Cutaneous Melanoma Mortality-to-Incidence Ratio and Its Association With Socioeconomic and Healthcare Factors in Canada: A National Ecological Study.

INTRODUCTION: The mortality-to-incidence ratio (MIR) can be used to approximate healthcare inequities and is helpful to understand/compare cancer survival between geographic regions/jurisdictions. We investigated cutaneous melanoma (CM) outcomes through MIR analysis in Canadian jurisdictions and census divisions (CDs) between 1992 and 2016. METHODS: Data were obtained from the national databases from 1992 to 2016 for all Canadian jurisdictions, except Quebec. Age-standardized overall and median MIRs were calculated per province per year, while crude MIRs were calculated for CDs. Generalized linear regression models were conducted to study the effect of province and year on MIR, while a mixed effect regression model was used to determine how healthcare and socioeconomic factors affect MIR, while accounting for possible clustering effects (eg, year and province). RESULTS: We identified 106,015 CM cases and 20,570 CM deaths between 1992 and 2016. National MIR from 1992 to 2016 demonstrated a significant linear decrease (P value < .0001). The national median MIR was 15.4 (ie, 0.154 × 100), whereby Manitoba (19.9), Ontario (19.5), Saskatchewan (18.5), British Columbia (16.1), and Newfoundland and Labrador (15.9) demonstrated higher MIRs than the Canadian average. CDs with the highest MIRs were commonly identified in the southern regions of provinces. No healthcare or socioeconomic factors were found to be significantly associated with higher MIR at the provincial level. CONCLUSION: MIRs have decreased at the national and provincial levels in recent decades, which is reassuring. Higher MIRs were noted in select rural CDs and in the Canadian territories, reinforcing the importance of proper dermatological care in all parts of the country.

The Role of Sex and Gender in Dermatology - From Pathogenesis to Clinical Implications.

BACKGROUND: Sex and gender have increasingly been recognized as significant risk factors for many diseases, including dermatological conditions. Historically, sex and gender have often been grouped together as a single risk factor in the scientific literature. However, both may have a distinct impact on disease incidence, prevalence, clinical presentation, severity, therapeutic response, and associated psychological distress. OBJECTIVES AND PROJECT DESCRIPTION: The mechanisms that underlie differences in skin diseases between males, females, men, and women remain largely unknown. The specific objectives of this review paper are:To highlight the biological differences between males and females (sex), as well as the sociocultural differences between men and women (gender) and how they impact the integumentary system.To perform a literature review to identify important sex- and gender-related epidemiological and clinical differences for various skin conditions belonging to a range of disease categories and to discuss possible biological and sociocultural factors that could explain the observed differences.To discuss dermatological skin conditions and gender-affirming treatments within the transgender community, a population of individuals who have a gender identity which is different than the gender identity they were assigned at birth. FUTURE IMPACT: With the rising number of individuals that identify as non-binary or transgender within our increasingly diverse communities, it is imperative to recognize gender identity, gender, and sex as distinct entities. By doing so, clinicians will be able to better risk-stratify their patients and select treatments that are most aligned with their values. To our knowledge, very few studies have separated sex and gender as two distinct risk factors within the dermatology literature. Our article also has the potential to help guide future prevention strategies that are patient-tailored rather than using a universal approach.

Pharmacological Agents Used in the Prevention and Treatment of Actinic Keratosis: A Review.

Actinic keratosis (AK) is among the most commonly diagnosed skin diseases with potentially life-threatening repercussions if left untreated. Usage of pharmacologic agents represents one of many therapeutic strategies that can be used to help manage these lesions. Ongoing research into these compounds continues to change our clinical understanding as to which agents most benefit particular patient populations. Indeed, factors such as past personal medical history, lesion location and tolerability of therapy only represent a few considerations that clinicians must account for when prescribing appropriate treatment. This review focuses on specific drugs used in either the prevention or treatment of AKs. Nicotinamide, acitretin and topical 5-fluorouracil (5-FU) continue to be used with fidelity in the chemoprevention of actinic keratosis, although some uncertainty persists in regard to which agents should be used in immunocompetent vs. immunodeficient/immunosuppressed patients. Topical 5-FU, including combination formulations with either calcipotriol or salicylic acid, as well as imiquimod, diclofenac and photodynamic light therapy are all accepted treatment strategies employed to target and eliminate AKs. Five percent of 5-FU is regarded as the most effective therapy in the condition, although the literature has conflictingly shown that lower concentrations of the drug might also be as effective. Topical diclofenac (3%) appears to be less efficacious than 5% 5-FU, 3.75-5% imiquimod and photodynamic light therapy despite its favorable side effect profile. Finally, traditional photodynamic light therapy, while painful, appears to be of higher efficacy in comparison to its more tolerable counterpart, daylight phototherapy.

