Uterine Corpus Invasion Research Articles

Comparison of the clinical outcomes of patients with stage IA-IIA2 cervical adenocarcinoma and squamous cell carcinoma after radical hysterectomy: A propensity score-matched real-world analysis.

To compare the pathological findings and survival outcomes of patients with 2009 FIGO stage IA-IIA2 cervical cancer between groups with adenocarcinoma (ADC) and squamous cell carcinoma (SCC) using the Chinese Cervical Cancer Clinical (FOUR-C) study database. Patients from 2004 to 2018 with cervical ADC and SCC who underwent radical hysterectomy were identified through the FOUR-C database. Propensity score matching (PSM) was conducted to balance baseline clinicopathological characteristics. The Kaplan-Meier method and Cox regression analysis were used to evaluate the prognostic effect of ADC on the 5-year overall survival (OS). We identified 1611 (9.8%) patients with ADC and 14 894 (90.2%) patients with SCC. Compared with SCC, ADC was significantly associated with an increased risk of death (odds ratio [OR] 1.40, 95% CI 1.12-1.74) and disease progression (OR 1.34, 95% CI 1.14-1.57). ADC had a greater propensity for lymph node metastasis, uterine corpus invasion, perineural invasion, and ovarian metastases than SCC (P < 0.05). After 1:2 PSM, significant differences were still observed between these two histology subtypes (OS: OR 1.43, 95% CI 1.10-1.86; DFS: OR 1.45, 95% CI 1.19-1.76). The subgroup analysis further showed a worse prognosis for patients with ADC than for patients with SCC among patients with any of the high- or intermediate- risk factors (OR 1.60, 95% CI 1.21-2.12), but no significant differences were observed for the patients with no risk factors (OR 0.71, 95% CI 0.32-1.58). ADC is an independent prognostic factor for shorter survival in surgically treated patients with cervical cancer presenting intermediate- or high-risk factors but does not affect survival outcomes in patients without any risk factors.

Effects of colpotomic approaches on prognosis and recurrence sites of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy

Objective: To investigate the factors affecting the prognosis of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy (LRH), and to compare the prognosis and recurrence sites of patients with different colpotomy paths. Methods: The clinical data of 965 patients with stage Ⅰa2-Ⅱa2 cervical cancer who underwent LRH in the First Affiliated Hospital of Army Medical University from January 2015 to December 2018 were collected. The median age was 47.0 years of all patients with a median follow-up of 62 months (48-74 months). Cox regression was used to perform the univariate and multivariate analysis of the clinicopathological factors associated with the prognosis that included disease-free survival (DFS) and overall survival (OS). Patients were categorized into LRH through vaginal colpotomy (VC group, n=475) and LRH through intracorporeal colpotomy (IC group, n=490) according to the colpotomic approaches. The prognosis and recurrence sites of patients in each group were compared. Results: (1) During the follow-up period, 137 cases recurred (14.2%, 137/965) and 98 cases died (10.2%, 98/965). The 5-year DFS and OS were 85.8% and 89.9%, respectively. In univariate analysis, positive vaginal margin (PVM) was significantly affected the 5-year OS of patients with cervical cancer (P=0.023), while clinical stage, maximum diameter of tumor, degree of pathological differentiation, lymph node metastasis (LNM), depth of cervical stromal invasion, parametrium involvement, and uterine corpus invasion (UCI) were significantly associated with 5-year DFS and OS in patients with cervical cancer (all P<0.05). In multivariate analysis, clinical stage (HR=1.882, 95%CI: 1.305-2.716), LNM (HR=2.178, 95%CI: 1.483-3.200) and UCI (HR=3.650, 95%CI: 1.906-6.988) were independent risk factors of 5-year DFS (all P<0.001). Clinical stage (HR=2.500, 95%CI: 1.580-3.956), LNM (HR=2.053, 95%CI: 1.309-3.218), UCI (HR=3.984, 95%CI: 1.917-8.280), PVM (HR=3.235, 95%CI: 1.021-10.244) were independent risk factors of 5-year OS (all P<0.05). (2) Different colpotomy paths did not significantly affect the 5-year DFS and OS of patients with stage Ⅰa2-Ⅱa2 cervical cancer. The 5-year DFS in VC group and IC group were 85.9% and 85.6% (P=0.794), and the 5-year OS were 90.8% and 89.3% (P=0.966), respectively. Recurrence patterns consisted of intraperitoneal recurrence, pelvic recurrence, vaginal stump recurrence, and lymph node and distant metastasis. The intraperitoneal recurrence rate of VC group was significantly lower than that of IC group [0.6%(3/468) vs 2.3% (11/485), P=0.037], while the rates of pelvic recurrence, vaginal stump recurrence, lymph node and distant metastasis and overall recurrence were not significantly different between two groups (all P>0.05). Subgroup analysis of patients with different clinical stages, LNM and UCI showed that statistical differences of the intraperitoneal recurrence rates between two groups were only in patients without LNM (0.5% vs 2.3%, P=0.030) or without UCI (0.7% vs 2.3%, P=0.037). Conclusions: Clinical stage, LNM, PVM and UCI are independent risk factors for the prognosis of patients with stage Ⅰa2-Ⅱa2 cervical cancer. For patients without LNM or UCI, LRH through VC could reduce the intraperitoneal recurrence rate, while it is not enough to improve 5-year DFS and OS of patients. Low proportion of intraperitoneal recurrence, intra-operative tumor cells spillage to vagina stump and pelvic cavity might be the explanation.

