Talía Malagón

Background: Multicancer early detection tests could be used for cancer screening, but may lead to harms, including false positive results and overdiagnosis of indolent tumors that would not have become clinically evident during that person's lifetime. We assessed the potential for these screening harms in the context of future population‐based screening with a multicancer early detection test. Methods: We used a microsimulation model to assess potential population‐level impacts of screening at ages 50–75 years with a multicancer early detection test in Canada. We assumed high test specificity (97%–99.1%) and test sensitivity increasing with cancer stage. The model includes latent indolent cancers that would not be diagnosed within that person's lifetime but can be overdiagnosed through screen‐detection. We calculated the yearly and cumulative lifetime probabilities of screening overdiagnosis and false positive test results, assuming a range of preclinical screen‐detectable periods (2–5 years). Results: An estimated 2.1%–6.0% of all yearly screen‐detected cancers with a multicancer screening test were predicted to be overdiagnoses across scenarios. The proportion of overdiagnosis varied by site and strongly increased with age, going from 1% at age 50 to over 10% of screen‐detected cancers by age 75. The test positive predictive value ranged from 15.9% to 77.6%, meaning that there could be 0.3–5.3 false positives with no underlying cancer for every true cancer case detected by the test. Conclusion: Population‐level multicancer screening with a multicancer early detection test would lead to screen‐related overdiagnosis; healthcare systems should consider how overdiagnoses and screening false positives may increase their follow‐up capacity and caseload.

Introduction: Cancer incidence rates in Canada have changed over the past 20 years due to changes in carcinogenic exposures and detection practices. We examined whether period or cohort effects are driving trends for 24 cancer sites across sociodemographic strata. Methods: The Canadian Census Health and Environment Cohorts are data linkages of respondents of the long-form census and National Household Survey (NHS) to the Canadian Cancer Registry from 2006 to 2021. We fitted age-period-cohort models to cancer incidence; cohort effects were stratified by sex, income, education level, immigration status, and racial group; period effects were stratified by age (=50 years). Results: There were 806,510 incident primary cancers diagnosed in 17.8M individuals over 140.7M person-years. Most cancer sites have experienced an increasing incidence by period effect countered by a decreasing incidence by cohort effect for birth cohorts born over the 20th century, with a trend reversal for some cancer sites in cohorts born in the 1980s-1990s. Cohort effects differed by sex, income, education level, immigration status, and racial group. There were larger relative period-effect increases in <50 year-olds for breast (female), colorectal, kidney & renal pelvis, and uterine cancer incidence, but not other cancers. Conclusions: Declining cohort effects likely reflect ongoing efforts in tobacco control, cervical and colorectal cancer screening, and improvements in living conditions across the 20th century. The causes of period increases in cancer incidence may include changes in detection practices from screening and incidental findings. The obesity epidemic has likely contributed to both period and cohort effects.

Background: Timely cancer diagnosis in children and adolescents is important to improving outcomes. We aimed to quantify time to diagnosis and assess variations by patient, demographic and system‐level factors. Procedure: We conducted a population‐based study of individuals aged 0–19 years diagnosed with one of 12 cancers from 2010 to 2022 in Québec, Canada. The diagnostic interval was defined as the time from first cancer‐related healthcare encounter to diagnosis. We calculated medians and interquartile ranges (IQRs) overall and by cancer type and used multivariable quantile regression to identify factors associated with time to diagnosis at the 25th, 50th and 75th percentiles. Results: Among 2927 patients, diagnostic intervals differed by cancer type, age and rurality, but not by sex, material or social deprivation. Median intervals were longest for carcinomas (100 days; IQR 33–192) and shortest for leukaemias (8 days; IQR 3–44). Older children had longer intervals. Compared with children living in Montréal, living in regional areas and other large urban centres was associated with longer 50th and 75th percentiles of time to diagnosis for hepatic (30 days; 95% confidence interval [CI], 6–53) and central nervous system (CNS) tumours (91 days; 95% CI, 23–159). Diagnostic intervals were shorter in 2020–2022 across several cancer sites, with CNS tumours showing reductions across all quantiles and a higher proportion of emergency department visits as the first cancer‐related healthcare encounter. Conclusion: Shorter diagnostic intervals in 2020–2022 suggest that pandemic‐related changes in care pathways may have expedited diagnosis for some cancers.

