David Forman
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Publication
Journal: CA - A Cancer Journal for Clinicians
April/21/2011
Abstract
The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.
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Journal: International Journal of Cancer
February/25/2015
Abstract
Estimates of the worldwide incidence and mortality from 27 major cancers and for all cancers combined for 2012 are now available in the GLOBOCAN series of the International Agency for Research on Cancer. We review the sources and methods used in compiling the national cancer incidence and mortality estimates, and briefly describe the key results by cancer site and in 20 large "areas" of the world. Overall, there were 14.1 million new cases and 8.2 million deaths in 2012. The most commonly diagnosed cancers were lung (1.82 million), breast (1.67 million), and colorectal (1.36 million); the most common causes of cancer death were lung cancer (1.6 million deaths), liver cancer (745,000 deaths), and stomach cancer (723,000 deaths).
Publication
Journal: International Journal of Cancer
May/2/2011
Abstract
Estimates of the worldwide incidence and mortality from 27 cancers in 2008 have been prepared for 182 countries as part of the GLOBOCAN series published by the International Agency for Research on Cancer. In this article, we present the results for 20 world regions, summarizing the global patterns for the eight most common cancers. Overall, an estimated 12.7 million new cancer cases and 7.6 million cancer deaths occur in 2008, with 56% of new cancer cases and 63% of the cancer deaths occurring in the less developed regions of the world. The most commonly diagnosed cancers worldwide are lung (1.61 million, 12.7% of the total), breast (1.38 million, 10.9%) and colorectal cancers (1.23 million, 9.7%). The most common causes of cancer death are lung cancer (1.38 million, 18.2% of the total), stomach cancer (738,000 deaths, 9.7%) and liver cancer (696,000 deaths, 9.2%). Cancer is neither rare anywhere in the world, nor mainly confined to high-resource countries. Striking differences in the patterns of cancer from region to region are observed.
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Journal: The Lancet Oncology
August/14/2012
Abstract
BACKGROUND
Infections with certain viruses, bacteria, and parasites have been identified as strong risk factors for specific cancers. An update of their respective contribution to the global burden of cancer is warranted.
METHODS
We considered infectious agents classified as carcinogenic to humans by the International Agency for Research on Cancer. We calculated their population attributable fraction worldwide and in eight geographical regions, using statistics on estimated cancer incidence in 2008. When associations were very strong, calculations were based on the prevalence of infection in cancer cases rather than in the general population. Estimates of infection prevalence and relative risk were extracted from published data.
RESULTS
Of the 12·7 million new cancer cases that occurred in 2008, the population attributable fraction (PAF) for infectious agents was 16·1%, meaning that around 2 million new cancer cases were attributable to infections. This fraction was higher in less developed countries (22·9%) than in more developed countries (7·4%), and varied from 3·3% in Australia and New Zealand to 32·7% in sub-Saharan Africa. Helicobacter pylori, hepatitis B and C viruses, and human papillomaviruses were responsible for 1·9 million cases, mainly gastric, liver, and cervix uteri cancers. In women, cervix uteri cancer accounted for about half of the infection-related burden of cancer; in men, liver and gastric cancers accounted for more than 80%. Around 30% of infection-attributable cases occur in people younger than 50 years.
CONCLUSIONS
Around 2 million cancer cases each year are caused by infectious agents. Application of existing public health methods for infection prevention, such as vaccination, safer injection practice, or antimicrobial treatments, could have a substantial effect on the future burden of cancer worldwide.
BACKGROUND
Fondation Innovations en Infectiologie (FINOVI) and the Bill & Melinda Gates Foundation (BMGF).
Publication
Journal: The Lancet Oncology
October/10/2012
Abstract
BACKGROUND
Cancer is set to become a major cause of morbidity and mortality in the coming decades in every region of the world. We aimed to assess the changing patterns of cancer according to varying levels of human development.
METHODS
We used four levels (low, medium, high, and very high) of the Human Development Index (HDI), a composite indicator of life expectancy, education, and gross domestic product per head, to highlight cancer-specific patterns in 2008 (on the basis of GLOBOCAN estimates) and trends 1988-2002 (on the basis of the series in Cancer Incidence in Five Continents), and to produce future burden scenario for 2030 according to projected demographic changes alone and trends-based changes for selected cancer sites.
