Publications by authors named "Ariana Znaor"

106 Publications

Environmental factors in declining human fertility.

Nat Rev Endocrinol 2021 Dec 15. Epub 2021 Dec 15.

Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.

A severe decline in child births has occurred over the past half century, which will lead to considerable population declines, particularly in industrialized regions. A crucial question is whether this decline can be explained by economic and behavioural factors alone, as suggested by demographic reports, or to what degree biological factors are also involved. Here, we discuss data suggesting that human reproductive health is deteriorating in industrialized regions. Widespread infertility and the need for assisted reproduction due to poor semen quality and/or oocyte failure are now major health issues. Other indicators of declining reproductive health include a worldwide increasing incidence in testicular cancer among young men and alterations in twinning frequency. There is also evidence of a parallel decline in rates of legal abortions, revealing a deterioration in total conception rates. Subtle alterations in fertility rates were already visible around 1900, and most industrialized regions now have rates below levels required to sustain their populations. We hypothesize that these reproductive health problems are partially linked to increasing human exposures to chemicals originating directly or indirectly from fossil fuels. If the current infertility epidemic is indeed linked to such exposures, decisive regulatory action underpinned by unconventional, interdisciplinary research collaborations will be needed to reverse the trends.
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http://dx.doi.org/10.1038/s41574-021-00598-8DOI Listing
December 2021

Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.

Nat Commun 2021 10 12;12(1):5945. Epub 2021 Oct 12.

Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy.

Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.
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http://dx.doi.org/10.1038/s41467-021-26151-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511029PMC
October 2021

Impact of the COVID-19 pandemic on population-based cancer registry.

Int J Cancer 2022 01 18;150(2):273-278. Epub 2021 Sep 18.

Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France.

The COVID-19 pandemic has caused disruptions to national health systems and impacted health outcomes worldwide. However, the extent to which surveillance systems, such as population-based cancer registration, have been affected was not reported. Here we sought to evaluate the effect of the pandemic on registry operations across different areas and development levels worldwide. We investigated the impact of COVID-19 on three main areas of cancer registry operations: staffing, financing and data collection. An online survey was administered to 750 member registries of the International Association for Cancer Registries. Among 212 responding registries from 90 countries, 65.6% reported a disruption in operations, ranging between 45% in south-eastern Asia and 87% in the Latin America and Caribbean. Active data collection was disrupted more than case notifications or hybrid methods. In countries categorized with low Human Development Index (HDI), a greater number of registries reported a negative impact (81.3%) than in very high HDI countries (57.8%). This contrast was highest in term of impact on financing: 9/16 (56%) registries in low HDI countries reported a current or an expected decline in funding, compared to 7/108 (7%) in very high HDI countries. With many cancer registries worldwide reporting disruption to their operations during the early COVID-19 pandemic, urgent actions are needed to ensure their continuity. Governmental commitment to support future registry operations as an asset to disease control, alongside a move toward electronic reporting systems will help to ensure the sustainability of cancer surveillance worldwide.
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http://dx.doi.org/10.1002/ijc.33792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8652711PMC
January 2022

Comparability and validity of cancer registry data in the northwest of Russia.

Acta Oncol 2021 Oct 23;60(10):1264-1271. Epub 2021 Aug 23.

Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France.

Background: Despite the elaborate history of statistical reporting in the USSR, Russia established modern population-based cancer registries (PBCR) only in the 1990s. The quality of PBCRs data has not been thoroughly analyzed. This study aims at assessing the comparability and validity of cancer statistics in regions of the Northwestern Federal District (NWFD) of Russia.

Material And Methods: Data from ten Russian regional PBCRs covering ∼13 million (∼5 million in St. Petersburg) were processed in line with IARC/IACR and ENCR recommendations. We extracted and analyzed all registered cases but focused on cases diagnosed between 2008 and 2017. For comparability and validity assessment, we applied established qualitative and quantitative methods.

Results: Data collection in NWFD is in line with international standards. Distributions of diagnosis dates revealed higher variation in several regions, but overall, distributions are relatively uniform. The proportion of multiple primaries between 2008 and 2017 ranged from 6.7% in Vologda Oblast to 12.4% in Saint-Petersburg. We observed substantial regional heterogeneity for most indicators of validity. In 2013-2017, proportions of morphologically verified cases ranged between 61.7 and 89%. Death certificates only (DCO) cases proportion was in the range of 1-14% for all regions, except for Saint-Petersburg (up to 23%). The proportion of cases with a primary site unknown was between 1 and 3%. Certain cancer types (e.g., pancreas, liver, hematological malignancies, and CNS tumors) and cancers in older age groups showed lower validity.

Conclusion: While the overall level of comparability and validity of PBCRs data of four out of ten regions of NWFD of Russia meets the international standards, differences between the regions are substantial. The local instructions for cancer registration need to be updated and implemented. The data validity assessment also reflects pitfalls in the quality of diagnosis of certain cancer types and patient groups.
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http://dx.doi.org/10.1080/0284186X.2021.1967443DOI Listing
October 2021

History and current status of cancer registration in Russia.

