Targeted RNA next generation sequencing analysis of cervical smears can predict the presence of hrHPV-induced cervical lesions

Contains fulltext : 251134.pdf (Publisher’s version ) (Open Access

Regulation Of The Interurban Coach Services In Brazil

Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Short-term surgical complications after radical hysterectomy—A nationwide cohort study

Introduction: Centralization has, among other aspects, been argued to have an impact on quality of care in terms of surgical morbidity. Next, monitoring quality of care is essential in identifying areas of improvement. This nationwide cohort study was conducted to determine the rate of short-term surgical complications and to evaluate its possible predictors in women with early-stage cervical cancer. Material and methods: Women diagnosed with early-stage cervical cancer, 2009 FIGO stages IB1 and IIA1, between 2015 and 2017 who underwent radical hysterectomy with pelvic lymphadenectomy in 1 of the 9 specialized medical centers in the Netherlands, were identified from the Netherlands Cancer Registry. Women were excluded if primary treatment consisted of hysterectomy without parametrial dissection or radical trachelectomy. Women in whom radical hysterectomy was aborted during the procedure, were also

Validation of the FAM19A4/mir124-2 DNA methylation test for both lavage- and brush-based self-samples to detect cervical (pre)cancer in HPV-positive women

Objectives DNA methylation analysis of cancer-related genes is a promising tool for HPV-positive women to identify those with cervical (pre)cancer (CIN3+) in need of treatment. However, clinical performance of methylation markers can be influenced by the sample type utilized. We describe a multiplex quantitative methylation-specific PCR that targets FAM19A4 and mir124-2 loci, to detect CIN3+ using both HPV-positive lavage- and brush self-samples. Methods We determined methylation thresholds for clinical classification using HPV-positive training sets comprising lavage self-samples of 182 women (including 40 with CIN3+) and brush self-samples of 224 women (including 61 with CIN3+). Subsequently, independent HPV-positive validation sets of 389 lavage self-samples (including 78 with CIN3+), and 254 brush self-samples (including 72 with CIN3+) were tested using the preset thresholds. Furthermore, the clinical performance of combined methylation analysis and HPV16/18 genotyping was determined. Results Training set analysis revealed similar FAM19A4 and mir124-2 thresholds for both self-sample types to yield highest CIN3+ sensitivity at 70% specificity. Validation set analysis resulted in a CIN3+ sensitivity of 70.5% (95%CI: 60.4-80.6) at a specificity of 67.8% (95%CI: 62.7-73.0) for lavage self-samples, and a CIN3+ sensitivity of 69.4% (95%CI: 58.8-80.1) at a 76.4% (95%CI: 70.2-82.6) specificity for brush self-samples. In combination with HPV16/18 genotyping, CIN3+ sensitivity and specificity were 88.5% (95%CI: 81.4-95.6) and 46.0% (95%CI: 40.4-51.5) for lavage self-samples, and 84.7% (95%CI: 76.4-93.0) and 54.9% (95%CI: 47.7-62.2) for brush self-samples. Conclusions FAM19A4/mir124-2 methylation analysis performs equally well in HPV-positive la

Implementation of HPV Self-sampling in Cervical Screening Programs Increases Participation Rates: A Literature Review

IntroductionCervical cancer screening primarily with high risk human papillomavirus (hr-HPV) proved to be more sensitive, in detecting CIN grade 2 or worse (CIN2 +), than the traditional cervical cytology. Primary hr-HPV detection opened up the possibility for vaginal self-sampling, as hr-HPV detection is easy to perform on a vaginal self-sample and showed to be reliable. The aim of this review is to explore the role of HPV self-sampling as a strategy to increase the participation rate in cervical screening programs. MethodsPubMed search on self-sampling HPV; including articles published within last 10 years; Meta-analyse, Randomized Controlled Trial, Review or Systematic Review.ResultsThe literature shows that HPV vaginal self-sampling is feasible, highly acceptable and above all has a high diagnostic accuracy in detecting HPV and CIN2 +. Furthermore, HPV self-sampling followed by Pap smear triage in hr-HPV positive women is cost-effective. Additionally offering mailed self-sample kits, ideally in combination with education, has been proven to improve participation and subsequently CIN2+ detection. ConclusionImplementation of HPV self-sampling in cervical screening programs offers opportunities to reach under screened women, not only in high-income countries, but especially in low- and medium-income countries and among ethnic minority women

Para-aortic lymphadenectomy in advanced stage cervical cancer, a protocol for comparing safety, feasibility and diagnostic accuracy of surgical staging versus PET-CT; PALDISC trial