RESULTS
In the highest HDI regions in 2008, cancers of the female breast, lung, colorectum, and prostate accounted for half the overall cancer burden, whereas in medium HDI regions, cancers of the oesophagus, stomach, and liver were also common, and together these seven cancers comprised 62% of the total cancer burden in medium to very high HDI areas. In low HDI regions, cervical cancer was more common than both breast cancer and liver cancer. Nine different cancers were the most commonly diagnosed in men across 184 countries, with cancers of the prostate, lung, and liver being the most common. Breast and cervical cancers were the most common in women. In medium HDI and high HDI settings, decreases in cervical and stomach cancer incidence seem to be offset by increases in the incidence of cancers of the female breast, prostate, and colorectum. If the cancer-specific and sex-specific trends estimated in this study continue, we predict an increase in the incidence of all-cancer cases from 12·7 million new cases in 2008 to 22·2 million by 2030.
CONCLUSIONS
Our findings suggest that rapid societal and economic transition in many countries means that any reductions in infection-related cancers are offset by an increasing number of new cases that are more associated with reproductive, dietary, and hormonal factors. Targeted interventions can lead to a decrease in the projected increases in cancer burden through effective primary prevention strategies, alongside the implementation of vaccination, early detection, and effective treatment programmes.
BACKGROUND
None.
Publication
Journal: Vaccine
May/6/2013
Abstract
The worldwide prevalence of infection with human papillomavirus (HPV) in women without cervical abnormalities is 11-12% with higher rates in sub-Saharan Africa (24%), Eastern Europe (21%) and Latin America (16%). The two most prevalent types are HPV16 (3.2%) and HPV18 (1.4%). Prevalence increases in women with cervical pathology in proportion to the severity of the lesion reaching around 90% in women with grade 3 cervical intraepithelial neoplasia and invasive cancer. HPV infection has been identified as a definite human carcinogen for six types of cancer: cervix, penis, vulva, vagina, anus and oropharynx (including the base of the tongue and tonsils). Estimates of the incidence of these cancers for 2008 due to HPV infection have been calculated globally. Of the estimated 12.7 million cancers occurring in 2008, 610,000 (Population Attributable Fraction [PAF]=4.8%) could be attributed to HPV infection. The PAF varies substantially by geographic region and level of development, increasing to 6.9% in less developed regions of the world, 14.2% in sub-Saharan Africa and 15.5% in India, compared with 2.1% in more developed regions, 1.6% in Northern America and 1.2% in Australia/New Zealand. Cervical cancer, for which the PAF is estimated to be 100%, accounted for 530,000 (86.9%) of the HPV attributable cases with the other five cancer types accounting for the residual 80,000 cancers. Cervical cancer is the third most common female malignancy and shows a strong association with level of development, rates being at least four-fold higher in countries defined within the low ranking of the Human Development Index (HDI) compared with those in the very high category. Similar disparities are evident for 5-year survival-less than 20% in low HDI countries and more than 65% in very high countries. There are five-fold or greater differences in incidence between world regions. In those countries for which reliable temporal data are available, incidence rates appear to be consistently declining by approximately 2% per annum. There is, however, a lack of information from low HDI countries where screening is less likely to have been successfully implemented. Estimates of the projected incidence of cervical cancer in 2030, based solely on demographic factors, indicate a 2% increase in the global burden of cervical cancer, i.e., in balance with the current rate of decline. Due to the relative small numbers involved, it is difficult to discern temporal trends for the other cancers associated with HPV infection. Genital warts represent a sexually transmitted benign condition caused by HPV infection, especially HPV6 and HPV11. Reliable surveillance figures are difficult to obtain but data from developed countries indicate an annual incidence of 0.1 to 0.2% with a peak occurring at teenage and young adult ages. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.
Publication
Journal: Gut
April/19/2015
Abstract
OBJECTIVE
The two major histological types of oesophageal cancer--adenocarcinoma (AC) and squamous cell carcinoma (SCC)--are known to differ greatly in terms of risk factors and epidemiology. To date, global incidence estimates for individual subtypes are still lacking. This study for the first time quantified the global burden of oesophageal cancer by histological subtype.
