The OncoSim model: development and use for better decision-making in Canadian cancer control.

The Canadian Partnership Against Cancer was created in 2007 by the federal government to accelerate cancer control across Canada. Its OncoSim microsimulation model platform, which consists of a suite of specific cancer models, was conceived as a tool to augment conventional resources for population-level policy- and decision-making. The Canadian Partnership Against Cancer manages the OncoSim program, with funding from Health Canada and model development by Statistics Canada. Microsimulation modelling allows for the detailed capture of population heterogeneity and health and demographic history over time. Extensive data from multiple Canadian sources were used as inputs or to validate the model. OncoSim has been validated through expert consultation; assessments of face validity, internal validity, and external validity; and model fit against observed data. The platform comprises three in-depth cancer models (lung, colorectal, cervical), with another in-depth model (breast) and a generalized model (25 cancers) being in development. Unique among models of its class, OncoSim is available online for public sector use free of charge. Users can customize input values and output display, and extensive user support is provided. OncoSim has been used to support decision-making at the national and jurisdictional levels. Although simulation studies are generally not included in hierarchies of evidence, they are integral to informing cancer control policy when clinical studies are not feasible. OncoSim can evaluate complex intervention scenarios for multiple cancers. Canadian decision-makers thus have a powerful tool to assess the costs, benefits, cost-effectiveness, and budgetary effects of cancer control interventions when faced with difficult choices for improvements in population health and resource allocation.

Using the Cancer Risk Management Model to evaluate the health and economic impacts of cytology compared with human papillomavirus DNA testing for primary cervical cancer screening in Canada.

BACKGROUND: In Canada, discussion about changing from cytology to human papillomavirus (hpv) dna testing for primary screening in cervical cancer is ongoing. However, the Canadian Task Force on Preventive Health Care has not yet made a recommendation, concluding that the evidence is insufficient. METHODS: We used the cervical cancer and hpv transmission models of the Cancer Risk Management Model to study the health and economic outcomes of primary cytology compared with hpv dna testing in 14 screening scenarios with varying screening modalities and intervals. Projected cervical cancer cases, deaths, colposcopies, screens, costs, and incremental cost-effectiveness were evaluated. We performed sensitivity analyses for hpv dna test costs. RESULTS: Compared with triennial cytology from age 25, 5-yearly hpv dna screening alone from age 30 resulted in equivalent incident cases and deaths, but 55% (82,000) fewer colposcopies and 43% (1,195,000) fewer screens. At hpv dna screening intervals of 3 years, whether alone or in an age-based sequence with cytology, screening costs are greater, but at intervals of more than 5 years, they are lower. Scenarios on the cost-effectiveness frontier were hpv dna testing alone every 10, 7.5, 5, or 3 years, and triennial cytology starting at age 21 or 25 when combined with hpv dna testing every 3 years. CONCLUSIONS: Changing from cytology to hpv dna testing as the primary screening test for cervical cancer would be an acceptable strategy in Canada with respect to incidence, mortality, screening and diagnostic test volumes.

Prevalence of self-reported hysterectomy among Canadian women, 2000/2001-2008.

BACKGROUND: Hysterectomy is one of the most frequently performed surgical procedures among Canadian women. The consequence is a population that no longer requires cervical cancer screening. The objective of our analysis was to provide more accurate estimates of eligible participation in cervical screening by estimating the age-specific prevalence of hysterectomy among Canadian women aged 20 to 69 by province and territory between 2000/2001 and 2008. METHODS: Self-reported hysterectomy prevalence was obtained from the 2000/2001, 2003 and 2008 Canadian Community Health Survey. Age-specific prevalence and 95% confidence intervals (CIs) were estimated for Canada and provinces and territories for the three time periods. RESULTS: Interprovincial variations in hysterectomy prevalence were observed among women in each age group and time period. Among women aged 50 to 59, prevalence was as high as 35.1% (95% CI: 25.8-44.3) (p<.01) in 2008 and appeared to decrease in all provinces from 2000/2001 to 2008. CONCLUSION: Interprovincial and time period variation suggest that using hysterectomy prevalence to adjust the population eligible for cervical cancer screening may be helpful to inform more comparable screening participation rates. In addition, both cervical cancer incidence and mortality rates can be adjusted by hysterectomy to ensure estimates across time and provinces and territories are also comparable.