Cancer Epidemiol 2021 08 2;73:101963. Epub 2021 Jun 2.

Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France.

Background: Russia, then part of the Union of Soviet Socialist Republics (the USSR), introduced compulsory cancer registration in 1953, but a clear overall contemporary description of the cancer surveillance system in Russia is not available.

Methods: We summarized historical landmarks and the development of the standards of classification and coding of neoplasms in Russia and described current population-based cancer registries' (PBCR) procedures and practices.

Results: Cancer registration is organized according to the administrative division of the Russian Federation. More than 600,000 cases are registered annually. All medical facilities, without exception, are required to notify the PBCR about newly diagnosed cases, and each regional PBCR is responsible for registering all cancers diagnosed in citizens residing in the region. The data collection can be described as passive and exhaustive. Hematological malignancies, brain, and CNS tumors are often not referred to cancer hospitals in some regions, explaining the problems in registering these cancers.

Conclusion: Russia's cancer registration system is population-based, and practices seem to be generally internationally comparable. However, coding practices and national guidelines are still outdated and not up to the most recent international recommendations. Further analyses are needed to assess the comparability, validity, completeness, and timeliness of Russia's PBCRs data.
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http://dx.doi.org/10.1016/j.canep.2021.101963DOI Listing
August 2021

Cervical cancer in the Newly Independent States of the former Soviet Union: Incidence will remain high without action.

Cancer Epidemiol 2021 08 8;73:101944. Epub 2021 May 8.

Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France.

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http://dx.doi.org/10.1016/j.canep.2021.101944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316603PMC
August 2021

Cancer statistics for the year 2020: An overview.

Int J Cancer 2021 Apr 5. Epub 2021 Apr 5.

Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon Cedex, France.

Our study briefly reviews the data sources and methods used in compiling the International Agency for Research on Cancer (IARC) GLOBOCAN cancer statistics for the year 2020 and summarises the main results. National estimates were calculated based on the best available data on cancer incidence from population-based cancer registries (PBCR) and mortality from the World Health Organization mortality database. Cancer incidence and mortality rates for 2020 by sex and age groups were estimated for 38 cancer sites and 185 countries or territories worldwide. There were an estimated 19.3 million (95% uncertainty interval [UI]: 19.0-19.6 million) new cases of cancer (18.1 million excluding non-melanoma skin cancer) and almost 10.0 million (95% UI: 9.7-10.2 million) deaths from cancer (9.9 million excluding non-melanoma skin cancer) worldwide in 2020. The most commonly diagnosed cancers worldwide were female breast cancer (2.26 million cases), lung (2.21) and prostate cancers (1.41); the most common causes of cancer death were lung (1.79 million deaths), liver (830000) and stomach cancers (769000).
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http://dx.doi.org/10.1002/ijc.33588DOI Listing
April 2021

Occupational socioeconomic risk associations for head and neck cancer in Europe and South America: individual participant data analysis of pooled case-control studies within the INHANCE Consortium.

J Epidemiol Community Health 2021 08 23;75(8):779-787. Epub 2021 Feb 23.

Division of Public Health, Department of Family and Preventive Medicine and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA.

Background: The association between socioeconomic disadvantage (low education and/or income) and head and neck cancer is well established, with smoking and alcohol consumption explaining up to three-quarters of the risk. We aimed to investigate the nature of and explanations for head and neck cancer risk associated with occupational socioeconomic prestige (a perceptual measure of psychosocial status), occupational socioeconomic position and manual-work experience, and to assess the potential explanatory role of occupational exposures.

Methods: Pooled analysis included 5818 patients with head and neck cancer (and 7326 control participants) from five studies in Europe and South America. Lifetime job histories were coded to: (1) occupational social prestige-Treiman's Standard International Occupational Prestige Scale (SIOPS); (2) occupational socioeconomic position-International Socio-Economic Index (ISEI); and (3) manual/non-manual jobs.

Results: For the longest held job, adjusting for smoking, alcohol and nature of occupation, increased head and neck cancer risk estimates were observed for low SIOPS OR=1.88 (95% CI: 1.64 to 2.17), low ISEI OR=1.74 (95% CI: 1.51 to 1.99) and manual occupations OR=1.49 (95% CI: 1.35 to 1.64). Following mutual adjustment by socioeconomic exposures, risk associated with low SIOPS remained OR=1.59 (95% CI: 1.30 to 1.94).

Conclusions: These findings indicate that low occupational socioeconomic prestige, position and manual work are associated with head and neck cancer, and such risks are only partly explained by smoking, alcohol and occupational exposures. Perceptual occupational psychosocial status (SIOPS) appears to be the strongest socioeconomic factor, relative to socioeconomic position and manual/non-manual work.
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http://dx.doi.org/10.1136/jech-2020-214913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292575PMC
August 2021

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

Lancet Oncol 2021 03 5;22(3):361-369. Epub 2021 Feb 5.

Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France. Electronic address:

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.
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http://dx.doi.org/10.1016/S1470-2045(20)30674-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014987PMC
March 2021

Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration.