Analysis of Lymph Node Metastasis and Risk Factors in 975 Patients with FIGO 2009 Stage IA–IIA Cervical Cancer

Objectives: The objective of this study was to summarize the rate of lymph node metastasis (LNM) of patients with stage IA–IIA cervical cancer and further analyze its distribution characteristics and related risk factors. Design: This study is a retrospective analysis of clinical data about cervical cancer. Participants: According to the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging standard, 975 patients with stage IA–IIA cervical cancer treated in our hospital from January 2010 to December 2018. Setting: This is a single-center study. Methods: The incidence and distribution of LNM were analyzed, and the influencing factors of cervical cancer LNM were analyzed using univariate and multivariate logistic regression. Results: In this study, the LNM rate was 14.8% (144/975), and a total of 20,288 lymph nodes were removed, among which 359 lymph nodes had metastasis. According to the number and frequency of metastatic lymph nodes in different regions, the metastatic rate was the highest in the external iliac regions. Univariate analysis showed that more than three pregnancies, tumor size >4 cm, gross type, FIGO stage, pathological type, positive lymphovascular space invasion (LVSI), deep cervical stromal invasion (outer half invasion), parametrial involvement, and uterine corpus invasion (UCI) were correlated with LNM (p < 0.05). Multivariate analysis showed that tumor lesion of >4 cm (odds ratio (OR) = 2.253, 95% confidence interval (CI): 1.486–3.416, p < 0.001), positive LVSI (OR = 5.353, 95% CI: 3.303–8.676, p < 0.001), deep cervical stromal invasion (OR = 3.461, 95% CI: 2.106–5.688, p < 0.001), and deep UCI (myometrial invasion ≥50%) (OR = 3.529, 95% CI: 1.321–9.427, p = 0.012) were independent risk factors for LNM. Limitations: Retrospective nature of the study and limitation to a single-center study are the limitations of the study. Conclusions: Patients with cervical cancer are more likely to have LNM with a tumor size of >4 cm, positive LVSI, deep cervical stromal invasion, or deep UCI. When these risk factors are present, the presence of LNM is possible, and attention should be paid. This study provides a certain reference value for predicting LNM risk for patients with early cervical cancer and for the stratified management of early cervical cancer treatment.

Nomogram Predicting Lymph Node Metastasis in the Early-Stage Cervical Cancer.

BackgroundAccurately predicting the risk level of lymph node metastasis is essential for the treatment of patients with early cervical cancer. The purpose of this study is to construct a new nomogram based on 2-deoxy-2-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and clinical characteristics to assess early-stage cervical cancer patients’ risk of lymph node metastasis.Materials and MethodsFrom January 2019 to November 2020, the records of 234 patients with stage IA-IIA [International Federation of Gynecology and Obstetrics (FIGO) 2018] cervical cancer who had undergone PET/CT examination within 30 days before surgery were retrospectively reviewed. A nomogram to predict the risk of lymph node metastasis was constructed based on it. The nomogram was developed and validated by internal and external validation. The validation cohorts included 191 cervical cancer patients from December 2020 to October 2021.ResultsFour factors [squamous cell carcinoma associated antigen (SCCA), maximum standardized uptake value of lymph node (nSUVmax), uterine corpus invasion in PET/CT and tumor size in PET/CT] were finally determined as the predictors of the nomogram. At the area under the receiver operating characteristic curve cohort was 0.926 in the primary and was 0.897 in the validation cohort. The calibration curve shows good agreement between the predicted probability and the actual probability. The decision curve analysis showed the clinical utility of the nomogram.ConclusionWe had established and verified a simple and effective nomogram, which can be used to predict the lymph node metastasis of cervical cancer patients before surgery.

