OBJECTIVE: The causal association of human papillomavirus (HPV) in uterine cervical cancer was well established and this oncogenic virus was reported to be a biomarker for overall recurrence and central pelvic recurrence. The objective of the present systematic review and meta-analysis was to assess the role of HPV DNA testing in early detection of recurrence among cervical cancer survivors after radiotherapy.METHODS: We performed a systematic review and meta-analysis by means of searching electronic databases for published articles between January 1984 and June 2018, on the basis of standard systematic review guidelines prescribed by major agencies namely Cochrane Collaboration (https://www.cochrane.org) and Campbell Collaboration (https://www.campbellcollaboration.org). The meta-analysis component was further modified appropriately for the synthesis of sensitivity and specificity results.RESULTS: A total of 1,055 cervical cancer cases who had received pelvic radiation with or without chemotherapy from ten cohort studies were evaluated. The overall pooled sensitivity and specificity of HPV DNA testing was 0.84 (95% confidence interval [CI]= 0.66–0.94) and 0.35 (95% CI=0.20–0.54) respectively. The positive likelihood ratio was 1.3 (95% CI=1.0–1.7) and the negative likelihood ratio was 0.45 (95% CI=0.18–1.10) with an estimated diagnostic odds ratio of 3 (95% CI=1–9).CONCLUSION: The screening for HPV DNA testing during follow-up facilitates early detection of recurrence after radiotherapy.
Cervix Uteri ; Cohort Studies ; Cooperative Behavior ; DNA ; Drug Therapy ; Female ; Follow-Up Studies ; Human Papillomavirus DNA Tests ; Humans ; Mass Screening ; Odds Ratio ; Oncogenic Viruses ; Radiotherapy ; Recurrence ; Sensitivity and Specificity ; Survivors ; Uterine Cervical Neoplasms

OBJECTIVE: There is no definitive guideline for the significance and cut-off value of squamous-cell carcinoma antigen (SCC-Ag) in cervical cancer. Thus, we analyzed the significance and optimal cut-off value of SCC-Ag for predicting tumor recurrence and patient survival in squamous-cell carcinoma of uterine cervix. METHODS: From January 2010 to October 2016, we enrolled 304 cervical cancer patients with squamous-cell carcinoma staging International Federation of Gynecology and Obstetrics (FIGO) Ib–IVa and treated with definitive chemoradiotherapy (CRT) followed by intra-cavitary radiotherapy (ICR). The cut-off value of SCC-Ag level for tumor recurrence was calculated using the receiver operating characteristic (ROC) curve. The recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan-Meier method to estimate the significance of SCC-Ag level. RESULTS: The optimal cut-off value of SCC-Ag level for predicting tumor recurrence was calculated and set at 4.0 ng/mL in the ROC curve. After a median follow-up period of 36.5 months, the 3-year RFS (56.6% vs. 80.2%, p < 0.001) and OS (72.1% vs. 86.8%, p=0.005) were significantly lower in SCC-Ag ≥4 ng/mL arm than in < 4 ng/mL arm. The 3-year locoregional recurrence (17.6% vs. 7.0%, p=0.012), distant metastasis (20.4% vs. 6.9%, p=0.002), and para-aortic recurrence (9.4% vs. 2.1%, p=0.012) rates were significantly higher in SCC-Ag ≥4 ng/mL arm than in SCC-Ag < 4 ng/mL arm. CONCLUSION: Pre-treatment SCC-Ag level higher than 4 ng/mL may be a useful predictor of tumor recurrence in patients with squamous-cell carcinoma of uterine cervix treated with definitive CRT and ICR.
Arm ; Cervix Uteri* ; Chemoradiotherapy* ; Female ; Follow-Up Studies ; Gynecology ; Humans ; Methods ; Neoplasm Metastasis ; Obstetrics ; Radiotherapy ; Recurrence* ; ROC Curve ; Uterine Cervical Neoplasms