Br J Cancer 2020 10 24;123(9):1456-1463. Epub 2020 Aug 24.

Institute of Oncology and Radiobiology, Havana, Cuba.

Background: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk.

Methods: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking.

Results: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx).

Conclusions: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.
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http://dx.doi.org/10.1038/s41416-020-01031-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592048PMC
October 2020

Use of cancer data for cancer control in the Eastern Mediterranean Region: Results of a survey among population-based cancer registries.

Int J Cancer 2021 02 13;148(3):593-600. Epub 2020 Aug 13.

Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France.

Data from population-based cancer registries (PBCR) are critical for planning, monitoring and evaluation of cancer control programs, but are frequently underutilized by key stakeholders. As part of the ongoing partnership of the International Agency for Research on Cancer (IARC) and the WHO Eastern Mediterranean Regional Office (EMRO) in cancer surveillance, we designed a cancer registry survey to assess the level of involvement of PBCR in national cancer control planning across the region. A questionnaire on registry characteristics, their contribution to cancer control and perceived barriers, was sent to 14 countries with operational PBCR. We obtained replies from Bahrain, Egypt, Iraq, Iran, Jordan, Kuwait, Lebanon, Morocco, Oman, Qatar, Saudi Arabia, Tunisia and the United Arab Emirates. We found a high participation of PBCR in cancer control planning (all registries involved, 46% routinely) and the evaluation of screening (92% registries involved, 46% routinely), but a much lower level of participation in palliative care and rehabilitation activities. Specified barriers included poor governance, a lack of awareness by policy makers, insufficient resources and a limited availability of data electronically, including mortality data. Appropriate planning to ensure the sustainability of PBCR (including the employment of permanent staff), increasing training, building research capacity and ensuring an efficient provision of high-quality data to policymakers, were among the proposed solutions. The results of our study reinforce the need for further tailoring of activities in support of cancer registration and enhanced networking among stakeholders, toward improving quality and use of cancer registry data for cancer control in the EMR.
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http://dx.doi.org/10.1002/ijc.33223DOI Listing
February 2021

Global trends in intrahepatic and extrahepatic cholangiocarcinoma incidence from 1993 to 2012.

Cancer 2020 06 4;126(11):2666-2678. Epub 2020 Mar 4.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

Background: Intrahepatic cholangiocarcinomas (ICCs) and extrahepatic cholangiocarcinomas (ECCs) are highly lethal bile duct tumors. Their incidence can be difficult to estimate because of changes in cancer coding over time. No studies to date have examined their global incidence and trends with high-quality topography- and histology-specific cancer registry data. Therefore, this study examined ICC and ECC incidence with the Cancer Incidence in Five Continents Plus database.

Methods: Regional and national cancer registry data were used to estimate age-standardized incidence rates (ASRs) per 100,000 person-years, 95% confidence intervals, and average annual percent changes (AAPCs) for ICC in 38 countries and for ECC in 33 countries from 1993 to 2012. ICC and ECC trends were tabulated and plotted by country. Rates versus birth cohort by age were plotted, and an age-period-cohort analysis was performed to assess age and cohort incidence rate ratios.

Results: The highest rates of ICC and ECC were in Asia, specifically South Korea (ASR for ICC, 2.80; ASR for ECC, 2.24), Thailand (ASR for ICC, 2.19; ASR for ECC, 0.71), and Japan (ASR for ICC, 0.95; ASR for ECC, 0.83). Between 1993 and 2012, incidence rates of both ICC and ECC increased in most countries. The largest ASR increases over the study period occurred in Latvia (AAPC, 20.1%) and China (AAPC, 11.1%) for ICC and in Thailand (AAPC, 8.8%) and Colombia (AAPC, 8.5%) for ECC.

Conclusions: In the 20 years examined, ICC and ECC incidence increased in the majority of countries worldwide. ICC and ECC incidence may continue to increase because of metabolic and infectious etiologic factors. Efforts to further elucidate risk factors contributing to these increases in incidence are warranted.
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http://dx.doi.org/10.1002/cncr.32803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323858PMC
June 2020

Recent cancer incidence trends in Ukraine and short-term predictions to 2022.

Cancer Epidemiol 2020 04 24;65:101663. Epub 2019 Dec 24.

Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France.

Background: Using data from the National Cancer Registry of Ukraine (NCRU), we analyzed recent trends in incidence rates (2003-2012) and used these to predict the future cancer incidence burden up to 2022.

Methods: All cancer cases (excluding non-melanoma of skin) for the years 2003-2012 were retrieved from the NCRU's database (n = 1,459,851). Age-standardized incidence rates (ASRs) were estimated and the numbers of new cases and incidence rates predicted for 2022 using age-period modeling.

Results: ASR increased from 2003 to 2012 for most cancers except lip and stomach cancers (in both sexes) and laryngeal and lung cancers (in males). Assuming these trends will continue, lung cancer will remain the most common male cancer in 2022 (ASR 40.5/100,000), followed by prostate cancer (36.8/100,000), colorectal cancer (34.6/100,000), and cancers of the oral cavity and pharynx (18.5/100,000). In females, the order of the four most common cancers will not change in 2022 compared with 2012, with cervical cancer remaining the fourth most common cancer (17.5/100,000). We predict an overall increase of 18 % in the number of cancer cases in Ukraine (relative to 2012) to 179,493 cases in 2022.

