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Purpose: This study is intended to compare dose-volume parameters evaluated using different forward planningoptimization techniques, involving two applicator systems in intracavitary brachytherapy for cervical cancer. It looks for the best applicator-optimization combination to fulfill recommended dose-volume objectives in different high-doserate (HDR) fractionation schedules. Material and methods: We used tandem-ring and Fletcher-style tandem-ovoid applicator in same patients in two fractions of brachytherapy. Six plans were generated for each patient utilizing 3 forward optimization techniques for each applicator used: equal dwell weight/times ('no optimization'), 'manual dwell weight/times', and 'graphical'. Plans were normalized to left point A and dose of 8 Gy was prescribed. Dose volume and dose point parameters were compared. Results: Without graphical optimization, maximum width and thickness of volume enclosed by 100% isodose line, dose to 90%, and 100% of clinical target volume (CTV); minimum, maximum, median, and average dose to both rectum and bladder are significantly higher with Fletcher applicator. Even if it is done, dose to both points B, minimum dose to CTV, and treatment time; dose to 2 cc (D2cc) rectum and rectal point etc.; D2cc, minimum, maximum, median, and average dose to sigmoid colon; D2cc of bladder remain significantly higher with this applicator. Dose to bladder point is similar (p > 0.05) between two applicators, after all optimization techniques. Conclusions: Fletcher applicator generates higher dose to both CTV and organs at risk (2 cc volumes) after all optimization techniques. Dose restriction to rectum is possible using graphical optimization only during selected HDR fractionation schedules. Bladder always receives dose higher than recommended, and 2 cc sigmoid colon always gets permissible dose. Contrarily, graphical optimization with ring applicators fulfills all dose volume objectives in all HDR fractionations practiced. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the most frequently diagnosed cancers and is a major cause of death from gynecologic cancers worldwide; the cancer burden from cervical cancer is especially heavy in less developed countries. Most cases of cervical cancer are caused by persistent infection with carcinogenic human papillomavirus (HPV) genotypes 16 and 18. Non-resolving inflammation caused by HPV infection provides a microenvironment that facilitates cancer development. Molecular alterations during the process of HPV-induced carcinogenesis are characterized by DNA methylation within the HPV genome, promoter hypermethylation of tumor suppressor genes in the host genome, as well as genomic instability caused by viral DNA integrating into the host genome. Catalytic polypeptide-like apolipoprotein B mRNA editing enzymes (APOBECs) normally function as part of the innate immune system. APOBEC expression is stimulated upon viral infection and plays an important role in HPVinduced cervical cancer. APOBECs catalyze the deamination of cytosine bases in nucleic acids, which leads to a conversion of target cytosine (C) to uracil (U) and consequently a change in the single-stranded DNA/RNA sequence. APOBEC proteins mediate the complex interactions between HPV and the host genome and link immunity and viral infection during HPV-driven carcinogenesis. Understanding the effects of APOBECs in HPV-induced cervical carcinogenesis will enable the development of better tools for HPV infection control and personalized prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: The clinical characteristics and outcomes of patients with metastatic recurrent cervical cancer remain poorly understood. The goals of the present study were to investigate the survival outcomes according to the recurrence site in a large cohort of cervical cancer patients.Methods and Materials: Of 1322 patients with primary cervical cancer from 2000 to 2013, 205 with recurrence after primary or adjuvant postoperative radiation were enrolled retrospectively. Aggressive salvage therapy (AST), which was defined as salvage therapy that aimed not only to relieve symptoms but also to ablate recurrent tumors by the single or combined application of surgical resection of local recurrence, metastasectomy, or metastasis-directed irradiation, followed by chemotherapy, was performed according to our institutional guidelines. The patterns of recurrence, application rate and mode of AST, and survival outcomes were evaluated retrospectively under approval from the institutional review board.Results: Regarding the pattern of recurrence, distant-only (DO) recurrence was most common (59.5%), followed by combined (21.5%), central (cervix or vaginal stump; 10.7%), and pelvic (pelvic lymph nodes or pelvic side wall; 8.3%) recurrence. Two subgroups (distant lymph nodes and lung parenchyma) of the DO group demonstrated remarkably good prognosis and were categorized as type A DO; the other subgroups were labeled type B DO. Patients with type A DO recurrence constituted 36% of all recurrences and 83.8% of them received AST. The 5-year overall survival rates were significantly greater in the type A DO group than in the other groups (44.8% in the type A DO group, 12.6% in the pelvic group, and 6.8% in the type B DO group).Conclusions: We identified a patient subgroup with favorable outcomes after salvage therapy, type A DO, defined as recurrence in the distant lymph nodes only or in the lung parenchyma only. A future prospective trial is needed to investigate whether AST improves survival in this group. [ABSTRACT FROM AUTHOR]

Purpose: Worse treatment outcomes can be expected with prolongation of the overall treatment time (OTT) during definitive chemoradiation therapy (CRT) for cervical cancer. In the adjuvant setting, data on the relative importance of the OTT and the importance of RT and chemotherapy synchronization are scarce. Using the National Cancer Database, we evaluated the effect of these treatment variables on overall survival in the adjuvant CRT setting.Methods and Materials: The present analysis included nonmetastatic cervical cancer patients undergoing hysterectomy followed by adjuvant CRT. The proportional hazard model was used to estimate the effect of prognostic factors (age, comorbidity, race, tumor size, tumor grade, tumor histologic type, number of high-risk pathologic factors) and time-related variables (surgery to RT start interval [SR], OTT [RT start to end dates], package time [from diagnosis date to CRT end date] and optimum CRT synchronization [whether chemotherapy and RT start dates coincided]) on survival.Results: Of 3051 patients, 60% finished RT within 7 weeks and 85% received optimum CRT. Among other factors, univariate analysis identified longer OTT (hazards ratio [HR] 1.33; P<.001), longer SR (HR 1.17; P=.05), and nonoptimum CRT timing (HR 1.21; P=.04) as poor prognosticators. Of these factors, SR (HR 1.20; P=.04) and OTT (HR 1.21; P=.002) retained significance on multivariate analysis. An OTT >7 weeks remained a significant factor even after propensity score matching (P=.04).Conclusions: The results of our analysis suggest that prolongation of the adjuvant CRT duration >7 weeks is associated with poor survival and SR of <8 weeks should be attempted whenever clinically feasible. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare the effectiveness of two sedative regimens, a benzodiazepine with either meperidine or fentanyl, in relieving pain in patients with cervical cancer undergoing intracavitary brachytherapy in terms of pain score and quality of life.Methods: Forty unselected outpatients undergoing brachytherapy (160 fractions) were enrolled with informed consent and randomized to receive a benzodiazepine with either meperidine or fentanyl. The perceived pain score according to a standard 10-item numeric rating scale was collected every 15 min during the procedure, and the perceived quality of life was determined at the end of each procedure using the EuroQol five-dimension questionnaire. The patients and medical staff members directly involved with the procedure were blinded to the medication used.Results: The patients' pain levels were mild in both analgesic groups. Meperidine appeared to be slightly more effective than fentanyl, although the differences in the average pain score and quality of life were not statistically significant.Conclusion: Both meperidine and fentanyl in combination with benzodiazepine were effective in relieving pain and discomfort in patients undergoing brachytherapy.Trial Registration: NCT02684942, ClinicalTrials.gov. [ABSTRACT FROM AUTHOR]

Background: To investigate whether poor glycemic control status has a negative impact on survival outcomes and tumor response to chemotherapy in patients receiving neoadjuvant chemotherapy (NACT) for locally advanced cervical cancer (LACC).Methods: A retrospective cohort study was conducted to examine LACC patients undergoing NACT and radical hysterectomy between 2002 and 2011. Patients were divided into three groups: patients without diabetes mellitus (DM), diabetic patients with good glycemic control, and diabetic patients with poor glycemic control. Hemoglobin A1c (HbA1c) levels were used to indicate glycemic control status. Recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed using log-rank tests and Cox proportional hazards models.Results: In total, 388 patients were included and had a median follow-up time of 39 months (range: 4-67 months). Diabetes mellitus (DM) was diagnosed in 89 (22.9%) patients, only 35 (39.3%) of whom had good glycemic control prior to NACT (HbA1c < 7.0%). In survival analysis, compared with patients with good glycemic control and patients without DM, patients with poor glycemic control (HbA1c ≥ 7.0%) exhibited decreased recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). In multivariate analysis, HbA1c ≥ 7.0% was identified as an independent predictor for decreased RFS (hazard ratio [HR] = 3.33, P < 0.0001), CSS (HR = 3.60, P < 0.0001) and OS (HR = 4.35, P < 0.0001). In the subgroup of diabetic patients, HbA1c ≥ 7.0% prior to NACT had an independent negative effect on RFS (HR = 2.18, P = 0.044) and OS (HR = 2.29, P = 0.012). When examined as a continuous variable, the HbA1c level was independently associated with decreased RFS (HR = 1.39, P = 0.002), CSS (HR = 1.28, P = 0.021) and OS (HR = 1.27, P = 0.004). Both good (odds ratio [OR] = 0.06, P < 0.0001) and poor glycemic control (OR = 0.04, P < 0.0001) were independently associated with a decreased likelihood of complete response following NACT.Conclusions: Poor glycemic control is an independent predictor of survival and tumor response to chemotherapy for patients receiving NACT for LACC. [ABSTRACT FROM AUTHOR]

