The impact of excluding or including Death Certificate Initiated (DCI) cases on estimated cancer survival: A simulation study

Background Population-based cancer registries strive to cover all cancer cases diagnosed within the population, but some cases will always be missed and no register is 100 % complete. Many cancer registries use death certificates to identify additional cases not captured through other routine sources, to hopefully add a large proportion of the missed cases. Cases notified through this route, who would not have been captured without death certificate information, are referred to as Death Certificate Initiated (DCI) cases. Inclusion of DCI cases in cancer registries increases completeness and is important for estimating cancer incidence. However, inclusion of DCI cases will generally lead to biased estimates of cancer survival, but the same is often also true if excluding DCI cases. Missed cases are probably not a random sample of all cancer cases, but rather cases with poor prognosis. Further, DCI cases have poorer prognosis than missed cases in general, since they have all died with cancer mentioned on the death certificates. Methods We performed a simulation study to estimate the impact of including or excluding DCI cases on cancer survival estimates, under different scenarios. Results We demonstrated that including DCI cases underestimates survival. The exclusion of DCI cases gives unbiased survival estimates if missed cases are a random sample of all cancer cases, while survival is overestimated if these have poorer prognosis. Conclusion In our most extreme scenarios, with 25 % of cases initially missed, the usual practice of including DCI cases underestimated 5-year survival by at most 3 percentage points

Exploring the impact of cancer registry completeness on international cancer survival differences: a simulation study

Background Data from population-based cancer registries are often used to compare cancer survival between countries or regions. The ICBP SURVMARK-2 study is an international partnership aiming to quantify and explore the reasons behind survival differences across high-income countries. However, the magnitude and relevance of differences in cancer survival between countries have been questioned, as it is argued that observed survival variations may be explained, at least in part, by differences in cancer registration practice, completeness and the availability and quality of the respective data sources. Methods As part of the ICBP SURVMARK-2 study, we used a simulation approach to better understand how differences in completeness, the characteristics of those missed and inclusion of cases found from death certificates can impact on cancer survival estimates. Results Bias in 1- and 5-year net survival estimates for 216 simulated scenarios is presented. Out of the investigated factors, the proportion of cases not registered through sources other than death certificates, had the largest impact on survival estimates. Conclusion Our results show that the differences in registration practice between participating countries could in our most extreme scenarios explain only a part of the largest observed differences in cancer survival

Determinants of acquisition and clearance of human papillomavirus infection in previously unexposed young women

Background Global variation in human papillomavirus (HPV) prevalence and persistence may be explained by differences in risk factors, such as sexual activity, oral contraceptive use, and behavioral factors. We evaluated determinants of acquisition and clearance of HPV infection among young women previously unexposed to HPV. Methods Five hundred thirty-four women aged 15 to 25 years who were cytology and HPV DNA negative, and seronegative for anti-HPV-16/18 antibodies, were recruited (July 2000–September 2001) from study centers in Brazil, the United States, and Canada (NCT00689741/NCT00120848). They were followed up for 76 months. Cervical samples were HPV genotyped via polymerase chain reaction. We used multivariable (forward stepwise, P = 0.15) Cox proportional hazards regression to estimate rate ratios (RR) and 95% confidence intervals (CI), separately according to length of follow-up time. Results On short-term follow-up (0–27 months), 257 (48%; 8535.80 person-months; incidence rate = 30.11; 95% CI, 26.64–34.02) incident HPV infections were detected. Marital status, lifetime number of sex partners, history of any sexually transmitted disease, and occasional use of oral contraceptives were strongly associated with acquisition of any HPV. Having 2 or more lifetime sex partners (RR, 2.03; 95% CI, 1.37–3.02) and a history of any sexually transmitted disease (RR, 1.98; 95% CI, 1.19–3.29) were the most important determinants of high-risk HPV (hrHPV) incidence. During the entire follow-up (0–76 months), an increased hrHPV clearance was found among women in North America (RR, 1.38; 95% CI, 1.08–1.78) and black women (RR, 1.64; 95% CI, 1.04–2.60). Greater number of lifetime partners was associated with reduced clearance rates for any HPV (RR, 0.65; 95% CI, 0.43–0.98). Conclusions We identified variation in risk of HPV acquisition and clearance among women unexposed to HPV at baseline

International variation in oesophageal and gastric cancer survival 2012–2014: differences by histological subtype and stage at diagnosis (an ICBP SURVMARK-2 population-based study)

