Impact of model calibration on cost-effectiveness analysis of cervical cancer prevention

Markov chain models are commonly used to simulate the natural history of human papillomavirus infection and subsequent cervical lesions with the aim of predicting future benefits of health interventions. Developing and calibrating these models entails making a number of critical decisions that will influence the ability of the model to reflect real conditions and predict future situations. Accuracy of selected inputs and calibration procedures are two of the crucial aspects for model performance and understanding their influence is essential, especially when involves policy decisions. The aim of this work is to assess the health and economic impact on cervical cancer prevention strategies currently under discussion according to the most common methods of model calibration combined with different accuracy degree of initial inputs. Model results show large differences on the goodness of fit and cost-effectiveness outcomes depending on the calibration approach used, and these variations may affect health policy decisions. Our findings strengthen the importance of obtaining good calibrated probability matrices to get reliable health and cost outcomes, and are directly generalizable to any cost-effectiveness analysis based on Markov chain models

Genome-wide association study identifies multiple susceptibility loci for diffuse large B-cell lymphoma

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 x 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 x 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 x 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 x 10(-13) and 3.63 x 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL

Eficiencia y sostenibilidad del cribado de cáncer de cérvix en el Sistema Nacional de Salud

Cérvix del útero; Cáncer; CribadoCèrvix uterí; Càncer; CribratgeCervix Uteri; Cancer; ScreeningInforme que proposa estratègies de cribratge de càncer de coll uterí eficients i econòmicament sostenibles a Espanya amb protocols específics per a tots els grups d'edat i segons els escenaris de vacunació davant del virus del papil·loma humà (VPH).Informe que propone estrategias de cribado de cáncer de cérvix eficientes y económicamente sostenibles en España con protocolos específicos para todos los grupos de edad y según los escenarios de vacunación frente al virus del papiloma humano (VPH

Genetic Susceptibility to Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the West and is an incurable malignancy. No firmly established evidence exists for environmental risk factors in the etiology of CLL. However, CLL is estimated to have one of the highest familial risks for a hematologic malignancy; this along with other evidence strongly supports an inherited genetic component. In the past 5 years, genome-wide association studies (GWAS) have provided the foundation for new avenues in the investigation of pathogenesis of this disease with 22 susceptibility loci currently identified. We review here the advances made in identifying these loci, the potential to translate these findings into clinical practice, and future directions needed to advance our understanding of the genetic susceptibility of CLL. (C) 2013 Elsevier Inc. All rights reserved

Association of antiretroviral therapy with high-risk human papillomavirus, cervical intraepithelial neoplasia, and invasive cervical cancer in women living with HIV: a systematic review and meta-analysis

Background The interactions between antiretroviral therapy (ART) and high-risk human papillomavirus (HPV) and cervical lesions in women living with HIV are poorly understood. We reviewed the association of ART with these outcomes. Methods We did a systematic review and meta-analysis by searching MEDLINE and Embase databases for cross-sectional or cohort studies published in English between Jan 1, 1996, and May 6, 2017, which reported the association of ART with prevalence of high-risk HPV or prevalence, incidence, progression, or regression of histological or cytological cervical abnormalities, or incidence of invasive cervcal cancer. Studies were eligible if they reported the association of combination ART or highly active ART use with the following outcomes: high-risk HPV prevalence; squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) prevalence, incidence, progression, or regression; and invasive cervical cancer incidence among women living with HIV. We did random-effects meta-analyses to estimate summary statistics. We examined heterogeneity with the I (2) statistic. This review is registered on the PROSPERO database at the Centre of Reviews and Dissemination, University of York, York, UK (registration number CRD42016039546). Findings We identified 31 studies of the association of ART with prevalence of high-risk HPV (6537 women living with HIV) and high grade cervical lesions (HSIL-CIN2+; 9288 women living with HIV). Women living with HIV on ART had lower prevalence of high-risk HPV than did those not on ART (adjusted odds ratio [aOR] 0.83, 95% CI 0.70-0.99; I-2= 51%, adjusted for CD4 cell count and ART duration), and there was some evidence of association with HSIL-CIN2+ (0.65, 0 .40-1.06; I-2=30%). 17 studies reported the association of ART with longitudinal cervical lesion outcomes. ART was associated with a decreased risk of HSIL-CIN2+ incidence among 1830 women living with HIV (0 .59, 0.40-0.87; I-2=0%), SIL progression among 6212 women living with HIV (adjusted hazard ratio [aHR] 0. 64, 95% CI 0.54-0.75; I-2= 18%), and increased likelihood of SIL or CIN regression among 5261 women living with HIV (1.54, 1.30-1.82; I-2= 0%). In three studies among 15 846 women living with HIV, ART was associated with a reduction in invasive cervical cancer incidence (crude HR 0.40, 95% CI 0.18-0.87, I-2= 33%). Interpretation Early ART initiation and sustained adherence is likely to reduce incidence and progression of SIL and CIN and ultimately incidence of invasive cervical cancer. Future cohort studies should aim to confirm this possible effect. Copyright (c) The Author(s). Published by Elsevier Ltd