Analysis of Geographic and Environmental Factors and Their Association with Cutaneous Melanoma Incidence in Canada.

BACKGROUND: Over 90% of skin cancers including cutaneous melanoma (CM) are related directly to sun exposure. Despite extensive knowledge on ultraviolet radiation's (UVR) detrimental impact, many still fail to implement sun protection/sun avoidance. Human behavior, attitudes, and cultural norms of individuals and communities heavily depend on the surrounding climate/environment. In many instances, the climate shapes the culture/norms of the society. Canada has vast geographic/environmental differences. METHODS: In the current ecological study, we sought to examine the relationship between various geographic and environmental factors and the distribution of CM incidence by Forward Sortation Area (FSA) postal code across Canada. CM incidence data were extracted from the Canadian Cancer Registry, while environmental data were extracted from the Canadian Urban Environmental Health Research Consortium (greenspace, as measured by the normalized difference vegetation index; annual highest temperature; absolute number and average length of yearly heat events; annual total precipitation [rain and snow]; absolute number and average length of events with precipitation [rain and snow]; and summer UVR index). The above geographic/environmental data by FSA were correlated with the respective CM incidence employing negative binomial regression model. RESULTS: Our analysis highlights that increases in annual average temperature, summer UVR, and greenspace were associated with higher expected incidence of CM cases, while higher number of annual heat events together with highest annual temperature and higher average number of annual rain events were associated with a decrease in CM incidence rate. This study also highlights regional variation in environmental CM risk factors in Canada. CONCLUSIONS: This national population-based study presents clinically relevant conclusions on weather/geographic variations associated with CM incidence in Canada and will help refine targeted CM prevention campaigns by understanding unique weather/geographic variations in high-risk regions.

Extracorporeal Photopheresis and Its Use in Clinical Dermatology in Canada

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used for over 35 years to treat numerous conditions. ECP was initially approved by the US FDA in 1988 for the treatment of Sézary syndrome, a leukemic form of cutaneous T-cell lymphoma (CTCL). Although CTCL remains the only FDA-approved indication, ECP has since been used off-label for numerous other conditions, including graft-versus-host disease (GvHD), systemic sclerosis, autoimmune bullous dermatoses, Crohn's disease, and prevention of solid organ transplant rejection. In Canada, ECP is mainly used to treat CTCL, acute and chronic GvHD, and in some instances systemic sclerosis. Herein, we review the current concepts regarding ECP mechanism of action, treatment considerations and protocols, and efficacy.

The Use of Retinoids for the Prevention and Treatment of Skin Cancers: An Updated Review.

Retinoids are natural and synthetic vitamin A derivatives that are effective for the prevention and the treatment of non-melanoma skin cancers (NMSC). NMSCs constitute a heterogenous group of non-melanocyte-derived skin cancers that impose substantial burdens on patients and healthcare systems. They include entities such as basal cell carcinoma and cutaneous squamous cell carcinoma (collectively called keratinocyte carcinomas), cutaneous lymphomas and Kaposi's sarcoma among others. The retinoid signaling pathway plays influential roles in skin physiology and pathology. These compounds regulate diverse biological processes within the skin, including proliferation, differentiation, angiogenesis and immune regulation. Collectively, retinoids can suppress skin carcinogenesis. Both topical and systemic retinoids have been investigated in clinical trials as NMSC prophylactics and treatments. Desirable efficacy and tolerability in clinical trials have prompted health regulatory bodies to approve the use of retinoids for NMSC management. Acceptable off-label uses of these compounds as drugs for skin cancers are also described. This review is a comprehensive outline on the biochemistry of retinoids, their activities in the skin, their effects on cancer cells and their adoption in clinical practice.

Epidemiologic trends and geographic distribution of patients with gallbladder and extrahepatic biliary tract cancers in Canada.