Objective: In Reunion Island, the standardized mortality rate for cervical cancer is 4.8/100,000 women, twice higher than in Metropolitan France. For locally advanced disease, the standard of care includes a treatment by brachytherapy. Nevertheless, brachytherapy was not available on the Island before 2016. The objective of this study was to assess the impact of the management of patients with invasive cervical cancer on mortality in Reunion.Methods: We have identified all the women hospitalized in one of the health care centers of the Island diagnosed with invasive cervical cancer between 01/01/2010 and 31/12/2015. The guidelines of the French Society of Gynecological Oncology (FSGO) were considered as the reference to evaluate professional practices. The characteristics that had an influence on global survival after log-rank test were included in a multivariate analysis according to the Cox Model.Results: Retrospective analysis identified 303 women meeting inclusion criteria. The assessment of professional practices showed that the decisions on 11.6% of the patients discussed during multidisciplinary meetings, were not applied, consequentially leading to a decrease in survival (p=0.001). A total of 156 patients (51.5%) were administered a treatment in accordance with the guidelines of the FSGO and had a better survival, even after multivariate analysis (HR 2.53 [CI 95% 1.55-4.14], p<10-3). Nonconformity was associated with the lack of access to brachytherapy on the Island. Women on the Island presented low rates of screening tests (cover rates 53.2%).Conclusion: The absence of treatment in accordance with the guidelines and decisions taken during multidisciplinary meetings and the absence of brachytherapy were associated to a higher mortality among patients with invasive cervical cancer in Reunion Island. We hope that the implementation of brachytherapy in Reunion will address these deficiencies. [ABSTRACT FROM AUTHOR]

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Background: Cervical cancer is a common cancer of women in developing countries, and radiotherapy still remains its predominant therapeutic treatment. Collagen type I alpha 1 (COL1A1) has been shown to have a radioresistance effect in previous studies. However, such effect of COL1A1 has not yet been revealed in cervical cancer. Methods: Expression of COL1A1 in cervical cancer tissues and normal tissues was assessed by qRT-PCR and immunohistochemistry. The effect of COL1A1 on radioresistance of human cervical cancer cell lines HeLa and CaSki was assessed using the colony formation assay. Apoptosis alterations were analyzed by flow cytometry. In addition, western blotting was used assessed the alterations of several critical apoptosis and signaling pathway related proteins. Results: The expression of COL1A1 was significantly increased in cervical cancer tissues compared with normal tissues at the mRNA and protein level. Further, based on COL1A1 knock down and COL1A1 activation cell models, a negative correlation was observed between COL1A1 expression level and radiosensitivity. Moreover, the findings are further supported by apoptosis analysis that COL1A1 activation could inhibit the apoptosis of cervical cancer cells. Subsequently, a significantly decreased expression of p-AKT and Bcl-2, increased expression of Caspase-3 were observed in the LY294002 plus radiation group compared with radiation alone group, while these influences caused by LY294002 or X-ray radiation were reversed after COL1A1 activation. Conclusions: To our knowledge, this is the only study to profile the mechanisms that COL1A1 plays a crucial role in cervical cells anti-apoptosis induced by radiation. Therefore, our identification of radioresistance-related COL1A1 in cervical cancer could be a starting point to explore the function of collagens, adding a new dimension to our understanding of the cervical cancer, assisting cancer biologists and clinical oncologists in novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is a predominantly human papillomavirus (HPV)-driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence.Methods: Patients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples.Results: The incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV-positive and 16 HPV genotypes were detected-mostly genotypes 16 (75%) and 18 (9%)-with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36-0.90; P = .016). Furthermore, the variant C allele was significantly overtransmitted in the population (P < .0003).Conclusion: Cervical cancer incidence displays bimodal curve peaking at a young age with secondary rebound at older age. The combination of relative low HPV infection and variant TP53 72C allele overtransmission provide a plausible explanation for the low incidence of cervical cancer in our population. Therefore, HPV screening and host SNP genotyping may provide more relevant biomarkers to gauge the risk of developing cervical cancer. Cancer 2017;123:2459-66. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Strengthening of the lower uterine segment and formation of a "closing apparatus" for carrying a subsequent pregnancy in the absence of the cervix in patients with cervical cancer after conserving treatment in the amount of radical transabdominaltrachelectomy. Materials and Research Methods: the study included 26 patients with cervical cancer of stage I in the reproductive age who received treatment in the amount of radical transabdominaltrachelectomy (RTT). In the course of surgery in the amount of RTT, after an imposition of an utero-vaginal anastomosis, the strengthening of the lower uterine segment by setting and fixing a mesh of TiNi and its modelling within the range from the lower uterine segment to the upper third of the vagina was performed. Results: with regard to the issue of strengthening the utero-vaginal anastomosis, the implant takes over the function of the basic "closing apparatus" of the uterine and provides functional support and stability of the utero-vaginal anastomosis against the effects of intrauterine and intraperitoneal pressure. Conclusion: the usefulness of a mesh implant of the superelasticTiNi is due to its biomechanical properties: it is not absorbed, but gets fused with the surrounding tissue and provides resistance of tissues to excessive strain. [ABSTRACT FROM AUTHOR]

We know that one of the main risk factors for cervical cancer is an infection with high-risk human papillomavirus (HR-HPV). Prostaglandins and their receptors are very important for the tumour growth and tumour-associated angiogenesis. Little is known about the expression of the Prostaglandin E receptor type 3 (EP3) or the Prostaglandin (PG)E2-EP3 signalling in cervical cancer, so the aim of the study was to analyse the expression of the EP3 receptor in cervical cancer and find prognostic factors in relation to survival; EP3 immunohistological staining of 250 cervical cancer slides was performed and analysed with a semi-quantitative score. The statistical evaluation was performed with Statistical Package for the Social Sciences (SPSS) to evaluate the staining results and the survival analyses of the cervical cancer cases. A significant difference was observed in EP3 expression in Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stadium I versus FIGO stadium II-IV cases. High expression of EP3 (IRS ≥ 1.5) in cervical cancer patients was correlated with poor prognosis in overall survival rates. Survival in adenocarcinoma (AC) of the cervix was lower than in squamous cell carcinoma (SCC). Cox regression analysis shows that EP3 is an independent prognosticator. In this study we could show that the membrane-bound prostaglandin receptor EP3 is an independent prognosticator for cervical cancer patient survival. Targeting the EP3 receptor seems to be an interesting candidate for endocrine therapy. Therefore, more research is needed on the influence of the receptor system and its influence on cervical cancer growth. [ABSTRACT FROM AUTHOR]

Aim of the study: To evaluate the clinicopathologic factors of early International Federation of Gynecology and Obstetrics (FIGO) stage I-II endometrioid endometrial cancer in a single institution and to emphasize factors contributing to recurrence. Material and methods: We selected several clinicopathologic factors including age, height, body weight, body mass index, cancer antigen-125, FIGO tumor grade, myometrial invasion, lymphovascular space invasion, estrogen receptor/ progesterone receptor status and adjuvant radiation therapy or systemic chemotherapy. Univariate and multivariate Cox proportional hazard model and Kaplan-Meier estimates were used for analyzing all clinicopathologic factors related to the risk of disease recurrence. Results: The median age was 55.05 years, and the median follow-up time was 35 months. Eleven patients (11%) showed disease recurrence, 3 patients - distant, and 8 patients - local metastasis. In univariate analysis, tumor grade (P = 0.0045) and lymphovascular space invasion (P = 0.0374) were associated with disease recurrence. Multivariate analysis demonstrated an association between any type of recurrence and lymphovascular space invasion (hazard ratio, HR, 6.308; 95% confidence interval, CI 1.851-11.484). Conclusions: Our study showed that the presence of lymphovascular space invasion is an important factor for disease recurrence in early endometrial cancer. Therefore, adjuvant systemic chemotherapy may be considered in patients with early endometrial cancer with lymphovascular space invasion. [ABSTRACT FROM AUTHOR]

