Search

Objective DCVAC/OvCa is an active cellular immunotherapy designed to stimulate an immune response against ovarian cancer. We explored the safety and efficacy of DCVAC/OvCa plus carboplatin and gemcitabine in platinum-sensitive ovarian cancer. Methods In this open-label, parallel-group, phase 2 trial ( ClinicalTrials.gov number NCT02107950 ), patients with platinum-sensitive ovarian cancer relapsing after first-line chemotherapy were randomized to DCVAC/OvCa and chemotherapy or chemotherapy alone. DCVAC/OvCa was administered every 3–6 weeks (10 doses). Endpoints included safety, progression-free survival (PFS; primary efficacy endpoint) and overall survival (OS; secondary efficacy endpoint). Results Between November 2013 and May 2015, 71 patients were randomized to chemotherapy in combination with DCVAC/OvCa or to chemotherapy alone. Treatment-emergent adverse events related to DCVAC/OvCa, leukapheresis and chemotherapy occurred in six (16.2%), two (5.4%), and 35 (94.6%) patients in the DCVAC/OvCa group. Chemotherapy-related events occurred in all patients in the chemotherapy group. Seven patients in the DCVAC/OvCa group were excluded from primary efficacy analyses due to failure to receive ≥1 dose of DCVAC/OvCa. PFS was not improved (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.42–1.28, P = 0.274, data maturity 78.1%). Median OS was significantly prolonged (by 13.4 months) in the DCVAC/OvCa group (HR 0.38, 95% CI 0.20–0.74, P = 0.003; data maturity 56.3%). A signal for enhanced surrogate antigen-specific T-cell activity was seen with DCVAC/OvCa. Conclusions DCVAC/OvCa combined with chemotherapy had a favorable safety profile in patients with platinum-sensitive ovarian cancer. DCVAC/OvCa did not improve PFS, but the exploratory analyses revealed OS prolongation and enhanced surrogate antigen-specific T-cell activity.

Simple Summary Despite advances in cancer research in recent years, efficient predictive biomarkers of tumor progression and metastatic spread for ovarian cancer are still missing. Therefore, we critically address recent findings in the field of non-coding RNAs (microRNAs and long non-coding RNAs) and DNA methylation in ovarian cancer patients as promising novel biomarkers of ovarian cancer progression. Abstract Ovarian cancer is one of the most common causes of death among gynecological malignancies. Molecular changes occurring in the primary tumor lead to metastatic spread into the peritoneum and the formation of distant metastases. Identification of these changes helps to reveal the nature of metastases development and decipher early biomarkers of prognosis and disease progression. Comparing differences in gene expression profiles between primary tumors and metastases, together with disclosing their epigenetic regulation, provides interesting associations with progression and metastasizing. Regulatory elements from the non-coding RNA families such as microRNAs and long non-coding RNAs seem to participate in these processes and represent potential molecular biomarkers of patient prognosis. Progress in therapy individualization and its proper targeting also rely upon a better understanding of interactions among the above-listed factors. This review aims to summarize currently available findings of microRNAs and long non-coding RNAs linked with tumor progression and metastatic process in ovarian cancer. These biomolecules provide promising tools for monitoring the patient’s response to treatment, and further they serve as potential therapeutic targets of this deadly disease.

The standard procedure in cervical cancer is radical hysterectomy (RH) and pelvic lymphadenectomy (PLND). Because of the increasing age of women at childbirth, fertility becomes a major challenge. We present 20 years of experience with two-step less radical fertility-sparing surgery in women with IA1, LVSI positive, IA2 and IB1 (2 cm, infiltration less than half of stromal invasions.Preoperative workout consisted of histopathological diagnosis and magnetic resonance imaging along with ultrasonographic volumetry. We then performed laparoscopic sentinel lymph node mapping (SLNM) with frozen section (FS) followed by PLND and "selective parametrectomy" (removal of afferent lymphatic channels from the paracervix) in case of a negative result. If verified by definitive histopathology, patients were treated by simple trachelectomy (IB1) or large cone (IA1/IA2) biopsy 1 week after primary surgery.From 1999 to 2018, 91 women were enrolled in the study (median age 29.1 years, range 21-40). Of these 91 women, 51 (56.0%) were nulliparous. The detection rate of SLNs was 100% per patient and the specific side detection rate 96.7%. Positive lymph nodes were diagnosed in nine cases (9.8%). These women then underwent RH. Fertility was spared in 80 women but 4 recurred locally (5.0%). The mortality rate was 0.0%. The median follow-up was 149 months.Less radical fertility-sparing surgery with SLNM is safe in cervical cancers2 cm at the largest diameter and infiltrating less than half of the cervical stroma. The recurrence rate is acceptable with no mortality. Morbidity with this procedure is low. Extended and accurate follow-up is necessary and human papillomavirus - high risk (HPV-HR tests seem to be useful in such follow-up assessment.

BACKGROUND: Awareness is growing that cancer can be treated during pregnancy, but the effect of this change on maternal and neonatal outcomes is unknown. The International Network on Cancer, Infertility and Pregnancy (INCIP) registers the incidence and maternal, obstetric, oncological, and neonatal outcomes of cancer occurring during pregnancy. We aimed to describe the oncological management and obstetric and neonatal outcomes of patients registered in INCIP and treated in the past 20 years, and assess associations between cancer type or treatment modality and obstetric and neonatal outcomes. METHODS: This descriptive cohort study included pregnant patients with cancer registered from all 37 centres (from 16 countries) participating in the INCIP registry. Oncological, obstetric, and neonatal outcome data of consecutive patients diagnosed with primary invasive cancer during pregnancy between Jan 1, 1996, and Nov 1, 2016, were retrospectively and prospectively collected. We analysed changes over time in categorical patient characteristics, outcomes, and treatment methods with log-binomial regression. We used multiple logistic regression to analyse preterm, prelabour rupture of membranes (PPROM) or preterm contractions, small for gestational age, and admission to the neonatal intensive care unit (NICU). The INCIP registry study is registered with ClinicalTrials.gov, number NCT00330447, and is ongoing. FINDINGS: 1170 patients were included in the analysis and 779 (67%) received treatment during pregnancy. Breast cancer was the most common malignant disease (462 [39%]). Every 5 years, the likelihood of receiving treatment during pregnancy increased (relative risk [RR] 1·10, 95% CI 1·05-1·15), mainly related to an increase of chemotherapeutic treatment (1·31, 1·20-1·43). Overall, 955 (88%) of 1089 singleton pregnancies ended in a livebirth, of which 430 (48%) of 887 pregnancies ended preterm. Each 5 years, we observed more livebirths (RR 1·04, 95% CI 1·01-1·06) and fewer iatrogenic preterm deliveries (0·91, 0·84-0·98). Our data suggest a relationship between platinum-based chemotherapy and small for gestational age (odds ratio [OR] 3·12, 95% CI 1·45-6·70), and between taxane chemotherapy and NICU admission (OR 2·37, 95% CI 1·31-4·28). NICU admission seemed to depend on cancer type, with gastrointestinal cancers having highest risk (OR 7·13, 95% CI 2·86-17·7) and thyroid cancers having lowest risk (0·14, 0·02-0·90) when compared with breast cancer. Unexpectedly, the data suggested that abdominal or cervical surgery was associated with a reduced likelihood of NICU admission (OR 0·30, 95% CI 0·17-0·55). Other associations between treatment or cancer type and outcomes were less clear. INTERPRETATION: Over the years, the proportion of patients with cancer during pregnancy who received antenatal treatment increased, especially treatment with chemotherapy. Our data indicate that babies exposed to antenatal chemotherapy might be more likely to develop complications, specifically small for gestational age and NICU admission, than babies not exposed. We therefore recommend involving hospitals with obstetric high-care units in the management of these patients. FUNDING: Research Foundation-Flanders, European Research Council, Charles University, Ministry of Health of the Czech Republic. ispartof: The Lancet Oncology vol:19 issue:3 pages:337-346 ispartof: location:England status: published