Poor Cervical Cancer Screening Attendance and False Negatives. A Call for Organized Screening

Objective: The objective of this study was to describe prior negative screening history and symptoms around the time of diagnosis of incident cervical cancer (CC) cases diagnosed between 2000 and 2010 within the Asturias public health system. Methods Records from 374 women diagnosed with CC between 2000 and 2010 from all public hospitals in Asturias were retrieved. Clinical information, FIGO stage and all previous cytological data were extracted from clinical and histopathological records. Proportional differences were assessed using chi-square tests. Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Inter-observer agreement in cytology was checked by comparing concordance values using k-statistics. Results No prior screening history was recorded in 60.7% of CC cases and its absence increased with age and advanced stage. Advanced stage (e.g., >= II) at diagnosis was associated with age (> 50 years) and adenocarcinoma (ADC) compared to younger women and those with a squamous cell carcinoma (SCC). False negative smears were identified in 27.1% of women with CC (ADC 52.6% vs. SCC 16.2%, p< 0.05). Conclusions Absence of prior screening history was common among CC cases. Organized actions to reduce "under screening"and the use of highly sensitive HPV-based tests could be useful strategies in reducing the burden of CC in Asturias

Worldwide use of HPV self-sampling for cervical cancer screening

An increasing body of evidence supports the validity of self-sampling as an alternative to clinician collection for primary Human Papillomavirus (HPV) screening. Self-sampling effectively reaches underscreened women and can be a powerful strategy in low- and high-resource settings for all target ages. This work aims to summarize the current use of HPV self-sampling worldwide. It is part of a larger project that describes cervical cancer screening programmes and produces standardized coverage estimates worldwide. A systematic review of the literature and official documents supplemented with a formal World Health Organisation country consultation was conducted. Findings show that the global use of HPV self-sampling is still limited. Only 17 (12%) of countries with identified screening programs recommend its use, nine as the primary collection method, and eight to reach underscreened populations. We identified 10 pilots evaluating the switch to self-sampling in well-established screening programs. The global use of self-sampling is likely to increase in the coming years. COVID-19's pandemic has prompted efforts to accelerate HPV self-sampling introduction globally, and it is now considered a key element in scaling up screening coverage. The information generated by the early experiences can be beneficial for decision-making in both new and existing programs

Global availability of data on HPV genotypedistribution in cervical, vulvar and vaginal disease and genotype-specific prevalence and incidence of HPV infection in females