METHODS
Where available, data from Cancer Incidence in Five Continents Vol. X (CI5X) were used to compute, age-specific, sex-specific and country-specific proportions of AC and SCC. Nine regional averages were computed for countries without CI5X data. The proportions were then applied to all oesophageal cancer cases from GLOBOCAN 2012 and age-standardised incidence rates calculated for both histological types.
RESULTS
Worldwide, an estimated 398,000 SCCs and 52,000 ACs of the oesophagus occurred in 2012, translating to incidence rates of 5.2 and 0.7 per 100,000, respectively. Although SCCs were most common in South-Eastern and Central Asia (79% of the total global SCC cases), the highest burden of AC was found in Northern and Western Europe, Northern America and Oceania (46% of the total global AC cases). Men had substantially higher incidence than women, especially in the case of AC (male to female ratio AC: 4.4; SCC: 2.7).
CONCLUSIONS
These first global estimates of oesophageal cancer incidence by histology suggested a high concentration of AC in high-income countries with men being at much greater risk. This quantification of incidence will aid health policy makers to plan appropriate cancer control measures in the future.
Publication
Journal: The Lancet
December/9/2012
Abstract
BACKGROUND
Country comparisons that consider the effect of fatal and non-fatal disease outcomes are needed for health-care planning. We calculated disability-adjusted life-years (DALYs) to estimate the global burden of cancer in 2008.
METHODS
We used population-based data, mostly from cancer registries, for incidence, mortality, life expectancy, disease duration, and age at onset and death, alongside proportions of patients who were treated and living with sequelae or regarded as cured, to calculate years of life lost (YLLs) and years lived with disability (YLDs). We used YLLs and YLDs to derive DALYs for 27 sites of cancers in 184 countries in 12 world regions. Estimates were grouped into four categories based on a country's human development index (HDI). We applied zero discounting and uniform age weighting, and age-standardised rates to enable cross-country and regional comparisons.
RESULTS
Worldwide, an estimated 169·3 million years of healthy life were lost because of cancer in 2008. Colorectal, lung, breast, and prostate cancers were the main contributors to total DALYs in most world regions and caused 18-50% of the total cancer burden. We estimated an additional burden of 25% from infection-related cancers (liver, stomach, and cervical) in sub-Saharan Africa, and 27% in eastern Asia. We noted substantial global differences in the cancer profile of DALYs by country and region; however, YLLs were the most important component of DALYs in all countries and for all cancers, and contributed to more than 90% of the total burden. Nonetheless, low-resource settings had consistently higher YLLs (as a proportion of total DALYs) than did high-resource settings.
CONCLUSIONS
Age-adjusted DALYs lost from cancer are substantial, irrespective of world region. The consistently larger proportions of YLLs in low HDI than in high HDI countries indicate substantial inequalities in prognosis after diagnosis, related to degree of human development. Therefore, radical improvement in cancer care is needed in low-resource countries.
BACKGROUND
Dutch Scientific Society, Erasmus University Rotterdam, and International Agency for research on Cancer.
Publication
Journal: The Lancet Oncology
March/31/2015
Abstract
BACKGROUND
High body-mass index (BMI; defined as 25 kg/m(2) or greater) is associated with increased risk of cancer. To inform public health policy and future research, we estimated the global burden of cancer attributable to high BMI in 2012.
METHODS
In this population-based study, we derived population attributable fractions (PAFs) using relative risks and BMI estimates in adults by age, sex, and country. Assuming a 10-year lag-period between high BMI and cancer occurrence, we calculated PAFs using BMI estimates from 2002 and used GLOBOCAN2012 data to estimate numbers of new cancer cases attributable to high BMI. We also calculated the proportion of cancers that were potentially avoidable had populations maintained their mean BMIs recorded in 1982. We did secondary analyses to test the model and to estimate the effects of hormone replacement therapy (HRT) use and smoking.