High-Dose-Rate Interstitial Brachytherapy for Deeply Situated Gynecologic Tumors Guided by Combination of Transrectal and Transabdominal Ultrasonography: A Technical Note.

Background and PurposeHigh-dose-rate interstitial brachytherapy (HDR-ISBT) is recommended to obtain a better local tumor control for uterine cancer patients in specific situations such as bulky lesions, an extension to the lateral parametrium, or tumors with irregular shapes. Our group uses real-time transrectal ultrasonography (TRUS) to guide freehand interstitial needle insertion. Occasionally, target tumors locate deeper beyond the rectum and cannot be visualized by TRUS. CT can guide needles to deeply located tumors, but in such cases, repeated image obtainment is required to achieve ideal needle localization. In this report, we present nine cases of patients who underwent HDR-ISBT for deeply situated tumors guided by a combination of transrectal and transabdominal ultrasonography (TR/TA-US).Material and MethodsNine uterine cancer patients whose tumors were located deeper than the reach of TRUS and underwent HDR-ISBT guided by TR/TA-US were presented. All nine cases had no distal organ metastasis and underwent external beam radiation therapy (EBRT) to the pelvic region for 45–50.4 Gy in 25–28 fractions followed by boost HDR-ISBT for deeply situated tumors guided by TR/TA-US.ResultsThere were seven cervical cancer and two endometrial cancer patients: six with extensive uterine corpus invasion, one cervical cancer with massive pelvic lymph node metastasis, one cervical cancer with postoperative pelvic recurrence, and one with left ovarian direct tumor invasion. The median follow-up period was 15 months (range 3–28 months). The average clinical target volume at the time of first HDR-ISBT was 131 ml (range 44–335 ml). The linear distance from the vaginal entrance to the deepest part of the tumor at first time brachytherapy of nine cases was 14.0 (9.0–17.0) cm. HDR-ISBT dose fractionation was 24–30 Gy in four or five fractions. Seven out of nine cases had no local recurrence in the follow-up period. One had local in-field recurrence 25 months after HDR-ISBT. Another case with carcinosarcoma could not obtain local control and underwent salvage hysterectomy for a residual uterine tumor 11 months after HDR-ISBT. Four cases had extra-field recurrence in lymph nodes or distant organs.ConclusionsIn brachytherapy for gynecologic malignancies, deeply situated tumors located out of reach of TRUS may obtain favorable local control by HDR-ISBT guided with TR/TA-US.

IPMI: Machine Learning-Aided Identification of Parametrial Invasion in Women with Early-Stage Cervical Cancer

Radical hysterectomy is a recommended treatment for early-stage cervical cancer. However, the procedure is associated with significant morbidities resulting from the removal of the parametrium. Parametrial cancer invasion (PMI) is found in a minority of patients but the efficient system used to predict it is lacking. In this study, we develop a novel machine learning (ML)-based predictive model based on a random forest model (called iPMI) for the practical identification of PMI in women. Data of 1112 stage IA-IIA cervical cancer patients who underwent primary surgery were collected and considered as the training dataset, while data from an independent cohort of 116 consecutive patients were used as the independent test dataset. Based on these datasets, iPMI-Econ was then developed by using basic clinicopathological data available prior to surgery, while iPMI-Power was also introduced by adding pelvic node metastasis and uterine corpus invasion to the iPMI-Econ. Both 10-fold cross-validations and independent test results showed that iPMI-Power outperformed other well-known ML classifiers (e.g., logistic regression, decision tree, k-nearest neighbor, multi-layer perceptron, naive Bayes, support vector machine, and extreme gradient boosting). Upon comparison, it was found that iPMI-Power was effective and had a superior performance to other well-known ML classifiers in predicting PMI. It is anticipated that the proposed iPMI may serve as a cost-effective and rapid approach to guide important clinical decision-making.

Significance of miR-141 and miR-340 in cervical squamous cell carcinoma.

