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Cervical cancer prevention in Japan, which had nearly halted due to misinformation, is now recovering through HPV vaccination and screening efforts. While significant progress has been made, much work remains, yet the recent improvements are highly encouraging.

Objectives To provide an overview of costs associated with the treatment of breast cancer-related lymphoedema (BCRL) and its possible sequelae, borne by patients or by society. Data sources According to the PRISMA guideline, a systematic literature search was carried out in four electronic databases: PubMed, Web of Science, Cochrane Clinical Trials and EMBASE. Searches were performed on October 1, 2018. Study selection Eligibility criteria: (1) expenses of adults (age > 18 years), (2) concerning patients with BCRL, (3) overview of (in)direct costs associated with BCRL, (4) expenses in which at least one type of conservative treatment modality for lymphoedema is included and/or costs for hospital admissions due to infections. Reviews and meta-analyses were excluded. Data extraction After assessing the risk of bias and level of evidence, quantitative data on (in)direct costs for BCRL treatment during a well-mentioned timeframe were extracted. Data synthesis Eight studies were included. Three studies reported on patient-borne costs related to BCRL. Mean direct costs per year borne by patients ranged between USD$2306 and USD$2574. Indirect costs borne by patients ranged between USD$3325 and USD$5545 per year. Five studies estimated society-borne costs related to BCRL from claims data, billing prices and providers’ services during 12 to 24 months of follow-up. Mean direct treatment costs after 1 year of decongestive lymphatic therapy (DLT) ranged between €799 (= USD$1126.60) and USD$3165. Conclusion This systematic review revealed that BCRL imposes a substantial economic burden on patients and society. However, more standardized high-quality health economic analyses among this field are required. Recent economic analyses related to BCRL treatment in Europe, Asia, Africa and South America are lacking. Worldwide, further scrutiny of the economic impact of DLT for BCRL in clinical settings is needed. Clinical trial registration number The review makes part of a double-blind, multi-center, randomized controlled trial (EFforT-BCRL trial), which is registered in clinicaltrials.gov (NCT02609724). CME reference S58689, EudraCT Number 2015-004822-33.

The article by Gentile et al [...]

► HPV-16, -18 and -45 account for approximately 90% of ADC worldwide. ► ADC is difficult to detect through current cervical screening methods. ► Prophylactic HPV vaccination may have a significant impact on the prevention of ADC. Although cervical screening has led to a significant decline of invasive cervical cancer (ICC) in developed countries, it remains the third leading cause of cancer in women worldwide. While the majority of the decline in ICC can be attributed to a reduction in squamous cell carcinoma (SCC), the incidence of cervical adenocarcinoma (ADC), absolute and relative to SCC, has been rising steadily, especially in younger women. This paper examines oncogenic human papillomavirus (HPV) infections, the risk of developing cervical ADC and its prognosis. It analyzes differences between ADC and SCC and considers current and future methods for prevention. PubMed, publicly available websites and congress abstracts were searched for data and literature. HPV-16, -18 and -45 account for approximately 90% of ADC worldwide. Typically, α-7 genotypes, which include HPV-18 and -45, are more commonly associated with ADC than SCC. The difficulty in detecting ADC through screening as well as changing sexual habits and increased HPV transmission may account for its increase; an increase in SCC may not be observed because of improved detection of pre-malignant SCC compared with pre-malignant ADC. HPV testing shows promise for screening women ≥30years of age, but α-7 genotypes may be underrepresented in precancerous lesions. Clinical trial data indicate that current vaccines have high efficacy against HPV-16/18-related cervical intraepithelial neoplasia. Moreover, these vaccines also demonstrate a different level of protection beyond the HPV vaccine types, therefore increasing the overall vaccine efficacy. Such broad coverage could translate into a considerable reduction in the incidence of ADC. Prophylactic HPV vaccination may have a significant impact on the prevention of ADC and may significantly impact future strategies for primary and secondary prevention of cervical cancer.