RESULTS
Worldwide, we estimate that 481,000 or 3.6% of all new cancer cases in adults (aged 30 years and older after the 10-year lag period) in 2012 were attributable to high BMI. PAFs were greater in women than in men (5.4% vs 1.9%). The burden of attributable cases was higher in countries with very high and high human development indices (HDIs; PAF 5.3% and 4.8%, respectively) than in those with moderate (1.6%) and low HDIs (1.0%). Corpus uteri, postmenopausal breast, and colon cancers accounted for 63.6% of cancers attributable to high BMI. A quarter (about 118,000) of the cancer cases related to high BMI in 2012 could be attributed to the increase in BMI since 1982.
CONCLUSIONS
These findings emphasise the need for a global effort to abate the increasing numbers of people with high BMI. Assuming that the association between high BMI and cancer is causal, the continuation of current patterns of population weight gain will lead to continuing increases in the future burden of cancer.
BACKGROUND
World Cancer Research Fund International, European Commission (Marie Curie Intra-European Fellowship), Australian National Health and Medical Research Council, and US National Institutes of Health.
Publication
Journal: International Journal of Cancer
January/5/2015
Abstract
We previously estimated that 660,000 cases of cancer in the year 2008 were attributable to the bacterium Helicobacter pylori (H. pylori), corresponding to 5.2% of the 12.7 million total cancer cases that occurred worldwide. In recent years, evidence has accumulated that immunoblot (western blot) is more sensitive for detection of anti-H. pylori antibodies than ELISA, the detection method used in our previous analysis. The purpose of this short report is to update the attributable fraction (AF) estimate for H. pylori after briefly reviewing new evidence, and to reassess the global burden of cancer attributable to H. pylori. We therefore reviewed the literature for studies comparing the risk of developing non-cardia gastric cancer (NCGC) in cases and controls, using both ELISA and multiple antigen immunoblot for detection of H. pylori. The results from prospective studies were combined, and the new pooled estimates were applied to the calculation of the AF for H. pylori in NCGC, then to the burden of infection-related cancers worldwide. Using the immunoblot-based data, the worldwide AF for H. pylori in NCGC increased from 74.7% to 89.0%. This implies approximately 120,000 additional cases of NCGC attributable to H. pylori infection for a total of around 780,000 cases (6.2% instead of 5.2% of all cancers). These updated estimates reinforce the role of H. pylori as a major cause of cancer.
Publication
Journal: British Medical Journal
June/29/2014
Abstract
OBJECTIVE
To determine whether searching for Helicobacter pylori and treating with eradication therapy leads to a reduction in incidence of gastric cancer among healthy asymptomatic infected individuals.
METHODS
Systematic review and meta-analysis of randomised controlled trials.
METHODS
Medline, Embase, and the Cochrane central register of controlled trials were searched through to December 2013. Conference proceedings between 2001 and 2013 were hand searched. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions.
METHODS
Randomised controlled trials examining the effect of at least seven days of eradication therapy on subsequent occurrence of gastric cancer in adults who tested positive for Helicobacter pylori but otherwise healthy and asymptomatic were eligible. The control arm had to receive placebo or no treatment. Subjects had to be followed for ≥ 2 years.
METHODS
Primary outcome, defined a priori, was the effect of eradication therapy on the subsequent occurrence of gastric cancer expressed as a relative risk of gastric cancer with 95% confidence intervals.
RESULTS
The search strategy identified 1560 citations, of which six individual randomised controlled trials were eligible. Fifty one (1.6%) gastric cancers occurred among 3294 individuals who received eradication therapy versus 76 (2.4%) in 3203 control subjects (relative risk 0.66, 95% confidence interval 0.46 to 0.95), with no heterogeneity between studies (I(2)=0%, P=0.60). If the benefit of eradication therapy was assumed to persist lifelong the number needed to treat was as low as 15 for Chinese men and as high as 245 for US women.
CONCLUSIONS
These data provide limited, moderate quality evidence that searching for and eradicating H pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but these data cannot necessarily be extrapolated to other populations.
Publication
Journal: Gastroenterology Clinics of North America
January/20/2014
Abstract
Gastric cancer is one of the major malignancies in the world. This article summarizes the current understanding of the worldwide burden of this disease, its geographic variation, and temporal trends. An overview is presented of known risk factors, including genetic, dietary, and behavioral, but focuses on Helicobacter pylori infection as the most important factor in noncardia gastric cancer. When the data and the literature allow, we distinguish between cardia and noncardia sub-sites, as it is now clear that these two anatomic locations present distinct and sometimes opposite epidemiological characteristics.