BackgroundWe investigated the expression and clinical significance of miR-141 and miR-340 in cervical squamous cell carcinoma (CSCC).MethodsExpression of miR-141 and miR-340 in CSCC, high-grade squamous intraepithelial lesion (HSIL), and normal cervical squamous epithelium were detected by qRT-PCR. PTEN was assessed by immunohistochemistry. Their relationship with clinicopathological features was analyzed.ResultsThe changes of miR-141 and miR-340 were different in CSCC, HSIL, and normal squamous epithelium (P = 0.030). miR-141 expression was statistically significant in gross type, differentiation, uterine corpus invasion, nerve invasion, vagina invasion, and FIGO stage in CSCC (P < 0.05). miR-340 expression was related to tumor size, differentiation, nerve invasion, lymph node metastasis, and FIGO stage in CSCC (P < 0.05). miR-141 and miR-340 expressions were statistically significant in different ages (P < 0.05) in HSIL. The AUC of miR-141 in CSCC diagnosis and that of miR-340 in HSIL diagnosis were 0.893 and 0.764, respectively. The sensitivity and the specificity of miR-141 for diagnosis of CSCC were 95.0% and 60.8%, respectively, while those of miR-340 for diagnosis of HSIL were 90.0 and 48.6%, respectively. miR-141 and miR-340 expressions are associated with PTEN expression (P = 0.002 and P < 0.001).ConclusionmiR-141 and miR-340 may be associated with their target gene PTEN and involved in the carcinogenesis of cervical squamous epithelium.

Uterine corpus invasion in cervical cancer: a multicenter retrospective case-control study.

To determine the accuracy of uterine corpus invasion (UCI) diagnosis in patients with cervical cancer and identity risk factors for UCI and depth of invasion. Clinical data of patients with cervical cancer who underwent hysterectomy between 2004 and 2016 were retrospectively reviewed. UCI was assessed on uterine pathology. Independent risk factors for UCI and depth of invasion were identified using binary and ordinal logistic regression models, respectively. A total of 2,212 patients with cervical cancer from 11 medical institutions in China were included in this study. Of these, 497 patients had cervical cancer and UCI, and 1,715 patients had cervical cancer and no UCI, according to the original pathology reports. Retrospective review of the original pathology reports revealed a missed diagnosis of UCI in 54 (10.5%) patients and a misdiagnosis in 36 (2.1%) patients. Therefore, 515 patients with cervical cancer and UCI (160 patients with endometrial invasion, 176 patients with myometrial invasion < 50%, and 179 patients with myometrial invasion ≥ 50%), and 1697 patients with cervical cancer without UCI were included in the analysis. Older age, advanced stage, tumor size, adenocarcinoma, parametrial involvement, resection margin involvement, and lymph node metastasis were independent risk factors for UCI. These risk factors, except resection margin involvement, were independently associated with depth of UCI. UCI may be missed or misdiagnosed in patients with cervical cancer on postoperative pathological examination. Older age, advanced stage, tumor size, adenocarcinoma, parametrial involvement, resection margin involvement, and lymph node metastasis were independent risk factors for UCI and depth of UCI, with the exception of resection margin involvement.

Clinical analysis of HPV58-positive cervical cancer

ObjectiveTo study the clinical features of HPV58-positive cervical cancer.MethodsA retrospective analysis of 347 patients with HPV58- or HPV16 positive cervical cancer from the Department of Gynecology Tumor of Guangxi Medical University Affiliated Cancer Hospital was performed. Molecular hybridization was used to detect HPV genotypes. The clinical features, including age, pathology, and invasion, were compared between the HPV58 positive and HPV16 positive cervical cancer groups.ResultsA total of 347 patients were eligible for this study, and the proportion of patients who were with poorly differentiated cancer (P = 0.015) was significantly higher in the HPV58 positive group. HPV58 positivity was an independent risk factor for poorly differentiated cancer [HR 2.156, 95% confidence interval: 1.167–3.984, P = 0.014]. The percentage of uterus corps invasion is significantly lower in HPV58 (p = 0.041), but HPV58 positivity is the independent risk factor for uterus corps invasion [HR = 3.985, 95% confidence interval: 1.066–14.893, P = 0.040]. The overall survival of HPV58-positive cervical cancer patients with uterine corpus invasion was significantly lower (P = 0.000). The age of patients in the HPV58-positive cervical cancer at advanced stage was significantly older (P = 0.045).ConclusionsHPV58-positive cervical cancer patients are at higher risk of poorly differentiated cancer and uterus corps invasion. The patients with HPV58 positive cervical cancer with uterus corps invasion may result a worse prognosis.