OBJECTIVE: To examine the association between tumor grade and survival for women with squamous cervical cancer. METHODS: This retrospective observational study utilized the Surveillance, Epidemiology, and End Result program data between 1983 and 2013 to examine women with squamous cervical cancer with known tumor differentiation grade. Multivariable analyses were performed to assess independent associations between tumor differentiation grade and survival. RESULTS: A total of 31,536 women were identified including 15,175 (48.1%) with grade 3 tumors, 14,084 (44.7%) with grade 2 neoplasms and 2,277 (7.2%) with grade 1 tumors. Higher tumor grade was significantly associated with older age, higher stage disease, larger tumor size, and lymph node metastasis (all, p < 0.001). In a multivariable analysis, grade 2 tumors (adjusted-hazard ratio [HR]=1.21; p < 0.001) and grade 3 tumors (adjusted-HR=1.45; p < 0.001) were independently associated with decreased cause-specific survival (CSS) compared to grade 1 tumors. Among the 7,429 women with stage II–III disease who received radiotherapy without surgical treatment, grade 3 tumors were independently associated with decreased CSS compared to grade 2 tumors (adjusted-HR=1.16; p < 0.001). Among 4,045 women with node-negative stage I disease and tumor size ≤4 cm who underwent surgical treatment without radiotherapy, grade 2 tumors (adjusted-HR=2.54; p=0.028) and grade 3 tumors (adjusted-HR=4.48; p < 0.001) were independently associated with decreased CSS compared to grade 1 tumors. CONCLUSION: Our study suggests that tumor differentiation grade may be a prognostic factor in women with squamous cervical cancer, particularly in early-stage disease. Higher tumor grade was associated with poorer survival.
Carcinoma, Squamous Cell* ; Cervix Uteri* ; Epidemiology ; Epithelial Cells* ; Female ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Observational Study ; Radiotherapy ; Retrospective Studies ; Uterine Cervical Neoplasms

OBJECTIVE: To compare the survival outcomes of patients with cervical squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) among patients with locally advanced cervical cancer that were treated with definitive radiotherapy. METHODS: The baseline characteristics and outcome data of patients with locally advanced cervical cancer who were treated with definitive radiotherapy between November 1993 and February 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to investigate the prognostic significance of AC/ASC histology. RESULTS: The patients with AC/ASC of the cervix exhibited significantly shorter overall survival (OS) (p=0.004) and progression-free survival (PFS) (p=0.002) than the patients with SCC of the cervix. Multivariate analysis showed that AC/ASC histology was an independent negative prognostic factor for PFS. Among the patients who displayed AC/ASC histology, larger tumor size, older age, and incomplete response to radiotherapy were found to be independent prognostic factors. PFS was inversely associated with the number of poor prognostic factors the patients exhibited (the estimated 1-year PFS rates; 100.0%, 77.8%, 42.8%, 0.0% for 0, 1, 2, 3 factors, respectively). CONCLUSION: Locally advanced cervical cancer patients with AC/ASC histology experience significantly worse survival outcomes than those with SCC. Further clinical studies are warranted to develop a concurrent chemoradiotherapy (CCRT) protocol that is specifically tailored to locally advanced cervical AC/ASC.
Adenocarcinoma ; Carcinoma, Adenosquamous ; Carcinoma, Squamous Cell* ; Cervix Uteri ; Chemoradiotherapy ; Disease-Free Survival ; Epithelial Cells* ; Female ; Humans ; Multivariate Analysis ; Radiotherapy* ; Retrospective Studies ; Uterine Cervical Neoplasms*

OBJECTIVETo investigate the clinical application of diffusion weighted imaging (DWI) in uterine cervical cancer and the apparent diffusion coefficient (ADC) value in diagnosis and predicting treatment response.

METHODSTwenty-eight patients with advanced primary cervical cancer confirmed by pathology and 10 cases of normal uterine cervix as control were recruited in this prospective clinical trial. To analyze the correlation between tumor volume measured in DWI and tumor maximum diameter measured according to the RECIST criteria. To compare the ADC value differences among the uterine cervical cancer, uterine myometrium, and normal uterine cervix. To compare the ADC values in 17 cancer patients before and after treatment.

RESULTSThe illustration of tumor boundary in DWI was superior to conventional T2WI and post-enhancement T1WI. The DWI with higher b value (2000 s/mm(2)) had a better signal-to-noise ratio. The tumor volume measured in DWI has good correlation with tumor maximum diameter according to RECIST criteria (r = 0.759, P < 0.01). When b = 800 s/mm(2), the ADC values of the uterine cervical cancer, uterine myometrium, and normal uterine cervix were (9.85 ± 1.55)×10(-3) mm(2)/s, (14.20 ± 2.80)×10(-3) mm(2)/s, and (14.14 ± 0.45) ×10(-3) mm(2)/s. When b = 2000 s/mm(2), the ADC values of the uterine cervical cancer, uterine myometrium and normal uterine cervix were (7.38 ± 0.98)×10(-3) mm(2)/s, (8.52 ± 2.38)×10(-3) mm(2)/s, and (8.60 ± 0.63)×10(-3) mm(2)/s, respectively. There were significant differences between the cervical cancer and normal cervix or uterine myometrium (P < 0.001 for both). When b = 800 s/mm(2), the ADC value was (9.85 ± 1.55)×110(-3) mm(2)/s before and (13.41 ± 2.93)×10(-3) mm(2)/s after treatment (P < 0.001). When b = 2000 s/mm(2), the ADC value was (7.38 ± 0.98)×10(-3) mm(2)/s before and (8.93 ± 1.92)×10(-3) mm(2)/s after treatment (P = 0.008). Univariate logistic regression analysis showed that 25% ADC, 50%ADC, and 75%ADC in the tumor ADC value histogram before treatment were significantly correlated to the treatment outcome of cervical cancer (P < 0.05 for all). Multivariate regression analysis showed that 25%ADC, 50%ADC, and 75%ADC in the tumor ADC value histogram before treatment were not significantly correlated to the treatment outcome of cervical cancer (P > 0.05 for all). The values of ROC curves were 25%ADC = 0.818, 50%ADC = 0.775, and 75%ADC = 0.716 (P > 0.05), however, the 25% ADC showed a relatively stronger statistical power.