Publication
Journal: Cancer
November/18/2012
Abstract
Cancer is an emerging public health problem in Africa. About 715,000 new cancer cases and 542,000 cancer deaths occurred in 2008 on the continent, with these numbers expected to double in the next 20 years simply because of the aging and growth of the population. Furthermore, cancers such as lung, female breast, and prostate cancers are diagnosed at much higher frequencies than in the past because of changes in lifestyle factors and detection practices associated with urbanization and economic development. Breast cancer in women and prostate cancer in men have now become the most commonly diagnosed cancers in many Sub-Saharan African countries, replacing cervical and liver cancers. In most African countries, cancer control programs and the provision of early detection and treatment services are limited despite this increasing burden. This paper reviews the current patterns of cancer in Africa and the opportunities for reducing the burden through the application of resource level interventions, including implementation of vaccinations for liver and cervical cancers, tobacco control policies for smoking-related cancers, and low-tech early detection methods for cervical cancer, as well as pain relief at the palliative stage of cancer.
Publication
Journal: European Journal of Cancer
August/23/2015
Abstract
BACKGROUND
Individual country- and cancer site-specific studies suggest that the age-adjusted incidence of many common cancers has increased in European populations over the past two decades. To quantify the extent of these trends and the recent burden of cancer, here we present a comprehensive overview of trends in population-based incidence of the five common cancers across Europe derived from a new web-based portal of the European cancer registries.
METHODS
Data on incidence for cancers of the colon and rectum, prostate, breast, corpus uteri and stomach diagnosed from 1988 to 2008 were obtained from the European Cancer Observatory for cancer registries from 26 countries. Annual age-standardised incidence rates and average annual percentage changes were calculated.
RESULTS
Incidence of four common cancers in eastern and central European countries (prostate, postmenopausal breast, corpus uteri and colorectum) started to approach levels in northern and western Europe, where rates were already high in the past but levelled off in some countries in recent years. Decreases in stomach cancer incidence were seen in all countries.
CONCLUSIONS
Increasing trends in incidence of the most common cancers, except stomach cancer, are bad news to public health but can largely be explained by well-known changes in society in the past decades. Thus, current and future efforts in primary cancer prevention should not only remain focussed on the further reduction of smoking but engage in the long-term efforts to retain healthy lifestyles, especially avoiding excess weight through balanced diets and regular physical exercise.
Publication
Journal: Carcinogenesis
December/19/2002
Abstract
Susceptibility to colorectal cancer, one of the most common forms of cancer in the Western world, has been associated with several environmental and dietary risk factors. Dietary exposure to food derived heterocyclic amine carcinogens and polycyclic aromatic hydrocarbons have been proposed as specific risk factors. Many polymorphic Phase I and Phase II drug metabolizing enzymes are responsible for the metabolism and disposition of these compounds and it is therefore possible that inheritance of specific allelic variants of these enzymes may influence colorectal cancer susceptibility. In a multicenter case-control study, 490 colorectal cancer patients and 593 controls (433 matched case-control pairs) were genotyped for common polymorphisms in the cytochrome P450 (CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2C9, CYP2C19 and CYP2D6), glutathione S-transferase (GSTM1, GSTP1 and GSTT1), sulfotransferase (SULT1A1 and SULT1A2), N-acetyl transferase 2 (NAT2), NAD(P)H:quinone oxidoreductase (NQO1), methylenetetrahydrofolate reductase (MTHFR), and microsomal epoxide hydrolase (EPHX1) genes. Matched case-control analysis identified alleles associated with higher colorectal cancer risk as carriage of CYP1A1*2C (OR = 2.15, 95% CI 1.36-3.39) and homozygosity for GSTM1*2/*2 (OR = 1.53, 95% CI 1.16-2.02). In contrast, inheritance of the CYP2A6*2 (OR = 0.51, 95% CI 0.28-1.06), CYP2C19*2 (OR = 0.72, 95% CI 0.52-0.98) and the EPHX1(His113) alleles were associated with reduced cancer risk. We found no association with colorectal cancer risk with NAT2 genotype or any of the other polymorphic genes associated with the metabolism and disposition of heterocyclic amine carcinogens. This data suggests that heterocyclic amines do not play an important role in the aetiology of colorectal cancer but that exposure to other carcinogens such as polycyclic aromatic hydrocarbons may be important determinants of cancer risk.