Purpose Breast cancer survivors face a high risk of developing breast cancer-related lymphedema (BCRL). Besides physical symptoms such as swelling, BCRL can have a psychosocial impact and lead to problems in daily functioning. Understanding contributing variables to problems in functioning yields possibilities to improve treatment modalities and consequently patients’ quality of life. Therefore, the aim of this study was to explore the association between patient-, lymphedema-, and cancer treatment-related variables with problems in functioning in patients with BCRL. Methods A cross-sectional study was performed in 185 patients with BCRL. Problems in daily functioning (dependent variable) were evaluated with the Lymph-ICF-UL questionnaire. Following independent variables were analysed by bi-variate and multivariable analyses, including a stepwise regression analysis: patient - related variables (age, BMI, physical activity level, education), lymphedema - related variables (excessive arm volume, duration of lymphedema, total pitting score, presence of hand edema, hardness of the tissue, lymphedema stage), and cancer treatment - related variables (type of surgery, surgery at the dominant side, radiotherapy, chemotherapy, hormone therapy, immunotherapy, TNM-classification). Results The Lymph-ICF-UL mean total score was 38% (± 21), representing a moderate amount of problems in general functioning. Multivariable regression analyses revealed that lower physical activity level and lower age are contributing factors to more problems in daily functioning. Stepwise regression analysis indicated that up to 8% of the variance in problems in functioning could be explained by physical activity level and age of patients with BCRL. Conclusion Especially patients with low physical activity level and younger patients experience more problems in functioning. For the determination of certain causal interactions, future longitudinal studies including other independent variables that might explain a higher amount of problems in functioning in this population, are warranted. Trial registration The study makes part of a double-blind, multi-center, randomized controlled trial (EFforT-BCRL trial), which is registered in clinicaltrials.gov (NCT02609724). CME reference S58689, EudraCT Number 2015-004822-33.

Host cell DNA methylation analysis in urine provides promising triage markers for women diagnosed with a high-risk (HR) human papillomavirus (HPV) infection. In this study, we have investigated a panel of six host cell methylation markers ( GHSR, SST, ZIC1, ASCL1, LHX8, ST6GALNAC5 ) in cervicovaginal secretions collected within the first part of the urine void (FVU) from a referral population. Cytology, histology, and HPV DNA genotyping results on paired FVU and cervical samples were available. Urinary median methylation levels from HR-HPV (n = 93) positive women were found to increase for all markers with severity of underlying disease. Significantly elevated levels were observed for GHSR and LHX8 in relation to high-grade cervical intraepithelial neoplasia (CIN2 +; n = 33), with area under de curve values of 0.80 (95% Confidence Interval (CI) 0.59–0.92) and 0.76 (95% CI 0.58–0.89), respectively. These findings are the first to support the assertion that methylation analysis of host cell genes is feasible in FVU and holds promise as molecular, triage strategy to discern low- from high-grade cervical disease in HR-HPV positive women. Molecular testing on FVU may serve to increase cervical cancer screening attendance in hard-to-reach populations whilst reducing loss to follow-up and await further optimization and validation studies.

PurposeDecongestive lymphatic treatment (DLT) is still the gold standard for treatment of breast cancer-related lymphedema (BCRL). With up to 17% of the patients treated for breast cancer developing BCRL, this morbidity imposes a tremendous financial burden for patients and society. Knowledge about this economic burden related to BCRL and its conservative treatment in a European setting is lacking. The aim of this prospective, longitudinal cohort study was to estimate the direct healthcare costs related to BCRL and its treatment in a European setting.MethodsPatients with BCRL were treated with DLT consisting of an intensive treatment phase of 3 weeks, followed by a maintenance treatment phase of 6 months. Additionally, the follow-up period comprised 6 months. During these 3 weeks and 12 months, all direct costs associated with the treatment of BCRL and its sequelae were documented through billing prices and a self-developed questionnaire which was administered after the intensive treatment phase, and subsequently 3-monthly during the entire period.ResultsA total of 194 patients were enrolled in this study. Of these, 17% (n = 32) showed lymphedema stage I, 56% (n = 109) had lymphedema stage IIa, and 27% (n = 53) had lymphedema stage IIb. Total direct healthcare costs per patient were €2248.93 on average during the entire period of 3 weeks of intensive treatments and 12 months of maintenance decongestive therapy. Within these mean direct costs, €1803.35 (80%) was accounted for statutory health insurances, and €445.58 (20%) was out-of-pocket expenses for patients.ConclusionThis study is one of the first standardized high-quality health economic analyses of BRCL treatment in Europe. The present study indicates that the price tag of BCRL treatment in Belgium is high not only for the health insurance but also for the patientsClinical trial registration numberThe study makes part of a double-blind, multi-center, randomized controlled trial (EFforT-BCRL trial), which is registered in clinicaltrials.gov (NCT02609724). CME reference S58689, EudraCT Number 2015-004822-33.