Influence of uterine corpus invasion on prognosis in stage IA2–IIB cervical cancer: A multicenter retrospective cohort study

ObjectiveTo determine the associations between the presence and depth of uterine corpus invasion and survival in patients with cervical cancer. MethodsClinical data of patients with stage IA2–IIB cervical cancer who underwent radical hysterectomy between 2004 and 2016 were retrospectively reviewed. Uterine corpus invasion was identified from a review of uterine pathology. Independent prognostic factors for 5-year disease-free survival (DFS) and overall survival (OS) were identified using multivariate forward stepwise Cox proportional hazards regression models. ResultsA total of 1414 patients with stage IA2–IIB cervical cancer from 11 medical institutions in China were included. Retrospective review of the original pathology reports revealed a missed diagnosis of uterine corpus invasion in 38 (13.4%) patients and a misdiagnosis in 20 (1.8%) patients. Therefore, 284 patients with cervical cancer and uterine corpus invasion (90 [31.7%] patients had endometrial invasion, 105 [37.0%] patients had myometrial invasion <50%, and 89 [31.3%] patients had myometrial invasion ≥50%), and 1130 patients with cervical cancer without uterine corpus invasion were included in the analysis. The 5-year DFS and OS were significantly shorter for patients with uterine corpus invasion compared to patients with no uterine corpus invasion. Myometrial invasion ≥50% was an independent prognostic factor associated with decreased 5-year DFS (aHR, 2.307, 95% CI, 1.588–3.351) and 5-year OS (aHR, 2.736, 95% CI, 1.813–4.130), while myometrial invasion <50% or endometrial invasion had no effect on patient outcomes. ConclusionsDiagnosis of uterine corpus invasion is frequently missed. Myometrial invasion ≥50% within the uterine corpus was an independent factor associated with worse prognosis in patients with cervical cancer, while myometrial invasion <50% or endometrial invasion had no effect on outcomes.

Uterine corpus invasion as a risk factor in patients with early-stage cervical carcinoma receiving radical surgery.

e17012 Background: To explore whether pathologically verified uterine corpus invasion (UCI) is a risk factor for patients with early-stage (IB1-IIA2) cervical carcinoma receiving radical surgery. Methods: A mathed-case comparison of early-stage cervical carcinoma patients with pathologically verified UCI to patients without UCI on a 1:1 ratio was conducted. High risk factors (lymph node metastasis, paremetrial invasion, vaginal margin invasion) and intermediate risk factors (lymphovascular space invasion (LVSI) and deep stromal invasion) were completely matched between UCI and non-UCI groups. Kaplan-Meier and Log-rank test were applied for univariate analysis, and COX proportional hazard regression models were used for multivariate analysis. Results: 1320 consecutive patients with cervical carcinoma received surgery in our centerfrom Jan. 1st2009 to Dec 31st2014. 79 (5.98%) cases with UCI were identified. Median follow-up time was 43 months. There were 22 cases with recurrence. In UCI group, the recurrence rate was 20.3% (16/79), and in non-UCI group the recurrence rate was 7.6% (6/79). On univariate analysis, SCC, neoadjuvant chemotherapy (NACT), lymph node metastasis, parametrial invasion, LVSI, deep stromal invasion, vaginal invasion and UCI were significantly associated with disease free survival (DFS). After multivariate analysis, UCI ( p= 0.02, RR3.832, 95% CI1.235-11.893)and lymph node metastasis ( p= 0.042, RR 2.890, 95% CI1.038-8.045) were still independent risk factors for deceased DFS. Conclusions: Pathologically verified uterine corpus invasion might be an independent risk factor for decreased DFS in patients with early-stage cervical carcinoma receiving radical surgery.