Publication
Journal: American Journal of Human Genetics
January/29/2006
Abstract
Testicular germ cell tumor (TGCT) is the most common cancer in young men. Despite a considerable familial component to TGCT risk, no genetic change that confers increased risk has been substantiated to date. The human Y chromosome carries a number of genes specifically involved in male germ cell development, and deletion of the AZFc region at Yq11 is the most common known genetic cause of infertility. Recently, a 1.6-Mb deletion of the Y chromosome that removes part of the AZFc region--known as the "gr/gr" deletion--has been associated with infertility. In epidemiological studies, male infertility has shown an association with TGCT that is out of proportion with what can be explained by tumor effects. Thus, we hypothesized that the gr/gr deletion may be associated with TGCT. Using logistic modeling, we analyzed this deletion in a large series of TGCT cases with and without a family history of TGCT. The gr/gr deletion was present in 3.0% (13/431) of TGCT cases with a family history, 2% (28/1,376) of TGCT cases without a family history, and 1.3% (33/2,599) of unaffected males. Presence of the gr/gr deletion was associated with a twofold increased risk of TGCT (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI] 1.3-3.6; P = .005) and a threefold increased risk of TGCT among patients with a positive family history (aOR 3.2; 95% CI 1.5-6.7; P = .0027). The gr/gr deletion was more strongly associated with seminoma (aOR 3.0; 95% CI 1.6-5.4; P = .0004) than with nonseminoma TGCT (aOR 1.5; 95% CI 0.72-3.0; P = .29). These data indicate that the Y microdeletion gr/gr is a rare, low-penetrance allele that confers susceptibility to TGCT.
Publication
Journal: Vaccine
July/30/2014
Abstract
Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. Despite the huge advances already achieved, there must be ongoing efforts including international advocacy to achieve widespread-optimally universal-implementation of HPV prevention strategies in both developed and developing countries. This article summarizes information from the chapters presented in a special ICO Monograph 'Comprehensive Control of HPV Infections and Related Diseases' Vaccine Volume 30, Supplement 5, 2012. Additional details on each subtopic and full information regarding the supporting literature references may be found in the original chapters.
Publication
Journal: The Lancet Oncology
April/20/2009
Abstract
BACKGROUND
The National Health Service (NHS) cancer plan for England was published in 2000, with the aim of improving the survival of patients with cancer. By contrast, a formal cancer strategy was not implemented in Wales until late 2006. National data on cancer patient survival in England and Wales up to 2007 thus offer the opportunity for a first formal assessment of the cancer plan in England, by comparing survival trends in England with those in Wales before, during, and after the implementation of the plan.
METHODS
We analysed population-based survival in 2.2 million adults diagnosed with one of 21 common cancers in England and Wales during 1996-2006 and followed up to Dec 31, 2007. We defined three calendar periods: 1996-2000 (before the cancer plan), 2001-03 (initialisation), and 2004-06 (implementation). We estimated year-on-year trends in 1-year relative survival for patients diagnosed during each period, and changes in those trends between successive periods in England and separately in Wales. Changes between successive periods in mean survival up to 5 years after diagnosis were analysed by country and by government office region of England. Life tables for single year of age, sex, calendar year, deprivation category, and government office region were used to control for background mortality in all analyses.
RESULTS
1-year survival in England and Wales improved for most cancers in men and women diagnosed during 1996-2006 and followed until 2007, although not all trends were significant. Annual trends were generally higher in Wales than in England during 1996-2000 and 2001-03, but higher in England than in Wales during 2004-06. 1-year survival for patients diagnosed in 2006 was over 60% for 12 of 17 cancers in men and 13 of 18 cancers in women. Differences in 3-year survival trends between England and Wales were less marked than the differences in 1-year survival. North-South differences in survival trends for the four most common cancers were not striking, but the North West region and Wales showed the smallest improvements during 2001-03 and 2004-06.