Norway has a low incidence and mortality rate of cervical cancer, which is mainly due to the high participation rate of women in cervical cancer screening. However, the attendance of cervical cancer screening was reported to be low among immigrant women. For this reason, we conducted a qualitative study to obtain better insight into perceived barriers and challenges to cervical cancer screening among Somali and Pakistani women in the Oslo region. A convenient sample of 35 (18 Pakistani, 17 Somali) women were recruited for the study in collaboration with Somali and Pakistani community partners. Focus group discussions were used to explore barriers and facilitators to cervical cancer screening, whereas the Ecological Model was used as the framework for the study. The study found three levels of barriers to cervical cancer screening. The individual level included a lack of understanding of the benefits of the screening. The sociocultural level included the stigma attached to the disease and the belief that women who are unmarried are sexually inactive. The system-related level included a lack of trust toward the health care system. Based on the study results, and using a common denominator approach for the immigrant groups included, the study recommends three communication strategies with the potential to improve women's participation in cervical cancer screening: 1) in-person communication and information material at health centers; 2) verbal communication with women through seminars and workshops to educate them about their risk of cancer and the importance of screening and 3) the initiation of better recall through SMS and letters written in native languages. Finally, an intervention study that compares the aforementioned strategies and proves their effectiveness in increasing immigrant women's participation in cervical cancer screening is recommended. [ABSTRACT FROM AUTHOR]

The investigation of specific genes will establish more useful biomarkers for accurate detection and management of gynecological cancers, especially patients with cervical cancer (CCP). The aim of this study was to evaluate the expression level of RIPK4 and EZH2 messenger RNA (RIPK4 and EZH2 mRNA) in CCP. Expression of RIPK4 and EZH2 in the tissues was determined by immunohistochemistry and qRT-PCR methods. Correlations of RIPK4 and EZH2 mRNA with clinical and pathological parameters were analyzed using the Fisher's exact test. The mRNA level of RIPK4 was significantly upregulated in tumor tissues compared with matched adjacent normal tissues (4.10 ± 0.89 vs. 1.5 ± 0.82; p = 0.021). EZH2 mRNA was increased in cancer tissues compared to normal tissues (3.54 ± 0.71 vs. 1.2 ± 0.65; p = 0.003). High expression of RIPK4 was observed in 25 patients (64.1%), whereas weak expression was seen in 14 cases (35.9%). Furthermore, the expression of RIPK4 was overexpressed in matched adjacent normal tissues (p = 0.004). FIGO stage and lymph node metastasis were significantly linked to a higher expression of RIPK4 (p < 0.05). Overexpression of EZH2 was found in 30 patients (76.9%) and was associated with FIGO stage, histological type, and lymph node metastasis (p < 0.05). In conclusion, our data suggest that RIPK4/EZH2 markers might be used as potential predictors of prognosis in cervical cancer. [ABSTRACT FROM AUTHOR]

Background: A high rate of glycolysis leading to elevated lactate content has been linked to poor clinical outcomes in patients with head and neck and cervical cancer treated with radiotherapy. Although the biological explanation for this relationship between lactate and treatment response remains unclear, there is a continued interest in evaluating strategies of targeting metabolism to enhance the effectiveness of radiotherapy. The goal of this study was to investigate the effect of metabolic-targeting through HIF-1α inhibition and the associated changes in glycolysis, oxygen consumption and response on the efficacy of high-dose single-fraction radiotherapy (HD-SFRT).Methods: HIF-1α wild-type and HIF-1α knockdown FaDu and ME180 xenograft tumors were grown in the hind leg of mice that were placed in an environmental chamber and exposed to different oxygen conditions (air-breathing and hypoxia). Ex vivo bioluminescence microscopy was used to measure lactate and ATP levels and the hypoxic fraction was measured using EF5 immunohistochemical staining. The oxygen consumption rate (OCR) in each cell line in response to in vitro hypoxia was measured using an extracellular flux analyzer. Tumor growth delay in vivo was measured following HD-SFRT irradiation of 20 Gy.Results: Targeting HIF-1α reduced lactate content, and increased both oxygen consumption and hypoxic fraction in these tumors after exposure to short-term continuous hypoxia. Tumors with intact HIF-1α subjected to HD-SFRT immediately following hypoxia exposure were less responsive to treatment than tumors without functional HIF-1α, and tumors irradiated under air breathing conditions regardless of HIF-1α status.Conclusions: Blocking the HIF1 response during transient hypoxic stress increased hypoxia, reduced lactate levels and enhanced response to HD-SFRT. This strategy of combining hypofractionated radiotherapy with metabolic reprogramming to inhibit anaerobic metabolism may increase the efficacy of HD-SFRT through increased oxygen consumption and complementary killing of radiosensitive and hypoxic, radioresistant cells. [ABSTRACT FROM AUTHOR]

Background: Class III radical hysterectomy (RH III)_plus pelvic lymphadenectomy is the standard surgery for early stage cervical cancer (CC) patients, the 5 year survival rate is about 90%, but pelvic floor disorders especially bladder dysfunction are common due to damaged vessels and nerve fibers following surgery. Transcutaneous electrical stimulation (TENS) treatment has been used to treat bladder disorders for many years, but its effect on cervical cancer patients, the best treatment time point and stimulated protocol, had never been assessed. The aim of this study is to investigate the efficacy of TENS treatment on lower urinary tract symptoms (LUTS) after RH III in CC patients.Methods/design: The study will be conducted as a clinical, multicentre, randomised controlled trial with balanced randomisation (1:1). The planned sample size is 208 participants (at 1:1 ratio, 104 subjects in each group). At 5-7 days after RH III, patients are screened according to operative and pathological findings. Enrolled participants are randomised into an intervention group (TENS plus conventional clinical care) or control group (conventional clinical care), with stratification by menopausal status (menopause vs. non-menopause) and surgical modality (laparoscopic RH or abdominal RH). Participants in both groups will be followed up at 14 days, 21 days, 28 days, 3 months, 6 months, 12 months, 18 months and 24 months after surgery. The primary endpoint is improvement rate of urination function which is defined as recovery (residual urine ≤50 ml) or improvement (residual urine 50-100 ml). Secondary endpoints include urodynamic parameter, urinary incontinence, anorectal function, pelvic function, quality of life (QOL), disease-free survival and adverse events. Primary endpoint analyses will be carried out by Cochran-Mantel-Haenszel tests taking into center effect.Discussion: To our knowledge this is the first trial to investigate the effect of TENS treatment on bladder function recovery after RH III among CC patients. This study will provide new information on TENS efficacy for bladder function recovery. Once confirmed, it may help to provide a new, non-invisive treatment for those postoperative CC patients with poor pelvic function, which would help improve their quality of life.Trial Registration: The study is registered to Clinical Trials.gov ( NCT02492542 ) on June 25, 2015. [ABSTRACT FROM AUTHOR]

Objective: Prior studies suggest an increased risk of cervical cancer among women with systemic lupus erythematosus. However, the relationship with immunosuppressive drugs is not well studied in US nationwide cohorts. We compared the risk of high-grade cervical dysplasia and cervical cancer among women with systemic lupus erythematosus who started immunosuppressive drugs versus hydroxychloroquine. Methods: We identified systemic lupus erythematosus patients initiating immunosuppressive drugs or hydroxychloroquine using claims data from two US commercial health plans and Medicaid (2000-2012). We used a validated claims-based algorithm to identify high-grade cervical dysplasia or cervical cancer. To account for potential confounders, including demographic factors, comorbidities, medication use, HPV vaccination status, and health care utilization, immunosuppressive drugs and hydroxychloroquine initiators were 1:1 matched on the propensity score. We used inverse varianceweighted, fixed effect models to pool hazard ratios from the propensity score-matched Medicaid and commercial cohorts. Results: We included 2451 matched pairs of immunosuppressive drugs and hydroxychloroquine new users in the commercial cohort and 7690 matched pairs in Medicaid. In the commercial cohort, there were 14 cases of cervical dysplasia or cervical cancer among immunosuppressive drugs users and five cases among hydroxychloroquine users (hazard ratio 2.47, 95% CI 0.89-6.85, hydroxychloroquine=ref). In Medicaid, there were 46 cases among immunosuppressive drugs users and 29 cases in hydroxychloroquine users (hazard ratio 1.24, 95% CI 0.78-1.98, hydroxychloroquine=ref). The pooled hazard ratio of immunosuppressive drugs was 1.40 (95% CI 0.92-2.12). Conclusion: Among women with systemic lupus erythematosus, immunosuppressive drugs may be associated with a greater, albeit not statistically significant, risk of high-grade cervical dysplasia and cervical cancer compared to patients receiving hydroxychloroquine alone. [ABSTRACT FROM AUTHOR]

