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Showing papers by "International Agency for Research on Cancer published in 2015"


Journal ArticleDOI
TL;DR: The GLOBOCAN series of the International Agency for Research on Cancer (IARC) as mentioned in this paper provides estimates of the worldwide incidence and mortality from 27 major cancers and for all cancers combined for 2012.
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).

24,414 citations


Journal ArticleDOI
TL;DR: A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests.
Abstract: Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests.

23,203 citations


Journal ArticleDOI
Mohsen Naghavi1, Haidong Wang1, Rafael Lozano1, Adrian Davis2  +728 moreInstitutions (294)
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as discussed by the authors, the authors used the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data.

5,792 citations


Journal ArticleDOI
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as discussed by the authors provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.

5,668 citations


Journal ArticleDOI
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as mentioned in this paper provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.

1,656 citations


Journal ArticleDOI
TL;DR: These assessments of the carcinogenicity of the consumption of red meat and processed meat will be published in volume 114 of the IARC Monographs.
Abstract: In October, 2015, 22 scientists from ten countries met at the International Agency for Research on Cancer (IARC) in Lyon, France, to evaluate the carcinogenicity of the consumption of red meat and processed meat. These assessments will be published in volume 114 of the IARC Monographs.

1,242 citations


Journal ArticleDOI
01 Mar 2015-Gut
TL;DR: 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.
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. Design 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.

1,046 citations


Journal ArticleDOI
TL;DR: Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast, and there is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma.
Abstract: Alcohol is a risk factor for cancer of the oral cavity, pharynx, oesophagus, colorectum, liver, larynx and female breast, whereas its impact on other cancers remains controversial. We investigated the effect of alcohol on 23 cancer types through a meta-analytic approach. We used dose–response meta-regression models and investigated potential sources of heterogeneity. A total of 572 studies, including 486 538 cancer cases, were identified. Relative risks (RRs) for heavy drinkers compared with nondrinkers and occasional drinkers were 5.13 for oral and pharyngeal cancer, 4.95 for oesophageal squamous cell carcinoma, 1.44 for colorectal, 2.65 for laryngeal and 1.61 for breast cancer; for those neoplasms there was a clear dose–risk relationship. Heavy drinkers also had a significantly higher risk of cancer of the stomach (RR 1.21), liver (2.07), gallbladder (2.64), pancreas (1.19) and lung (1.15). There was indication of a positive association between alcohol consumption and risk of melanoma and prostate cancer. Alcohol consumption and risk of Hodgkin’s and Non-Hodgkin’s lymphomas were inversely associated. Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma.

812 citations


Journal ArticleDOI
TL;DR: The continuation of current patterns of population weight gain will lead to continuing increases in the future burden of cancer, and the need for a global effort to abate the increasing numbers of people with high BMI is emphasised.
Abstract: Summary 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. Findings 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. Interpretation 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. Funding 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.

718 citations


Journal ArticleDOI
TL;DR: The purpose of this short report is to update the attributable fraction (AF) estimate for H. pylori in NCGC, and to reassess the global burden of cancer attributable to H. Pylori as a major cause of cancer.
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.

673 citations


Journal ArticleDOI
TL;DR: Although RCC incidence is still increasing in most countries, stabilisation of mortality trends has been achieved in many highly developed countries and there are marked absolute differences and opposing RCC mortality trends in countries categorised as areas of higher versus lower human development, and these gaps appear to be widening.

