish CC subtypes using non-invasive methods. To investigate whether multiparametric magnetic resonance imaging (MRI)-based radiomics analysis can differentiate CC subtypes and explore tumor heterogeneity. This study retrospectively analyzed 96 patients with CC (squamous cell carcinoma [SCC] = 50, adenocarcinoma [AC] = 46) who underwent pelvic MRI before surgery. Radiomics features were extracted from the tumor volumes on five sequences (sagittal T2-weighted imaging [T2SAG], transverse T2-weighted imaging [T2TRA], sagittal contrast-enhanced T1-weighted imaging [CESAG], transverse contrast-enhanced T1-weighted imaging [CETRA], and apparent diffusion coefficient [ADC]). Clustering and logistic regression were used to examine the distinguishing capabilities of radiomics features extracted from five different MR sequences. Among the 105 extracted radiomics features, there were 51, 38, 37, and 2 features that showed intergroup differences for T2SAG, T2TRA, ADC, and CESAG, respectively (all P < 0.05). AC had greater textural heterogeneity than SCC (P < 0.05). Upon unsupervised clustering of significantly different features, T2SAG achieved the highest accuracy (0.844; sensitivity = 0.920; specificity = 0.761). The largest area under the curve (AUC) for classification ability was 0.86 for T2SAG. Hence, the radiomics model from five combined MR sequences (AUC = 0.89; accuracy = 0.81; sensitivity = 0.67; specificity = 0.94) exhibited better differentiation ability than any MR sequence alone. Multiparametric MRI-based radiomics models may be a promising method to differentiate AC and SCC. AC showed more heterogeneous features than SCC.

Exploration of potential therapeutic and prognostic value of CXC chemokines in cervical squamous cell carcinoma and endocervical adenocarcinoma based on bioinformatics analysis.

Cervical cancer, as the second most common female malignancy, brings a great health burden to women worldwide. Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are the most common histological subtypes of cervical cancer. CXC chemokines (CXCLs) within the tumor microenvironment can modulate carcinogenesis and progression. The present study aimed to explore the therapeutic and prognostic value of different CXCLs in CESC. ONCOMINE, GEPIA, cBioPortal, TRRUST, GeneMANIA, STRING and TIMER were utilized to explore the expression, mutation and function of CXCLs in CESC, as well as their correlation with pathological and survival features of CESC patients. We found that the mRNA expression levels of CXCL1/8/9/10/11/13/16/17 in CESC were upregulated compared with normal cervical tissues, whereas CXCL12 was downregulated. No significant correlation was found between the expression levels and pathological stage of CESC patients. CESC patients with high expression of CXCL1/2/3/4/5/8 were significantly associated with poor overall survival, additionally, low mRNA level of CXCL3 was associated with better disease-free survival. Besides, a high mutation rate (43%) of CXCLs in CESC was observed. Depicted by co-expression analysis, the expression of CXCL1/2/3/6/8 showed a modest to strong correlation, while that of CXCL9/10/11/13 showed a very strong correlation. Differentially expressed CXCLs primarily functioned in chemokine signaling pathway and inflammation response, such as cell chemotaxis, chemokine activity and chemokine receptor binding. We also found the association of CXCLs with the tumor-infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells) in CESC patients. The present study elucidated that CXCLs may have the potential to be novel therapeutic targets and prognosis predictors of CESC patients.

Immune Signature-Based Subtypes of Cervical Squamous Cell Carcinoma Tightly Associated with Human Papillomavirus Type 16 Expression, Molecular Features, and Clinical Outcome

Substantial heterogeneity exists within cervical cancer that is generally infected by human papillomavirus (HPV). However, the most common histological subtype of cervical cancer, cervical squamous cell carcinoma (CSCC), is poorly characterized regarding the association between its heterogeneity and HPV oncoprotein expression. We filtered out 138 CSCC samples with infection of HPV16 only as the first step; then we compressed HPV16 E6/E7 expression as HPVpca and correlated HPVpca with the immunological profiling of CSCC based on supervised clustering to discover subtypes and to characterize the differences between subgroups in terms of the HPVpca level, pathway activity, epigenetic dysregulation, somatic mutation frequencies, and likelihood of responding to chemo/immunotherapies. Supervised clustering of immune signatures revealed two HPV16 subtypes (namely, HPV16-IMM and HPV16-KRT) that correlated with HPVpca and clinical outcomes. HPV16-KRT is characterized by elevated expression of genes in keratinization, biological oxidation, and Wnt signaling, whereas HPV16-IMM has a strong immune response and mesenchymal features. HPV16-IMM exhibited much more epigenetic silencing and significant mutation at FBXW7, while MUC4 and PIK3CA were mutated frequently for HPV16-KRT. We also imputed that HPV16-IMM is much more sensitive to chemo/immunotherapy than is HPV16-KRT. Our characterization tightly links the expression of HPV16 E6/E7 with biological and clinical outcomes of CSCC, providing valuable molecular-level information that points to decoding heterogeneity. Together, these results shed light on stratifications of CSCC infected by HPV16 and shall help to guide personalized management and treatment of patients.