BACKGROUND: Gallbladder and biliary tract cancers are rare malignancies that carry a poor prognosis. Research on their epidemiologic trends is scarce. METHODS: We performed a retrospective analysis of the data in Canada using population-based cancer registries from 1992 to 2010. The incidence and mortality of gallbladder and extrahepatic bile duct cancers were examined at the levels of provinces/territories, cities, and Forward Sortation Area (FSA) postal codes. RESULTS: The incidence and mortality rates decreased over the study period. The average national incidence rate of gallbladder and biliary tract cancers was 30.92 cases per million individuals per year. Higher than average incidence rates were observed in Manitoba, Saskatchewan and Québec; there were contiguous regions with high incidence in Saskatchewan and Manitoba that suggest an area of putative case clustering. Higher incidence of gallbladder cancer was observed in women, whereas higher incidence of extrahepatic bile duct cancers was noted in men. Lower socioeconomic status and Hispanic race were found to be risk factors for gallbladder and biliary tract cancers. CONCLUSION: This is the first study to analyze the burden of gallbladder and biliary tract cancers in Canada. The geographic clustering trends present new avenues for research on environmental triggers.

Penile Invasive Squamous Cell Carcinoma: Analysis of Incidence, Mortality Trends, and Geographic Distribution in Canada.

BACKGROUND: Penile invasive squamous cell carcinoma (SCC) is a rare disease with several known risk factors. However, few studies have assessed its incidence, mortality, and temporal trends. OBJECTIVE: Our objectives are to analyze the epidemiology of penile SCC in Canada and to examine patient distribution with this cancer across Canada in order to elucidate population risk factors. METHODS: Three independent cancer registries were used to retrospectively analyze demographic data from Canadian men diagnosed with penile invasive SCC between 1992 and 2010. The Canadian Census of Population was used to calculate incidence and mortality rates at the province and Forward Sortation Area levels. RESULTS: The overall age-adjusted incidence rate was 6.08 cases per million males. Four provinces with statistically significantly higher incidence rates were identified. The national crude incidence rates increased linearly between 1992 and 2010, whereas the age-adjusted incidence rates showed no significant increase during this time period. The overall age-adjusted mortality rate was 1.88 deaths per million males per year. The province of Saskatchewan had significantly higher mortality rates. There was no increase in crude or age-adjusted mortality rates between 1992 and 2010. There was a significant positive correlation between incidence rates and obesity, Caucasian ethnicity, and lower socioeconomic status. CONCLUSION: This study was able to establish geographic variation for this malignancy at the provincial level. Although there are many established risk factors for penile SCC, our results suggest that the increase in crude incidence rates observed is largely due to the aging population.

Multiple myeloma epidemiology and patient geographic distribution in Canada: A population study.

BACKGROUND: Multiple myeloma (MM) is a malignancy of mature plasma cells. Environmental risk factors identified for this malignancy, among others, include farming and exposure to pesticides. METHODS: Using 3 independent population-based databases (the Canadian Cancer Registry, le Registre Québécois du Cancer, and Canadian Vital Statistics), this study analyzed patients' clinical characteristics and the incidence, mortality, and geographic distribution of MM cases in Canada during 1992-2015. RESULTS: In total, ~32,065 patients were identified, and 53.7% were male. The mean age at the time of diagnosis was 70 ± 12.1 years. The average incidence rate in Canada was 54.29 cases per million individuals per year, and linear regression modeling showed a steady rise in the annual rate of 0.96 cases per million individuals per year. At the provincial level, Quebec and Ontario had significantly higher incidence rates than the rest of Canada. An analysis of individual municipalities and postal codes showed lower incidence rates in large metropolitan areas and in high-latitude regions of the country, whereas high incidence rates were observed in smaller municipalities and rural areas. Land use analysis demonstrated increased density of crop farms and agricultural industries in high-incidence areas. A comparison with the available data from 2011-2015 showed several consistent trends at provincial, municipal, and regional levels. CONCLUSIONS: These results provide a comprehensive analysis of the MM burden in Canada. Large metropolitan cities as well as high-latitude regions were associated with lower MM incidence. Higher incidence rates were noted in smaller cities and rural areas and were associated with increased density of agricultural facilities.

Analysis of incidence, mortality trends, and geographic distribution of breast cancer patients in Canada.