CONCLUSIONS
The findings indicate slightly faster improvement in 1-year survival in England than in Wales during 2004-06, whereas the opposite was true during 2001-03. This reversal of survival trends in 2001-03 and 2004-06 between England and Wales is much less obvious for 3-year survival. These different patterns of survival suggest some beneficial effect of the NHS cancer plan for England, although the data do not so far provide a definitive assessment of the effectiveness of the plan.
Publication
Journal: Human Molecular Genetics
April/12/2006
Abstract
A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the disease.
Publication
Journal: American Journal of Epidemiology
February/22/2011
Abstract
To evaluate the association between gastric cancer susceptibility and inflammation-related gene polymorphisms, the authors conducted a series of meta-analyses using a predefined protocol. Genes investigated were those coding for the interleukin (IL) proteins (IL1B, IL1RN, IL8, and IL10) and for tumor necrosis factor-alpha. Gastric cancers were stratified by histologic subtype and anatomic subsite, by Helicobacter pylori infection status, by geographic location (Asian or non-Asian study population), and by a quantitative index of study quality. All published literature and meeting abstracts from the period 1990-2006 were considered. Results consistently supported increased cancer risk for IL1RN2 carriers; the increased risk was specific to non-Asian populations and was seen for intestinal and diffuse cancers, distal cancers, and, to a lesser extent, cardia cancers. Analyses restricted to high-quality studies or H. pylori-positive cases and controls also showed significant associations with both carrier status and homozygosity status. In Asian populations, reduced risk was observed in association with IL1B-31C carrier status. This effect was also observed in analyses restricted to high-quality studies. These results indicate the importance of stratification by anatomic site, histologic type, H. pylori infection, and country of origin. Study quality considerations, both laboratory and epidemiologic, can also affect results and may explain, in part, the variability in results published to date.
Publication
Journal: Gut
July/13/2011
Abstract
OBJECTIVE
To assess the variation in risk-adjusted 30-day postoperative mortality for patients with colorectal cancer between hospital trusts within the English NHS.
METHODS
Retrospective cross-sectional population-based study of data extracted from the National Cancer Data Repository.
METHODS
All providers of major colorectal cancer surgery within the English NHS.
METHODS
All 160,920 individuals who underwent major resection for colorectal cancer diagnosed between 1998 and 2006 in the English NHS. Main outcome measures National patterns of 30-day postoperative mortality were examined and logistic binary regression was used to study factors associated with death within 30 days of surgery. Funnel plots were used to show variation between trusts in risk-adjusted mortality.
RESULTS
Overall 30-day mortality was 6.7% but decreased over time from 6.8% in 1998 to 5.8% in 2006. The largest reduction in mortality was seen in 2005 and 2006. Postoperative mortality increased with age (15.0% (95% CI 14.1% to 15.9%) for those aged >80 years), comorbidity (24.2% (95% CI 22.0% to 26.5%) for those with a Charlson comorbidity score ≥ 3), stage of disease (9.9% (95% CI 9.3% to 10.6%) for patients with Dukes' D disease), socioeconomic deprivation (7.8% (95% CI 7.2% to 8.4%) for residents of the most deprived quintile) and operative urgency (14.9% (95% CI 14.2% to 15.7%) for patients undergoing emergency resection). Risk-adjusted control charts showed that one trust had consistently significantly better outcomes and three had significantly worse outcomes than the population mean.
CONCLUSIONS
Significant variation in 30-day postoperative mortality following major colorectal cancer surgery existed between NHS hospitals in England throughout the period 1998-2006. Understanding the underlying causes of this variation between surgical providers will make it possible to identify and spread best practice, improve outcomes and, ultimately, reduce 30-day postoperative mortality following colorectal cancer surgery.