Predictors for pathological parametrial invasion in clinical stage IIB cervical cancer

ObjectiveTo examine predictors of pathological parametrial invasion in clinical stage IIB cervical cancer, and to examine prognostic factors in pathological stage IIB disease. MethodsThis study is an ancillary analysis of a nation-wide retrospective cohort examining 6,003 clinical stage IB-IIB cervical cancers. Women with clinical stage IIB disease who underwent primary radical hysterectomy with lymphadenectomy were examined (n = 714). Multivariate analysis was performed to identify independent clinico-pathological factors for pathological parametrial invasion and to identify independent prognostic factors in pathological stage IIB disease. ResultsParametrial invasion was identified on the surgical specimen in 400 cases (56.0%, 95% confidence interval 52.4–59.7). On multivariate analysis, deep stromal invasion (DSI, adjusted-OR 3.922), multiple pelvic nodal metastases (adjusted-OR 3.266), lympho-vascular space invasion (adjusted-OR 2.333), and uterine corpus invasion (adjusted-OR 1.656) remained independent tumor factors for pathological parametrial invasion. In classification-tree models, tumors with DSI and multiple pelvic nodal metastases had the highest incidence of pathological parametrial invasion (75.0–87.7%); contrary, tumors without DSI had the lowest incidence (21.9%). Among patients with pathological stage IIB disease, the absolute difference in 5-year disease-free survival rates was 57.2%, ranging between 80.9% in those with squamous histology with none/single pelvic nodal metastasis and 23.7% in those with non-squamous histology with multiple pelvic nodal metastases. ConclusionIn clinical stage IIB cervical cancer, accuracy for pathological parametrial invasion is low-modest. With absence of DSI, only one in five clinical stage IIB diseases has pathological stage IIB disease. Survival of pathological stage IIB varies widely and is largely dependent on nodal factors.

Early Cervical Cancer: Predictive Relevance of Preoperative 3-Tesla Multiparametric Magnetic Resonance Imaging.

Objective We assess the predictive significance of preoperative 3-Tesla multiparametric MRI findings. Methods A total of 260 patients with FIGO IA2-IIA cervical cancer underwent primary surgical treatment between 2007 and 2016. Univariable and multivariable logistic regression analyses were used to assess the incremental prognostic significance. Results The clinical predictive factors associated with pT2b disease were MRI parametrial invasion (PMI) (adjusted odds ratio (AOR) 3.77, 95% confidence interval(CI) 1.62-8.79; P=0.02) and MRI uterine corpus invasion (UCI) (AOR 9.99, 95% CI 4.11-24.32; P<0.0001). In multivariable analysis, for underdiagnoses, histologically squamous carcinoma versus adenocarcinoma and adenosquamous carcinoma (AOR 2.07, 95% CI 1.06-4.07; P=0.034) and MRI tumor size (AOR 0.76, 95% CI 0.63-0.92; P=0.005) were significant predictors; for overdiagnoses, these results were MRI tumor size (AOR 1.51, 95% CI 1.06-2.16; P=0.023), MRI PMI (AOR 71.73, 95% CI 8.89-611.38; P<0.0001) and MRI UCI (AOR 0.19, 95% CI 0.01-1.01; P=0.051). Conclusion PMI and UCI on T2-weighted images through preoperative 3T MRI are useful coefficients for accurate prediction of the pT2b stage; however, careful surveillance is required. Therefore, preoperative decision-making for early cervical cancer patients based on MRI diagnosis should be considered carefully, particularly in the presence of factors that are known to increase the likelihood of misdiagnosis.

Uterine corpus invasion is a risk factor in patients with early-stage cervical carcinoma receiving radical surgery

Objective: To explore whether pathologically verified uterine corpus invasion (UCI) is a risk factor for patients with early-stage (IB1–IIA2) cervical carcinoma receiving radical surgery.

Ovarian preservation in adenocarcinoma of the uterine cervix

BackgroundAn upward trending incidence in cervical adenocarcinoma (ADC) has been reported in many countries. Because non-squamous histology has been associated with increased risk of ovarian metastases (OM), bilateral oophorectomy is commonly performed for ADC without due consideration for ovarian preservation, degrading the quality of life for young premenopausal patients.MethodsSubjects were patients with International Federation of Gynecology and Obstetrics (FIGO) stage I–IIB cervical ADC who underwent radical hysterectomy, including pelvic lymphadenectomy and bilateral salpingo-oophorectomy at our institution between Oct. 2006 and Sept. 2014. Clinicopathologic variables were studied by univariate and multivariate analyses.ResultsOf the 312 patients enrolled in the study, 14 patients (4.5%) developed OM. Multivariate analysis revealed that uterine corpus involvement (odds ratio [OR] 5.178, p = 0.019), parametrial involvement (OR 14.125, p = 0.005) and vaginal infiltration (OR 4.167, p = 0.047) were independently associated with metastasis. OM had no effect on either relapse-free survival (95% confidence interval [CI]: 0.077–4.095, p = 0.57) or overall survival (95% CI: 0.893–9.820, p = 0.076).ConclusionCervical ADC is associated with an increased risk of OM. Ovarian preservation surgery in cervical ADC may be safe for young patients at an early FIGO stage without deep stromal, endometrial or perineural invasion, and particularly without uterine corpus invasion, parametrial involvement and infiltration into the vagina.