Transmission of human papillomavirus (HPV) is a premise for development of cervical dysplasia and genital warts. This cross-sectional study assesses concordance of HPV types present in genital warts or cervical dysplasia in women and genital infection of their monogamous male partners in conjunction with seroprevalence of HPV-6,-11,-16 and -18 antibodies. Blood was taken from both women and men, as well a smear of the urogenital area of men. HPV DNA detection in women was done in fixed paraffin embedded tissues under histological control. Of 143 couples who agreed to participate in the study, 68 met inclusion criteria. Type-specific concordance was observed in 32.5% (13/40) of couples in which women had genital warts and in 32.1% (9/28) of couples in which women had cervical dysplasia. In multivariate analysis only smoking in women was associated with concordance (p

Currently, three prophylactic HPV vaccines are commercially available to prevent HPV 16/18 infection and associated lesions. The aim of the study was to assess markers of HPV infection in women/girls before vaccination and to ascertain the prevalence and spectrum of post-vaccination HPV types. Three hundred and thirty subjects of which 75 were virgins were enrolled. Before the first dose of the HPV vaccine and 1, 3 and 5 years after the completion of HPV vaccination, the samples for cytology, HPV detection and anti-HPV antibody response were taken. At enrolment, HPV DNA was detected in 38% of sexually active girls/women. At the first, second and third follow-up, HPV DNA was found in 40, 45, and 39% of them. The seroprevalence rates to HPV 6, 11, 16 and 18 in these subjects were 31, 21, 18 and 10%. On the follow-up significantly higher levels of antibodies to HPV 16/18 were found after application of divalent vaccine. Results of the study demonstrate high prevalence of HPV infection in young women. In a substantial number of women, HPV-specific antibodies as well as high-risk HPV types were detected. HPV-specific antibodies were also frequently found in non-sexually active girls. The acquisition of HPV after the onset of sexual life was very fast.

Epithelial ovarian cancer (EOC) has the highest mortality among gynecological carcinomas. The lack of specific markers for prognostic determination of EOC progression hinders the search for novel effective therapies. The aim of the present study was (i) to explore differences in expressions of ATP-binding cassette (ABC) and solute carrier (SLC) transporter genes, genes associated with drug metabolism and cell cycle regulation between control ovarian tissues (n = 14), primary EOCs (n = 44) and intraperitoneal metastases (n = 29); (ii) to investigate associations of gene expression levels with prognosis of patients with intraperitoneal metastases. In all tissue samples, transcript levels of the above target genes were assessed using quantitative real-time PCR. Gene expression levels were compared between particular tissue types and evaluated with regard to progression-free survival (PFS) and drug-resistance status of patients with metastases. Gene expression of ABCA7 significantly increased and that of ESR2 decreased in the order control ovarian tissues - primary EOCs - metastases. High expressions of ABCA2/8/9/10, ABCB1, ABCC9, ABCG2, ATP7A, SLC16A14, and SOD3 genes were significantly associated with longer progression-free survival of patients. In intraperitoneal metastases, expression of all of these genes highly correlated and indicated prognostic profile. Transporters from the ABCA family, ABCG2, and ESR2 are involved mainly in lipid metabolism, membrane transport, and cell proliferation. These processes are thus probably the most important for EOC progression. Based on these results, we have proposed novel markers of ovarian carcinoma progression and metastatic spread which might be potentially useful as therapeutic targets. Their significance should be further explored on a larger independent set of patients.

Introduction/Background The purpose of the study is to present our clinical experience, pregnancy management and long term obstetrical outcome after less radical fertility sparing surgery SLNM + laparoscopic lymphadenectomy + simple trachelectomy or large recone. Methodology From 1999–2018, 91 women with squamous or adenocarcinoma with tumor less than 20 mm in the largest diameter and infiltration less than half of cervical stroma underwent laparoscopic SLNI and select extirpation of afferent parametrial channel and frozen section (FS) of SLN and laparoscopic pelvic lymphadenectomy or only SLN. Second step is simple trachelectomy without cerclage or large recone. Results Fertility was definitely spared in 76 women. 3 women (3.3%) not plan pregnancy, 9 currently plan pregnancy in future (9.9%), 64 women (84.2%) wish to be pregnant and 53 was pregnant (82.8%). From 76 fertility spared, 53 was pregnant - pregnancy rate 69.7%, 44 women have 50 baby - delivery rate was 57.9%. 37 was term pregnancy (74%), extreme premature 24–27w - 2 baby (4%), premature (28–32w) - 2 baby (4%), premature (33–37w) - 9 baby (18%). 22 unsuccessful pregnancy (5 artericial abortion, 11 spontaneus abortion in 1 trimestr, 4 spontaneus abortion in 2 trimestr, 2 GEU. Two women after hysterectomy have two baby with donor mother. Conclusion SLNM and laparoscopic pelvic lymphadenectomy with simple trachelectomy or large recone in small volume cervical cancer (less than 2cm in the largest diameter and less than half of stromal invasion) have excellent pregnancy result. This work was supported by Charles University research program PROGRES Q 28 (Oncology). Disclosure Nothing to disclose.

Objectives Purpose of study was to determine long term experience of less radical surgery, sentinel lymph node identification (SLNI) with Tc99+blue day with laparoscopic surgery. Methods From 1999 to 2018, 91 women with tumor less than 20 mm in largest diameter, infiltration less than half of cervical stroma underwent SLNI, frozen section (FS) of SLN, extirpation of afferent parametrial lymphatic channel, pelvic lymphadenectomy or only SLN. FS SLN positive patients underwent radical hysterectomy. Seven days after final histopathological processing of dissected nodes, large cone or simple trachelectomy was performed. Results 15 women (16.5%) lost fertility. 9 women had positive lymph nodes (9.9%), 2 close invasive margin (2.2%), so radical hysterectomy was performed. Four cases had SIL in margin or patient decision, had laparoscopic hysterectomy. One patient N1 had recurrence and died of disease. All other are in complete remission. Fertility was save in 76 cases. Three central recurrences (isthmic part of uterus) were observed (3.9%), one died (1.3%), 2 are in CR 15 and 7 years. We have no distant recurrence. 62 of 76 women whose reproductive ability had been maintained tried to conceive (82%). Of these 62 women, 49 became pregnant (79%) in total 76 pregnancies. 43 mothers gave birth to 48 children, two children were by surrogate mothers. Conclusions Less radical fertility sparing surgery in early cervical cancer can be feasible method that yields high, successful pregnancy rate. This work was supported by the Charles University research program PROGRES Q 28 (Oncology).