Purpose: Human papillomavirus (HPV) infection and HPV-associated diseases impact health-related quality of life (HRQOL). We aimed to measure HRQOL in women with HPV-positive test results, cervical intraepithelial neoplasia (CIN), or cervical cancer in Latin America. Methods: We enrolled women aged 18 to 75 years from Bolivia, Colombia, Honduras, Peru, and Uruguay. We used the EQ-5D-5L instrument to calculate EQ-5D index scores with country-specific sets of health preferences when available. We calculated medians and interquartile ranges (IQR) of EQ-5D index and conducted an exploratory analysis comparing HRQOL loss by diagnosis and country with a gamma regression. Results: We present results from 1,073 participants. Median age was 43 years (IQR: 34-52). The EQ-5D index scores by diagnosis were as follows: HPV-positive test alone 0.906 (standard deviation [SD]: 0.129), CIN1: 0.891 (SD: 0.136), CIN2: 0.892 (SE: 0.124), CIN3: 0.870 (SD: 0.138), and cervical cancer: 0.737 (SD: 0.268). HRQOL was associated with age, diagnosis, and country; there was a significant decreasing trend in HRQOL with worsening health state. Women with cervical cancer had a 3.19-fold higher HRQOL loss than women with an HPV-positive test alone or CIN1. We also found significant differences in HRQOL loss across countries, after adjustment for diagnosis and sociodemographic factors. Conclusion: HRQOL decreased with diagnosis severity, with significant differences between countries. To conduct cost-effectiveness modeling on HPV preventive interventions, obtaining accurate HRQOL estimates is essential. This process should consider the diverse local health preferences influenced by sociodemographic and cultural factors, as well as the population’s beliefs and experiences regarding health. PLAIN ENGLISH SUMMARY: Human papillomavirus (HPV) infection can cause precancerous lesions and cervical cancer, but there is limited information about how these conditions affect women’s quality of life, especially in low- and middle-income countries where the disease burden is highest. This study aimed to measure quality of life among women with HPV-positive test results, precancerous cervical lesions, and cervical cancer in Latin America. We included 1,073 women aged 18 to 75 years from Bolivia, Colombia, Honduras, Peru, and Uruguay. Participants completed the EQ-5D-5L, an internationally validated questionnaire used to measure health-related quality of life. We found that quality of life worsened as disease severity progressed. Women with cervical cancer experienced a 3.19-fold greater loss in quality of life compared with women who had an HPV-positive test result or mild precancerous lesions (CIN1). We also found important differences between countries. These findings provide locally relevant quality-of-life estimates that can be used in future economic evaluations to help identify the most efficient strategies for preventing and treating cervical cancer and precancerous lesions in Latin America.

Background: Multicancer early detection tests could be used for cancer screening, but may lead to harms, including false positive results and overdiagnosis of indolent tumours that would not have become clinically evident during that person's lifetime. We assessed the potential for these screening harms in the context of future population-based screening with a multicancer early detection test. Methods: We used a microsimulation model to assess potential population-level impacts of screening at ages 50-75 years with a multicancer early detection test in Canada. We assumed high test specificity (97-99.1%) and test sensitivity increasing with cancer stage. The model includes latent indolent cancers that would not be diagnosed within that person's lifetime but can be overdiagnosed through screen-detection. We calculated the yearly and cumulative lifetime probabilities of screening overdiagnosis and false positive test results, assuming a range of preclinical screen-detectable periods (2-5 years). Results: An estimated 2.1-6.0% of all yearly screen-detected cancers with a multicancer screening test were predicted to be overdiagnoses across scenarios. The proportion of overdiagnosis varied by site, and strongly increased with age, going from 1% at age 50 to over 10% of screen-detected cancers by age 75. The test positive predictive value ranged from 15.9%-77.6%, meaning that there could be 0.3-5.3 false positives with no underlying cancer for every true cancer case detected by the test. Conclusion: Population-level multicancer screening with a multicancer early detection test would likely not lead to substantial screen-related overdiagnosis. Healthcare systems should consider how screening false positives may increase their diagnostic service caseload.

Background: Timely cancer diagnosis in children and adolescents is critical to improving outcomes, yet substantial variation in diagnostic intervals persists across cancer types and care settings. We aimed to quantify time to diagnosis and assess variations by patient, demographic, and system-level factors. Methods: We conducted a retrospective population–based study of children and adolescents aged 0–19 years diagnosed with one of 12 common cancers between 2010 and 2022 in Quebec, Canada. The diagnostic interval was defined as the time from first cancer-related healthcare encounter to diagnosis. We calculated medians and interquartile ranges (IQR) overall and by cancer type and used multivariable quantile regression to identify factors associated with time to diagnosis at the 25th, 50th, and 75th percentiles. Results: Among 2,927 individuals with cancer, diagnostic intervals varied by cancer type and age. Median intervals were longest for carcinomas (100 days; IQR 33–192) and shortest for leukemias (8 days; IQR 3–44). Compared with children living in Montreal, living in regional areas and other large urban centres was associated with longer 50th and 75th percentiles of time to diagnosis for hepatic and central nervous system (CNS) tumours. Diagnostic intervals were shorter in the post–pandemic period (2020–2022) across several cancer sites, with CNS tumours showing reductions across all quantiles. Interpretation: Diagnostic timeliness differed by cancer type, age, and rurality, but not by sex, material, or social deprivation. The shorter diagnostic intervals observed in the post–pandemic period suggest that pandemic–related changes in care pathways may have expedited diagnosis for some cancers.

Supplementary Table 3: Comparison of age-specific cancer incidence rates between CanCHECs and the Canadian Cancer Registry.

Supplementary Table 4: Comparison of age-standardized incidence rates between CanCHECs and GLOBOCAN world regions of origin.