Significance of uterine corpus tumor invasion in early-stage cervical cancer

ObjectiveTo examine characteristics and survival outcomes of women with surgically-treated cervical cancer exhibiting uterine corpus tumor invasion. MethodsWe utilized The Surveillance, Epidemiology, and End Results Program to identify cervical cancer patients who underwent hysterectomy between 1973 and 2003. Logistic regression models were used to identify risk factors for uterine corpus tumor invasion on multivariable analysis. Association of uterine corpus tumor invasion and cause-specific survival (CSS) from cervical cancer was examined with Cox proportional hazard regression models on multivariable analysis. ResultsWe identified 837 (4.9%) cases of uterine corpus invasion and 16,237 (95.1%) cases of non-invasion. Median follow-up time was 14.0 years. There were 1642 deaths due to cervical cancer. Uterine corpus invasion was independently associated with older age, non-squamous histology, high-grade tumors, large tumor size, and nodal metastasis on multivariable analysis (all, P < 0.001). On univariable analysis, uterine corpus tumor invasion was significantly associated with decreased CSS compared to the non-invasion (5-year rates, 79.0% versus 94.5%, P < 0.001). After controlling for other significant prognostic factors, uterine corpus tumor invasion remained an independent prognostic factor for decreased CSS (adjusted-hazard ratio 1.45, 95% confidence interval 1.21–1.74). Among stage T1b cases (n = 6730), uterine corpus tumor invasion remained an independent prognostic factor for decreased CSS (adjusted-hazard ratio 1.95, 95%CI 1.47–2.60). Uterine corpus tumor invasion was significantly associated with decreased CSS in stage T1b1 disease (74.5% versus 90.7%, P < 0.001) and in stage T1b2 disease (67.0% versus 79.5%, P = 0.01). ConclusionUterine corpus tumor invasion is an independent prognostic factor for decreased survival of women with early-stage cervical cancer.

Glut-1 expression in small cervical biopsies is prognostic in cervical cancers treated with chemoradiation

Background/purposeChemoradiation (CRT) is standard therapy for locally advanced cervical cancer (LACC). However, there is a lack of biomarkers to identify patients at high relapse-risk. We examine metabolic (glucose transporter-1 [Glut-1]), hypoxic (hypoxia inducible factor [HIF-1α]; carbonic anhydrase [CA-9]) and proliferative (Ki-67) markers for prognostic utility in LACC. Materials/methods60 LACC patients treated with CRT had pre-treatment biopsies. Immunohistochemistry was performed for Glut-1, HIF-1a and CA-9, to generate a histoscore from intensity and percentage staining; and Ki-67 scored by percentage of positive cells. For each biomarker, treatment response and survival was compared between low and high-staining groups by logrank testing and multivariate analyses. ResultsHigh Glut-1 expression was associated with inferior progression-free survival (PFS), (hazard ratio [HR] 2.8, p=0.049) and overall survival (OS), (HR 5.0, p=0.011) on multifactor analysis adjusting for stage, node positivity, tumour volume and uterine corpus invasion. High Glut-1 correlated with increased risk of distant failure (HR 14.6, p=0.001) but not local failure. Low Glut-1 was associated with higher complete metabolic response rate on post-therapy positron emission tomography scan (odds ratio 3.4, p=0.048). Ki-67 was significantly associated with PFS only (HR 1.19 per 10 units increase, p=0.033). Biomarkers for hypoxia were not associated with outcome. ConclusionsHigh Glut-1 in LACC is associated with poor outcome post CRT. If prospectively validated, Glut-1 may help select patients for more intensive treatment regimens.

Long noncoding RNA CCHE1 promotes cervical cancer cell proliferation via upregulating PCNA.

