and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEWThe GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs).FINDINGS In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCEThe results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

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DNA methylation is the main epigenetic event for gene silencing and is associated with carcinogenesis. In this meta-analysis, we evaluated the association between the methylation of the promoter regions of APC, CADM1, CCNA1, CDH1, DAPK, FHIT, HIC1, MAL, MGMT, hMLH1, P16, PAX1, RAR-β, and RASSF1 genes and the risk of cervical cancer development and progression. Overall, 194 eligible studies were identified assessing the associations of promoter methylation status of aforementioned genes with low- and high-grade squamous intraepithelial lesions (LSIL and HSIL) and cervical cancer development. The majority of studies were conducted on Caucasian and Asian populations, whereas rare studies were available on the African population. Promoter methylation frequencies were shown to be significantly higher in LSIL and HSIL cervical cancer cases as compared to control specimens for CADM1, CCNA1, CDH1, DAPK1, FHIT, MAL, P16, PAX1, RAR-β, and RASSF1 genes. A moderate association was found between HIC promoter methylation, whereas APC, MGMT, and hMLH1 promoter methylation was not correlated with cervical cancer development. Promoter methylation could be considered as a noninvasive biomarker for early cervical lesions, making them highly promising targets for a personalized therapeutic approach.

Background: Genetic diversity in Plasmodium falciparum poses a major threat to malaria control and elimination interventions. Characterization of the genetic diversity of P. falciparum strains can be used to assess intensity of parasite transmission and identify potential deficiencies in malaria control programmes, which provides vital information to evaluating malaria elimination efforts. This study investigated the P. falciparum genetic diversity and genotype multiplicity of infection in parasite isolates from cases with uncomplicated P. falciparum malaria in Southwest Ethiopia. Methods: A total of 80 P. falciparum microscopy and qPCR positive blood samples were collected from study participants aged 6 months to 60 years, who visited the health facilities during study evaluating the efficacy of artemetherlumefantrine from September-December, 2017. Polymorphic regions of the msp-1 and msp-2 were genotyped by nested polymerase chain reactions (nPCR) followed by gel electrophoresis for fragment analysis. Results: Of 80 qPCR-positive samples analysed for polymorphisms on msp-1 and msp-2 genes, the efficiency of msp-1 and msp-2 gene amplification reactions with family-specific primers were 95% and 98.8%, respectively. Allelic variation of 90% (72/80) for msp-1 and 86.2% (69/80) for msp-2 were observed. K1 was the predominant msp-1 allelic family detected in 20.8% (15/72) of the samples followed by MAD20 and RO33. Within msp-2, allelic family FC27 showed a higher frequency (26.1%) compared to IC/3D7 (15.9%). Ten different alleles were observed in msp-1 with 6 alleles for K1, 3 alleles for MAD20 and 1 allele for RO33. In msp-2, 19 individual alleles were detected with 10 alleles for FC27 and 9 alleles for 3D7. Eighty percent (80%) of isolates had multiple genotypes and the overall mean multiplicity of infection was 3.2 (95% CI 2.87-3.46). The heterozygosity indices were 0.43 and 0.85 for msp-1 and msp-2, respectively. There was no significant association between multiplicity of infection and age or parasite density. Conclusions: The study revealed high levels of genetic diversity and mixed-strain infections of P. falciparum populations in Chewaka district, Ethiopia, suggesting that both endemicity level and malaria transmission remain high and that strengthened control efforts are needed in Ethiopia.

Background The efficacy of artemether-lumefantrine (AL) for treatment of uncomplicated Plasmodium falciparum malaria in south-western Ethiopia is poorly documented. Regular monitoring of drug efficacy is an important tool for supporting national treatment policies and practice. This study investigated the therapeutic efficacy of AL for the treatment of P. falciparum malaria in Ethiopia. Methods The study was a one-arm, prospective, evaluation of the clinical and parasitological, responses to directly observed treatment with AL among participants 6 months and older with uncomplicated P. falciparum malaria. Real-time polymerase chain reaction (PCR) and nested PCR reaction methods were used to quantify and genotype P. falciparum . A modified protocol based on the World Health Organization 2009 recommendations for the surveillance of anti-malarial drug efficacy was used for the study with primary outcomes, clinical and parasitological cure rates at day-28. Secondary outcomes assessed included patterns of fever and parasite clearance. Cure rate on day-28 was assessed by intention to treat (ITT) and per protocol (PP) analysis. Parasite genotyping was also performed at baseline and at the time of recurrence of parasitaemia to differentiate between recrudescence and new infection. Results Of the 80 study participants enrolled, 75 completed the follow-up at day-28 with ACPR. For per protocol (PP) analysis, PCR-uncorrected and-corrected cure rate of AL among the study participants was 94.7% (95% CI 87.1–98.5) and 96% (95% CI 88.8–99.2), respectively. For intention to treat (ITT) analysis, the cure rate was 90% (95% CI 88.8–99.2). Based on Kaplan–Meier survival estimate, the cumulative incidence of failure rate of AL was 3.8% (95% CI 1.3–11.4). Only three participants 3.8% (95% CI 0.8–10.6) of the 80 enrolled participants were found to be positive on day-3. The day three-positive participants were followed up to day 28 and did not correspond to treatment failures observed during follow-up. Only 7.5% (6/80) of the participants were gametocyte-positive on enrollment and gametocytaemia was absent on day-2 following treatment with AL. Conclusions The therapeutic efficacy of AL is considerably high (above 90%). AL remained highly efficacious in the treatment of uncomplicated malaria in the study area resulted in rapid fever and parasite clearance as well as low gametocyte carriage rates despite the use of this combination for more than 15 years.