Multidrug resistance to anticancer drugs, which is often associated with enhanced expression of the ATP‑binding cassette (ABC) transporter P‑glycoprotein (encoded by the ABCB1 gene) may limit the effects of cancer therapy. Epigenetic regulation of ABCB1 expression may thus have a clinical impact. A detailed assessment of ABCB1 promoter methylation is of importance for predicting therapy outcome and prognosis. Thus, validated methods for the analysis of ABCB1 promoter methylation are urgently required. In the present study, high‑resolution melting (HRM) analysis of the CpG island regions covering the distal promoter of the ABCB1 gene was developed and compared with pyrosequencing. In addition, the clinical effects of the methylation status of the ABCB1 promoter were analyzed in patients with breast and ovarian carcinoma prior and subsequent to chemotherapy treatment. HRM analysis of ABCB1 methylation correlated with the results of pyrosequencing (P=0.001) demonstrating its analytical validity and utility. Hypermethylation of the analyzed ABCB1 promoter region was significantly correlated with low levels of the ABCB1 transcript in tumors from a subset of patients with breast and ovarian carcinoma prior to chemotherapy but not following treatment. Finally, high ABCB1 transcript levels were observed in tumors of patients with short progression‑free survival prior to chemotherapy. Our data suggest the existence of functional epigenetic changes in the ABCB1 gene with prognostic value in tumor tissues of patients with breast and ovarian carcinoma. The clinical importance of such changes should be further evaluated.

BackgroundTreatment of cervical cancer during pregnancy is often complex and challenging. This study aimed to analyze current patterns of practice in the management of pregnant patients diagnosed with cervical cancer.MethodsThis was a matched cohort study comprising patients managed for cervical cancer during pregnancy from six European centers. Patient information was retrieved from the dataset of the International Network for Cancer, Infertility and Pregnancy from 1990 to 2012. Each center matched its patients with two non-pregnant controls for age (±5 years) and International Federation of Gynecology and Obstetrics (FIGO) 2009 stage. Information on age, histological type, grade, lymphovascular space invasion, stage, tumor size, method of diagnosis, site of recurrence, delivery, date of recurrence, and date of death was recorded. Progression-free survival was compared using multivariable Cox proportional hazards regression.ResultsA total of 132 pregnant patients and 256 controls were analyzed. The pregnant patients (median age 34 years, range 21–43) were diagnosed at a median gestational age of 18.4 weeks of pregnancy (range 7–39). Stage distribution during pregnancy was 14.4% for stage IA, 47.0% for IB1, 18.9% for IB2, and 19.7% for II-IV. For treatment during pregnancy, 17.4% of the patients underwent surgery, 16.7% received neoadjuvant chemotherapy, 26.5% delayed their treatment, 12.9% had a premature delivery, and 26.5% had their pregnancy terminated. Median follow-up was 84 months (67 months for pregnant and 95 months for non-pregnant patients). The unadjusted hazard ratio of pregnancy for progression-free survival was 1.18 (95% confidence interval 0.74 to 1.88).ConclusionSurgery and chemotherapy is increasingly used in the management of pregnant patients with cervical cancer and prognosis is similar to that of non-pregnant patients.

5521 Background: Most patients with EOC relapse despite PDS and CMT. Autologous DCVAC can present tumor antigens to elicit a durable immune response. We hypothesized that adding DCVAC to CMT stimulates antitumor immunity and improves clinical outcomes. Methods: Key eligibility criteria were FIGO stage III EOC (serous, endometrioid, or mucinous), post-PDS with < 1 cm maximal residuum, no prior systemic therapy, and ECOG 0-2. In part 1, patients were randomized up to 6 weeks after PDS, 1:1:1, into arm A (A; DCVAC concomitant with CMT), arm B (B; DCVAC sequential after CMT), and arm C (C; CMT). Patients were stratified by tumor residuum (0 or < 1 cm). CMT consisted of 6 cycles of carboplatin (AUC 5-7) and paclitaxel (175 mg/m2). Patients in A and B received up to 10 doses of DCVAC (1×107 DCs/dose). The primary endpoint was radiologically assessed progression-free survival (PFS). The key secondary endpoint was overall survival (OS). Results presented refer to a protocol-defined modified intention-to-treat population (mITT) including patients who received ≥1 CMT dose in C or ≥1 DCVAC dose in A and B. Results: Between November 2013 and March 2016, 99 patients were randomized. At the final analysis, the mITT included 31 patients in A, 29 patients in B, and 30 patients in C. Key baseline characteristics and DCVAC exposure were comparable across treatment arms. Median PFS was 20.3 months in A, not reached in B, and 21.4 months in C, with corresponding HRs (95% CI) compared to C of 0.98 (0.48-2.00) in A and 0.39 (0.16-0.96) in B. The PFS benefit in B was statistically significant (p = 0.034) This was supported by a non-significant trend in OS in A and B. Median OS was not reached in any arm at the time of median follow-up of 66 months (34% of events). Patients with low CD8+ T-cell counts (CD8Lo) in tumor samples in A and B had significantly improved clinical outcomes compared to patients in C with CD8Lo: median PFS gain of 6 months (19 vs 13 months) and a more robust OS gain (median not reached vs 31 months), with minimal difference between A and B. This effect could not be attributed to statistical differences in high CD8+ T-cell counts (CD8Hi) density patients. These findings indicated the best clinical outcome in DCVAC patients with immunologically “cold” tumors in both DCVAC arms. DCVAC showed a good safety profile with only 8 DCVAC-related adverse events (Grade 1-2). Conclusions: DCVAC improved PFS and OS outcomes in patients with newly diagnosed EOC, predominantly in patients with immunologically “cold” tumors, thus representing a promising treatment option in this patient population. Clinical trial information: NCT02107937.

Because of a notable increase in age at delivery, the incidence of malignancy diagnosed during pregnancy has substantially increased. This review aims to summarize the literature and expert knowledge on gynecologic cancers diagnosed in pregnancy regarding epidemiology, examination and staging procedures, description of treatment modalities and management of gynecological malignancies with special interest in cervical and ovarian cancer. Thorough attention is paid to the surgery and chemotherapy administration for early-stage cervical cancer diagnosed during pregnancy.

