Genetic variations in CYP2A6, CYP2E1, GSTM1, GSTT1 genes and the risk of Nasopharyngeal carcinoma in North African population.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a multifactorial malignancy associated with both genetic and environmental factors. Polymorphic deletions of the phase I and phase II genes involved in the detoxification of potential carcinogens may be a risk factor for nasopharyngeal carcinoma. In this study, we investigated the relationship between CYP2E1 (rs3813867), CYP2A6, GSTM1(rs1183423000) and GSTT1(rs1601993659) gene variations and NPC risk in North African countries with the highest incidence of NPC (Morocco, Algeria and Tunisia). and the evaluation of the potential use of these variants as potential biomarkers for NPC management. METHODS: A total of 600 NPC cases and 545 controls frequency-matched on ethnicity, sex, age and childhood household type, were recruited from three North African countries (Morocco, Algeria and Tunisia) and analysed. Genotyping of CYP2A6 and CYP2E1(rs3813867) was performed by polymerase chain reaction restriction (PCR)-fragment length polymorphism (RFLP) analysis and the GSTM1 (rs1183423000) and GSTT1(rs1601993659) genetic variations were evaluated using the PCR technique. RESULTS: The genotype distributions of CYP2E1(rs3813867), CYP2A6, GSTM1(rs1183423000) and GSTT1(rs1601993659) genotypes did not differ significantly among NPC cases and controls (p > 0.05). Furthermore, our data did not reveal any association with smoking and the studied variants, even when the samples were stratified by the duration period of smoking. CONCLUSION: In this large studied North African population, our findings suggest that the functional CYP2E1, CYP2A6, GSTM1 and GSTT1 variations did not influence NPC susceptibility.

Breast and cervical cancer screening practices in nine countries of Eastern Europe and Central Asia: A population-based survey.

BACKGROUND: Eastern Europe and Central Asia (EECA) countries have higher cervical and breast cancer mortality rates and later stage at diagnosis compared with the rest of WHO European Region. The aim was to explore current early detection practices including "dispensarization" for breast and cervix cancer in the region. METHODS: A questionnaire survey on early detection practices for breast and cervix cancer was sent to collaborators in 11 countries, differentiating services in the primary health setting, and population-based programs. Responses were received from Armenia, Belarus, Georgia, Kazakhstan, Kyrgyzstan, the Russian Federation (Arkhangelsk, Samara and Tomsk regions), Tajikistan, Ukraine, and Uzbekistan. RESULTS: All countries but Georgia, Kyrgyzstan, and the Russian Federation had opportunistic screening by clinical breast exam within "dispensarization" program. Mammography screening programs, commonly starting from age 40, were introduced or piloted in eight of nine countries, organized at national oncology or screening centres in Armenia, Belarus and Georgia, and within primary care in others. Six countries had "dispensarization" program for cervix cancer, mostly starting from the age 18, with smears stained either by Romanowsky-Giemsa alone (Belarus, Tajikistan and Ukraine), or alternating with Papanicolaou (Kazakhstan and the Russian Federation). In parallel, screening programs using Papanicolaou or HPV test were introduced in seven countries and organized within primary care. CONCLUSION: Our study documents that parallel screening systems for both breast and cervix cancers, as well as departures from evidence-based practices are widespread across the EECA. Within the framework of the WHO Initiatives, existing opportunistic screening should be replaced by population-based programs that include quality assurance and control.

Evolution of the joint International Atomic Energy Agency (IAEA), International Agency for Research on Cancer (IARC), and WHO cancer control assessments (imPACT Reviews).

Before 2005, cancer and other non-communicable diseases were not yet health and development agenda priorities. Since the 2005 World Health Assembly Resolution, which encouraged WHO, the International Agency for Research on Cancer (IARC), and the International Atomic Energy Agency (IAEA) to jointly work on cancer control, progress was achieved in low-income and middle-income countries on a small scale. Recently, rapid acceleration in UN collaboration and global cancer activities has focused attention in global cancer control. This Policy Review presents the evolution of the IAEA, IARC, and WHO joint advisory service to help countries assess needs and capacities throughout the comprehensive cancer control continuum. We also highlight examples per country, showcasing a snapshot of global good practices to foster an exchange of experiences for continuous improvement in the integrated mission of Programme of Action for Cancer Therapy (imPACT) reviews and follow-up support. The future success of progress in cancer control lies in the high-level political and financial commitments. Linking the improvement of cancer services to the strengthening of health systems after the COVID-19 pandemic will also ensure ongoing advances in the delivery of care across the cancer control continuum.