Background: Country-level HPV genotyping data may be sought by decision-makers to gauge the genotype-specific burden of HPV-related diseases in their jurisdiction and assess the potential impact of HPV vaccines. We investigated, by country, the availability of published literature on HPV genotypes in cervical, vaginal and vulvar cancers and intraepithelial neoplasms (CINs, VaINs and VINs) and on prevalence and incidence of genital HPV infections among women without clinically manifest disease. Findings: Primary sources of publications were the PubMed/Medline and EMBASE databases. Original studies or meta-analyses published from 2000, covering genotypes 16 and 18 and at least one of genotypes 31/33/45/52/58, were included. Key exclusion criteria were language not English, cervical lesions not histologically confirmed (cytology only), special populations (e.g., immunocompromised) and, for cervical studies, small population (<50). A total of 727 studies reporting HPV genotype-specific data were identified: 366 for cervical cancers and CINs, 43 for vulvar or vaginal cancers and VINs/VaINs, and 395 and 21 for infection prevalence and incidence, respectively, in general female population samples. A large proportion of studies originated from a small set of countries. Cervical cancer/CIN typing data was scarce for several regions with the highest cervical cancer burden, including Eastern, Middle and Western Africa, Central America, South-East Asia, South Asia, and Eastern Europe. Data for vulvar/vaginal disease was limited outside of Europe and North America. Conclusions: Although a large body of published HPV genotype-specific data is currently available, data gaps exist for genotype-specific infection incidence and several world regions with the highest cervical cancer burden

Scoping Review On Cancer Prevention In Immigrants Living In Spain

[spa] Fundamentos: La prevención secundaria del cáncer de mama, cuello uterino y colon se realiza mediante cribado. España en la última década ha presentado una importante oleada de migración, es conocido que los inmigrantes presentan más desigualdades de acceso a los servicios de salud respecto a la población autóctona. El objetivo es identificar lagunas en la investigación sobre la prevención del cáncer en los inmigrantes residentes en España. Métodos: Se realizó una revisión bibliográfica. La fuente de información fueron las bases de datos Medline/ Pubmed y MEDES-MEDicina en español y el período de búsqueda entre 1998 y 2012. Se utilizaron tres filtros temáticos: relacionados con cáncer, inmigración y geografía. Los criterios de inclusión fueron estudios de prevención del cáncer y la salud de la población inmigrante procedente de Latinoamérica, África, Asia y originario de Europa del Este y desarrollados en España. Se elaboró un protocolo ad hoc de recogida de información. Resultados: Se incluyeron 5 estudios de los 237 revisados. Los estudios incluidos fueron escritos en inglés. Cuatro de los cinco estudios utilizaron como variable de inmigración el país de origen. Un 80% de los estudios realizaron encuestas transversales. Los principales resultados fueron que la población inmigrante realizaba menos detección precoz de cáncer de mama y de cuello uterino. Por otro lado las trabajadoras sexuales presentaron porcentajes de positividad para tipos de alto riesgo oncogénicos del virus del papiloma humano. Conclusiones: Existe escasa bibliografía referente a la prevención del cáncer mediante programas de cribado en la población inmigrante. Es importante evaluar los circuitos de cribado y sus registros para mejorarlos y así poder ejecutar programas para identificar mejor los grupos poblacionales más vulnerables.[eng] Background: Secondary prevention of breast cancer, cervix and colon is performed by screening. Spain in the last decade has presented a major wave of migration; it is known that immigrants have more inequalities in access to health services compared to the native population. The objective is to review the published studies and identify gaps in research on cancer prevention among immigrants living in Spain. Methods: We have conducted a scoping review. The sources of information were the databases Medline (Pubmed) and MEDES - medicine in Spanish (1998-2012). We used three thematic filters: concerning to Cancer, immigration and geographic. Inclusion criteria were studies of cancer prevention and health of immigrants from Latin America, Africa, Asia and Eastern Europe and developed in Spain. We developed an ad hoc data collection protocol. Results: We included five studies of 237 reviewed. The included studies are written in English and published in journals with impact factor. Most studies have used country of origin as the immigration variable 80 % of the studies conducted cross-sectional surveys. Immigrant population had a lower participation of early detection of breast and cervical cancer. Women reported to be sex workers were more likely to be human papillomavirus positive for high risk types. Conclusion: There is little information on cancer prevention through screening programs in the immigrant population. It is important to evaluate and improve the screening circuits and registries to implement programs to better identify the most vulnerable population groups