Journal ArticleDOI
TL;DR: The results provide compelling evidence that investment in radiotherapy not only enables treatment of large numbers of cancer cases to save lives, but also brings positive economic benefits.
Abstract: Summary Radiotherapy is a critical and inseparable component of comprehensive cancer treatment and care. For many of the most common cancers in low-income and middle-income countries, radiotherapy is essential for effective treatment. In high-income countries, radiotherapy is used in more than half of all cases of cancer to cure localised disease, palliate symptoms, and control disease in incurable cancers. Yet, in planning and building treatment capacity for cancer, radiotherapy is frequently the last resource to be considered. Consequently, worldwide access to radiotherapy is unacceptably low. We present a new body of evidence that quantifies the worldwide coverage of radiotherapy services by country. We show the shortfall in access to radiotherapy by country and globally for 2015–35 based on current and projected need, and show substantial health and economic benefits to investing in radiotherapy. The cost of scaling up radiotherapy in the nominal model in 2015–35 is US$26·6 billion in low-income countries, $62·6 billion in lower-middle-income countries, and $94·8 billion in upper-middle-income countries, which amounts to $184·0 billion across all low-income and middle-income countries. In the efficiency model the costs were lower: $14·1 billion in low-income, $33·3 billion in lower-middle-income, and $49·4 billion in upper-middle-income countries—a total of $96·8 billion. Scale-up of radiotherapy capacity in 2015–35 from current levels could lead to saving of 26·9 million life-years in low-income and middle-income countries over the lifetime of the patients who received treatment. The economic benefits of investment in radiotherapy are very substantial. Using the nominal cost model could produce a net benefit of $278·1 billion in 2015–35 ($265·2 million in low-income countries, $38·5 billion in lower-middle-income countries, and $239·3 billion in upper-middle-income countries). Investment in the efficiency model would produce in the same period an even greater total benefit of $365·4 billion ($12·8 billion in low-income countries, $67·7 billion in lower-middle-income countries, and $284·7 billion in upper-middle-income countries). The returns, by the human-capital approach, are projected to be less with the nominal cost model, amounting to $16·9 billion in 2015–35 (–$14·9 billion in low-income countries; –$18·7 billion in lower-middle-income countries, and $50·5 billion in upper-middle-income countries). The returns with the efficiency model were projected to be greater, however, amounting to $104·2 billion (–$2·4 billion in low-income countries, $10·7 billion in lower-middle-income countries, and $95·9 billion in upper-middle-income countries). Our results provide compelling evidence that investment in radiotherapy not only enables treatment of large numbers of cancer cases to save lives, but also brings positive economic benefits.

Journal ArticleDOI
TL;DR: These assessments will be published as volume 112 of the IARC Monographs in March, 2015.
Abstract: DOI: http://dx.doi.org/10.1016/S1470-2045(15)70134-8 Article Info  Summary  Full Text  Tables and Figures  References In March, 2015, 17 experts from 11 countries met at the International Agency for Research on Cancer (IARC; Lyon, France) to assess the carcinogenicity of the organophosphate pesticides tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate (table). These assessments will be published as volume 112 of the IARC Monographs.

Journal ArticleDOI
TL;DR: The International Agency for Research on Cancer (IARC) has updated its 2002 guidelines on screening for breast cancer, drawing on data from studies completed in the past 15 years.
Abstract: The International Agency for Research on Cancer (IARC) has updated its 2002 guidelines on screening for breast cancer, drawing on data from studies completed in the past 15 years.

Journal ArticleDOI
TL;DR: Global trends in female breast cancer rates are decreasing in most high-income countries, despite increasing or stable incidence rates, and the increasing incidence and mortality rates in a number of countries are of concern, particularly those undergoing rapid changes in human development.
Abstract: Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related death among women worldwide. Herein, we examine global trends in female breast cancer rates using the most up-to-date data available. Methods: Breast cancer incidence and mortality estimates were obtained from GLOBOCAN 2012 (globocan.iarc.fr). We analyzed trends from 1993 onward using incidence data from 39 countries from the International Agency for Research on Cancer and mortality data from 57 countries from the World Health Organization. Results: Of 32 countries with incidence and mortality data, rates in the recent period diverged—with incidence increasing and mortality decreasing—in nine countries mainly in Northern/Western Europe. Both incidence and mortality decreased in France, Israel, Italy, Norway, and Spain. In contrast, incidence and death rates both increased in Colombia, Ecuador, and Japan. Death rates also increased in Brazil, Egypt, Guatemala, Kuwait, Mauritius, Mexico, and Moldova. Conclusions: Breast cancer mortality rates are decreasing in most high-income countries, despite increasing or stable incidence rates. In contrast and of concern are the increasing incidence and mortality rates in a number of countries, particularly those undergoing rapid changes in human development. Wide variations in breast cancer rates and trends reflect differences in patterns of risk factors and access to and availability of early detection and timely treatment. Impact: Increased awareness about breast cancer and the benefits of early detection and improved access to treatment must be prioritized to successfully implement breast cancer control programs, particularly in transitioning countries. Cancer Epidemiol Biomarkers Prev; 24(10); 1495–506. ©2015 AACR .