Abdominal radical trachelectomy has been identified as a surgical option for fertility preservation in cervical cancer patients, particularly in pregnant women who strongly desire to continue their pregnancy. Since this procedure requires operating in the uterus, the hardness of the uterus can affect the ease of surgery. Generally, sevoflurane is used for anesthesia in non-obstetric surgery for pregnant women because uterine relaxation is advantageous for uterine blood flow maintenance. However, the use of sevoflurane during radical trachelectomy has not been thoroughly evaluated. Here, we report on anesthesia use in three cases of abdominal radical trachelectomy during pregnancy. Propofol enabled maintenance of uterine tension while not significantly affecting fetal growth. It is important to consider maintenance of uterine tension and fetal circulation in anesthesia management. During the operation, we performed an ultrasound examination every 30 min to confirm fetal well-being. Although frequent fetal heart rate monitoring of the pre-viable fetus is not recommended, if fetal bradycardia is detected, sevoflurane may then be used to improve fetal circulation. Additionally, if the fetal heartbeat stops, a radical hysterectomy would then be required. Therefore, we consider that fetal heart rate monitoring during this procedure is necessary, and propofol is suitable as an anesthetic for this surgery during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: Stage IB-IIA cervical carcinoma can be equally cured either by radical surgery or radiotherapy (RT). Albeit such policies show the same efficacy, they carry a different morbidity. This is an update after 20 years of a previously published randomized trial of RT vs. surgery in the treatment of stage IB-IIA cervical cancers to assess long-term survival and morbidity and the different pattern of relapse between the 2 modalities. Methods: Between September 1986 and December 1991, women referred for a newly diagnosed stage IB and IIA cervical carcinoma were randomized to radical surgery or RT. The primary outcome measures were long-term survival and complications rate. The secondary outcome was recurrence of the disease. Results: Three-hundred forty-three eligible women were randomized: 172 to radical surgery and 171 to external RT. Minimum follow-up was 19 years. Thirty-three patients (10%) died of intercurrent disease (31 cases) or fatal complications (2 cases). Twenty-year overall survival is 72% and 77% in the 2 treatment groups (p=0.280), respectively. As a whole, 94 recurrences (28%) were observed. Median time to relapse was 13.5 (surgery group) and 11.5 months (radiotherapy group) (p=0.100), respectively. Multivariate analysis confirms that risk factors for survival are histotype (p=0.020), tumor diameter (p=0.008), and lymph node status (p<0.001). Conclusion: The results of the present study seem to suggest that there is no treatment of choice for early stage cervical carcinoma in terms of survival. Long term follow-up confirms that the best treatment for the individual patient should take into account clinical factors such as menopausal status, comorbidities, histological type, and tumor diameter. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study was to evaluate temporal trends in the volume of cervical cancer brachytherapy cases available to trainees as a potential contributing factor to national trends toward decreased utilization of brachytherapy for locally advanced cervical cancer. Methods and Materials The National Cancer Database was queried to identify a cohort of women diagnosed with locally advanced cervical cancer during 2004–2013 who received primary radiation therapy. We identified academic facilities that reported radiation therapy and brachytherapy delivery the study period, categorized facilities based on annual number of cases, and evaluated temporal trends. Results A total of 6290 patients treated at 220 facilities were evaluated. During the study period, the proportion of facilities with higher brachytherapy volume remained stable. The trend of each grouping was not significant ( p > 0.05) with the exception of centers treating one case per year, which demonstrated a decrease over time ( p = 0.022). Conclusions Our analysis suggests that cervical cancer case volume at academic institutions, available for resident training, was stable throughout the study period. These findings suggest that targeting resident educational programs should not be the highest priority for interventions to improve rates of appropriate brachytherapy utilization for cervical cancer. [ABSTRACT FROM AUTHOR]

Purpose In image-guided adaptive brachytherapy (IGABT), dose distributions are optimized for each fraction. Optimum fractional dose can be constant or adapted to previous fractions and a conjecture about the future ones. We evaluate the efficacy of different fraction size schemes, derived from total IGABT dose constraints, against constant per-fraction constraints. Methods and Materials This retrospective planning study included 20 IGABT patients where four different fractionation schedules were compared based on modern planning recommendations. A total high-risk–clinical target volume D 90 (minimum dose in 90% of the volume) dose aim of 90.0 Gy with constant per-fraction organs at risk (OARs) dose constraint planning (CONST) was compared with conservative and aggressive fractionation compensation (COMP) techniques. COMP allows variations in the per-fraction dose constraints. Dose accumulation was performed through dose summation at a given volume and equivalent uniform dose (EUD) worst-case dose estimates. Results No significant differences were identifiable between dose metrics of CONST and COMP in the total patient population. However, a subgroup of patients with alternating dose-limiting OARs had significant benefit from COMP. Median high-risk–clinical target volume dose escalation ranged from 5% to 12%, whereas OAR dose increases were lower and ranged from 3% to 8%. EUD-based planning delivered similar tumor doses, although slightly lower OAR doses. By distributing the treatment aim over an increased number of treatment fractions, median tumor dose could be increased by a further 8% per additional treatment fraction at the same OAR dose levels for both CONST and COMP. Conclusions COMP is effective in patients with alternating dose-limiting OARs and is enhanced using more treatment fractions and EUD constraints. [ABSTRACT FROM AUTHOR]

Background To test the hypothesis that atlas-based active bone marrow (ABM)-sparing intensity modulated radiation therapy (IMRT) yields similar dosimetric results compared to custom ABM-sparing IMRT for cervical cancer patients. Methods We sampled 62 cervical cancer patients with pre-treatment FDG-PET/CT in training ( n = 32) or test ( n = 30) sets. ABM was defined as the subvolume of the pelvic bone marrow (PBM) with standardized uptake value (SUV) above the mean on the average FDG-PET image (ABM Atlas ) vs. the individual’s PET (ABM Custom ). Both were deformed to the planning CT. Overlap between the two subvolumes was measured using the Dice coefficient. Three IMRT plans designed to spare PBM, ABM Atlas , or ABM Custom were compared for 30 test patients. Dosimetric parameters were used to evaluate plan quality. Results ABM Atlas and ABM Custom volumes were not significantly different ( p = 0.90), with a mean Dice coefficient of 0.75, indicating good agreement. Compared to IMRT plans designed to spare PBM and ABM Custom , ABM Atlas -sparing IMRT plans achieved excellent target coverage and normal tissue sparing, without reducing dose to ABM Custom (mean ABM Custom dose 29.4 Gy vs. 27.1 Gy vs. 26.9 Gy, respectively; p = 0.10); however, PTV coverage and bowel sparing were slightly reduced. Conclusions Atlas-based ABM sparing IMRT is clinically feasible and may obviate the need for customized ABM-sparing as a strategy to reduce hematologic toxicity. [ABSTRACT FROM AUTHOR]

Purpose: This study assessed the effect of marital status on stage at diagnosis and survival in women with cervical cancer.Methods: Cervical cancer cases diagnosed between 2000 and 2010 were identified from the Surveillance, Epidemiology and End Results (SEER) program. Patient demographic and clinical characteristics were compared by marital status. Multivariate logistic and Cox proportional hazard regression models were performed to calculate odds ratios of advanced stage at diagnosis and hazard ratios of death risk respectively.Results: Among 31 425 women, 46% of cases were married at the time of diagnosis. Married women were more commonly diagnosed at a localized stage (55%) compared to other non-marital groups (47% of singles, 42% of separated/divorced, and 28% of widowers, p < 0.001). After controlling for age, race/ethnicity, period of diagnosis, histology, and SEER area, single [adjusted odds ratio (aOR) 1.41; 95% Confidence Interval (CI) 1.33-1.49], separated/divorced [aOR 1.44; 95% CI 1.34-1.55], and widowed women [aOR 1.43; 95% CI 1.31-1.58] were all more likely to be diagnosed at an advanced stage compared to married women. In terms of prognosis, single (adjusted hazard ratio (aHR) 1.35; 95% CI 1.28-1.43), separated/divorced (aHR 1.22; 95% CI 1.15-1.29), and widowed women (aHR 1.28; 95% CI 1.19-1.36) had significant increased risk of death compared to married women. Adjusting for insurance status did not change the findings.Conclusion: Being married is associated with earlier diagnosis and a more favorable prognosis for cervical cancer among US women. Interventions to improve prognosis for unmarried women, including increasing use of cervical cancer screenings, are warranted. [ABSTRACT FROM AUTHOR]