TITRE: Prévalence de l'hystérectomie autodéclarée chez les Canadiennes, 2000-2001 à 2008. INTRODUCTION: L'hystérectomie est l'une des interventions chirurgicales les plus souvent pratiquées chez les Canadiennes. Le dépistage du cancer du col de l'utérus n'est donc plus nécessaire dans cette population. Notre analyse visait à obtenir des estimations plus exactes de la participation au dépistage du cancer du col utérin dans la population admissible en déterminant la prévalence de l'hystérectomie selon l'âge chez les Canadiennes de 20 à 69 ans, par province ou territoire, entre 2000-2001 et 2008. MÉTHODOLOGIE: Les données relatives à la prévalence de l'hystérectomie autodéclarée ont été tirées de l'Enquête sur la santé dans les collectivités canadiennes de 2000-2001, de 2003 et de 2008. Nous avons estimé la prévalence selon l'âge et les intervalles de confiance (IC) à 95 % pour le Canada et les provinces et territoires pour les trois périodes. RÉSULTATS: Des variations interprovinciales de la prévalence de l'hystérectomie ont été observées chez les femmes dans chaque groupe d'âge et au cours de chaque période. Chez les femmes de 50 à 59 ans, la prévalence a semblé diminuer dans toutes les provinces entre 2000-2001 et 2008, le plus haut taux provincial atteint en 2008 étant 35,1% (IC à 95%: 25,8 à 44,3; p < 0,01). CONCLUSION: Les variations selon les provinces et au cours du temps laissent penser qu'il pourrait être bon d'utiliser la prévalence de l'hystérectomie pour ajuster la population admissible au dépistage du cancer du col de l'utérus, de manière à obtenir des taux plus comparables de participation. Il est en outre possible d'ajuster à la fois les taux d'incidence du cancer du col utérin et de mortalité par cancer du col utérin de façon à ce que les estimations dans le temps et pour l'ensemble des provinces et territoires soient comparables.

KLK6 and KLK13 predict tumor recurrence in epithelial ovarian carcinoma.

BACKGROUND: The human kallikrein-related peptidase family consists of 15 genes. Twelve of these genes are overexpressed in ovarian cancer and may represent potential markers for diagnosis, prognosis, and/or response to treatment. The aim of this study was to determine the prognostic significance of kallikrein-related peptidase 6 (KLK6) and kallikrein-related peptidase 13 (KLK13) in epithelial ovarian cancer by quantifying gene expression levels with tumour pathology and patient survival data. METHODS: Total RNA was isolated from 106 patients diagnosed with primary ovarian cancer, as well as 8 normal ovary controls. Samples were analysed by quantitative real-time PCR for KLK6 and KLK13 expression. Correlation between kallikrein gene expression and clinical characteristics was evaluated with the chi(2)-test. Survival analysis was performed using Kaplan-Meier and Cox proportional hazards regression models. RESULTS: Expression levels of both KLK6 and KLK13 mRNA were significantly increased in invasive cancers relative to normal ovaries (P=0.002 and 0.039 respectively). High KLK6 and KLK13 expression was an indicator of poor prognosis, with patients having a shorter recurrence-free survival (P=0.002 and 0.027 respectively). High KLK6 expression was also significantly associated with lower overall survival (P=0.011). When subjected to multivariate analysis, patients with either high KLK6 or KLK13 were 3- and 2.2-fold, respectively, more likely to have a recurrence than patients with low kallikrein expression. CONCLUSION: These data show increased mRNA expression of KLK6 and KLK13 in ovarian cancer compared to normal ovarian tissues. High KLK6 or KLK13 expression in primary ovarian tumours can significantly predict prognosis in terms of recurrence-free survival and overall survival. In all, this study shows KLK6 and KLK13 as potential biomarkers and may be therapeutic targets for treatment of ovarian cancer.