Infrared thermography technology has improved dramatically in recent years and is gaining renewed interest in the medical community for applications in skin tissue identification applications. However, there is still a need for an optimized measurement setup and protocol to obtain the most appropriate images for decision making and further processing. Nowadays, various cooling methods, measurement setups and cameras are used, but a general optimized cooling and measurement protocol has not been defined yet. In this literature review, an overview of different measurement setups, thermal excitation techniques and infrared camera equipment is given. It is possible to improve thermal images of skin lesions by choosing an appropriate cooling method, infrared camera and optimized measurement setup.

•We compared 9vHPV vaccine immunogenicity in women 27–45 vs 16–26 years of age.•9vHPV vaccine elicited noninferior anti-HPV antibodies in mid-adult vs young women.•9vHPV vaccine was well tolerated in both groups of women.•Data support bridging of 9vHPV vaccine efficacy from young to mid-adult women. Efficacy of the nine-valent human papillomavirus (9vHPV; HPV types 6/11/16/18/31/33/45/52/58) vaccine was demonstrated in a phase 3 study in women 16–26 years of age. We present a phase 3 immunogenicity and safety study of the 9vHPV vaccine in women 27–45 versus 16–26 years of age. This international, open-label study (NCT03158220) was conducted in women 16–45 years of age. Participants (16–26 years, n = 570 and 27–45 years, n = 642) received a three-dose 9vHPV vaccination regimen (day 1, month 2, month 6). Month 7 geometric mean titers (GMTs) and seroconversion percentages to anti-HPV 6/11/16/18/31/33/45/52/58 were assessed. Participants were followed for safety throughout the study. At month 7, anti-HPV 6/11/16/18/31/33/45/52/58 GMTs in women 27–45 years were compared to those in women 16–26 years of age. The primary hypothesis of non-inferiority of anti-HPV 16/18/31/33/45/52/58 GMTs in older versus younger women was met. The lower bound of the GMT ratio 95% confidence interval (27–45 years to 16–26 years) was 0.60–0.67 depending on HPV type, exceeding the non-inferiority margin of 0.5 for all HPV types. Month 7 seroconversion percentages in women 27–45 years of age were >99% for all HPV types. Injection-site and vaccine-related systemic adverse events (AEs) were observed in 87.5% and 25.1% of women 16–26 years, and 85.2% and 24.1% of women 27–45 years of age, respectively; no vaccine-related serious AEs were reported and no deaths occurred during the study. The 9vHPV vaccine elicited non-inferior anti-HPV GMTs in women 27–45 years compared with women 16–26 years of age for HPV 16/18/31/33/45/52/58. The vaccine was generally well tolerated with a similar AE profile across the age groups. These data support bridging 9vHPV vaccine efficacy findings in women 16–26 years to women 27–45 years of age. Clinical trial registration NCT03158220.

Background Interventions to reach women who do not participate regularly in screening may reduce the risk of cervical cancer. Self-collection of a vaginal specimen has been shown to increase participation. The relative clinical accuracy of human papillomavirus (HPV) testing on first-void urine (with Colli-Pee) and on vaginal self-samples versus on cervical clinician-collected samples is being investigated in the VALHUDES trial. The current study assesses attitudes and experiences regarding self-sampling among women enrolled in VALHUDES. Methods Questionnaires from 515 women (age 25–64 years [ N  = 498]; < 25 [ N  = 10], age ≥ 65 [ N  = 3], enrolled between December 2017 - January 2020) referred to colposcopy because of previous cervical abnormalities and enrolled in VALHUDES (NCT03064087) were analysed. Results Of the 515 participants, nearly all women confirmed that self-sampling may help in reaching under-screened women (93%). Nevertheless, 44% of the participants stated before starting collection that a clinician-collected sample is more effective than a self-collected sample. After self-sampling, the large majority of women (> 95%) declared that instructions for self-collection were clear, that collection was easy, and that they were confident about having performed the procedure correctly, for both urine and vaginal collection. However, a proportion of women found self-sampling unpleasant (9.5% [49/515] for urine collection; 18.6% [96/515] and 15.5% [80/515] for vaginal sampling with cotton swabs or plastic brushes, respectively). For their next screening round, 57% would prefer self-sampling whereas 41% opted for collection by a clinician. Among women preferring self-sampling, 53% would choose for urine collection, 38% for vaginal self-collection and 9% had no preference. Age did not modify preferences. Conclusion We conclude that both urine and vaginal self-sampling are well accepted by women, with a preference for urine sampling. Although the large majority of women are confident in their ability to perform self-sampling, four to five over ten women preferred specimen collection by a clinician. Trial registration The study VALHUDES was registered in ClinicalTrials.gov (identifier: NCT03064087 ).