Conclusion: The anticipated increase in the number of cancer patients in Ukraine clearly has knock-on effects on a healthcare system undergoing reforms. Tobacco control appears to be the only functioning aspect of cancer prevention in the country, and there is a need for a broader national cancer control plan. The continued monitoring and evaluation of implemented cancer control measures by the NCRU will help prioritize targets and allocate future resources to cancer services.
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http://dx.doi.org/10.1016/j.canep.2019.101663DOI Listing
April 2020

Testicular cancer incidence predictions in Europe 2010-2035: A rising burden despite population ageing.

Int J Cancer 2020 08 28;147(3):820-828. Epub 2019 Dec 28.

Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France.

Testicular cancer is the most common cancer among young men of European ancestry, with about one-third of all cases occurring in Europe. With the historically increasing trends in some high-incidence populations reported to have stabilised in recent years, we aimed to assess recent trends and predict the future testicular cancer incidence burden across Europe. We extracted testicular cancer (ICD-10 C62) incidence data from Cancer Incidence in Five Continents Volumes VII-XI and complemented this with data published by registries from 28 European countries. We predicted cancer incidence rates and the number of incident cases in Europe in the year 2035 using the NORDPRED age-period-cohort model. Testicular cancer incidence rates will increase in 21 out of 28 countries over the period 2010-2035, with trends attenuating in the high-incidence populations of Denmark, Norway, Switzerland and Austria. Although population ageing would be expected to reduce the number of cases, this demographic effect is outweighed by increasing risk, leading to an overall increase in the number of cases by 2035 in Europe, and by region (21, 13 and 32% in Northern, Western and Eastern Europe, respectively). Declines are however predicted in Italy and Spain, amounting to 12% less cases in 2035 in Southern Europe overall. In conclusion, the burden of testicular cancer incidence in Europe will continue to increase, particularly in historically lower-risk countries. The largest increase in the number of testicular cancer patients is predicted in Eastern Europe, where survival is lower, reinforcing the need to ensure the provision of effective treatment across Europe.
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http://dx.doi.org/10.1002/ijc.32810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612086PMC
August 2020

International trends in hepatocellular carcinoma incidence, 1978-2012.

Int J Cancer 2020 07 5;147(2):317-330. Epub 2019 Nov 5.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.

Primary liver cancer, the major histology of which is hepatocellular carcinoma (HCC), is the second leading cause of cancer death worldwide. We comprehensively examined recent international trends of primary liver cancer and HCC incidence using population-based cancer registry data. Incidence for all primary liver cancer and for HCC by calendar time and birth cohort was examined for selected countries between 1978 and 2012. For each successive 5-year period, age-standardized incidence rates were calculated from Volumes V to XI of the Cancer Incidence in Five Continents (CI5) series using the online electronic databases, CI5plus. Large variations persist in liver cancer incidence globally. Rates of liver cancer remain highest in Asian countries, specifically in the East and South-East, and Italy. However, rates in these high-risk countries have been decreasing in recent years. Rates in India and in most countries of Europe, the Americas and Oceania are rising. As the population seroprevalence of hepatitis B virus (HBV) continues to decline, we anticipate rates of HCC in many high-risk countries will continue to decrease. Treatment of hepatitis C virus (HCV) is likely to bring down rates further in some high-rate, as well as low-rate, countries with access to effective therapies. However, such gains in the control of liver cancer are at risk of being reversed by the growing obesity and diabetes epidemics, suggesting diabetes treatment and primary prevention of obesity will be key in reducing liver cancer in the longer-term.
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http://dx.doi.org/10.1002/ijc.32723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470451PMC
July 2020

Laryngeal Cancer Risks in Workers Exposed to Lung Carcinogens: Exposure-Effect Analyses Using a Quantitative Job Exposure Matrix.

Epidemiology 2020 01;31(1):145-154

University of Hong Kong, Hong Kong, China.

Introduction: Various established occupational lung carcinogens are also suspected risk factors for laryngeal cancer. However, individual studies are often inadequate in size to investigate this relatively rare outcome. Other limitations include imprecise exposure assessment and inadequate adjustment for confounders.

Methods: This study applied a quantitative job exposure matrix (SYN-JEM) for four established occupational lung carcinogens to five case-control studies within the International Head and Neck Cancer Epidemiology Consortium. We used occupational histories for 2256 laryngeal cancer cases and 7857 controls recruited from 1989 to 2007. We assigned quantitative exposure levels for asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined (to address highly correlated exposures) via SYN-JEM. We assessed effects of occupational exposure on cancer risk for males (asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined) and females (asbestos and respirable crystalline silica), adjusting for age, study, tobacco smoking, alcohol consumption, and asbestos exposure where relevant.