A high density of tumor-infiltrating CD8+ T cells and CD20+ B cells correlates with prolonged survival in patients with a wide variety of human cancers, including high-grade serous ovarian carcinoma (HGSC). However, the potential impact of mature dendritic cells (DCs) in shaping the immune contexture of HGSC, their role in the establishment of T cell-dependent antitumor immunity, and their potential prognostic value for HGSC patients remain unclear. We harnessed immunohistochemical tests and biomolecular analyses to demonstrate that a high density of tumor-infiltrating DC-LAMP+ DCs is robustly associated with an immune contexture characterized by TH1 polarization and cytotoxic activity. We showed that both mature DCs and CD20+ B cells play a critical role in the generation of a clinically favorable cytotoxic immune response in HGSC microenvironment. In line with this notion, robust tumor infiltration by both DC-LAMP+ DCs and CD20+ B cells was associated with most favorable overall survival in two independent cohorts of chemotherapy-naive HGSC patients. Our findings suggest that the presence of mature, DC-LAMP+ DCs in the tumor microenvironment may represent a novel, powerful prognostic biomarker for HGSC patients that reflects the activation of clinically relevant anticancer immunity. Citation Format: Iva Truxova, Lenka Kasikova, Michal Hensler, Petr Skapa, Jan Laco, Ladislav Pecen, Lucie Belicova, Ivan Praznovec, Michael J. Halaska, Tomas Brtnicky, Eva Salkova, Lukas Rob, Roman Kodet, Jeremy Goc, Catherine Sautes-Fridman, Wolf Herman Fridman, Ales Ryska, Lorenzo Galluzzi, Radek Spisek, Jitka Fucikova. Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B76.

screening intervalCarcinoma of the uterine cervix is the fourth most common malignant tumor in women worldwide. It is estimated that in 2012 there will be 528,000 new cases and 266,000 deaths in the world. A large majority of the global burden occurs in developing countries, where 445,000 cases and 230,000 deaths from cervical cancer take place annually

Background Tregs play a suppressive role in the control of antitumour immunity. In this study we evaluated the relevance of prospective monitoring of peripheral blood regulatory T cells (Tregs) as a potential prognostic marker of future outcome of epithelial ovarian cancer in patients with or without a metronomic chemotherapy. Methods 46 patients diagnosed with the ovarian cancer were enrolled in the study and divided into groups according to the stage of the disease, outcome of the surgery and treatment received. Proportions of Tregs in the peripheral blood samples were evaluated using flow cytometry. Results We show that the early stage of the disease and absence of the tumor residuum after radical surgery are the most important factors predicting a favourable clinical outcome in the ovarian cancer. We did not show any significant effect of consolidation chemotherapy with metronomic doses of etoposide or cyclophosphamide on the peripheral blood Tregs and on the clinical outcome. The slope of the Tregs trend line was a significant predictor of an early relapse, even after controlling for stage and tumor residuum after the surgical debulking by using the Cox proportional hazard model. Conclusions This study shows that the faster kinetics of Tregs increase in the peripheral blood, expressed as the slope of the Tregs trend line, is a significant predictor of ovarian cancer early relapse hazard. However, due to its relatively low specificity, the informative value of regular monitoring of Tregs kinetics in the peripheral blood for the subsequent clinical outcome is limited.

ObjectiveThe aim of this study was to prospectively monitor the patients’ quality of life (QoL) after vulvar cancer surgery.DesignThe design was prospective clinical study.SettingThe study was set in the Department of Obstetrics and Gynecology, 2nd Medical Faculty of the Charles University and University Hospital Motol, Prague, Czech Republic.MethodsA group of 36 patients underwent vulvar cancer surgery: 24 patients were subject to inguinofemoral lymphadenectomy (RAD) and 12 to sentinel lymph node biopsy. To evaluate QoL, the European Organisation for Research and Treatment of Cancer, QoL questionnaires (QLQ-C30 and QLQ-CX24) were administered to patients before and 6 and 12 months after surgery.ResultsIn patients with vulvar cancer after inguinofemoral lymphadenectomy, increased fatigue and impaired lymphedema were observed. In the group of patients after sentinel lymph node biopsy, none of the QoL variables worsened postoperatively. Comparing both groups 12 months after surgery, the RAD group had significantly worse outcomes in body image and cognitive functioning than the sentinel lymph node biopsy group.Patients in the RAD group, who received adjuvant radiotherapy (n = 13), had worse QoL in symptom experience (P < 0.05) at 6 and 12 months after the surgery than patients without radiotherapy (n = 11).ConclusionsLess radical surgery showed objectively better QoL results.

ObjectiveThe aim of this study was to develop clinically relevant and evidence-based guidelines as part of European Society of Gynaecological Oncology’s mission to improve the quality of care for women with gynecologic cancers across Europe.MethodsThe European Society of Gynaecological Oncology Council nominated an international development group made of practicing clinicians who provide care to patients with vulvar cancer and have demonstrated leadership and interest in the management of patients with vulvar cancer (18 experts across Europe). To ensure that the statements are evidence based, the current literature identified from a systematic search has been reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group (expert agreement). The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 181 international reviewers including patient representatives independent from the development group.ResultsThe guidelines cover diagnosis and referral, preoperative investigations, surgical management (local treatment, groin treatment including sentinel lymph node procedure, reconstructive surgery), radiation therapy, chemoradiation, systemic treatment, treatment of recurrent disease (vulvar recurrence, groin recurrence, distant metastases), and follow-up.

Objective 28 women under 35years with early-stage cervical cancer and strong desire for fertility preservation that do not fulfil standard criteria for fertility-sparing surgery (tumour larger than 2cm or with deep of infiltration more than half of stroma) were included in prospective study. Methods Dose-dense neoadjuvant chemotherapy (NAC) was performed on all 28 patients in 10-day intervals: cisplatin plus ifosfamide in squamous cell cancer (15 women—53.6%) or cisplatin plus doxorubicin in adenocarcinoma (13 women—46.3%). Patients underwent laparoscopic lymphadenectomy and vaginal simple trachelectomy after NAC. Patients with positive lymph nodes or inadequate free surgical margins underwent radical hysterectomy. Results No residual disease was found in 6 women (21.4%), microscopic disease was observed in 11 women (39.3%) and macroscopic tumour in was observed in 11 women (39.3%). Ten women (35.7%) lost fertility. Four women (20%) after fertility-sparing surgery recurred, two died of the disease (10%). Fertility was spared in 20 (71.4%) women and 10 of them became pregnant (50%). Eight women delivered ten babies (6 term and four preterm deliveries). There were two miscarriages in second trimester (in one woman) and one in first trimester. One woman underwent four unsuccessful cycles of IVF, one failed to become pregnant and one recurred too early. Two women underwent chemoradiotherapy for recurrence and lost chance for pregnancy. Conclusions Downstaging by NAC in IB1 and IB2 cervical cancer before fertility-sparing surgery is still an experimental procedure, but shows some promise. Long-term results in relation to oncological outcome for this concept are still needed.