Journal ArticleDOI
TL;DR: 15 new loci associated with breast cancer at P < 5 × 10−8 are identified, and one association appears to be driven by an amino acid substitution encoded in EXO1, which is found in women of European ancestry.
Abstract: Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.

Journal ArticleDOI
TL;DR: 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.

Journal ArticleDOI
TL;DR: The use of the 10 key characteristics of carcinogens as a basis for organizing data on mechanisms of carcinogenesis are described and a graphical representation of the identified mechanistic information is constructed.
Abstract: Background:A recent review by the International Agency for Research on Cancer (IARC) updated the assessments of the > 100 agents classified as Group 1, carcinogenic to humans (IARC Monographs Volum...

Journal ArticleDOI
TL;DR: HBV and HCV are predominant causes of HCC in virtually all world areas, with a growing fraction of H CC cases in several countries attributable to HCV.

Journal ArticleDOI
TL;DR: The status of population‐based cancer registries worldwide are assessed, the techniques used in CI5 to evaluate their quality are described and the notable variation in the incidence rates of selected cancers contained within Volume X of CI5 is highlighted.
Abstract: Cancer Incidence in Five Continents (CI5), a longstanding collaboration between the International Agency for Research on Cancer and the International Association of Cancer Registries, serves as a unique source of cancer incidence data from high-quality population-based cancer registries around the world. The recent publication of Volume X comprises cancer incidence data from 290 registries covering 424 populations in 68 countries for the registration period 2003-2007. In this article, we assess the status of population-based cancer registries worldwide, describe the techniques used in CI5 to evaluate their quality and highlight the notable variation in the incidence rates of selected cancers contained within Volume X of CI5. We also discuss the Global Initiative for Cancer Registry Development as an international partnership that aims to reduce the disparities in availability of cancer incidence data for cancer control action, particularly in economically transitioning countries, already experiencing a rapid rise in the number of cancer patients annually.


Journal ArticleDOI
TL;DR: Up-to-date estimates of the cancer burden in Europe alongside the description of the varying distribution of common cancers at both the regional and country level provide a basis for establishing priorities to cancer control actions in Europe.

Journal ArticleDOI
20 Oct 2015-BMJ
TL;DR: A linear increase in the rate of cancer with increasing radiation exposure is suggested and the risk per unit of radiation dose for cancer among radiation workers was similar to estimates derived from studies of Japanese atomic bomb survivors.
Abstract: Study question Is protracted exposure to low doses of ionising radiation associated with an increased risk of solid cancer? Methods In this cohort study, 308 297 workers in the nuclear industry from France, the United Kingdom, and the United States with detailed monitoring data for external exposure to ionising radiation were linked to death registries. Excess relative rate per Gy of radiation dose for mortality from cancer was estimated. Follow-up encompassed 8.2 million person years. Of 66 632 known deaths by the end of follow-up, 17 957 were due to solid cancers. Study answer and limitations Results suggest a linear increase in the rate of cancer with increasing radiation exposure. The average cumulative colon dose estimated among exposed workers was 20.9 mGy (median 4.1 mGy). The estimated rate of mortality from all cancers excluding leukaemia increased with cumulative dose by 48% per Gy (90% confidence interval 20% to 79%), lagged by 10 years. Similar associations were seen for mortality from all solid cancers (47% (18% to 79%)), and within each country. The estimated association over the dose range of 0-100 mGy was similar in magnitude to that obtained over the entire dose range but less precise. Smoking and occupational asbestos exposure are potential confounders; however, exclusion of deaths from lung cancer and pleural cancer did not affect the estimated association. Despite substantial efforts to characterise the performance of the radiation dosimeters used, the possibility of measurement error remains. What this study adds The study provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality. Although high dose rate exposures are thought to be more dangerous than low dose rate exposures, the risk per unit of radiation dose for cancer among radiation workers was similar to estimates derived from studies of Japanese atomic bomb survivors. Quantifying the cancer risks associated with protracted radiation exposures can help strengthen the foundation for radiation protection standards. Funding, competing interests, data sharing Support from the US Centers for Disease Control and Prevention; Ministry of Health, Labour and Welfare of Japan; Institut de Radioprotection et de Surete Nucleaire; AREVA; Electricite de France; US National Institute for Occupational Safety and Health; US Department of Energy; and Public Health England. Data are maintained and kept at the International Agency for Research on Cancer.