Long noncoding RNAs (lncRNAs) have been shown to play important roles in carcinogenesis and progression. However, the roles and functional mechanisms of lncRNAs in cervical cancer remain largely unknown. In this study, we found that cervical carcinoma high-expressed lncRNA 1 (lncRNA-CCHE1) was significantly upregulated in cervical cancer tissues. The higher expression of CCHE1 was significantly correlated with large tumor size, advanced Federation of Gynecology and Obstetrics stage, uterine corpus invasion, and poor survival. Gain-of-function and loss-of-function experiments demonstrated that CCHE1 overexpression promotes the proliferation of cervical cancer cell. By contrast, the depletion of CCHE1 inhibits the proliferation of cervical cancer cells. RNA pull-down assays confirmed that CCHE1 physically associates with proliferating cell nuclear antigen (PCNA) messenger RNA, consequently enhances the expression of PCNA. The expression of CCHE1 and PCNA is significantly correlated in cervical cancer tissues. The depletion of PCNA abolishes the effects of CCHE1 on the proliferation of cervical cancer cells. Taken together, these findings indicate that CCHE1 plays a pivotal role in cervical cancer cell proliferation via increasing PCNA expression and serves as a potential prognostic biomarker and therapeutic target in human cervical cancer.

Distribution of human papillomavirus genotypes in early-stadge cervical adenocarcinoma and its clinical significance

To explore the distribution of high-risk HPV-genotypes in early-stage cervical adenocarcinoma and understand the clinical significance of HPV genotyping. From June 2000 to May 2010, a total of 101 paraffin surgical specimens of cervical adenocarcinoma were genotyped by nested polymerase chain reaction (nested PCR). The associations of HPV18 with clinicopathological parameters and survival were further analyzed. DNA extraction was successfully performed for 96 samples. The HPV-positive rate of early-stage cervical adenocarcinoma was 95.8% (92/96). Two common HPV types were HPV16 (59.4%) and HPV18 (60.4%). The prevalence rates of single, double and multiple HPV infections were 22.9%, 32.3% and 40.6% respectively. The positive rates of lymph node metastasis and vascular involvement with HPV18 infection were 27.6% and 22.4% versus 7.9% and 7.9% for those without HPV18 infection.Univariate analysis showed that positive surgical margin, uterine corpus invasion, lymph node metastasis and HPV18 infection were the predictive factors for poor prognosis of patients with cervical adenocarcinoma. Multivariate analysis revealed that lymph node metastasis was an independent prognostic factor for both disease-free and overall survivals. And uterine corpus invasion was an independent prognostic factor of overall survival for early-stage cervical adenocarcinoma patients. HPV16 and HPV18 are major types responsible for early-stage cervical adenocarcinoma.Infection with HPV18 is prone to lymph node metastasis and vascular involvement.However, there is no correlation with disease-free survival or overall survival.

Hemoglobin Level in Cervical Cancer

Hemoglobin (Hb) is a prognostic factor in cervical cancer, but the underlying mechanisms remain unknown. In this study, we hypothesized that low Hb level, either before or during radiotherapy (RT), is a surrogate for a more infiltrative and therefore aggressive disease, with uterine corpus invasion and nodal metastases. Prospectively collected data of patients with locally advanced cervical cancer treated with curative intent using chemoradiation at a tertiary academic center was reviewed. All eligible patients had a positron emission tomographic scan and pelvic magnetic resonance imaging. Hemoglobin levels before RT and Hb nadir during RT were collected from the medical record. The median follow-up for 263 eligible patients was 38.7 months. Ninety-six patients (36.5%) had both uterine corpus invasion and positron emission tomography-positive nodal disease (C+N+). Patients with pretreatment Hb level of less than 120 g/L were more likely to have C+N+ disease (47%) compared with patients with a high pretreatment Hb level (32%; P = 0.034). The 3-year disease-free survival and overall survival (OS) were significantly lower in the C+N+ group compared with the remaining patients (40.1% vs 76.1%, P < 0.001, and 59.7% vs 83.1%, P < 0.001, respectively). Patients with low Hb nadir were more likely to have a C+N+ disease (P < 0.001), and low Hb nadir during RT was significantly an indicator of a higher recurrence rate (P = 0.002) and lower OS (P < 0.001). In multifactor analysis, statistically significant prognostic factors for OS included histology, high-echelon nodal involvement, tumor volume on magnetic resonance imaging, C+N+ status, and Hb nadir during treatment. Pretreatment Hb level was not an independent prognostic factor. The combination of corpus invasion and nodal metastases is associated with lower Hb level and inferior prognosis. Because C+N+ state is related to tumor growth from early invasion to the time of presentation, it is unlikely that the correction of Hb level during treatment will have a major impact on outcome.