Rationale and Purpose: The FLUTE Study to Evaluate Fluorography Mass Screening for Tuberculosis and Other Diseases, as Conducted in Eastern Europe and Central Asia Countries.

In Belarus and several EECA countries, periodic population-based chest X-ray "fluorography programme" use as a mass screening tool for the diagnosis of tuberculosis (TB) has been used for decades. This mass screening has also often been justified for the early detection of lung cancer (LC), although no mortality benefits were demonstrated by screening with chest X-ray in international randomized trials. In Belarus, fluorography testing is mandatory every one to three years for all adults depending on age and the so-called "risk groups". The World Bank and WHO estimate that Belarus spends USD11 million annually on mass fluorography screening and advocate for more targeted screening approaches to increase diagnostic yield for TB and not to use it for screening for LC. The study is a retrospective review of medical records to assess the yield of fluorography to detect true cases of LC and/or TB in asymptomatic patients in two rural and two urban districts in Belarus for 2015-2017 with positive screening results for presumed of TB or LC. The study provided the rationale to implement the improved policy and practices regarding the role of fluorography in the early detection of LC and TB in Belarus and elsewhere.

Progress in reducing premature mortality from cancer and cardiovascular disease in the former Soviet Union, 2000-19.

BACKGROUND: A reduction in non-communicable diseases premature mortality by one-third by 2030 is one of the targets of the UN Sustainable Development Goals (SDG3.4). We examined the mortality profiles in the Newly Independent States of the former Soviet Union (NIS) and the European Union (EU) and assessed progress in reductions of premature mortality from cancer, as compared to cardiovascular disease (CVD). METHODS: We used WHO's Global Health Estimates and GLOBOCAN 2020 to examine current mortality profiles and computed the unconditional probabilities of dying at ages 30-70 from CVD and cancer for the years 2000-19 in both sexes, using a linear extrapolation of this trend to predict whether the target of a one-third reduction, as set in 2015, would be met in 2030. RESULTS: CVD was the main cause of premature death in the NIS (43%), followed by cancer (23%), inversely from the EU with 42% cancer and 24% CVD deaths. The NIS achieved major reductions in premature CVD mortality, although the probabilities of death in 2019 remained about five times higher in the NIS compared to the EU. For cancer, mortality reductions in most NIS were quite modest, other than large declines seen in Kazakhstan (44%) and Kyrgyzstan (30%), with both on course to meet the 2030 target. CONCLUSIONS: Limited progress in cancer control in the NIS calls for policy action both in terms of structural changes towards universal health coverage, and scaling up of national cancer control plans, including a shift from opportunistic to evidence-based early detection practices.

Translating Research to Action: The Development of a Pediatric Palliative Cancer Care Advocacy Tool in Eurasia.

PURPOSE: The Assessing Doctors' Attitudes on Palliative Treatment study was conducted in 11 Eurasian countries to assess physician knowledge of and structural barriers to integration of palliative care into pediatric oncology. After publication, regional collaborators identified the need to disseminate country-specific study results locally and provide policy recommendations to inform stakeholders. METHODS: The Assessing Doctors' Attitudes on Palliative Treatment report was developed with Eurasian and St Jude pediatric palliative care and oncology experts to summarize study findings and deliver country-level data to local stakeholders. In parallel, an assessment was developed to explore how regional collaborators intend to use the report to improve local advocacy and dissemination of research findings. The country report and assessment were translated to English, Russian, and Mongolian. RESULTS: Country-specific two-page reports display study findings on pediatric palliative care education, access to pediatric palliative care services, and barriers to and timing of integration with cancer care, alongside clinical and policy recommendations. These reports were distributed to collaborators in 11 countries. Assessment results (N = 30) demonstrated that regional collaborators planned to distribute the report to institutional and government stakeholders, aiming to increase access to pediatric palliative care services (77%), establish a community-based palliative care network (70%), and increase opportunities for specialization (70%). CONCLUSION: We describe the development of an evidence-based advocacy tool to inform local health and education policy in Eurasia. This summary report of study findings, translated to local languages and adapted to a broader audience, is currently used to advocate for greater access and quality of palliative care for children with cancer. This work may serve as the basis for future dissemination efforts of scientific research.