18 F-fluorodeoxyglucose PET/CT ( 18 F-FDG-PET/CT) is widely applied in oncology for disease staging, assessment of therapy response, relapse diagnosis, follow-up and target volume delineation. In particular, it can detect early response during chemoradiotherapy (interim) because functional modifications usually precede morphological ones. This ability is crucial to the radiation oncologist for the management of patients, to avoid persisting with ineffective therapy − often leading toxicity − and to shift to potentially more effective alternatives. Interim 18 F FDG-PET imaging in rectal and cervical cancer, the main malignancies of the pelvic district, has been applied and a broad literature is available, although some results are discordant. This systematic review summarizes the application of 18 F FDG-PET/CT during the chemoradiotherapy of locally advanced pelvic malignancies in order to clarify its capability to predict response and prognosis and its potential role to tailor therapy, which seems to be validated in rectal cancer, whilst less conclusive in cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Breast and cervical cancer are the most common cancers affecting women. The symptom distresses experienced by cancer survivors are critical factors influencing their quality of life (QOL). This study investigated the QOL of breast and cervical cancer survivors, their physical, psychological and social conditions.Methods: The participants were older than 20 years, had been diagnosed with breast or cervical cancer for more than 2 years, and had completed their cancer treatment. The survey incorporated the QOL questionnaires developed by the European Organization of Research and Treatment for Cancer and a self-designed questionnaire.Results: The mean age at diagnosis was 48.89 ± 8.53 years for the breast cancer survivors and 49.00 ± 10.30 years for the cervical cancer survivors. The corresponding QOL scores were 75.33 ± 20.25 and 75.56 ± 17.93. The factors influencing QOL of breast cancer survivors were household income, number of comorbidities, stage of cancer, type of cancer treatment and duration of illness, whereas the factor related to QOL of cervical cancer survivors was only household income.Conclusions: The QOL of the two groups was similar. Healthcare providers should demonstrate greater concern toward breast and cervical cancer survivors. [ABSTRACT FROM AUTHOR]

Objective: In the UK, women are requested to attend a cervical cancer test every 3 years as part of the NHS Cervical Screening Programme. This analysis compares the determinants of a cervical cancer screening examination with the determinants of a GP visit in the same year and investigates if cervical cancer screening participation is more likely for women who visit their GP. Methods: A recursive probit model was used to analyse the determinants of GP visits and cervical cancer screening examinations. GP visits were considered to be endogenous in the cervical cancer screening examination. The analysed sample consisted of 52,551 observations from 8,386 women of the British Household Panel Survey. Results: The analysis showed that a higher education level and a worsening self-perceived health status increased the probability of a GP visit, whereas smoking decreased the probability of a GP visit. GP visits enhanced the uptake of a cervical cancer screening examination in the same period. The only variables which had the same positive effect on both dependent variables were higher education and living with a partner. The probability of a cervical cancer screening examination increased also with previous cervical cancer screening examinations and being in the recommended age groups. All other variables had different results for the uptake of a GP visit or a cervical cancer screening examination. Conclusions: Most of the determinants of visiting a GP and cervical cancer screening examination differ from each other and a GP visit enhances the uptake of a smear test. [ABSTRACT FROM AUTHOR]

Bevacizumab became the first molecular antibody to show survival benefit in advanced cervical cancer. In the GOG-0240 (Paclitaxel and Cisplatin or Topotecan With or Without Bevacizumab in Treating Patients With Stage IVB, Recurrent, or Persistent Cervical Cancer) trial, it improved overall survival by a significant 3.7 months over platinum doublet chemotherapy alone. However, this discovery is not likely to improve the status of global cervical cancer because more than 85% of patients with cervical cancer live in low- and middle-income countries and cannot afford bevacizumab. This commentary looks at the options by which this drug can be made more affordable and cost-effective for patients in low- and middle-income countries. We also discuss other important questions related to its affordability and cost issues such as the optimal number of cycles and personalizing the treatment. Finally, we emphasize that although the unaffordability of bevacizumab in cervical cancer seems to be a very important issue, the best cost-effective strategy against cervical cancer is prevention with screening and vaccination. [ABSTRACT FROM AUTHOR]

Background Further research is required for evaluating the use of ADC histogram analysis in more advanced stages of cervical cancer treated with definitive chemoradiotherapy (CRT). Purpose To investigate the utility of apparent diffusion coefficient (ADC) histogram derived from diffusion-weighted magnetic resonance images in cervical cancer patients treated with definitive CRT. Material and Methods The clinical and radiological data of 50 patients with histologically proven cervical squamous cell carcinoma treated with definitive CRT were retrospectively analyzed. The impact of clinicopathological factors and ADC histogram parameters on prognostic factors and treatment outcomes was assessed. Results The mean and median ADC values for the cohort were 1.043 ± 0.135 × 10-3 mm2/s and 1.018 × 10-3 mm2/s (range, 0.787-1.443 × 10-3 mm2/s). The mean ADC was significantly lower for patients with advanced stage (≥IIB) or lymph node metastasis compared with patients with stage

Purpose For patients with cervical cancer the delivery of chemotherapy with radiotherapy improves survival compared with radiotherapy alone. However, high rates of acute hematologic toxicity occur when combining both therapies due to the damage of the red bone marrow (RBM). This study aimed to reduce the radiation damage to the RBM. A tool has been developed for semi-automatic delineation of the red bone marrow based on MR-only. This delineation can be included into the treatment planning process to reduce the volume of RBM irradiated in patients receiving pelvic radiation therapy. Methods 13 patients with cervical cancer were enrolled. All the patients underwent MR, CT and FDG-PET imaging. A tool for RBM determination from water and fat MR images was developed. Our MR-based RBM tool was optimized and validated with the FDG-PET scans of the patients. Results Our tool identified RBM regions in the pelvic area. The mean total volume of these regions was 34% of the pelvic bone marrow. The corresponding SUV values based on the FDG-PET scans were above the reported threshold of active/red bone marrow. Conclusion This study shows that delineations of the RBM for the radiotherapy with RBM sparing can be generated semi-automatically using MR scans only. [ABSTRACT FROM AUTHOR]

Purpose To implement coverage probability (CovP) for dose planning of simultaneous integrated boost (SIB) of pathologic lymph nodes in locally advanced cervical cancer (LACC). Material and methods CovP constraints for SIB of the pathological nodal target (PTV-N) with a central dose peak and a relaxed coverage at the perimeter were generated for use with the treatment planning system Eclipse: PTV-N D98 >90%, CTV-N D98 >100% and CTV-N D50 >101.5% of prescribed dose. Dose of EBRT was 45 Gy/25 fx with a SIB of 55–57.5 Gy depending on expected dose from brachytherapy (BT). Twenty-five previously treated patients with 47 boosted nodes were analysed. Nodes were contoured on cone beam CT (CBCT) and the accumulated dose in GTV-N CBCT and volume of body, pelvic bones and bowel receiving >50 Gy (V50) were determined. Results Nearly all nodes (89%) were visible on CBCT and showed considerable concentric regression during EBRT. Total EBRT and BT D98 was >57 Gy EQD2 in 98% of the visible nodes. Compared to treatment plans aiming for full PTV-N coverage, CovP significantly reduced V50 of body, bones and bowel ( p < 0.001) Conclusion CovP is clinically feasible for SIB of pathological nodes and significantly decreases collateral SIB dose to nearby OAR. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the utility of a standardized qualitative scoring system for treatment response assessment at 18F-FDG PET-CT in patients undergoing chemoradiotherapy for locally advanced cervical carcinoma and correlate this with subsequent patient outcome. Methods: Ninety-six consecutive patients with locally advanced cervical carcinoma treated with radical chemoradiotherapy (CRT) in a single centre between 2011 and 2014 underwent 18F-FDG PET-CT approximately 3 months post-treatment. Tumour metabolic response was assessed qualitatively using a 5-point scale ranging from background level activity only through to progressive metabolic disease. Clinical and radiological (MRI pelvis) follow-up was performed in all patients. Progression-free (PFS) and overall survival (OS) was calculated using the Kaplan-Meier method (Mantel-Cox log-rank) and correlated with qualitative score using Chi-squared test. Results: Forty patients (41.7 %) demonstrated complete metabolic response (CMR) on post-treatment PET-CT (Score 1/2) with 38 patients (95.0 %) remaining disease free after a minimum follow-up period of 18 months. Twenty-four patients (25.0 %) had indeterminate residual uptake (ID, Score 3) at primary or nodal sites after treatment, of these eight patients (33.3 %) relapsed on follow-up, including all patients with residual nodal uptake (n = 4Eleven11 of 17 patients (64.7 %) with significant residual uptake (partial metabolic response, PMR, Score 4) subsequently relapsed. In 15 patients (15.6 %) PET-CT demonstrated progressive disease (PD, Score 5) following treatment. Kaplan-Meier analysis showed a highly statistically significant difference in PFS and OS between patients with CMR, indeterminate uptake, PMR and PD (Log-rank, P < 0.0001). Chi-squared test demonstrated a highly statistically significant association between increasing qualitative score and risk of recurrence or death ( P < 0.001). Conclusion: Use of a 5-point qualitative scoring system to assess metabolic response to CRT in locally advanced cervical carcinoma predicts survival outcome and this prognostic information may help guide further patient management. [ABSTRACT FROM AUTHOR]