MGL Ligand Expression Is Correlated to Lower Survival and Distant Metastasis in Cervical Squamous Cell and Adenosquamous Carcinoma.

Cervical cancer is the fourth most common cancer type in women worldwide and is characterized by a highly immune-suppressive microenvironment. Here, we describe aberrant glycosylation as a factor mediating this immunosuppressive microenvironment. Expression of a specific carbohydrate ligand for the immune-regulatory C-type lectin MGL was correlated to poor disease-specific survival and distant recurrences in squamous cell carcinoma (SCC) and adenosquamous carcinoma (ASC), the most common histological subtypes of cervical cancer. MGL ligand expression was also associated with lymph node metastasis, the absence of CD14+ myeloid cells and the presence of CD14−CD163+ myeloid cells. Indeed, expression of the MGL receptor itself could be detected on CD163+ cells, suggesting that MGL+ myeloid cells are able to interact locally with MGL ligand+ tumor cells. Additionally, MGL ligand expression correlated to the occurrence of PIK3CA mutations, the most frequently observed oncogenic alteration in cervical cancer. In conclusion, we present prognostic value for MGL ligand expression in SCC/ASC patients, which further supports an immune evasive role for the C-type lectin MGL in the tumor immune compartment.

Completion surgery after chemoradiotherapy for cervical cancer – is there a role? UK Cancer Centre experience of hysterectomy post chemo-radiotherapy treatment for cervical cancer

The standard treatment for locally advanced cervical cancer is chemo-radiotherapy. The presence of the residual disease after treatment is directly related to the relapse risk and to poor survival. There is a lack of consensus on the role of a subsequent surgery due to morbidity concerns. Oncological and peri-operative outcomes of completion surgery for cervical cancer were reviewed by retrospective descriptive analysis of the eligible cases between March 2012 and March 2016. Fifteen women were identified. Ten (66.7%) had a residual tumour on their post-treatment MRI. Surgical histology indicated a residual cancer in 26.7%. There were three distant recurrences. Bowel and urinary complications were most commonly reported. Offering surgery to women with a residual cervical tumour found on MRI after chemo-radiation is beneficial, despite clear risks from the dual-modality treatment. A less radical surgery is preferable. An MRI has a reasonable negative predictive value, but this study has highlighted the need to further examine the role of MRI in predicting the residual disease and recurrence.Impact statementWhat is already known on this subject? The standard treatment for locally advanced cervical cancer is chemo-radiotherapy. The presence of residual disease after treatment is directly related to the relapse risk and poor survival. There is a lack of consensus on the role of a subsequent surgery due to morbidity concerns. The current evidence in the UK is limited, but across the world it appears that surgery can be beneficial for patients with incomplete chemo-radiotherapy, for certain histological subtypes of cervical cancer or for bulky residual disease.What do the results of this study add? The mode of surgery is more debateable, and this study concludes that both the laparoscopic and open surgeries are acceptable, but that radical surgery should be avoided as this contributes to a significant post-operative morbidity. This study explores the role of MRI imaging in predicting the residual disease and cervical cancer recurrence, concluding that a negative MRI post-chemoradiotherapy has a good negative predictive value for squamous cell cervical cancer, but otherwise can be unreliable.What are the implications of these findings for clinical practice and/or further research? An additional explored role of the MRI in predicting a recurrence in a larger cohort will be required, and it is likely that an additional assessment with PET-CT scanning will improve specificity.

Challenges in the management of neuroendocrine cervical cancer during pregnancy: A case report.

Large-cell neuroendocrine carcinoma (LCNEC) is an uncommon histological subtype of cervical cancer that is associated with poor survival and its occurrence during pregnancy is particularly rare. We herein present the case of a female patient who was diagnosed with cervical LCNEC during pregnancy. The patient declined pregnancy termination and was treated with neoadjuvant chemotherapy with cisplatin and etoposide, without associated toxicity and with good fetal development. At 31.4 weeks of gestation, the fetus was delivered by caesarean section, and the patient underwent radical nerve-sparing hysterectomy with bilateral adnexectomy, along with pelvic and inframesenteric para-aortic lymphadenectomy. The patient received adjuvant chemoradiotherapy and there was no evidence of recurrence or metastasis at 38 months postoperatively. The baby has also been followed up, without any signs of neurodevelopmental disorders. To the best of our knowledge, the present report describes the first case of LCNEC with pregnancy-preserving management in the literature to date.

Jagged-1 induced molecular alterations in HPV associated invasive squamous cell and adenocarcinoma of the human uterine cervix

The majority of cervical cancer (CC) cases are attributable to HPV infection. Altered Notch pathway signals and HPV are believed to modify clinicopathogenesis of CC, however, the involvement of each molecular player and its mechanism is still not known. Jagged-1 (JAG1) is one of the ligands that induce Notch pathway. The involvement of JAG1 in the modulation of a disease condition is not very clear. Hence, this study aims to study the role of JAG1 in HPV-16/18 associated different histological sub-types of CC, especially ADC. 40 non-neoplastic cervical tissues, 30 precancer and 118 tumor specimens (total 188 tissue biopsies) were studied for the expression of the JAG1 protein through immunohistochemistry, immunoblotting and for HPV infection. Two folds increase of cytoplasmic (Mean ± S.E, 3.67 ± 0.33; p = 0.0001) and nuclear (3.70 ± 0.38, p = 0.0001) JAG1 expression was identified in normal (N) vs precancer and three folds cytoplasmic (4.44 ± 0.17, p = 0.0001) and nuclear (4.64 ± 0.17; p = 0.0001) in N vs. ISCC. Total 85% of ADC patients were found to be infected with HPV, which were 100% infected with HPV-16. These findings suggest the complex synergistic interplay between JAG1 and HPV in regulating clinicopathological progression of CC through its deregulation.