Objective To provide the first international comparison of oesophageal and gastric cancer survival by stage at diagnosis and histological subtype across high-income countries with similar access to healthcare. Methods As part of the ICBP SURVMARK-2 project, data from 28 923 patients with oesophageal cancer and 25 946 patients with gastric cancer diagnosed during 2012–2014 from 14 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were included. 1-year and 3-year age-standardised net survival were estimated by stage at diagnosis, histological subtype (oesophageal adenocarcinoma (OAC) and oesophageal squamous cell carcinoma (OSCC)) and country. Results Oesophageal cancer survival was highest in Ireland and lowest in Canada at 1 (50.3% vs 41.3%, respectively) and 3 years (27.0% vs 19.2%) postdiagnosis. Survival from gastric cancer was highest in Australia and lowest in the UK, for both 1-year (55.2% vs 44.8%, respectively) and 3-year survival (33.7% vs 22.3%). Most patients with oesophageal and gastric cancer had regional or distant disease, with proportions ranging between 56% and 90% across countries. Stage-specific analyses showed that variation between countries was greatest for localised disease, where survival ranged between 66.6% in Australia and 83.2% in the UK for oesophageal cancer and between 75.5% in Australia and 94.3% in New Zealand for gastric cancer at 1-year postdiagnosis. While survival for OAC was generally higher than that for OSCC, disparities across countries were similar for both histological subtypes. Conclusion Survival from oesophageal and gastric cancer varies across high-income countries including within stage groups, particularly for localised disease. Disparities can partly be explained by earlier diagnosis resulting in more favourable stage distributions, and distributions of histological subtypes of oesophageal cancer across countries. Yet, differences in treatment, and also in cancer registration practice and the use of different staging methods and systems, across countries may have impacted the comparisons. While primary prevention remains key, advancements in early detection research are promising and will likely allow for additional risk stratification and survival improvements in the future

Prognostic value of non-invasive scores based on liver stiffness measurement, spleen diameter and platelets in HIV-infected patients

BACKGROUND AND AIMS: People living with HIV (PLWH) are at high risk for advanced chronic liver disease and related adverse outcomes. We aimed to validate the prognostic value of non-invasive scores based on liver stiffness measurement (LSM) and on markers of portal hypertension (PH), namely platelets and spleen diameter, in PLWH. METHODS: We combined data from eight international cohorts of PLWH with available non-invasive scores, including LSM and the composite biomarkers liver stiffness-spleen size-to-platelet ratio score (LSPS), LSM-to-Platelet ratio (LPR) and PH risk score. Incidence and predictors of all-cause mortality, any liver-related event and classical hepatic decompensation were determined by survival analysis, controlling for competing risks for the latter two. Non-invasive scores were assessed and compared using area under the receiver operating curve (AUROC). RESULTS: We included 1695 PLWH (66.8% coinfected with hepatitis C virus). During a median follow-up of 4.7 (interquartile range 2.8-7.7) years, the incidence rates of any liver-related event, all-cause mortality and hepatic decompensation were 13.7 per 1000 persons-year (PY) (95% confidence interval [CI], 11.4-16.3), 13.8 per 1000 PY (95% CI, 11.6-16.4) and 9.9 per 1000 PY (95% CI, 8.1-12.2), respectively. The AUROC of LSM was similar to that of the composite biomarkers, ranging between 0.83 and 0.86 for any liver-related event, 0.79-0.85 for all-cause mortality and 0.87-0.88 for classical hepatic decompensation. All individual non-invasive scores remained independent predictors of clinical outcomes in multivariable analysis. CONCLUSIONS: Non-invasive scores based on LSM, spleen diameter and platelets predict clinical outcomes in PLWH. Composite biomarkers do not achieve higher prognostic performance compared to LSM alone

Prognostic value of non-invasive scores based on liver stiffness measurement, spleen diameter and platelets in HIV-infected patients.

BACKGROUND AND AIMS People living with HIV (PLWH) are at high risk for advanced chronic liver disease and related adverse outcomes. We aimed to validate the prognostic value of non-invasive scores based on liver stiffness measurement (LSM) and on markers of portal hypertension (PH), namely platelets and spleen diameter, in PLWH. METHODS We combined data from eight international cohorts of PLWH with available non-invasive scores, including LSM and the composite biomarkers liver stiffness-spleen size-to-platelet ratio score (LSPS), LSM-to-Platelet ratio (LPR) and PH risk score. Incidence and predictors of all-cause mortality, any liver-related event and classical hepatic decompensation were determined by survival analysis, controlling for competing risks for the latter two. Non-invasive scores were assessed and compared using area under the receiver operating curve (AUROC). RESULTS We included 1695 PLWH (66.8% coinfected with hepatitis C virus). During a median follow-up of 4.7 (interquartile range 2.8-7.7) years, the incidence rates of any liver-related event, all-cause mortality and hepatic decompensation were 13.7 per 1000 persons-year (PY) (95% confidence interval [CI], 11.4-16.3), 13.8 per 1000 PY (95% CI, 11.6-16.4) and 9.9 per 1000 PY (95% CI, 8.1-12.2), respectively. The AUROC of LSM was similar to that of the composite biomarkers, ranging between 0.83 and 0.86 for any liver-related event, 0.79-0.85 for all-cause mortality and 0.87-0.88 for classical hepatic decompensation. All individual non-invasive scores remained independent predictors of clinical outcomes in multivariable analysis. CONCLUSIONS Non-invasive scores based on LSM, spleen diameter and platelets predict clinical outcomes in PLWH. Composite biomarkers do not achieve higher prognostic performance compared to LSM alone