Purpose This study was conducted to describe the trends and age-period-cohort effects on the incidence and mortality rate of cervical cancer in Korea. Materials and Methods The incidence and mortality rate of cervical cancer among ≥ 20-year-old women from 1993 to 2012 were obtained from the Korea Central Cancer Registry and the Korean Statistical Information Service. Age-standardized rates were calculated and Joinpoint regression was used to evaluate the trends in the incidence and mortality rate. Age-period-cohort analysis was performed to investigate the independent effects of age, period and cohort. Results The incidence of cervical cancer decreased from 32.8 per 100,000 in 1993 to 15.9 per 100,000 in 2012 (annual percent change [APC], -3.9%; 95% confidence interval [CI], -4.2% to -3.6%). The mortality rate decreased from 5.2 per 100,000 in 1993 to 2.1 per 100,000 in 2012 (APC, -4.8%; 95% CI, -5.1% to -4.4%); however, the incidence and mortality rates among young women (< 30 years old) increased. An age-period-cohort model of the incidence and mortality rate showed decreasing period effects between 1993 and 2008 and decreasing cohort effects between 1928 and 1973, while birth cohorts after 1973 exhibited slight increases in the incidence and mortality rate of cervical cancer. Conclusion Recent decreases in the incidence and mortality rate of cervical cancer were due to decreases in the period and cohort effects, which reflect the implementation of a cancer screening program and changes in lifestyle. However, our findings also highlighted an increase in cohort effects on the incidence and mortality rate among young women born after 1973. [ABSTRACT FROM AUTHOR]

Introduction: Conservative treatments including cold knife cone biopsy (CKC) or loop electrosurgical excision procedure (LEEP) are fertility-preserving alternatives to hysterectomy. The risks of persistent cervical neoplasia in women with negative surgical margins following conservative treatment of adenocarcinoma-in-situ (AIS) are uncertain. This study aims to investigate the risk of persistent or recurrent cervical neoplasia [AIS, adenocarcinoma and/or high-grade cervical squamous intraepithelial neoplasia (CIN)] and compliance with follow-up recommendations in conservatively treated women with AIS and negative histopathological margins.Material and Methods: A retrospective, population-based study of Western Australian women treated by CKC or LEEP for AIS between 2001 and 2012. Histopathology reports were reviewed for demographic information, treatment procedures and clinicopathological factors. Primary outcomes were the diagnosis of cervical neoplasia during follow-up (defined as <12 months) and surveillance (≥12 months) periods.Results: The cohort comprised 360 women, with 175 (48.6%) initially treated by CKC and 185 (51.4%) treated by LEEP. The median patient age at time of excisional treatment was 30.0 years (range 18-64 years) and the median follow-up time was 3.9 years (range six months to 12.2 years). During the follow-up and surveillance periods, seven (1.9%) women were diagnosed with CIN 2/3, 10 (2.8%) with AIS, and one (0.3%) with cervical adenocarcinoma, despite their initial excision specimens having negative histological margins.Conclusion: In this study, there was a low but significant risk of persistent or recurrent cervical neoplasia in women who had initial conservative management of AIS with negative histopathological margins. [ABSTRACT FROM AUTHOR]

Purpose: To quantify longitudinal changes in active bone marrow (ABM) distributions within unirradiated (extrapelvic) and irradiated (pelvic) bone marrow (BM) in cervical cancer patients treated with concurrent chemoradiation therapy (CRT).Methods and Materials: We sampled 39 cervical cancer patients treated with CRT, of whom 25 were treated with concurrent cisplatin (40 mg/m2) and 14 were treated with cisplatin (40 mg/m2) plus gemcitabine (50-125 mg/m2) (C/G). Patients underwent 18F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and 1.5 to 6.0 months after treatment. ABM was defined as the subvolume of bone with standardized uptake value (SUV) above the mean SUV of the total bone. The primary aim was to measure the compensatory response, defined as the change in the log of the ratio of extrapelvic versus pelvic ABM percentage from baseline to after treatment. We also quantified the change in the proportion of ABM and mean SUV in pelvic and extrapelvic BM using a 2-sided paired t test.Results: We observed a significant increase in the overall extrapelvic compensatory response after CRT (0.381; 95% confidence interval [CI]: 0.312, 0.449) and separately in patients treated with cisplatin (0.429; 95% CI: 0.340, 0.517) and C/G (0.294; 95% CI: 0.186, 0.402). We observed a trend toward higher compensatory response in patients treated with cisplatin compared with C/G (P=.057). Pelvic ABM percentage was reduced after CRT both in patients receiving cisplatin (P<.001) and in those receiving C/G (P<.001), whereas extrapelvic ABM percentage was increased in patients receiving cisplatin (P<.001) and C/G (P<.001). The mean SUV in pelvic structures was lower after CRT with both cisplatin (P<.001) and C/G (P<.001). The mean SUV appeared lower in extrapelvic structures after CRT in patients treated with C/G (P=.076) but not with cisplatin (P=.942). We also observed that older age and more intense chemotherapy regimens were correlated with a decreased compensatory response on multivariable analysis. In patients treated with C/G, mean pelvic bone marrow dose was found to be negatively correlated with the compensatory response.Conclusion: Patients have differing subacute compensatory responses after CRT, owing to variable recovery in unirradiated marrow. Intensive chemotherapy regimens appear to decrease the extrapelvic compensatory response, which may lead to increased hematologic toxicity. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to determine the feasibility and detection rates and clarify the most effective combination of injected tracer types for sentinel lymph node (SLN) mapping in uterine cervical cancer in patients who have undergone laparoscopic surgery or neoadjuvant chemotherapy (NAC). Methods: A total of 119 patients with cervical cancer underwent SLN biopsy at radical hysterectomy using three types of tracers. The various factors related to side-specific detection rate, sensitivity, and false negative (FN) rate were analyzed. Results: The SLN detection rates using 99m-technetium (99mTc)-tin colloid, indigo carmine, and indocyanine green (ICG) were 85.8%, 20.2%, and 61.6%, respectively. The patients with ≥2-cm-diameter tumors and those who received NAC had lower detection rates than those with <2-cm-diameter tumors (75.7% vs. 91.5%, p<0.01) and those who did not receive NAC (67.9% vs. 86.3%, p<0.01), respectively. Laparoscopic procedures had a higher detection rate than laparotomy (100.0% vs. 77.1%, p<0.01). No factors significantly affected the sensitivity; however, the patients with ≥2-cm-diameter tumors (86.0% vs. 1.4%, p<0.01), NAC (19.4% vs. 2.2%, p<0.01), and those who underwent laparotomy (7.4% vs. 0%, p<0.01) had an unfavorable FN rate. Conclusion: Among the examined tracers, 99mTc had the highest detection of SLN mapping in patients with uterine cervical cancer. Patients with local advanced cervical cancer with/without NAC treatment might be unsuited for SLN mapping. SLN mapping is feasible and results in an excellent detection rate in patients with <2-cm-diameter cervical cancer. Laparoscopic surgery is the best procedure for SLN detection in patients with early-stage disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cervical cancer is the fourth most frequent type of cancer in women worldwide and its occurrence is strongly associated to high risk genotypes 16/18/31/33/35/39/45/51/52/56/58/59/66 of human papillomavirus (HPV). This observational study aimed to investigate the status of HPV infection in a cohort of 725 Romanian women requesting specialty services in a clinic of gynaecology from Bucharest. In our cohort, the HPV genotype 16 was by far most frequently identified and it was followed by genotypes 51, 31, 52 and 18 (prevalence of 37.5; 13.9; 13.4; 11.8; 10.6% respectively). Its presence increased significantly in women having HSIL cytology, compared to cases with less severe cytology results. We found also very low use of vaccination and HPV testing. Due to methodologic limitations, our results cannot be generalised in the Romanian women population and further research is needed for this purpose. However, our results suggest the need for a stronger public health approach for prevention and control of cervical cancer in Romania. [ABSTRACT FROM AUTHOR]