Pretherapeutic staging of locally advanced cervical cancer: Inframesenteric paraaortic lymphadenectomy accuracy to detect paraaortic metastases in comparison with infrarenal paraaortic lymphadenectomy.

Extended-field chemoradiation therapy is usually performed in patients with locally advanced cervical cancer (LACC) and paraaortic (PA) node metastases. Considering the very low rate of skip metastases above inferior mesenteric artery, ilio-inframesenteric paraaortic lymph node dissection (IM-PALND) seems to be an adequate pattern of PALND. Our objective was to assess the accuracy of this management to determine PA nodal status in comparison with infrarenal paraaortic lymphadenectomy (IR-PALND) in case of squamous or glandular cervical cancer. All patients with LACC and negative MRI and PET/CT imaging at paraaortic level had laparoscopic staging (followed, if negative, by extraperitoneal paraaortic lymphadenectomy). From January 2011 to September 2015, patients who had IM-PALND were included and were compared to a previous historical series of IR-PALND patients. The two groups differed only at the upper level of dissection. Characteristics of nodal involvement at paraaortic level depending on level of dissection, PET/CT imaging and histology were studied. 119 women were included in our study, with 56 patients in the IM-PALND group and 63 in the IR-PALND group. In the IM-PALND group, fewer nodes were resected (p<0.001). There was no difference between the two groups regarding nodal status at paraaortic level (p=0.77). Patterns of nodal involvement were similar whichever the histological subtype of cervical cancer (squamous or glandular). IM-PALND appears to be equally effective to assess paraaortic nodal involvement in LACC for both histological subtypes - glandular and squamous carcinomas - and to select patients for extended-field chemoradiation therapy.

The impact of examined lymph node count on survival in squamous cell carcinoma and adenocarcinoma of the uterine cervix.

IntroductionThe prognostic impact of the number of examined lymph nodes (ELNs) in different histological subtypes of cervical cancer remains unclear. We aimed to assess the impact of the number of ELNs in stage IA2–IIA cervical cancer with different histological subtypes.MethodsData of patients with stage IA2–IIA squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the uterine cervix between 1988 and 2013 were retrieved from the Surveillance, Epidemiology, and End Results program. Univariate and multivariate Cox regression analyses were performed to analyze the effect of number of ELNs on cause-specific survival (CSS) and overall survival (OS).ResultsThe final data set identified 11,830 patients including 7,920 (66.9%) women with SCC and 3,910 (33.1%) with AC. The median number of ELNs was 19. The multivariate analysis indicated that the number of ELNs was an independent prognostic factor influencing CSS and OS, both as a continuous or a categorical variable. Patients with a higher number of ELNs had better survival outcomes. In SCC subtype, the number of ELNs was also the independent prognostic factor of CSS and OS in node-positive patients, but not in patients with node-negative disease. In AC patients, ELN count was not an independent predictor of CSS and OS regardless of lymph node status.ConclusionThe number of ELNs is an independent prognostic factor in patients with stage IA2–IIB cervical cancer. A higher number of ELNs is associated with better survival outcomes, especially in the node-positive SCC subtype.

Bioinformatics and in vitro experimental analyses identify the selective therapeutic potential of interferon gamma and apigenin against cervical squamous cell carcinoma and adenocarcinoma.

The clinical management and treatment of cervical cancer, one of the most commonly diagnosed cancers and a leading cause of cancer-related female death, remains a huge challenge for researchers and health professionals. Cervical cancer can be categorized into two major subtypes: common squamous cell carcinoma (SCC) and adenocarcinoma (AC). Although it is a relatively rare histological subtype of cervical cancer, there has been a steady increase in the incidences of AC. Therefore, new strategies to treat cervical cancer are urgently needed. In this study, the potential uses of IFNγ-based therapy for cervical cancer were evaluated using bioinformatics approaches. Gene expression profiling identified that cell cycle dysregulation was a major hallmark of cervical cancer including SCC and AC subtypes, and was associated with poor clinical outcomes for cervical cancer patients. In silico and in vitro experimental analyses demonstrated that IFNγ treatment could reverse the cervical cancer hallmark and induce cell cycle arrest and apoptosis. Furthermore, we demonstrated that apigenin could enhance the anticancer activity of IFNγ in a HeLa cervical AC cell line by targeting cyclin-dependent kinase 1. Taken together, the present study suggests the selective therapeutic potential of IFNγ alone or in combination with apigenin for managing cervical SCC and AC.