CONCLUSIONSDWI helps to confirm the morphology and exact target zone of the tumor for radiotherapy. DWI volume measurement is well correlated with RECIST criteria, particularly in volume measurement of irregular tumors. ADC value has a potential in quantitatively monitoring treatment response and predicting outcome of cervical cancers.

Adenocarcinoma ; diagnosis ; drug therapy ; pathology ; radiotherapy ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Squamous Cell ; diagnosis ; drug therapy ; pathology ; radiotherapy ; Case-Control Studies ; Cervix Uteri ; pathology ; Cisplatin ; therapeutic use ; Diffusion Magnetic Resonance Imaging ; Female ; Humans ; Middle Aged ; Myometrium ; pathology ; Prospective Studies ; ROC Curve ; Radiotherapy, Conformal ; Treatment Outcome ; Tumor Burden ; Uterine Cervical Neoplasms ; diagnosis ; drug therapy ; pathology ; radiotherapy

PURPOSE: The purpose of this retrospective study was to evaluate the efficacy and feasibility of short-course hypofractionated radiotherapy (RT) for the palliation of uterine cervical cancer. MATERIALS AND METHODS: Seventeen patients with cancer of the uterine cervix, who underwent palliative hypofractionated 3-dimensional conformal radiotherapy between January 2002 and June 2012, were retrospectively analyzed. RT was delivered to symptomatic lesions (both the primary mass and/or metastatic regional lymph nodes). The total dose was 20 to 25 Gy (median, 25 Gy) in 5 Gy daily fractions. RESULTS: The median follow-up duration was 12.2 months (range, 4 to 24 months). The median survival time was 7.8 months (range, 4 to 24 months). Vaginal bleeding was the most common presenting symptom followed by pelvic pain (9 patients). The overall response rates were 93.8% and 66.7% for vaginal bleeding control and pelvic pain, respectively. Nine patients did not have any acute side effects and 7 patients showed minor gastrointestinal toxicity. Only 1 patient had grade 3 diarrhea 1 week after completion of treatment, which was successfully treated conservatively. Late complications occurred in 4 patients; however, none of these were of grade 3 or higher severity. CONCLUSION: Short-course hypofractionated RT was effective and well tolerated as palliative treatment for uterine cervical cancer.
Cervix Uteri ; Diarrhea ; Female ; Follow-Up Studies ; Humans ; Palliative Care ; Pelvic Pain ; Radiotherapy* ; Radiotherapy, Conformal ; Retrospective Studies ; Uterine Cervical Neoplasms* ; Uterine Hemorrhage

OBJECTIVETo evaluate the results of surgical treatment for central recurrence or persistent local lesion of uterine cervical carcinoma following full-dose radiotherapy.

METHODSForty-seven patients were diagnosed having central recurrence or persistent local lesion of uterine cervical carcinoma following full-dose radiotherapy. The patients were treated surgically: extrafascial hysterectomy was performed in 37 cases, radical hysterectomy in 7, and modified radical hysterectomy in 3. Their clinicopathological features were retrospectively reviewed.

RESULTSCentral recurrence or persistent local lesion was confirmed by pathology in 36 patients, while negative in 11. For patients receiving extrafascial hysterectomy, the median survival time and 5-year survival rate were 22 months and 40.4%, while for radical hysterectomy corresponding figures were 26 months and 40.0%. The mean operation time for the extrafascial hysterectomy and the radical or modified hysterectomy was 2.5 and 3.8 hours, respectively. The mean blood loss was 272.1 and 610.0 ml, respectively. The postoperative morbidity was 21.6% for extrafascial hysterectomy and 70.0% for radical or modified hysterectomy (P = 0.007).

CONCLUSIONFor some patients with central recurrence or persistent local lesion of uterine cervical carcinoma following full-dose radiotherapy, surgical intervention may achieve long time survival. Extrafascial hysterectomy is a feasible and effective treatment for some selected patients.