Objective The endpoint of this prospective study is to evaluate response rate, survival and toxicity of high-dose density neoadjuvant chemotherapy (NAC) in bulky IB cervical cancer. Material and methods Between January 1998 and December 2009, 154 women were enrolled into study. Three patients were withdrawn. Of the 151 women, 119 had stage IB2 cervical cancer (78.8%) and 32 had stage IB1 cancer (21.2%) infiltrating the whole cervical stroma. Women received 3–4 cycle cisplatin-75 mg/m2 and ifosfamide-2 g/m2 in cases of squamous-cell cancer or cisplatin-75 mg/m2 and doxorubicin-35 mg/m2 in adenocarcinoma every 10 days and then underwent radical hysterectomy type III. Patients who had non-resectable disease underwent chemoradiotherapy. Results The overall response rate (reduction of tumor volume more than 50%) was 78.8%. Reduction of tumor volume less than 50% was seen in 15.2%. Tumor progression during chemotherapy occurred in nine patients (6.0%). There were positive lymph-nodes in 26 patients (18.3%) of the 142 that underwent surgery. 38 women underwent adjuvant radiotherapy (26.7%). There were 26 recurrences (17.2%). After surgery 20 women recurred from 142 (14.1%) and after primary radiotherapy 6 from 9 women recurred (66.7%). 25 of 151 women died from disease (16.5%). At the time of the study, surgery was performed in 118 women 5 or more years ago, 19 of them died of disease. Five-year specific survival is 83.6%. Grade 3–4 neutropenia was found in only 7.3% of the women, and grade 3–4 thrombocytopenia were found in 1.3%. Conclusion High-dose density NAC appears to be feasible in the treatment IB bulky cervical cancer and toxicity is acceptable. Adjuvant radiotherapy was used only in 26.7%.

We conducted a cross-sectional study on the occurrence of a specific type of genital human papillomavirus (HPV) among long-term monogamous male partners of women with cervical dysplasia and genital warts. The purpose of the study was to improve knowledge with regards to the management of these couples. The presence of genital HPV-DNA was detected by PCR with broad spectrum primers followed by hybridization. 82 males met the study criteria, 41 in each group. Genital HPV-DNA prevalence was 67.5% in the genital warts group and 72.2% in the cervical dysplasia group. The prevalence of high risk HPVs was higher in the cervical dysplasia group, while low risk HPVs were more prevalent in the genital warts group (p

// Kamila Kloudova 1, 3 , Hana Hromadkova 1 , Simona Partlova 1, 3 , Tomas Brtnický 2 , Lukas Rob 2 , Jiřina Bartůňkova 1 , Michal Hensler 3 , Michael J. Halaska 2 , Radek Spisek 1, 3 , Anna Fialova 1, 3 1 Department of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic 2 Department of Obstetrics and Gynaecology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic 3 Research Department, Sotio, Prague, Czech Republic Correspondence to: Anna Fialova, email: askallova@centrum.cz Keywords: high-grade serous epithelial ovarian cancer, tumor-associated antigens, immunotherapy, cancer cell lines Received: January 13, 2016 Accepted: May 26, 2016 Published: June 14, 2016 ABSTRACT In order to select a suitable combination of cancer cell lines as an appropriate source of antigens for dendritic cell-based immunotherapy of ovarian cancer, we analyzed the expression level of 21 tumor associated antigens (BIRC5, CA125, CEA, DDX43, EPCAM, FOLR1, Her-2/neu, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MUC-1, NY-ESO-1, PRAME, p53, TPBG, TRT, WT1) in 4 established ovarian cancer cell lines and in primary tumor cells isolated from the high-grade serous epithelial ovarian cancer tissue. More than 90% of tumor samples expressed very high levels of CA125, FOLR1, EPCAM and MUC-1 and elevated levels of Her-2/neu, similarly to OVCAR-3 cell line. The combination of OV-90 and OVCAR-3 cell lines showed the highest overlap with patients’ samples in the TAA expression profile.

Cervical cancer is one of the four most common malignancies in pregnancy. The coincidence of cancer diagnosed in pregnancy generally increases. Because pregnancy itself does not negatively influence the prognosis of cervical cancer patients, pregnancy-preserving management should be considered as majority of cases are diagnosed at the early stage of disease. Pelvic lymphadenectomy as a staging procedure can be safely performed until the 22nd gestational week. Abdominal or vaginal radical trachelectomy during pregnancy poses unacceptable risk to mother and foetus and therefore this procedure is not recommended. Neoadjuvant chemotherapy represents one of the most applicable treatment options in pregnancy-preserving management. Treatment decision must be done within an experienced, multidisciplinary team.

BackgroundLower-limb lymphedema is one of the most disabling adverse effects of vulvar cancer surgery. Multifrequency Bioelectrical Impedance Analysis (MFBIA) is a modern noninvasive method to detect lymphedema. The first aim of this study was to prospectively determine the prevalence of secondary lower-limb lymphedema after surgical treatment for vulvar cancer using objective methods, circumference measurements and MFBIA technique. The second aim was to compare quality of life (QoL) before and 6 months after vulvar surgery.MethodsTwenty-nine patients underwent vulvar cancer surgery in our study: 17 underwent inguinofemoral lymphadenectomy (RAD), and 12 underwent sentinel lymph node biopsy (CONS). Patients were examined before and 6 months after vulvar surgery by measuring the circumference of the lower limbs and with MFBIA. A control group of 27 healthy women was also measured. To evaluate QoL, the European Organisation for Research and Treatment of Cancer (EORTC) QoL questionnaires (QLQ-C30 and QLQ-CX24) were administered to patients before and 6 months after surgery.ResultsUsing circumference measurement, 9 lymphedemas (31%) were diagnosed: 3 (25%) in the CONS and 6 (37.5%) in the RAD group (P= 0.69). After vulvar surgery, patients in the RAD group reported more fatigue and worsening of physical and role functioning. When comparing both groups, the RAD group had significantly worse parameters in social functioning, fatigue, and dyspnea.ConclusionsLower radicality in inguinofemoral lymphadenectomy shows a trend toward lower morbidity and significantly improves QoL. Multifrequency Bioelectrical Impedance Analysis was tested in these patients as a noninvasive, objective method for lymphedema detection. Detection of lymphedema based on subjective evaluations proved to have an unsatisfactory sensitivity. Less radical surgery showed objectively better results in QoL.

Cancer of the cervix is the second most common cancer in women worldwide and the fourth leading cause of cancer mortality in women. Early cervical cancer stage IB1 includes a broad range of disease from clinically undetectable microinvasive cancer to bulky tumours that infiltrated the entire cervix. This article reviews the literature about risk factors and surgical radicality and fertility-sparing surgery in early cervical cancer. The review evaluates selection criteria, preoperative management and the most frequent surgical procedures used for individually tailored surgery for cervical cancer.

There are several types of fertility saving procedures that can be done in patients with cervical cancer, which differ in terms of surgical approach and extent of paracervical resection. This review assesses oncological and pregnancy results after different procedures. The oncological results of vaginal radical trachelectomies (VRT) and abdominal radical trachelectomies (ART) are similar for tumours less than 2 cm in size, and are now considered safe surgical procedures. Oncological outcomes of VRT and ART in tumours larger than 2 cm are also identical, but the results cannot be considered satisfactory. Preliminary findings of less radical procedures (ie, deep cone and simple trachelectomy) in patients with tumours less than 2 cm, and negative sentinel and other pelvic lymph nodes, are comparable with the results of VRT and ART. Downstaging tumours larger than 2 cm by neoadjuvant chemotherapy is still an experimental procedure and will need multicentre cooperation to verify its oncological safety. Pregnancy results vary statistically with the different methods.