Background/aim: Telomerase activity is influenced by hTERT transcriptional regulation, shelterin, and posttranscriptional alternative splicing. Telomerase shelterin such as POT1 is highly correlated with various cancers. However, the profile of POT1 in cervical cancer has not been clearly identified. Therefore, it is important to identify its profile in cervical cancer biopsy tissue and normal cervical smears. Materials and methods: Biopsy tissue of cervical cancer patients and normal cervical smears were characterized using SDS-PAGE and western blot. Sixteen biopsy tissues of cervical cancer patients and 15 normal cervical smears were measured for POT1 level using ELISA. Results: The inline band at 70 kDa indicated that all samples had protein that was identified as POT1. Western blot showed that telomerase antibody only recognized POT1 in biopsy tissue of cervical cancer patients. There was a significant difference (P = 0.01) in POT1 level between biopsy tissue of cervical cancer patients and normal cervical smears. Conclusion: POT1 was identified at 70 kDa in biopsy tissue of cervical cancer patients and its level was higher than that in normal cervical smears. The high level of POT1 in the biopsy tissue of cervical cancer patients showed the influence of this shelterin component in cervical carcinogenesis and also cell immortalization. [ABSTRACT FROM AUTHOR]

Chromatin remodeling alters gene expression in carcinoma tissue. Although cervical cancer is the fourth most common cancer in women worldwide, a systematic study about the prognostic value of specific changes in the chromatin structure, such as histone acetylation or histone methylation, is missing. In this study, the expression of histone H3 acetyl K9, which is known to denote active regions at enhancers and promoters, and histone H3 tri methyl K4, which preferentially identifies active gene promoters, were examined as both show high metastatic potential. A panel of patients with cervical cancer was selected and the importance of the histone modifications concerning survival-time (overall survival and relapse-free survival) was analyzed in 250 cases. Histone H3 acetyl K9 staining was correlated with low grading, low FIGO (TNM classification and the International Federation of Gynecology and Obstetrics) status, negative N-status and low T-status in cervical cancer, showing a higher expression in adenocarcinoma than in squamous cell carcinoma. Cytoplasmic expression of histone H3 tri methyl K4 in a cervical cancer specimen was correlated with advanced T-status and poor prognosis. While cytoplasmic H3K4me3 expression seemed to be a marker of relapse-free survival, nuclear expression showed a correlation to poor prognosis in overall survival. Within this study, we analyzed the chemical modification of two histone proteins that are connected to active gene expression. Histone H3 acetyl K9 was found to be an independent marker of overall survival. Histone H3 tri methyl K4 was correlated with poor prognosis and it was found to be an independent marker of relapse-free survival. Therefore, we could show that chromatin remodeling plays an important role in cervical cancer biology. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE: Effective treatment of Uterus Cervical Carcinoma (UCC) rely heavily on the precise pre-surgical staging. The conventional International Federation of Gynecology and Obstetrics (FIGO) system based on clinical examination is being applied worldwide for UCC staging. Yet its performance just appears passable. Thus, this study aims to investigate the value of applying Magnetic Resonance Imaging (MRI) with clinical examination in staging of UCC. MATERIALS AND METHODS: A retrospective dataset involving 164 patients diagnosed with UCC was enrolled in this study. The mean age of this study population was 46.1 years (range, 28-75 years). All patients underwent operations and UCC types were confirmed by pathological examinations. The tumor stages were determined by two experienced Gynecologist independently based on FIGO examinations and MRI. The diagnostic results were also compared with the post-operative pathologic reports. Statistical data analysis on diagnostic performance was then done and reported. RESULTS: The study results showed that the overall accuracy of applying MRI in UCC staging was 82.32%, while using FIGO staging method, the staging accuracy was 59.15%. CONCLUSIONS: MRI is suitable to evaluate tumor extent with high accuracy, and it can offer more objective information for the diagnosis and staging of UCC. Compared with clinical examinations based on FIGO, MRI illustrated relatively high accuracy in evaluating UCC staging, and is worthwhile to be recommended in future clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the effects of body mass index (BMI) on survival in cervical cancer patients who had undergone surgery and radiotherapy (RT). Materials and Methods: We retrospectively reviewed the medical records of 70 cervical cancer patients who underwent surgery and RT from 2007 to 2012. Among them, 40 patients (57.1%) had pelvic lymph node metastases at the time of diagnosis. Sixty-seven patients (95.7%) had received chemotherapy. All patients had undergone surgery and postoperative RT. Median BMI of patients was 22.8 kg/m² (range, 17.7 to 35.9 kg/m²). Results: The median duration of follow-up was 52.3 months (range, 16 to 107 months). Twenty-four patients (34.3%) showed recurrence. Local failure, regional lymph nodal failure, and distant failure occurred in 4 (5.7%), 6 (8.6%), and 17 (24.3%) patients, respectively. The 5-year actuarial pelvic control rate was 83.4%. The 5-year cancer-specific survival (CSS) and disease-free survival (DFS) rates were 85.1% and 65.0%, respectively. The presence of pelvic lymph node metastases (n = 30) and being overweight or obese (n = 34, BMI = 23 kg/m²) were poor prognostic factors for CSS (p = 0.003 and p = 0.045, respectively). Of these, pelvic lymph node metastasis was an independent prognostic factor (p = 0.030) for CSS. Conclusion: Overweight or obese cervical cancer patients showed poorer survival outcomes than normal weight or underweight patients. Weight control seems to be important in cervical cancer patients to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: To find out the knowledge, attitude and practice regarding cervical cancer screening among women. Materials and methods: A descriptive cross-sectional study design was used to collect data from 96 women. Each woman was selected alternately from Gynae Out-Patient Department of Teaching Hospital. Data was collected by using semi-structured interview schedule to find out knowledge and practice and Likert scale to find out the attitude regarding cervical cancer screening. Data was analyzed by using SPSS version 20.0 and interpreted in terms of descriptive and inferential statistics. Results: Out of 96 women, mean age was 38.83 ± 6.57 and 90.6% respondents followed Hinduism. More than three fourth (85.4%) were literate and 59.4% were housewife. Only 9.4% were involved in cervical cancer prevention and screening awareness programme and 2.1% had family history of cervical cancer. As per the findings, only 34.4% and 27.8% had adequate knowledge and practice respectively whereas cent percent women had favorable attitude. Only education level of women was statistically significant with level of knowledge regarding cervical cancer screening (p = 0.041). There was strong negative correlation between knowledge score and practice score regarding cervical cancer screening among women (r = -0.194). Conclusion: Considerable proportions of women have inadequate knowledge and practice regarding cervical cancer screening. Therefore cervical cancer screening health camps and awareness program should be conducted at community level for women to increase the level of knowledge and practice regarding cervical cancer screening. [ABSTRACT FROM AUTHOR]