Results: Among females, odds ratios (ORs) were increased for ever versus never exposed. Among males, P values for linear trend were <0.05 for estimated cumulative exposure (all agents) and <0.05 for exposure duration (respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined); strongest associations were for asbestos at >90th percentile cumulative exposure (OR = 1.3, 95% confidence interval [CI] = 1.0, 1.6), respirable crystalline silica at 30+ years duration (OR = 1.4, 95% CI = 1.2, 1.7) and 75th-90th percentile cumulative exposure (OR = 1.4, 95% CI = 1.1, 1.8), chromium-VI at >75th percentile cumulative exposure (OR = 1.9, 95% CI = 1.2, 3.0), and chromium-VI and nickel combined at 20-29 years duration (OR = 1.5, 95% CI = 1.1, 2.2).

Conclusions: These findings support hypotheses of causal links between four lung carcinogens (asbestos, respirable crystalline silica, chromium-VI, and nickel) and laryngeal cancer.
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http://dx.doi.org/10.1097/EDE.0000000000001120DOI Listing
January 2020

International Trends in the Incidence of Testicular Cancer: Lessons from 35 Years and 41 Countries.

Eur Urol 2019 11 17;76(5):615-623. Epub 2019 Jul 17.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Background: Incidence rates of testicular cancer (TC) have been increasing in many countries since, at least, the mid-20th century without clear explanation. Examining the varying trends across countries and time provides clues to understanding the causes of TC.

Objective: We have presented incidence data from 41 countries and evaluated incidence trends for the 35-yr period from 1978 to 2012.

Design, Setting, And Participants: Cancer registry data from Cancer Incidence in Five Continents (CI5) volumes V-XI, CI5plus, and the NORDCAN database were analysed.

Outcome Measurements And Statistical Analysis: Age-standardised rates of TC overall and by histological type were calculated. A joinpoint regression model of the natural log-transformed rates was used to calculate the average annual percent change (AAPC) in incidence. Age-period-cohort modelling was used to examine the effect of birth cohort on rates.

Results And Limitations: While the highest incidence of TC remains in Northern Europe, the gap is closing between higher- and lower-incidence regions. Age-period-cohort modelling found flattening of risk among recent cohorts in Denmark and the UK, a steady increase in risk in the USA (particularly for seminomas), and an increase in risk among more recent cohorts in Costa Rica, Croatia, and Slovakia.

Conclusions: The gap between low- and high-incidence countries is closing due to increases in the former and stabilisation in the latter. Understanding the causes of these and other differences in incidence rates between, and within, countries may help further our understanding of the aetiology of this cancer.

Patient Summary: We examined the rates of testicular cancer in different countries over time. These rates have been increasing, although the rates in high-incidence countries seem to be slowing down, while rates in low-incidence countries are catching up. These trends might help us understand what is causing testicular cancer in general.
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http://dx.doi.org/10.1016/j.eururo.2019.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653517PMC
November 2019

Joint effects of intensity and duration of cigarette smoking on the risk of head and neck cancer: A bivariate spline model approach.

Oral Oncol 2019 07 17;94:47-57. Epub 2019 May 17.

International Agency for Research on Cancer, Lyon, France.

Objectives: This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures.

Materials And Methods: We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework.

Results: For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30  years. In former smokers who quit ≥10  years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers.

Conclusion: Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.
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http://dx.doi.org/10.1016/j.oraloncology.2019.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7117823PMC
July 2019

Global patterns and trends in the incidence of non-Hodgkin lymphoma.

Cancer Causes Control 2019 May 20;30(5):489-499. Epub 2019 Mar 20.

Section of Cancer Surveillance, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372, Lyon CEDEX 08, France.

Purpose: Despite an increasing understanding of the pathology and genetics of non-Hodgkin lymphoma (NHL), global reports on variations in the incidence of NHL remain limited in their number and scope.

Methods: To provide a situation analysis, national incidence estimates for NHL in 185 countries for the year 2018 were obtained from the GLOBOCAN database. We also used recorded incidence data from Cancer Incidence in Five Continents (CI5) plus for years of diagnosis 1980-2012 to examine temporal trends.

Results: NHL ranked as the 5th to 9th most common cancer in most countries worldwide, with almost 510,000 new cases estimated in 2018. Observed incidence rates of NHL 2008-2012 varied markedly by world region: among males, rates were highest among Israel Jews [age-standardized (world) rate of 17.6 per 100,000), Australia (15.3), US whites (14.5), Canada (13.7), and Portugal (13.3)]. Where data were available, most populations exhibited stable or slightly increasing incidence rates; in North America, parts of Europe, and Oceania the rising incidence rates were generally observed until the 1990s, with a stabilization seen thereafter.

Conclusion: Marked variations in NHL incidence rates remain in populations in each world region. Special attention should be given to further etiological research on the role of endemic infections and environmental exposures, particularly in Africa, Asia, and Latin America. To permit internationally comparable statistics, an equal focus on addressing the quality of hematological information in population-based registries is also warranted.
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http://dx.doi.org/10.1007/s10552-019-01155-5DOI Listing
May 2019

Proportion of cancers attributable to major lifestyle and environmental risk factors in the Eastern Mediterranean region.