Cervical cancer testing among women aged 30-49 years in the WHO European Region.

BACKGROUND: Screening programs play an important role in a comprehensive strategy to prevent cervical cancer, a leading cause of death among women of reproductive age. Unfortunately, there is a dearth of information about rates of cervical cancer testing, particularly in Eastern Europe and Central Asia where levels of cervical cancer are among the highest in the WHO European Region. The purpose of this article is to report on the lifetime prevalence of cervical cancer testing among females aged 30-49 years from across the WHO European region, and to describe high-level geographic and socioeconomic differences. METHODS: We used data from the European Health Information Survey and the WHO STEPwise approach to Surveillance survey to calculate the proportions of women who were tested for cervical cancer. RESULTS: The percentage of tested women ranged from 11.7% in Azerbaijan to 98.4% in Finland, with the lowest percentages observed in Azerbaijan, Tajikistan and Uzbekistan. Testing was lower in Eastern Europe (compared to Western Europe), among low-income countries and among women with lower levels of education. CONCLUSION: Effective cervical cancer screening programs are one part of a larger strategy, which must also include national scale-up of human papilloma virus vaccination, screening and treatment.

Comparison of breast cancer and cervical cancer stage distributions in ten newly independent states of the former Soviet Union: a population-based study.

BACKGROUND: Screening for breast cancer and cervical cancer in the newly independent states of the former Soviet Union is largely opportunistic, and countries in the region have among the highest cervical cancer incidence in the WHO European Region. We aimed to compare the stage-specific distributions and changes over time in breast cancer and cervical cancer incidence in the newly independent states of the former Soviet Union. METHODS: We collected breast cancer and cervical cancer incidence data from official statistics from Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Republic of Moldova, Russian Federation, Ukraine, and Uzbekistan for the years 2008-17 by tumour, node, metastasis (TNM) stage, and by age where population-based cancer registry data were available. We used log-linear regression to quantify the changes over time in age-standardised rates. FINDINGS: During the period 2013-17, more than 50% of breast cancer cases across the analysed countries, and more than 75% of breast cancer cases in Belarus, Kazakhstan, and Ukraine, were registered at stages I-II. The proportion of stage I breast cancer cases was highest in the screening age group (50-69 years) compared with other ages in Moldova and the Russian registries, but was highest in those aged 15-49 years in Georgia and Ukraine. Breast cancer stage-specific incidence rates increased over time, most prominently for stage I cancers. For cervical cancer, the proportions of cancers diagnosed at a late stage (stages III and IV) were high, particularly in Moldova and Armenia (>50%). The proportion of stage I cervical cancer cases decreased with age in all countries, whereas the proportions of late stage cancers increased with age. Stage-specific incidence rates of cervical cancer generally increased over the period 2008-17. INTERPRETATION: Our results suggest modest progress in early detection of breast cancer in the newly independent states of the former Soviet Union. The high proportions of early-stage disease in the absence of mammography screening (eg, in Belarus) provide a benchmark for what is achievable with rapid diagnosis. For cervical cancer, there is a need to tackle the high burden and unfavourable stage-specific changes over time in the region. A radical shift in national policies away from opportunistic screening toward organised, population-based, quality-assured human papillomavirus vaccination and screening programmes is urgently needed. FUNDING: Union for International Cancer Control, WHO Regional Office for Europe, and Ministry of Health of Ukraine.

Conceptual Framework to Guide Early Diagnosis Programs for Symptomatic Cancer as Part of Global Cancer Control.

Diagnosing cancer earlier can enable timely treatment and optimize outcomes. Worldwide, national cancer control plans increasingly encompass early diagnosis programs for symptomatic patients, commonly comprising awareness campaigns to encourage prompt help-seeking for possible cancer symptoms and health system policies to support prompt diagnostic assessment and access to treatment. By their nature, early diagnosis programs involve complex public health interventions aiming to address unmet health needs by acting on patient, clinical, and system factors. However, there is uncertainty regarding how to optimize the design and evaluation of such interventions. We propose that decisions about early diagnosis programs should consider four interrelated components: first, the conduct of a needs assessment (based on cancer-site-specific statistics) to identify the cancers that may benefit most from early diagnosis in the target population; second, the consideration of symptom epidemiology to inform prioritization within an intervention; third, the identification of factors influencing prompt help-seeking at individual and system level to support the design and evaluation of interventions; and finally, the evaluation of factors influencing the health systems' capacity to promptly assess patients. This conceptual framework can be used by public health researchers and policy makers to identify the greatest evidence gaps and guide the design and evaluation of local early diagnosis programs as part of broader cancer control strategies.