In this study, the relationship between ovarian function and ovarian limited dose in radiotherapy was evaluated in young patients with cervical cancer who underwent ovarian transposition (Fig1B). Moreover, the novel ovarian dose limit for a better preservation of ovarian function in intensity-modulated radiation therapy ( IMRT) was determined. We retrospectively analyzed data from 86 patients with cervical cancer who received radical hysterectomy and ovarian transposition from January 2013 to June 2015. In agreement with the National Comprehensive Cancer Network Guidelines ( NCCN) for Cervical Cancer Version 2.2015, 65 patients with pathological high-risk factors were administered adjuvant radiotherapy-20 of them received three-dimensional conformal radiotherapy (Observation Group A), 24 patients received IMRT with no limitation on radiation dose to ovaries (Observation Group B), and 21 patients underwent IMRT with limited radiation dose(V10<20%) to ovaries (Observation Group C). Twenty-one patients without any predetermined high-risk factors did not received radiation therapy (Control Group D). Patients from all four groups were followed up, and sex hormone levels (E2, P, follicle-stimulating hormone [ FSH], LH) before radiation, postradiation, 3 month, and 6 month after the radiation therapy were measured by electrochemiluminescence immunoassay. Subsequently, changes in sex hormone levels in all four groups of patients at various time points were analyzed. The levels of sexual hormones (E2, P, FSH, LH) before radiation, postradiation, 3 month, and 6 month after the radiation therapy in patients from all three observation groups were significantly lower than those in patients of the control group ( P < 0.05). There was no statistically significant difference in the levels of sex hormones in patients of the control group at different time points ( P > 0.05). Within each observation group, there was a statistically significant difference in the sex hormone levels in patients before the radiation and after the radiation ( P < 0.05); however, when data from all three observation groups were compared, only the difference in the levels of FSH and LH between the patients from Group A and Group C was statistically significant ( P < 0.05). The results of receiver-operating characteristic ( ROC) curve analysis suggested that limiting ovarian radiation dose to V7.5 < 26% in IMRT prevents the disruption of ovarian function (area under ROC curve was 0.740, confidence interval [ CI] = 0.606-0.874). In young patients with cervical cancer who underwent radical hysterectomy and ovarian transposition without receiving adjuvant radiotherapy, ovarian endocrine function was well preserved. In patients who received any type of postoperative radiotherapy, ovarian function was affected, suggesting that the standard ovarian limited dose used in IMRT disrupted ovarian function. The results of the ROC curve analysis suggested that the new optimal dose limit of V7.5 < 26% should be used in IMRT to preserve ovarian function ( P = 0.003). [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is one of the most common and lethal cancers in West Africa. Even though vaccines that protect against the most common Human papillomavirus (HPV) strains, 16 and 18, are currently in use in developed countries, the implementation of these vaccines in developing countries has been painfully slow, considering the pre-eminence of HPV-associated cervical cancer among women in those countries. Aim: We performed serological and PCR-based assessment of blood and tissue specimens obtained from women undergoing cervical cancer-related surgery at a major urban hospital in Bamako. Since several therapeutic HPV vaccines are currently in clinical trials, we also assessed willingness to participate in HPV cancer vaccine trials. Methods: Blood and biopsy samples of 240 women were evaluated for HPV types 16 and 18 by serology and PCR. Knowledge regarding the HPV vaccine and autonomy to decide to vaccinate their own child was assessed with a standardized questionnaire. Results: HPV 16 and 18 were identified in 137/166 (82.5%) cervical cancer biopsy samples by PCR. Co-infection with both HPV 16 and 18 was significantly more frequent in women over 50 years of age than in younger women (63.0% vs. 37.0%). 44% of study participants said they would be willing to vaccinate their child with HPV vaccine. Only 39% of women participating in this study reported that they would be able to make an autonomous decision to receive HPV vaccination. Permission from a male spouse or head of household was identified as important for participation by 59% of the women. Conclusion: This study provides strong support for the introduction of currently available HPV vaccines in Mali, and also provides key information about conditions for obtaining informed consent for HPV vaccine trials and HPV vaccination in Mali. [ABSTRACT FROM AUTHOR]

Background: Cervical Cancer (CC) is the number one cancer among women in sub-Saharan Africa. Although CC is preventable, most women in developing countries do not have access to screening.Methods: This cross-sectional study was conducted to determine the prevalence and risk factors for cervical lesions using visual inspection with acetic acid (VIA) among 112 HIV positive and 161 negative women aged 18-69 years.Results: The presence of cervical lesions was greater among HIV positive (22.9%) than HIV negative women (5.7%; p < 0.0001). In logistic models, the risk of cervical lesions among HIV positive women was 5.24 times higher when adjusted by age (OR 5.24, CI 2.31-11.88), and 4.06 times higher in a full model (OR 4.06, CI 1.61-10.25), than among HIV negative women. In the age-adjusted model women who had ≥2 lifetime sexual partners were 3 times more likely (OR 3.00, CI 1.02-8.85) to have cervical lesions compared to women with one lifetime partner and the odds of cervical lesions among women with a history of STIs were 2.16 greater (OR 2.16, CI 1.04-4.50) than among women with no previous STI. In the fully adjusted model women who had a previous cervical exam were 2.5 times more likely (OR 2.53, CI 1.06-6.05) to have cervical lesions than women who had not.Conclusions: The high prevalence of HIV infection and the strong association between HIV and cervical lesions highlight the need for substantial scale-up of cervical screening to decrease the rate of CC in Swaziland. [ABSTRACT FROM AUTHOR]

Cervical lymph node metastasis is common in patients with papillary thyroid carcinoma (PTC). Salmonella species are rarely reported as causative agents in focal infections of the head and neck. The cooccurrence of lymph node metastasis from PTC and a bacterial infection is rare. This report describes a 76-year-old woman with a cervical lymph node metastasis from PTC and Salmonella infection of the same lymph node. The patient presented with painful swelling in her left lateral neck region for 15 days, and neck ultrasonography and computed tomography showed a cystic mass along left levels II–IV. The cystic mass was suspected of being a metastatic lymph node; modified radical neck dissection was performed. Histopathological examination confirmed the presence of PTC in the resected node and laboratory examination of the combined abscess cavity confirmed the presence of Salmonella Typhi. Following antibiotic sensitivity testing of the cultured Salmonella Typhi, she was treated with proper antibiotics. Cystic lesions in lymph nodes with metastatic cancer may indicate the presence of cooccurring bacterial infection. Thus, culturing of specimen can be option to make accurate diagnosis and to provide proper postoperative management. [ABSTRACT FROM AUTHOR]

Context:Genetic polymorphisms in genes of the base excision repair (BER) pathway appear to modulate the therapy response of cancer patients. PARP1 protein recognizes the DNA strand damage and facilitates the subsequent recruitment of BER proteins. Few studies have reported an association betweenPARP1 Val762Alapolymorphism (rs1136410) and cancer therapy response. Objective:The purpose of our study was to determine whetherPARP1 Val762Alapolymorphism have prognostic value in patients with cervical cancer. Materials and methods:Two hundred and sixty adult patients, with histologically confirmed cervical cancer, at FIGO-stages IB2-IVA, primarily treated with concurrent chemotherapy (cisplatin) and radiotherapy. Overall survival (OS) and disease-free survival (DFS) were the primary end points of the analysis. ThePARP1 Val762Alagenetic variants were analyzed by allelic discrimination by real-time PCR. Results:We observed that peri- and postmenopausal women carrying the C-allele present a statistically significant lower OS and DFS (log-rank test,p = 0.008 andp = 0.006, respectively) among those with early stage cervical cancer. Cox regression analysis confirmed these results, after adjustment for other prognostic factors (for OS: HR, 3.70; 95%CI, 1.32–10.38;p = 0.013 and for DFS: HR, 3.97; 95%CI, 1.59–9.93;p = 0.003). Conclusions:This is the first study evaluating the effect of PARP1 Val762Ala polymorphism in treatment response in cervical cancer patients. PARP1 genotypes may contribute as an independent prognostic factor in cervical cancer, being useful in predicting the clinical outcome. [ABSTRACT FROM PUBLISHER]

The aims of the present study were to investigate the distribution of human papillomavirus (HPV) genotypes in cervical lesions, and the association between different HPV genotypes and cervical lesions. Between January 2013 and June 2014, the HPV type determinations of nucleic acid by use of fluorescence polymerase chain reaction (PCR) method of 15,192 outpatients in China-Japan Friendship Hospital were performed and the infection status was analyzed. The results showed that: i) 2,366 Cases were HPV positive and 12,826 cases were HPV negative, the overall infection rate was 15.57% (2,366/15,192), in which a single genotype of HPV infection rate was 11.63% (1,767/15,192), and multiple genotypes of HPV infection rate was 3.94% (599/15,192); ii) HPV16, HPV52 and HPV58 infections were the most common HPV genotypes, the infection rates were 3.95% (600/15,192), 2.86% (435/15,192) and 2.67% (406/15,192), respectively; and iii) According to the gold standard of histopathological analysis via hematoxylin-eosin staining, HPV16, HPV52 and HPV58 accounted for 58.80% (154/267) of all CIN2 or above squamous epithelial lesions. Furthermore, three cases with pathological changes of the cervical severe glandular epithelium were all HPV18 infection. The difference was statistically significant (χ2=60.74, P<0.001). Single HPV subtype infection was primarily associated with HPV16, HPV52 and HPV58. In conclusion, HPV type detection had a may be important in screening of cervical lesions as a difference in pathogenic ability was noted among different HPV genotypes. As cervical cancer is an infectious disease, HPV testing may help detect more precancerous lesions, thus reducing the morbidity and mortality of cervical cancer. HPV16, HPV52 and HPV58 were associated with severe cervical squamous epithelial lesions; HPV18 was associated with cervical severe glandular cell pathological changes, although it was not the most common HPV genotype in China. When positive, a clinical cervical examination should be conducted, including colposcopy and biopsy. [ABSTRACT FROM AUTHOR]