Adenocarcinoma ; pathology ; radiotherapy ; surgery ; Adult ; Aged ; Brachytherapy ; Carcinoma, Squamous Cell ; pathology ; radiotherapy ; surgery ; Cervix Uteri ; pathology ; surgery ; Cesium Radioisotopes ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; methods ; Iridium Radioisotopes ; therapeutic use ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Radiotherapy Dosage ; Radiotherapy, High-Energy ; Retrospective Studies ; Survival Rate ; Uterine Cervical Neoplasms ; pathology ; radiotherapy ; surgery ; Young Adult

Spontaneous intraperitoneal bladder rupture is a rare complication of radiation therapy. We report an unusual case of spontaneous intraperitoneal bladder rupture 17 years after pelvic radiotherapy for carcinoma of the cervix in a 59-year-old woman who underwent prompt surgical repair.
Cervix Uteri ; Female ; Humans ; Middle Aged ; Radiotherapy* ; Rupture* ; Urinary Bladder* ; Uterine Cervical Neoplasms*

OBJECTIVETo analyze the characteristics of cervical minimal deviation adenocarcinoma (MDA) and the methods of diagnosis and treatment.

METHODSA retrospective study was carried out to evaluate the clinical and pathological data of 15 patients with MDA treated from 1992 to 2007.

RESULTSThe average age of the 15 patients was 42.3 years. The main symptoms were increased discharge and irregular vaginal bleeding. Preoperative Pap smears showed adenocarcinoma in 3 cases (27.3%). The diagnosis of MDA was confirmed in 8 cases by cervical punch biopsies (53.3%) and 2 cases by conization. Several cysts were noted in sections of the endocervix. Microscopic examination showed glands irregular in size and shape. However, the deviation of tumor cells was minimal. Immunohistochemistry revealed positive expression of CEA and alpha-SMA. The mean follow-up time was 51.0 months. The overall 5-year survival rate was 85.7%. Four cases experienced recurrence in the vagina and pelvis at 2 years after operation. Three cases died of the disease relapse with an average survival time of 36.3 months.

CONCLUSIONCervical minimal deviation adenocarcinoma is rare, with minimal deviation of cell shape from the normal cervical cells and difficult in diagnosis. A deep biopsy or conization is necessary when punch biopsy is not sufficient for diagnosis. Immunohistochemistry is helpful to make an accurate diagnosis. Surgery is the first choice for cervical minimal deviation adenocarcinoma. Radiotherapy and/or chemotherapy should be given if needed. The prognosis can be improved if a proper treatment plan is carried out.

Actins ; metabolism ; Adenocarcinoma ; diagnosis ; pathology ; therapy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoembryonic Antigen ; metabolism ; Cervix Uteri ; pathology ; Chemotherapy, Adjuvant ; Cisplatin ; administration & dosage ; Conization ; Epirubicin ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Follow-Up Studies ; Humans ; Hysterectomy ; methods ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Papanicolaou Test ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Rate ; Uterine Cervical Neoplasms ; diagnosis ; pathology ; therapy ; Vaginal Smears

OBJECTIVE: Clinical evaluation of tumor size in cervical cancer is often difficult. Digital imaging technique using computer has shown an eye opening progress. Quantitative analysis of tumor size or tumor volume using magnetic resonance imaging (MRI) has been reported as useful in the prediction of prognosis in patients with cervical cancer. The purpose of this study was to evaluate whether quantitative analysis can further improve the efficacy of using MR imaging to predict the prognosis of cervical cancer. METHODS: MRI on 0.5- or 1.5-T scanners was performed in 93 consecutive women with invasive carcinoma of the uterine cervix. Initial tumor diameter and volume were determined on T2-weighted images; volume was calculated by the standard technique of multiplying the sum of the areas by the slice thickness. Patients were treated by radical surgery, radiotherapy, or a concurrent chemoradiotherapy based on clinical International Federation of Gynecology and Obstetrics (FIGO) stage and individual patient criteria. Clinical data (patient age and FIGO stage), MRI-derived tumor dimensions (diameter and volume), and histological findings (tumor invasion depth and histological type) were associated and linked to patient outcome. RESULTS: Tumor volume on MRI was significantly associated with recurrence of cervical cancer (P=0.018). Univariate analysis demonstrated graphically that MRI-derived tumor volume and clinical stage were associated with progression-free survival. CONCLUSION: Our preliminary results suggest that tumor volume, determined by pretreatment MRI, predict progression-free survival for patients with invasive cervical carcinoma. This study reveals the value of MRI as an adjunctive tool to clinical evaluation of invasive cervical cancer.
Cervix Uteri ; Chemoradiotherapy ; Disease-Free Survival ; Female ; Gynecology ; Humans ; Magnetic Resonance Imaging* ; Obstetrics ; Prognosis* ; Radiotherapy ; Recurrence ; Tumor Burden* ; Uterine Cervical Neoplasms