Journal ArticleDOI
06 Mar 2015-Gut
TL;DR: This study has, for the first time, quantified global incidence patterns of CGC and NCGC providing new insights into the global burden of these cancers.
Abstract: Objective Globally, gastric cancer incidence shows remarkable international variation and demonstrates distinct characteristics by the two major topographical subsites, cardia (CGC) and non-cardia (NCGC). Because global incidence estimates by subsite are lacking, we aimed to describe the worldwide incidence patterns of CGC and NCGC separately. Design Using Cancer Incidence in Five Continents Volume X (CI5X), we ascertained the proportions of CGC and NCGC by country, sex and age group ( Results According to our estimates, in 2012, there were 260 000 cases of CGC (ASR 3.3 per 100 000) and 691 000 cases of NCGC (ASR 8.8) worldwide. The highest regional rates of both gastric cancer subsites were in Eastern/Southeastern Asia (in men, ASRs: 8.7 and 21.7 for CGC and NCGC, respectively). In most countries NCGC occurred more frequently than CGC with an average ratio of 2:1; however, in some populations where NCGC incidence rates were lower than the global average, CGC rates were similar or higher than NCGC rates. Men had higher rates than women for both subsites but particularly for CGC (male-to-female ratio 3:1). Conclusions This study has, for the first time, quantified global incidence patterns of CGC and NCGC providing new insights into the global burden of these cancers. Country-specific estimates are provided; however, these should be interpreted with caution. This work will support future investigations across populations.

Journal ArticleDOI
TL;DR: Significant evidence is found of a relationship between NO2, as a proxy for traffic-sourced air pollution exposure, with lung cancer, and the International Agency for Research on Cancer recently classified outdoor air pollution and particulate matter as carcinogenic.
Abstract: Background and objectiveExposure to traffic-related air pollutants is an important public health issue. Here, we present a systematic review and meta-analysis of research examining the relationship...

Journal ArticleDOI
TL;DR: The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health.

Journal ArticleDOI
24 Sep 2015-Thyroid
TL;DR: A large proportion of TC cases diagnosed in high-resource countries in the last two decades are likely to be due to diagnostic changes, and this proportion has progressively increased over time, and it is likely to grow further in the future.
Abstract: Background: Thyroid cancer (TC) incidence is rising in many countries, but the corresponding mortality is constant or declining. Incidence increases appear largely restricted to small papillary TC in young/middle-age individuals. We compared age-specific incidence rates across countries and time periods in order to estimate the fraction of TC possibly attributable to increased surveillance of the thyroid gland (diagnostic changes) following the introduction of neck ultrasonography in the 1980s. Methods: We focused on high-resource countries, including four Nordic countries, England and Scotland, France, Italy, the United States, Australia, Japan, and the Republic of Korea. Before the 1970s, TC incidence in Nordic countries increased proportionally to the second power of age, consistent with the multistage model of carcinogenesis. Using this historical observation for reference, we attributed the progressive departure from linearity of the age curves in each country to an increased detection of asymptomati...