Publication
Journal: International Journal of Cancer
May/2/2011
Abstract
The Cancer Incidence in Five Continents (CI5) series comprises nine volumes that bring together peer-reviewed results from population-based cancer registries worldwide. The aim of each is to make available comparable data on cancer incidence from as wide a range of geographical locations as possible. In addition, the existence of long time series of data allows the evolution of risk in different populations over time to be studied. The CI5 I-IX database brings together the results from all nine volumes, spanning a period of some 50 years. In addition, unpublished annual data, with more diagnostic detail, are made available for many cancer registries with 15 or more years of recent data. We describe the construction and composition of the CI5 databases, and provide examples of how they can be used to prepare tables and graphs comparing incidence rates between populations. This is the classical role of descriptive statistics: to allow formulation of hypotheses that might explain the observed differences (geographically, over time, in population subgroups) and that can be tested by further study. Such statistics are also essential components in the planning and evaluation of cancer control programmes.
Publication
Journal: Gastroenterology
December/2/2004
Abstract
OBJECTIVE
The evidence that proton pump inhibitor (PPI) therapy affects symptoms of nonulcer dyspepsia is conflicting. We conducted a systematic review to evaluate whether PPI therapy had any effect in nonulcer dyspepsia and constructed a health economic model to assess the cost-effectiveness of this approach.
METHODS
Electronic searches were performed using the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, and SIGLE until September 2002. Dyspepsia outcomes were dichotomized into cured/improved versus same/worse. Results were incorporated into a Markov model comparing health service costs and benefits of PPI with antacid therapy over 1 year.
RESULTS
Eight trials were identified that compared PPI therapy with placebo in 3293 patients. The relative risk of remaining dyspeptic with PPI therapy versus placebo was .86 (95% confidence interval, .78-.95; P = .003, random-effects model) with a number needed to treat of 9 (95% confidence interval, 5-25). There was statistically significant heterogeneity between trials (heterogeneity chi(2) = 30.05; df = 7; P < .001). The PPI strategy would cost an extra US dollar 278/month free from dyspepsia if the drug cost US dollar 90/month. If a generic price of US dollar 19.99 is used, then a PPI strategy costs an extra US dollar 57/month free from dyspepsia. A third-party payer would be 95% certain that PPI therapy would be cost-effective, provided they were willing to pay US dollar 94/month free from dyspepsia.
CONCLUSIONS
PPI therapy may be a cost-effective therapy in nonulcer dyspepsia, provided generic prices are used.
Publication
Journal: International Journal of Cancer
February/10/2003
Abstract
Infection with Helicobacter pylori (H. pylori), especially CagA+ strains, has been associated with an increased risk of noncardia gastric adenocarcinoma. The relationship with junctional cancer (adenocarcinomas of the esophagus and gastric cardia combined) has not been adequately investigated, although some studies have reported a reduced risk associated with H. pylori and CagA seroseropositivity. We investigated this question in a subset of cases and controls from a recently completed, large population-based case-control study of gastric and esophageal adenocarcinomas in Los Angeles County. Using established antigen-specific ELISAs, serum IgG antibodies to H. pylori whole-cell antigens (Helico-G) and CagA were measured in population controls (n = 356) and patients with incident esophageal adenocarcinoma (n = 80), gastric cardia cancer (n = 87) or distal gastric cancers (noncardia gastric adenocarcinoma) (n = 127). After controlling for demographic characteristics (age, gender, race, birthplace, education), smoking and body mass index, seropositivity for H. pylori was associated with a statistically significant increased risk of distal gastric cancer (adjusted odds ratio [OR] = 1.85, 95% confidence interval [CI] = 1.03, 3.32) but the risk of junctional cancer was not increased (adjusted OR = 1.26, 95% CI = 0.82, 1.94). The risk of junctional cancer was not changed when CagA and H. pylori were both considered, but the risk of distal gastric cancer was further increased. Subjects who were seropositive for both CagA and H. pylori compared to those who were seronegative for H. pylori showed a risk of 2.20 (95% CI = 1.13, 4.26) for distal gastric cancer and 0.86 (95% CI = 0.47, 1.59) for junctional cancer. Although tests for interaction between smoking and H. pylori were not statistically significant for junctional or distal gastric cancers, risk for both tumor types tended to be higher among current smokers who were also H. pylori seropositive. In conclusion, we find no evidence that infection with CagA+ strains of H. pylori reduces risk of esophageal and gastric cardia adenocarcinoma in this population. Our findings confirm the positive association between risk of distal gastric cancer and infection with H. pylori infection, especially CagA+ strains.
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