Int J Cancer 2020 02 29;146(3):646-656. Epub 2019 Apr 29.

Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France.

Cancer is a major contributing cause of morbidity and mortality in the Eastern Mediterranean region. The aim of the current study was to estimate the cancer burden attributable to major lifestyle and environmental risk factors. We used age-, sex- and site-specific incidence estimates for 2012 from IARC's GLOBOCAN, and assessed the following risk factors: smoking, alcohol, high body mass index, insufficient physical activity, diet, suboptimal breastfeeding, infections and air pollution. The prevalence of exposure to these risk factors came from different sources including peer-reviewed international literature, the World Health Organization, noncommunicable disease Risk Factor Collaboration, and the Food and Agriculture Organization. Sex-specific population-attributable fraction was estimated in the 22 countries of the Eastern Mediterranean region based on the prevalence of the selected risk factors and the relative risks obtained from meta-analyses. We estimated that approximately 33% (or 165,000 cases) of all new cancer cases in adults aged 30 years and older in 2012 were attributable to all selected risk factors combined. Infections and smoking accounted for more than half of the total attributable cases among men, while insufficient physical activity and exposure to infections accounted for more than two-thirds of the total attributable cases among women. A reduction in exposure to major lifestyle and environmental risk factors could prevent a substantial number of cancer cases in the Eastern Mediterranean. Population-based programs preventing infections and smoking (particularly among men) and promoting physical activity (particularly among women) in the population are needed to effectively decrease the regional cancer burden.
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http://dx.doi.org/10.1002/ijc.32284DOI Listing
February 2020

Essential TNM: a registry tool to reduce gaps in cancer staging information.

Lancet Oncol 2019 02;20(2):e103-e111

Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada; Union for International Cancer Control, Geneva, Switzerland.

Accurate information on the extent of disease around the time of diagnosis is an important component of cancer care, in defining disease prognosis, and evaluating national and international cancer control policies. However, the collection of stage data by population-based cancer registries remains a challenge in both high-income and low and middle-income countries. We emphasise the lack of availability and comparability of staging information in many population-based cancer registries and propose Essential TNM, a simplified staging system for cancer registries when information on full Tumour, Node, Metastasis (TNM) is absent. Essential TNM aims at staging cancer in its most advanced disease form by summarising the extent of disease in the order of distant metastasis (M), regional lymph node involvement (N), and tumour size or extension, or both (T). Flowcharts and rules have been developed for coding these elements in breast, cervix, prostate, and colon cancers, and combining them into stage groups (I-IV) that correspond to those obtained by full TNM staging. Essential TNM is comparable to the Union for International Cancer Control TNM stage groups and is an alternative to providing staging information by the population-based cancer registries that complies with the objectives of the Global Initiative for Cancer Registry Development.
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http://dx.doi.org/10.1016/S1470-2045(18)30897-0DOI Listing
February 2019

Epidemiology of Bladder Cancer: A Systematic Review and Contemporary Update of Risk Factors in 2018.

Eur Urol 2018 12 26;74(6):784-795. Epub 2018 Sep 26.

Academic Urology Unit, University of Sheffield, Sheffield, UK.

Context: Bladder cancer (BC) is a significant health problem, and understanding the risk factors for this disease could improve prevention and early detection.

Objective: To provide a systematic review and summary of novel developments in epidemiology and risk factors for BC.

Evidence Acquisition: A systematic review of original articles was performed by two pairs of reviewers (M.G.C., I.J., F.E., and K.P.) using PubMed/Medline in December 2017, updated in April 2018. To address our primary objective of reporting contemporary studies, we restricted our search to include studies from the last 5yr. We subdivided our review according to specific risk factors (PICO [Population Intervention Comparator Outcome]).

Evidence Synthesis: Our search found 2191 articles, of which 279 full-text manuscripts were included. We separated our manuscripts by the specific risk factor they addressed (PICO). According to GLOBOCAN estimates, there were 430000 new BC cases and 165000 deaths worldwide in 2012. Tobacco smoking and occupational exposure to carcinogens remain the factors with the highest attributable risk. The literature was limited by heterogeneity of data.

Conclusions: Evidence is emerging regarding gene-environment interactions, particularly for tobacco and occupational exposures. In some populations, incidence rates are declining, which may reflect a decrease in smoking. Standardisation of reporting may help improve epidemiologic evaluation of risk.

Patient Summary: Bladder cancer is common worldwide, and the main risk factors are tobacco smoking and exposure to certain chemicals in the working and general environments. There is ongoing research to identify and reduce risk factors, as well as to understand the impact of genetics on bladder cancer risk.
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http://dx.doi.org/10.1016/j.eururo.2018.09.001DOI Listing
December 2018

The public health challenge of liver cancer in Mongolia.

Lancet Gastroenterol Hepatol 2018 10;3(10):660-662

Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon 69372, France.