Улучшение показателей по неинфекционным заболеваниям: барьеры и возможности систем здравоохранения: страновая оценка – Туркменистан

В Туркменистане высокий уровень преждевременной смертности от неинфекционных заболеваний (НИЗ). Вероятность преждевременной смерти (в возрасте 30–69 лет) от одного из основных НИЗ составляет 26,9%. Значительные социально-экономические последствия этой ситуации для развития страны обусловливают необходимость срочного укрепления потенциала системы здравоохранения для эффективного реагирования на растущее бремя НИЗ. В Туркменистане в этом направлении уже достигнут значительный прогресс, например, в решении проблемы распространенности поведенческих факторов риска и в модернизации инфраструктуры медицинских учреждений, имеется также политическая приверженность, однако показатели по контролю НИЗ все еще нуждаются в улучшении.В настоящем докладе приведен обзор проблем и возможностей системы здравоохранения Туркменистана применительно к наращиванию основных услуг профилактики, ранней диагностики и лечения НИЗ. Также освещены примеры передовой практики борьбы против табака. По результатам оценки сформулированы рекомендации для дальнейших действий.

Better noncommunicable disease outcomes: challenges and opportunities for health systems: Turkmenistan country assessment

Premature mortality due to noncommunicable diseases (NCDs) is high in Turkmenistan. The probability of dying prematurely (between the ages of 30 and 70 years) from one of the major NCDs is 26.9%. This has significant socioeconomic consequences for the development of the country and calls for immediate strengthening of the health system to respond to the growing burden of NCDs. Despite political commitment and significant progress, for example in reducing the prevalence of behavioural risk factors and in upgrading the health facility infrastructure, the outcomes of NCDs could still be improved.This report reviews the challenges and opportunities of the health system in Turkmenistan for scaling up core services for the prevention, early diagnosis and management of NCDs. The report also provides examples of good practice in tobacco control. Policy recommendations are made for further action, based on the assessment.

Joint effect of smoking and NQO1 C609T polymorphism on undifferentiated nasopharyngeal carcinoma risk in a North African population.

BACKGROUND: Nasopharyngeal carcinoma (NPC) has a higher incidence in North Africa than in most parts of the world. In addition to environmental factors such as Epstein-Barr virus infection and chemical carcinogen exposure, genetic susceptibility has been reported to play a key role in the development of NPC. NAD(P)H: quinone oxidoreductase 1 is a cytosolic enzyme that protects cells from oxidative damage. A C to T transition at position 609 in the NQO1 gene (OMIM: 125860) has been shown to alter the enzymatic activity of the enzyme and has been associated with increased risk to several cancers. This study investigates for the first time the effect of this polymorphism on NPC susceptibility in a North African population. METHODS: The NQO1 C609T polymorphism was genotyped using PCR-RFLP in 392 NPC cases and 365 controls from Morocco, Algeria, and Tunisia. RESULTS: The allele frequencies and distributions of genotypes did not differ between cases and controls (p > 0.05). When stratifying according to smoking status, we observed two-fold higher NPC risk in ever-smokers carrying the CT or TT genotype. Multiple logistic regression analysis revealed that there was a significant interaction between T allele and smoking status (OR = 1.95, 95% CI = 1.20-3.19; interaction p = 0.007). CONCLUSION: In this North African population, the functional NQO1 polymorphism was associated with a significantly higher risk of NPC among smokers and did not affect the risk among nonsmokers.

Prevalence of mucosal and cutaneous human papillomavirus in Moroccan breast cancer.