The role of neoadjuvant chemotherapy (NAC) in "bulky" and locally advanced cervical cancer has been of interest for the last 25 years, and in many countries, NAC has become the standard of care. In the present paper, we review our 10 years' experience with high-dose-density NAC in cervical cancer management in 141 women (CervNAC I protocol). High-dose-density neoadjuvant chemotherapy and radical surgery has resulted in high clinical response rates and seems to be feasible in the management of stage IB bulky cervical cancer. Neoadjuvant chemotherapy reduces tumor volume and positivity of lymph nodes and thus minimizes the need for postoperative radiotherapy or chemoradiotherapy. Tumor size reduction and node negativity allows less radical surgical procedures such as modified radical hysterectomy or nerve-sparing radical hysterectomy. Early and especially late toxicity of our high-dose density chemotherapy is acceptable. Neoadjuvant chemotherapy followed by surgery represents a valid alternative to primary chemoradiotherapy in young and sexually active patients. Five-year survival in patients who underwent surgery in our study was 80.6%.Currently, 3 papers with 3 approaches have been published on NAC before fertility-sparing surgery. One of the limitations of fertility-preserving surgery is deep stromal invasion and tumors larger than 2 cm. The idea underlying NAC is to reduce the size of the cervical tumor to preserve fertility. In the present paper, we also review our experience with high-dose-density NAC in fertility-sparing surgery in 15 women (LAP3-NAC protocol).

e17515Background: When pts with EOC relapse, their response to subsequent therapy is reduced. We hypothesized that autologous DCVAC could potentiate the antitumor response to ct and delay progressi...

5509Background: Most pts with EOC relapse after PDS and ct. Autologous DCVAC can present tumor antigens to elicit a durable immune response. We hypothesized that adding DCVAC to ct could improve ou...

Summary Cancer of the cervix is the second most common cancer in women worldwide, with about 500 000 new cases and 273 000 deaths reported annually. Ideal surgical management of cervical cancer should reduce early and late morbidity without compromising oncological disease control. Type of surgical radicality in early cervical cancer should be a consequence of exact preoperative and intraoperative assessments of risk factors. During the past 15 years, substantial progress has been made in understanding the neuroanatomy of the autonomic pelvic plexus. This progress has resulted in individually tailored surgery for cervical cancer. The concept of preservation of autonomic nerves during radical hysterectomy has become standard in many oncogynaecological centres. Nerve-sparing radical hysterectomy and individually tailored surgery, in comparison with standard radical hysterectomy, have led to a much improved quality of life. Since 2008, there has been a new classification of radical hysterectomy, which includes nerve-sparing techniques. 5-year survival in early stage cervical cancer is 88–97% and more than 50% of women are younger than 50 years of age. Thus, we must take into consideration the quality of life of these patients. In this Review, we focus on the neuroanatomy of the pelvis and the possible damage of autonomic nerves, and suggest options for the sparing of these nerves during surgery for cervical cancer.

An expert panel was formed for the 6th biennial International Sentinel Node Society to review the status of sentinel lymph node biopsy (SLNB) in gynecologic oncology. This paper presents the opinion of the experts who participated regarding indications for SLNB, technical considerations, and directions for future investigation.

Objective The purpose of this pilot study was to evaluate the feasibility and safety of a less radical surgery; laparoscopic lymphadenectomy followed by a simple vaginal hysterectomy in sentinel lymph node (SLN) negative early cervical cancer patients. Treatment-associated morbidity and oncological outcome were evaluated. Patients and methods From December 2000 to September 2007, 60 patients (50 squamous and 10 adenocarcinoma patients) in stages 3-IA1, 11-IA2 and 46-IB1 with median age of 44.6 years (range 33–64 years) were enrolled. Patients were selected based on favorable cervical tumors (IA1 with lymph-vascular space invasion [LVSI], IA2 and IB1 with tumor size less than 20 mm and less than half of stromal invasion). All patients underwent laparoscopic SLN identification using frozen section (FS). Negative SLN patients underwent complete pelvic laparoscopic lymphadenectomy and vaginal hysterectomy. FS positive patients underwent radical hysterectomy with low paraaortic lymphadenectomy. Results The average number of sentinel nodes per side was 1.4 with detection rate per side of 95%. The average number of removed nodes was 23.2. Five patients (8.3%) were SLN positive. There were two false negative FS results (both were micrometastases in SLN). Median follow-up was 47 months (range 12–92). There were no recurrences in 55 SLN negative patients and in 5 SLN positive patients. Conclusion Lymphatic mapping and SLN identification improved safety in less radical surgery in early stage cervical cancer. This preliminary study showed that it is both feasible and safe to reduce the radicality of parametrial resection for small tumor volume in SLN negative patients. Results also indicated that treatment-associated morbidity is low.

Introduction:Endometrial cancer incidence increases over the age of 65 and lymphadenectomy in these women is a morbid procedure. Sentinel lymph node (SLN) should avoid extensive lymphadenectomy in node negative patients. The aim of this prospective study is to determine the feasibility and usefulness of lymphatic mapping and SLN identification in the management of endometrial cancer.Methods:From January 2004 to December 2007 101 women with endometrial cancer participated in the study. We injected 99Tc hysteroscopically, peritumorally 2 hours before laparotomy in 24 women. We applied 99Tc and blue dye subserously after laparotomy and before adhesiolysis in 67 women. Ten patients with metastatic disease in ovary, omentum, peritoneum, and bulky nodes were excluded from analysis.Results:We detected SLN in 12 women (50%) in hysteroscopic group and in 49 women (73.1%) in subserous group. We identified 133 SLNs in 61 women. We found 20 SLNs (15.0%) in supraobturator region, 78 (58.6%) in external iliac area, 11 (8.3%) in paraaortal area, 13 (9.8%) on common iliac artery, 8 (6.0%) in medial part of lateral parametrium, and 3 (2.3%) in presacral area.Conclusions:Sentinel lymph node identification is a new strategy that can be used to examine nodal status with a high successful rate in breast, cervical, and vulvar cancer. Results in endometrial cancer are not as successful, however. In the future, it will be necessary to find optimal timing, the best route of application, and the "right" size of the 99mTc particles. Subserous application seems to be superior to hysteroscopic application.

Objective The purpose of prospective study is to determine incidence and distribution of pelvic lymph node(LN) involvement, sentinel lymph node(SLN) involvement and pathologic parametrial involvement(PI) in stage Ia2 and small Ib1 cervical cancer. PI is defined as positive parametrial LN or discontinuous malignant cells in parametrium. Methods After radical abdominal hysterectomy, 158 women patients were stratified into two groups based on tumour size: In Group 1 (91 women) tumours were less than 20 mm and less than half of stromal invasion. In Group 2 (67 women) tumours were between 20 and 30 mm and infiltration was not more than 2/3 of cervical stroma. Results In Group 1 positive SLN was detected in 11(12.1%) patients; of these, 3 (27.3%) had positive PI. In 80 women with negative SLN PI was not detected. In Group 2 positive SLN was detected in 14 (20.9%) patients: PI was found in four (28.6%) of these 14 patients. No PI was detected in 53 women with negative SLN. Conclusion No PI was observed in early cervical cancer if SLNs were negative. However, we found PI in 28.0% of women with positive SLN. Statistical analysis revealed that the results were highly significant. Based on our results, radical removal of parametrium in SLN negative patients is questionable.