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http://dx.doi.org/10.1016/S2468-1253(18)30243-7DOI Listing
October 2018

A case-control study of HIV infection and cancer in the era of antiretroviral therapy in Rwanda.

Int J Cancer 2018 09 26;143(6):1348-1355. Epub 2018 Apr 26.

International Agency for Research on Cancer, Lyon, France.

The aim of this study was to assess the association between HIV infection and cancer risk in Rwanda approximately a decade after the introduction of antiretroviral therapy (cART). All persons seeking cancer care at Butaro Cancer Center of Excellence (BCCOE) in Rwanda from 2012 to 2016 were routinely screened for HIV, prior to being confirmed with or without cancer (cases and controls, respectively). Cases were coded according to ICD-O-3 and converted to ICD10. Associations between individual cancer types and HIV were estimated using adjusted unconditional logistic regression. 2,656 cases and 1,196 controls differed by gender (80.3% vs. 70.8% female), age (mean 45.5 vs. 37.7 years), place of residence and proportion of diagnoses made by histopathology (87.5% vs. 67.4%). After adjustment for these variables, HIV was significantly associated with Kaposi Sarcoma (n = 60; OR = 110.3, 95%CI 46.8-259.6), non-Hodgkin lymphoma (NHL) (n = 265; OR = 2.5, 1.4-4.6), Hodgkin lymphoma (HL) (n = 76; OR = 5.2, 2.3-11.6) and cancers of the cervix (n = 560; OR = 5.9, 3.8-9.2), vulva (n = 23; OR = 17.8, 6.3-50.1), penis (n = 29; OR = 8.3, 2.5-27.4) and eye (n = 17; OR = 4.7, 1.0-25.0). Associations varied by NHL/HL subtype, with that for NHL being limited to DLBCL (n = 56; OR = 6.6, 3.1-14.1), particularly plasmablastic lymphoma (n = 6, OR = 106, 12.1-921). No significant associations were seen with other commonly diagnosed cancers, including female breast cancer (n = 559), head and neck (n = 116) and colorectal cancer (n = 106). In conclusion, in the era of cART in Rwanda, HIV is associated with increased risk of a range of infection-related cancers, and accounts for an important fraction of cancers presenting to a referral hospital.
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http://dx.doi.org/10.1002/ijc.31537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099235PMC
September 2018

Genetic Contributions to The Association Between Adult Height and Head and Neck Cancer: A Mendelian Randomization Analysis.

Sci Rep 2018 03 14;8(1):4534. Epub 2018 Mar 14.

Section of Hygiene, Institute of Public Health, Università Cattolica del Sacro Cuore, IRCCS Fondazione Policlinico 'Agostino Gemelli', Rome, Italy.

With the aim to dissect the effect of adult height on head and neck cancer (HNC), we use the Mendelian randomization (MR) approach to test the association between genetic instruments for height and the risk of HNC. 599 single nucleotide polymorphisms (SNPs) were identified as genetic instruments for height, accounting for 16% of the phenotypic variation. Genetic data concerning HNC cases and controls were obtained from a genome-wide association study. Summary statistics for genetic association were used in complementary MR approaches: the weighted genetic risk score (GRS) and the inverse-variance weighted (IVW). MR-Egger regression was used for sensitivity analysis and pleiotropy evaluation. From the GRS analysis, one standard deviation (SD) higher height (6.9 cm; due to genetic predisposition across 599 SNPs) raised the risk for HNC (Odds ratio (OR), 1.14; 95% Confidence Interval (95%CI), 0.99-1.32). The association analyses with potential confounders revealed that the GRS was associated with tobacco smoking (OR = 0.80, 95% CI (0.69-0.93)). MR-Egger regression did not provide evidence of overall directional pleiotropy. Our study indicates that height is potentially associated with HNC risk. However, the reported risk could be underestimated since, at the genetic level, height emerged to be inversely associated with smoking.
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http://dx.doi.org/10.1038/s41598-018-22626-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852094PMC
March 2018

Evaluation of data quality at the National Cancer Registry of Ukraine.

Cancer Epidemiol 2018 04 22;53:156-165. Epub 2018 Feb 22.

Cancer Surveillance Section, International Agency for Research on Cancer, Lyon, France. Electronic address:

Background: Cancer notification has been mandatory in Ukraine since 1953, with the National Cancer Registry of Ukraine (NCRU) established in 1996. The aim of this study was to provide a comprehensive evaluation of the data quality at the NCRU.

Methods: Qualitative and semi-quantitative methods were used to assess the comparability, completeness, validity and timeliness of cancer incidence data from the NCRU for the period 2002-2012.

Results: Cancer registration procedures at the NCRU are in accordance with international standards and recommendations. Semi-quantitative methods suggested the NCRU's data was reasonably complete, although decreases in age-specific incidence and mortality rates in the elderly indicated some missing cases at older ages. The proportion of microscopically-verified cases increased from 73.6% in 2002 to 82.3% in 2012, with death-certificate-only (DCO) proportions stable at around 0.1% and unknown stage recorded in 9.6% of male and 7.5% of female solid tumours. Timeliness was considered acceptable, with reporting >99% complete within a turn-around time of 15 months.