Contains fulltext : 190733.pdf (publisher's version ) (Open Access)Background: Currently, a PET-CT is used to assess the need for extended field radiotherapy of para-aortic lymph nodes (PALN) in International Federation of Gynaecology and Obstetrics (FIGO) stage IB2, IIA2-IVA (locally advanced stage) cervical cancer. A small study established a sensitivity and specificity estimate for PALN metastases of 50% (95% CI; 7-93%) and 83% (95% CI; 52-98%), respectively. Surgical staging of PALN may lead to a higher diagnostic accuracy. However, surgical staging of para-aortic lymph nodes in locally advanced stage cervical cancer is not common practice. Therefore, a phase 2 randomised controlled trial is needed to assess its safety and feasibility. Methods/design: In addition to standard imaging (MRI or CT scan) with PET-CT, 30 adult women with FIGO stage IB2, IIA2-IVA cervical cancer will be randomised to receive either surgical staging or usual PET-CT staging. Administering extended field radiotherapy will be based on lymphadenectomy results for the intervention group and on the PET-CT results for the control group. Follow-up visits at 0, 3, 6, 9 and 12 months will assess health-related quality of life and progression-free survival.Primary safety and feasibility outcomes of surgical staging will be assessed by calculating means with 95% confidence intervals for duration of surgery, number of complications, blood loss, nodal yield after para-aortic lymphadenectomy and treatment delay due to surgical staging. Secondary patient-centred outcomes on quality of life and first year survival will be documented and compared between the two groups. Estimates of sensitivity, specificity and negative and positive predictive values of MRI, PET-CT and surgical staging will be presented with 95% CI.. All analysis will be performed according to the intention to treat principle. Discussion: This study will assess safety and feasibility, expressed as the number and severity of complications, effect on quality of life and the treatment delay due to surgically staging para-aortic lymph nodes in locally advanced cervical cancer. It will provide insight in the diagnostic accuracy of the PET-CT and detection rate of missed (micro)metastases due to surgical staging. This information will be used to assess the necessity for a phase 3 study on the diagnostic accuracy of the PET-CT and surgical staging. If a phase 3 study is deemed necessary, current data can be used for sample size calculation of such a phase 3 study. Trial registration: Nederlands Trial Register/Dutch Trial Registry (www.trialregister.nl), NTR4922. Registered on 24 November 2014

[Use of oral contraceptives and increased risk of cervical cancer]

Contains fulltext : 69205.pdf (publisher's version ) (Closed access)A recently published meta-analysis and a large cohort study showed independently that use of oral contraceptives (OC) leads to an increased relative risk (RR) of cervical cancer. This RR increased with the duration of OC use and was 1.90 after 5 years or more (95% CI: 1.69-2.13). The increased RR decreased after cessation of OC use and was normal again Io years later. Longstanding OC use enhances human papillomavirus (HPV) transcription and decreases HPV clearance, resulting in more frequent persistence of HPV, an increase of cervical intraepithelial neoplasia, and an increased RR of cervical cancer. The increase in cervical cancer by OC is, however, associated with a fully compensatory decrease in the incidence of other malignancies, in particular ovarian cancer and endometrial cancer. Based on these findings, there are no reasons to discourage the use of OC by women in the Netherlands

Pretreatment Retroperitoneal Para-aortic Lymph Node Staging in Advanced Cervical Cancer: A Review

Item does not contain fulltextOBJECTIVE: The aims of this study were to evaluate the safety and impact of pretreatment surgical para-aortic lymph node staging (PALNS) in advanced cervical cancer (International Federation of Gynecology and Obstetrics stage IB2-IVA) and to evaluate the preoperative imaging of PALNs. METHODS: We searched in PubMed and the Cochrane Library to identify data investigating the role of surgical PALNS. Selection criteria included English-language and advanced-stage cervical cancer (International Federation of Gynecology and Obstetrics stage IB2-IVA) articles. RESULTS: Twenty-two articles were included. Para-aortic lymph node metastases were present in 18% (range, 8%-42%) of all patients with cervical cancer stage IB to IVA. The proportions of positive para-aortic nodes on histological analysis with suspicious para-aortic nodes on imaging (positive predictive value) were 20% to 66%, 0% to 27%, 86% to 100%, and 50% to 75% for computed tomographic (CT) scan, magnetic resonance imaging (MRI) scan, positron emission tomography (PET), and PET-CT, respectively. The negative predictive values of the imaging techniques were 53% to 92% for CT scan, 75% to 91% for MRI, 87% to 94% for PET, and 83% to 92% for PET-CT. The proportions of histologically proven PALN metastasis with normal findings on imaging were 9% to 35% for CT scan and MRI, 4% to 11% for PET, and 6% to 15% for PET-CT. The mean complication rate of PALNS is 9%, with a range of 4% to 24%, with lymphocysts being the most common complication. CONCLUSIONS: Pretreatment surgical PALN dissection or sampling is feasible, with low complication rates and short delay in starting treatment. Pretreatment PET or PET-CT is the most accurate imaging method in detecting PALN metastases but has limitations detecting microscopic tumor volumes. Even with normal findings on PET-CT, PALN metastases are present in 4% to 15% of patients. Positive PALNs in stage IB2 to IVA cervical cancer will lead to modification of treatment and may lead to better overall and disease-free survival

Barriers to follow-up of abnormal Papanicolaou smears among women in Leon, Nicaragua.

Item does not contain fulltextCervical cancer screening programmes only succeed when the coverage, screening, treatment and follow-up of any abnormal results are of high quality. This study investigates the screening coverage and the quality of the follow-up of cervical cancer screening of women in Leon, Nicaragua, as well as the factors affecting coverage and barriers to follow-up. Two hundred and thirty-four sexually active women attending a public health centre (54), a public health post (63), or the gynaecology department of the public HEODRA hospital (117), were invited to answer an orally administered questionnaire. The screening coverage of cervical cancer was calculated and the follow-up after finding an abnormal screening result was assessed. The coverage was 60.6% (95% confidence interval 54.4-66.8%). One hundred and sixty-eight women (87%) were informed about the results. Eighteen (10, 7%) of the women who were informed about the results, were advised to have follow-up and 12 (66, 7%) of them did. Barriers to follow-up were financial constraints, pregnancy, postponement and absence of instruments/electricity. This study shows that the screening coverage and cytology services are adequate, but that there is insufficient follow-up and/or treatment after an abnormal screening result. In order to achieve a lower incidence and mortality of cervical cancer, follow-up and treatment after an abnormal screening result need to be improved. A visual inspection with acetic acid may be an attractive alternative.1 januari 201