We report five patients with early-stage cervical cancer who do not fulfill criteria of fertility-sparing surgery (tumor more than 2 cm in the biggest diameter or infiltrating more than half of stroma). Five patients received three cycles of dose density neoadjuvant chemotherapy (NAC) at a 10-day interval: cisplatin plus ifosfamide in squamous cell cancer or plus doxorubicin in adenocarcinoma with good tolerance. After NAC, they underwent laparoscopic pelvic lymphadenectomy and vaginal simple trachelectomy. Two patients had no residual tumor, two had only microscopic residual disease, and one had macroscopic residual disease. Two women became pregnant 5 and 8 months after surgery, one delivered in term healthy baby and one is now in the second trimester of pregnancy without any complications. NAC followed by fertility-sparing surgery seems to be feasible treatment for women with tumor bigger than 2 cm or infiltrated more than half of the stroma.

The number of patients given neoadjuvant chemotherapy (NAC) followed by fertility-sparing surgery in cervical cancer is still scarce. Only a few centres perform these procedures, and thus, such procedures remain largely in the experimental stage. Patients that do not fulfil the criteria for standard fertility-sparing procedure can be included in studies with NAC followed by fertility-sparing procedure. We must consider that both oncological and pregnancy outcomes are important. Patients with only microscopic disease after NAC are apparently the best candidates for fertility-sparing surgery. Current data are not sufficient to identify the optimal procedure after NAC [abdominal radical trachelectomy (ART) or vaginal radical trachelectomy (VRT) or simple trachelectomy]. Some evidence suggests that pregnancy outcome is better after simple trachelectomy as compared with VRT or ART. Long-term results regarding oncological outcome for this concept are still lacking. Adjuvant chemotherapy in patients with histopathological risk factors (lymphovascular space involvement (LVSI), macroscopic residual disease) would decrease a risk of recurrence.

Cervical cancer is one of the most common cancers in women worldwide. Because it often affects women of childbearing age (19–45 years), fertility-sparing surgery is an important issue. The article reviews current viable fertility-sparing options with a special focus on trachelectomy, including vaginal radical trachelectomy, abdominal radical trachelectomy and simple trachelectomy. Neoadjuvant chemotherapy is also discussed. Finally, the decision to proceed with fertility-sparing treatment should be a patient-driven process.

Regional lymph node status is the most important prognostic factor for survival in patients with early cervical cancer. Pelvic lymph node dissections are routinely performed as part of standard surgical treatment. Systematic pelvic lymphadenectomy is associated with short- and long-term morbidities. The chapter discusses single components of sentinel lymph node mapping (SLNM) and results related to the detection of sentinel lymph nodes. SLNM biopsy performed by an experienced team for small volume tumors (

Objectives The aim of the study was to compare an ultrasound-based prediction formula of Shepard, Hadlock, our new equation and equation of Nahum based on maternal characteristics. Study design Two groups of 125 (group A) and 130 (group B) healthy term pregnant women were sampled. Standard ultrasonographic measurements were performed and maternal characteristics recorded. A new birth weight equation was developed by multiple stepwise regression analysis from the group A data and then compared to the different birth weight prediction equations of Hadlock, Shepard and Nahum on group B. Results New prediction equation: log10 EFW = 0.64041 × BPD − 0.03257 × BPD2 + 0.00154 × AC × FL. Our new (Halaska) and Hadlock's ultrasound estimations are comparable. Both equations are superior to Shepard and Nahum's equations. The Nahum equation is comparable to the Shepard estimation. Halaska equation tends to have the highest overall accuracy, Hadlock's estimation predicts better fetuses over 4000 g, but this needs to be further validated. Conclusions The Halaska and Hadlock's estimations are comparable to one another; the Nahum equation is comparable to Shepard's and can be used as simple, inexpensive and approximative estimate.

Cervical glandular neoplasias (CGN) present a challenge for cervical cancer prevention due to their complex histopathology and difficulties in detecting preinvasive stages with current screening practices. Reports of human papillomavirus (HPV) prevalence and type‐distribution in CGN vary, providing uncertain evidence to support prophylactic vaccination and HPV screening. This study [108288/108290] assessed HPV prevalence and type‐distribution in women diagnosed with cervical adenocarcinoma in situ (AIS, N = 49), adenosquamous carcinoma (ASC, N = 104), and various adenocarcinoma subtypes (ADC, N = 461) from 17 European countries, using centralised pathology review and sensitive HPV testing. The highest HPV‐positivity rates were observed in AIS (93.9%), ASC (85.6%), and usual‐type ADC (90.4%), with much lower rates in rarer ADC subtypes (clear‐cell: 27.6%; serous: 30.4%; endometrioid: 12.9%; gastric‐type: 0%). The most common HPV types were restricted to HPV16/18/45, accounting for 98.3% of all HPV‐positive ADC. There were variations in HPV prevalence and ADC type‐distribution by country. Age at diagnosis differed by ADC subtype, with usual‐type diagnosed in younger women (median: 43 years) compared to rarer subtypes (medians between 57 and 66 years). Moreover, HPV‐positive ADC cases were younger than HPV‐negative ADC. The six years difference in median age for women with AIS compared to those with usual‐type ADC suggests that cytological screening for AIS may be suboptimal. Since the great majority of CGN are HPV16/18/45‐positive, the incorporation of prophylactic vaccination and HPV testing in cervical cancer screening are important prevention strategies. Our results suggest that special attention should be given to certain rarer ADC subtypes as most appear to be unrelated to HPV., What's new? Cervical cancer occurs in several different types; while Pap smears do a fine job of preventing one type, they fall short when it comes to another. Cervical adenocarcinoma (ADC) can look very different from case to case, and is more difficult to identify. This study characterized the HPV subtypes most commonly associated with ADC. Most commonly found were HPV 16, 18, and 45; thus, many of these cancers could be prevented by vaccination. The rarer subtypes of ADC had less of a link to HPV infection, and these cancers warrant special attention to develop better screening tools.