BACKGROUND: Due to recent technical improvements and some encouraging new results, there has been a resurgence of interest in the possibility that a substantial proportion of breast cancers (BCs) may be caused by viral infections, including Human papillomavirus (HPV). The aim of this study was to determine the prevalence of mucosal and cutaneous HPV in tumours from Moroccan BC patients. MATERIALS AND METHODS: Frozen tumours from 76 BC cases and 12 controls were evaluated for the presence of 62 HPV-types using highly sensitive assays that combine multiplex polymerase chain reaction and bead-based Luminex technology. RESULTS: HPV DNA was found in 25.0% of BC tumours and only 8.3% of controls. Beta and gamma HPV types were found in 10.5% and 6.6% of BC tumours, respectively. High-risk mucosal types HPV16 and 18 were not detected in the subjects, but other probable/possible high-risk or high-risk -HPV types (HPV51, 52, 58, 59, and 66) were found in 5.3% of BC tumours. Statistical analysis showed no significant difference between, controls, BC cases and the inflammatory status (p > 0.05). CONCLUSION: HPV DNA was found 3 times as frequently in the BC tumours as in the controls. However, this difference requires confirmation in a larger sample.

Better noncommunicable disease outcomes: challenges and opportunities for health systems: Serbia country assessment

Despite positive trends, life expectancy in Serbia is well below the average for the WHO European Region.The probability of dying from one of the main noncommunicable diseases (NCDs) between the ages of30 and 69 years is 20%. This has significant socioeconomic consequences for the development of thecountry and calls for an immediate strengthening of the health system to respond to the growing burdenof NCDs. Despite significant progress and political commitment in Serbia, the outcomes of NCDs couldstill be improved. This report reviews the challenges and opportunities facing the health system in Serbiain scaling up core services for the prevention, early diagnosis and management of NCDs. The report alsoprovides examples of good practice in care. Policy recommendations are made for further action, based onthe assessment.

No association between TGF-ß1 polymorphisms and risk of nasopharyngeal carcinoma in a large North African case-control study.

BACKGROUND: Genetic susceptibility plays a key role in the development of nasopharyngeal carcinoma (NPC) and in fact the disease presents with an unusually high incidence in certain regions of the world like North Africa. We investigated the association between polymorphism of the Transforming growth factor-ß1 (TGF-ß1) and risk of NPC in North Africa. TGF-ß1 is a multifunctional cytokine that acts as both a tumor suppressor and a stimulator of cancer development; it has been shown to influence risk of numerous other carcinomas including lung, breast and prostate cancer. METHODS: TGF-ß1 polymorphisms C-509T and T869C were studied in a large North African sample of 384 NPC cases and 361 controls, matched for age, sex and urban or rural residence in childhood. Genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No association was observed between individual single nucleotide polymorphisms or their haplotypes and NPC susceptibility (for TGF-ß1 C-509T: OR = 0.74; 95 % CI 0.46 - 1.18; for TGF-ß1 T869C: OR = 0.86; 95 % CI 0.56 - 1.31), even when the samples were stratified by age, gender and TNM stage. CONCLUSION: Contrary to what has been observed in Asian samples, in our North African sample, the TGF-ß1 C-509T and T869C polymorphisms did not substantially influence NPC susceptibility.

Prevalence of papillomaviruses, polyomaviruses, and herpesviruses in triple-negative and inflammatory breast tumors from algeria compared with other types of breast cancer tumors.

BACKGROUND: The possible role of viruses in breast cancer etiology remains an unresolved question. We hypothesized that if some viruses are involved, it may be in a subgroup of breast cancers only. Epidemiological arguments drove our interest in breast cancer subgroups that are more frequent in Africa, namely inflammatory breast cancer (IBC) and triple-negative breast cancer. We tested whether viral prevalence was significantly higher in these subgroups. MATERIALS AND METHODS: One hundred fifty-five paraffin-embedded malignant breast tumors were randomly selected at the pathology laboratory of the University Hospital of Annaba (Algeria) to include one third of IBC and two thirds of non-IBC. They were tested for the presence of DNA from 61 viral agents (46 human papillomaviruses, 10 polyomaviruses, and 5 herpesviruses) using type-specific multiplex genotyping assays, which combine multiplex PCR and bead-based Luminex technology. RESULTS: Viral DNA was found in 22 (17.9%) of 123 tumors. The most prevalent viruses were EBV1 and HPV16. IBC tumors carried significantly more viruses (any type) than non-IBC tumors (30% vs. 13%, p<0.04). Similarly, triple-negative tumors displayed higher virus-positivity than non-triple-negative tumors (44% vs. 14%, p<0.009). CONCLUSIONS: Our results suggest an association between the presence of viral DNA and aggressive breast cancer phenotypes (IBC, triple-negative). While preliminary, they underline the importance of focusing on subgroups when studying viral etiology in breast cancer. Further studies on viruses in breast cancer should be conducted in much larger samples to confirm these initial findings.