Progress in cancer survival, mortality, and incidence in seven high-income countries 1995–2014 (ICBP SURVMARK-2): a population-based study

© 2019 World Health Organization Background: Population-based cancer survival estimates provide valuable insights into the effectiveness of cancer services and can reflect the prospects of cure. As part of the second phase of the International Cancer Benchmarking Partnership (ICBP), the Cancer Survival in High-Income Countries (SURVMARK-2) project aims to provide a comprehensive overview of cancer survival across seven high-income countries and a comparative assessment of corresponding incidence and mortality trends. Methods: In this longitudinal, population-based study, we collected patient-level data on 3·9 million patients with cancer from population-based cancer registries in 21 jurisdictions in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the UK) for seven sites of cancer (oesophagus, stomach, colon, rectum, pancreas, lung, and ovary) diagnosed between 1995 and 2014, and followed up until Dec 31, 2015. We calculated age-standardised net survival at 1 year and 5 years after diagnosis by site, age group, and period of diagnosis. We mapped changes in incidence and mortality to changes in survival to assess progress in cancer control. Findings: In 19 eligible jurisdictions, 3 764 543 cases of cancer were eligible for inclusion in the study. In the 19 included jurisdictions, over 1995–2014, 1-year and 5-year net survival increased in each country across almost all cancer types, with, for example, 5-year rectal cancer survival increasing more than 13 percentage points in Denmark, Ireland, and the UK. For 2010–14, survival was generally higher in Australia, Canada, and Norway than in New Zealand, Denmark, Ireland, and the UK. Over the study period, larger survival improvements were observed for patients younger than 75 years at diagnosis than those aged 75 years and older, and notably for cancers with a poor prognosis (ie, oesophagus, stomach, pancreas, and lung). Progress in cancer control (ie, increased survival, decreased mortality and incidence) over the study period was evident for stomach, colon, lung (in males), and ovarian cancer. Interpretation: The joint evaluation of trends in incidence, mortality, and survival indicated progress in four of the seven studied cancers. Cancer survival continues to increase across high-income countries; however, international disparities persist. While truly valid comparisons require differences in registration practice, classification, and coding to be minimal, stage of disease at diagnosis, timely access to effective treatment, and the extent of comorbidity are likely the main determinants of patient outcomes. Future studies are needed to assess the impact of these factors to further our understanding of international disparities in cancer survival. Funding: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; The Scottish Government; Western Australia Department of Health; and Wales Cancer Network

Lung cancer risk in never-smokers: a population-based case-control study of epidemiologic risk factors

<p>Abstract</p> <p>Background</p> <p>We conducted a case-control study in the greater Toronto area to evaluate potential lung cancer risk factors including environmental tobacco smoke (ETS) exposure, family history of cancer, indoor air pollution, workplace exposures and history of previous respiratory diseases with special consideration given to never smokers.</p> <p>Methods</p> <p>445 cases (35% of which were never smokers oversampled by design) between the ages of 20-84 were identified through four major tertiary care hospitals in metropolitan Toronto between 1997 and 2002 and were frequency matched on sex and ethnicity with 425 population controls and 523 hospital controls. Unconditional logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the associations between exposures and lung cancer risk.</p> <p>Results</p> <p>Any previous exposure to occupational exposures (OR total population 1.6, 95% CI 1.4-2.1, OR never smokers 2.1, 95% CI 1.3-3.3), a previous diagnosis of emphysema in the total population (OR 4.8, 95% CI 2.0-11.1) or a first degree family member with a previous cancer diagnosis before age 50 among never smokers (OR 1.8, 95% CI 1.0-3.2) were associated with increased lung cancer risk.</p> <p>Conclusions</p> <p>Occupational exposures and family history of cancer with young onset were important risk factors among never smokers.</p