Because the biological spectrum of human papillomavirus (HPV) genotypes present in cervical cancer lesions varies according to the geographical region studied, and because little genotype information is available for Central and Eastern European countries, we studied the endemic HPV-genotype spectrum in cervical samples collected from women visiting gynaecological departments of selected hospitals in the Czech Republic. In a series of 389 samples, 171 (44.0%) were positive for HPV DNA using a consensus-primer polymerase chain reaction (PCR). Genotyping of the HPV PCR products was done using dot-blot hybridisation with type-specific oligonucleotide probes and thermocycle DNA sequencing. Twenty-two different HPV types were detected, HPV-16 being the most prevalent type irrespective of severity of the lesions (55.0%). Multiple HPV types were found in 16.4% of our HPV-DNA-positive samples. The prevalence of HPV infection was 23.0% in women with normal findings and 59.4% in patients with cervical neoplasia, and increased significantly with the severity of the disease: 52.9% in low-grade lesions, 58.0% in high-grade lesions, and 73.5% in cervical carcinomas (P for trend < .00001). In the sera of 191 subjects, 89 with normal findings and 102 with different forms of cervical neoplasia, the prevalence of HPV-specific IgG antibodies was tested by an enzyme-linked immunosorbent assay (ELISA) using virus-like particles (VLPs) of HPV-16, -18, and -33. Antibodies were significantly more prevalent in HPV-DNA-positive than in HPV-DNA-negative women and there was no association with age. In agreement with the results of HPV genotyping, antibodies reactive with HPV-16 VLPs were the most frequent and, moreover, their prevalence increased with the cervical lesion severity. About half of the subjects with smears in which either HPV-16 or HPV-33 DNA had been detected possessed antibodies reactive with homotypic VLPs. With HPV-18-DNA-positive subjects, however, fewer than 25% displayed homotypic antibodies. In general, subjects older than 30 years of age had antibodies reactive to HPV-specific VLPs more often than subjects younger than 30 years of age. In women with benign findings, the seropositivity to HPV-16, -18, and -33 VLPs increased with age, whereas in women with cervical neoplasia the seropositivity decreased with age.

Controversies exist about indication criteria for fertility-sparing surgery, optimal preoperative and intraoperative management, sentinel lymph node mapping, and intraoperative frozen section. We discuss optimal surgical radicality of fertility-sparing procedures that vary according to the radicality of the resection of paracervical tissue, surgical technique of lymphadenectomy, and technique to reconstruct the neocervix. Neoadjuvant chemotherapy incorporation into the management is one of the topics under current research. Follow-up of the patients needs to include long-term oncological results, fertility and pregnancy results, and quality of life.

Objectives To monitor fetal anemia during administration of chemotherapy to the fetus's mother. Study design Between 2007 and 2012 six patients with malignancy diagnosed during pregnancy were included in our prospective study. For evaluation of fetal anemia, peak systolic velocimetry (PSV) of the middle cerebral artery is considered the best method. The patients were repeatedly examined one day before and on the third day after the administration of chemotherapy. At least three measurements were performed and the highest value was used as appropriate. Multiples of the median (MoM) were calculated using the website http://www.perinatology.com/calculators/MCA.htm . When the MoM reached 1.29, moderate anemia was diagnosed. Results The women's average age was 30 years. The average gestational age at diagnosis was 20.7 weeks of pregnancy. Borderline fetal anemia was detected in only in one patient. After delivery newborns were examined by standard pediatric evaluation and blood count was provided. There was no evidence of any newborn anemia. Conclusions Chemotherapy administered during pregnancy is becoming more frequent due to increasing knowledge and data on such cases. Close monitoring of the fetus should be performed in specialized centers. For detection of chemotherapy-induced anemia, PSV measurement should be employed.

The prognosis of endometrial cancer (EC) is generally favorable, while lymph node status remains the most important prognostic factor. Sentinel lymph node mapping (SLNM) could help to find women in whom adjuvant therapy could be omitted. This review analyzes different techniques of injection and histopathologic elaboration of SLNM in EC. Results of studies on SLNM in ECs seem to be promising, but only a small series have been published so far. The studies are subdivided into three groups by the technique of injection (hysteroscopic, subserosal and cervical). Range of detection rate for SLNM varies from 45 to 100%. Hysteroscopic injection is not easy to learn; moreover, exact peritumoral injection in large tumors is often impossible. Subserosal administration of tracer is difficult during laparoscopic or robotic surgery. Cervical injection is quite a controversial technique because distribution of SLNs in ECs is different from cervical cancer; moreover, there is no large study using cervical injection with systematic pelvic and para-aortic lymphadenectomy.

BackgroundThe HPV prevalence and genotype distribution are important for the estimation of the impact of HPV-based cervical cancer screening and HPV vaccination on the incidence of diseases etiologically linked to HPVs. The HPV genotype distribution varies across different geographical regions. Therefore, we investigated the type-specific HPV prevalence in Czech women and men with anogenital diseases.MethodsWe analyzed 157 squamous cell carcinoma samples, 695 precancerous lesion samples and 64 cervical, vulvar and anal condylomata acuminate samples. HPV detection and typing were performed by PCR with GP5+/6+ primers, reverse line blot assay and sequencing.ResultsThirty different HPV genotypes were detected in our study, HPV 16 being the most prevalent type both in precancerous lesions (45%) and squamous cell carcinomas (59%). In benign lesions, HPV 6 (72%) was the most common type. Altogether, 61% of carcinoma samples and 43% of precancerous lesion samples contained HPV 16 and/or 18. The presence of HPV types related to the vaccinal ones (HPV 31, 45, 33, 52, 58) were detected in 16% of carcinoma samples and 18% of precancerous lesion samples. HPV 16 and/or 18 were present in 76% of cervical cancer samples, 33% of CIN1, 43% CIN2 and 71% of CIN3 samples. HPV types 6 and/or 11 were detected in 84% samples of condylomata acuminate samples.ConclusionsThe prevalence of vaccinal and related HPV types in patients with HPV-associated diseases in the Czech Republic is very high. We may assume that the implementation of routine vaccination against HPV would greatly reduce the burden of HPV-associated diseases in the Czech Republic.

Objective:Lymphedema is a severe postoperative complication in oncological surgery. Multifrequency bioelectrical impedance analysis (MFBIA) is a new method for early lymphedema detection. The objective was to establish the methodology of MFBIA for lower-limb lymphedema and to detect a lymphedema in patients undergoing cervical cancer surgery.Methods:From a population of 60 patients undergoing cervical cancer surgery, 39 underwent radical hysterectomy Wertheim III (RAD group), and 21 underwent conservative surgery (laparoscopic lymphadenectomy plus simple trachelectomy/simple hysterectomy - CONS group). A control group of 29 patients (CONTR group) was used to determine the SD of impedance at zero frequency (R0). Patients were examined before surgery and at 3 and 6 months after surgery by MFBIA and by measuring the circumference of the lower limbs.Results:No differences were found between the CONS and RAD groups on age, height, weight, and histopathologic type of tumor. However, the number of dissected lymph nodes differed significantly between the groups (17.3 in the CONS group vs 25.8 in the RAD group,P= 0.0012). The SD ofR0in the CONTR group was 36.0 and 39.0 for the right and the left leg, respectively. No difference in prevalence of lymphedema based on circumference method was found (35.9% in the RAD and 47.6% in the CONS groups, not statistically significant).Conclusions:No difference in the prevalence of lymphedema was found between the CONS and RAD groups. A methodology for MFBIA for the detection of lower-limb lymphedema was described.