Journal ArticleDOI
TL;DR: 4 years after vaccination of women aged 15-25 years, one and two doses of the HPV- 16/18 vaccine seem to protect against cervical HPV-16/18 infections, similar to the protection provided by the three-dose schedule.
Abstract: Summary Background There is some evidence to suggest that one or two doses of the HPV vaccine provides similar protection to the three-dose regimen. The main aim of the study was to ascertain HPV-16/18 vaccine efficacy in both full and naive cohorts and to explore protection conferred against non-vaccine HPV types, by number of doses received. Methods Summary data from the Costa Rica Vaccine Trial (CVT; NCT00128661) and ~the PATRICIA trial (NCT001226810), two phase 3, double-blind, randomised controlled clinical trials of the HPV-16/18 AS04-adjuvanted vaccine in young women, were combined in a post-hoc analysis (GlaxoSmithKline [GSK] e-track number 202142) to investigate the efficacy of fewer than three doses of the HPV-16/18 vaccine after 4 years of follow-up. Women were randomly assigned to receive three doses of the HPV-16/18 vaccine or to a control vaccine; yet, some received fewer doses. After exclusion of women with less than 12 months of follow-up or those who were HPV-16/18 DNA-positive at enrolment (for the HPV-16/18 endpoint), we calculated vaccine efficacy against one-time detection of incident HPV infections after three, two, and one dose(s). The primary study endpoint was one-time detection of first incident HPV-16/18 infections accumulated during the follow-up phase. Findings We assessed vaccine efficacy against incident HPV-16/18 infection in the modified total vaccinated cohort (22 327 received three doses, 1185 two doses, 543 one dose). Vaccine efficacy against incident HPV-16/18 infections for three doses was 77·0% (95% CI 74·7–79·1), two doses was 76·0% (62·0–85·3), and one dose was 85·7% (70·7–93·7). Vaccine efficacy against incident HPV-31/33/45 infections for three doses was 59·7% (56·0–63·0), two doses was 37·7% (12·4–55·9), and one dose was 36·6% (–5·4 to 62·2). Vaccine efficacy against incident HPV-16/18 infection for two-dose women who received their second dose at 1 month was 75·3% (54·2–87·5) and 82·6% (42·3–96·1) for those who received the second dose at 6 months (CVT data only). Vaccine efficacy against HPV-31/33/45 for two-dose women who received their second dose at 6 months (68·1%, 27·0–87·0; CVT data only), but not those receiving it at one month (10·1%, −42·0 to 43·3), was similar to the three-dose group. Interpretation 4 years after vaccination of women aged 15–25 years, one and two doses of the HPV-16/18 vaccine seem to protect against cervical HPV-16/18 infections, similar to the protection provided by the three-dose schedule. Two doses separated by 6 months additionally provided some cross-protection. These data argue for a direct assessment of one-dose efficacy of the HPV-16/18 vaccine. Funding US National Cancer Institute, National Institutes of Health Office of Research on Women's Health, and Ministry of Health of Costa Rica (CVT); GlaxoSmithKline Biologicals SA (PATRICIA).

Journal ArticleDOI
TL;DR: In this paper, differences in HPV-related cancer and infection burden by gender and anatomic site are reviewed, with nearly 100% of cervical, 88% of anal, and <50% of lower genital tract and oropharyngeal cancers attributable to HPV.
Abstract: Human papillomaviruses (HPVs) cause cancer at multiple anatomic sites in men and women, including cervical, oropharyngeal, anal, vulvar and vaginal cancers in women and oropharyngeal, anal and penile cancers in men. In this EUROGIN 2014 roadmap, differences in HPV-related cancer and infection burden by gender and anatomic site are reviewed. The proportion of cancers attributable to HPV varies by anatomic site, with nearly 100% of cervical, 88% of anal and <50% of lower genital tract and oropharyngeal cancers attributable to HPV, depending on world region and prevalence of tobacco use. Often, mirroring cancer incidence rates, HPV prevalence and infection natural history varies by gender and anatomic site of infection. Oral HPV infection is rare and significantly differs by gender; yet, HPV-related cancer incidence at this site is several-fold higher than at either the anal canal or the penile epithelium. HPV seroprevalence is significantly higher among women compared to men, likely explaining the differences in age-specific HPV prevalence and incidence patterns observed by gender. Correspondingly, among heterosexual partners, HPV transmission appears higher from women to men. More research is needed to characterize HPV natural history at each anatomic site where HPV causes cancer in men and women, information that is critical to inform the basic science of HPV natural history and the development of future infection and cancer prevention efforts.

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TL;DR: This study identifies new loci associated with pancreatic cancer risk in North America, Central Europe and Australia and replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERT and CLPTM1) and 13q12.4 (NR5A2), a region with previous suggestive evidence in Han Chinese.
Abstract: Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A and mismatch-repair genes and low-penetrance loci are associated with increased risk. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19-1.34, P = 1.42 × 10(-14)), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84-0.92, P = 1.41 × 10(-8)) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85-0.93, P = 2.35 × 10(-8)). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09-1.19, P = 3.36 × 10(-9)), a region with previous suggestive evidence in Han Chinese. We replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERT and CLPTM1), 13q12.2 (PDX1), 1q32.1 (NR5A2), 7q32.3 (LINC-PINT), 16q23.1 (BCAR1) and 22q12.1 (ZNRF3). Our study identifies new loci associated with pancreatic cancer risk.