Conclusion: While timely reporting of national data reflects the advantages of a mandatory data collection system, a low DCO% and observed age-specific declines suggest possible underreporting of incidence and mortality data, particularly at older ages. Overall, the evaluation indicates that the data are reasonably comparable and thus may be used to describe the magnitude of the cancer burden in Ukraine. Given its central role in monitoring and evaluation of cancer control activities, ensuring the sustainability of NCRU operations throughout the process of healthcare system reform is of utmost importance.
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http://dx.doi.org/10.1016/j.canep.2018.02.002DOI Listing
April 2018

Cancer surveillance in northern Africa, and central and western Asia: challenges and strategies in support of developing cancer registries.

Lancet Oncol 2018 02;19(2):e85-e92

Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France.

The Global Initiative for Cancer Registry Development partnership, led by the International Agency for Research on Cancer (IARC), was established in response to an overwhelming need for high-quality cancer incidence data from low-income and middle-income countries. The IARC Regional Hub for cancer registration in North Africa, Central and West Asia was founded in 2013 to support capacity building for cancer registration in each of the countries in this region. In this Series paper, we advocate the necessity for tailored approaches to cancer registration given the rapidly changing cancer landscape for this region, and the challenges faced at a national level in developing data systems to help support this process given present disparities in resources and health infrastructure. In addition, we provide an overview of the status of cancer surveillance and activities country-by-country, documenting tailored approaches that are informing local cancer-control policy, and potentially curbing the growing cancer burden across the region.
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http://dx.doi.org/10.1016/S1470-2045(18)30019-6DOI Listing
February 2018

The influence of smoking, age and stage at diagnosis on the survival after larynx, hypopharynx and oral cavity cancers in Europe: The ARCAGE study.

Int J Cancer 2018 07 23;143(1):32-44. Epub 2018 Feb 23.

Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon, France.

Head and neck cancer (HNC) is a preventable malignancy that continues to cause substantial morbidity and mortality worldwide. Using data from the ARCAGE and Rome studies, we investigated the main predictors of survival after larynx, hypopharynx and oral cavity (OC) cancers. We used the Kaplan-Meier method to estimate overall survival, and Cox proportional models to examine the relationship between survival and sociodemographic and clinical characteristics. 604 larynx, 146 hypopharynx and 460 OC cancer cases were included in this study. Over a median follow-up time of 4.6 years, nearly 50% (n = 586) of patients died. Five-year survival was 65% for larynx, 55% for OC and 35% for hypopharynx cancers. In a multivariable analysis, we observed an increased mortality risk among older (≥71 years) versus younger (≤50 years) patients with larynx/hypopharynx combined (LH) and OC cancers [HR = 1.61, 95% CI 1.09-2.38 (LH) and HR = 2.12, 95% CI 1.35-3.33 (OC)], current versus never smokers [HR = 2.67, 95% CI 1.40-5.08 (LH) and HR = 2.16, 95% CI 1.32-3.54 (OC)] and advanced versus early stage disease at diagnosis [IV versus I, HR = 2.60, 95% CI 1.78-3.79 (LH) and HR = 3.17, 95% CI 2.05-4.89 (OC)]. Survival was not associated with sex, alcohol consumption, education, oral health, p16 expression, presence of HPV infection or body mass index 2 years before cancer diagnosis. Despite advances in diagnosis and therapeutic modalities, survival after HNC remains low in Europe. In addition to the recognized prognostic effect of stage at diagnosis, smoking history and older age at diagnosis are important prognostic indicators for HNC.
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http://dx.doi.org/10.1002/ijc.31294DOI Listing
July 2018

Malignant melanoma incidence trends in a Mediterranean population following socioeconomic transition and war: results of age-period-cohort analysis in Croatia, 1989-2013.

Melanoma Res 2017 10;27(5):498-502

aAndrija Stampar School of Public Health, School of Medicine, University of Zagreb, Zagreb, Croatia bSection of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France.

The aim of this study was to analyse trends of malignant melanoma incidence in Croatia for men and women of different age groups by birth cohorts and time periods, and to interpret them in the context of national socioeconomic changes over time and the possible implications for future prevention in South-Eastern European postcommunist countries with high mortality rates. We used the Croatian National Cancer Registry data to analyse incidence trends of malignant melanoma of the skin (ICD-9 code 172 and ICD-10 code C43) in men and women aged 25-79 years by age-period-cohort modelling. Over the 25-year period, the incidence was increasing by 5.0% annually in men and 4.6% in women. The age-period model provided the best fit for data in both sexes, with steeply increasing incidence rates, followed by a stabilization after the 2000s. On the cohort scale, incidence rates increased in successive generations of men, whereas in women, the risk of malignant melanoma attenuated in recent cohorts. Even if some progress has been achieved in recent years, the increasing melanoma incidence without concomitant declines in mortality would indicate a need to rekindle prevention efforts in the country taking the specific socioeconomic context into account.
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http://dx.doi.org/10.1097/CMR.0000000000000385DOI Listing
October 2017
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