BACKGROUND/PURPOSE: Breast cancer is the malignancy with the highest incidence rate excluding non-melanoma skin cancers, and the second leading cause of cancer-related deaths among Canadian women. Many modifiable risk factors have been linked to the pathogenesis of this disease. The purpose of this study is to analyze the epidemiology of breast cancer in Canada and to examine its geographic distribution to help identify new risk factors for this disease. METHODS: Three independent population-based cancer registries were used to retrospectively analyze demographic data from Canadian women diagnosed with invasive breast cancer across all provinces and territories between 1992 and 2010. The incidence and mortality rates were assessed at the provincial, city, and forward sortation area (FSA) postal code levels. RESULTS: The overall age-adjusted incidence rate was 114.4 cases per 100,000 females per year. Six provinces and several groups of FSAs had significantly higher incidence rates. There was a significant increase in incidence and decrease in mortality rates between 1992 and 2010. The overall mortality rate was 31.5 deaths per 100,000 females per year. However, three provinces had significantly higher mortality rates. CONCLUSION: By identifying high-incidence areas for breast cancer, our study will help identify patient populations that are at higher risk for this malignancy. It will also act as a foundation for future studies to establish novel risk factors for this disease.

Incidence, Mortality, and Spatiotemporal Distribution of Cutaneous Malignant Melanoma Cases Across Canada.

BACKGROUND: We recently reported a steady increase in the incidence and mortality of cutaneous malignant melanoma (CMM) in Canada during 1992-2010. OBJECTIVES: The objective of this article is to examine the distribution of Canadian CMM patients at the level of provinces, cities, and forward sortation area (FSA) postal codes. METHODS: Using 3 Canadian population-based registries, we conducted an in-depth examination of the incidence and mortality trends for 72 565 Canadian CMM patients over the period 1992-2010. RESULTS: We found that among 20- to 39-year-olds, the incidence of CMM in women (7.17 per 100 000 individuals) was significantly higher than in men (4.60 per 100 000 individuals per year). Women age 80 years and older had an incidence of CMM (58.46 cases per 100 000 women per year) more than 4 times greater than the national average (12.29 cases per 100 000 population per year) and a corresponding high mortality rate (20.18 deaths per 100 000 women per year), when compared with the Canadian melanoma mortality of 2.4 deaths per 100 000 per year. In other age groups men had higher incidence and corresponding melanoma mortality rates. We also studied CMM incidence by province, city, and FSA postal codes and identified several high-incidence communities that were located near the coast/waterfronts. In addition, plotting latitude measures for cities and FSAs vs CMM incidence rate confirmed the inverse relationship between geographical latitude and incidence of melanoma in Canada (slope = -0.22 ± 0.05). CONCLUSIONS: This research may help develop sex-, age- and geographic region-specific recommendations to decrease the future burden of CMM in Canada.

Evaluation of weather and environmental factors and their association with cutaneous melanoma incidence: A national ecological study.

Background: Cutaneous melanoma (CM) is a significant contributor to skin cancer-related mortality globally and in Canada. Despite the well-established link between ultraviolet (UV) radiation exposure and skin cancer risk, there remains a gap in population-level interventions and persistent misconceptions about sun exposure and impact of environment on individual behavior. Objective: The current study provides an ecological analysis using latest available data (2011-2017) to define geographic/environmental contributors to the CM landscape in Canada. Methods: Utilizing Canadian Cancer Registry and Canadian Urban Environmental Health Research Consortium data, we analyzed 39,605 CM cases occurring in Canada from 2011 to 2017. Environmental data, including UV radiation, greenspace (normalized difference vegetation index), temperature, heat events, and precipitation was used to evaluate the effect of environment on CM incidence rates across Forward Sortation Area postal codes. Results: Forward Sortation Areas with increased CM incidence were associated with higher annual average temperature, snowfall, heat events, normalized difference vegetation index, and vitamin D-weighted UV exposure. Conversely, factors associated with decreased incidence included an increased annual highest temperature, rain precipitation, and a longer duration of heat events. Limitations: This study is subject to ecological bias and findings should be interpreted with caution. Conclusion: This study further substantiates associations between specific environmental factors and CM incidence.

A Comprehensive Analysis of Skin Cancer Concerns and Protective Practices in Manitoba, Canada, Highlights Lack of Skin Cancer Awareness and Predominance of High-Risk Sun Exposure Behaviors.

The rapidly increasing skin cancer rates in Canada are alarming, with current data estimating that 1/3 of Canadians will be affected in their lifetime. Thus, deeper understanding of high-risk sun exposure behaviors is needed to help counter this trend. Only limited action has been taken by federal/provincial governments to reduce skin cancer incidence. A cross-sectional survey study was conducted in Manitoba, with frequency counts, means, and percentages used to encapsulate responses. Age- and gender-adjusted odds ratios were calculated using logistic regression analyses. Our study identified worrying inadequacies in sun protective behaviors and attitudes, with the threat of such high-risk behaviors amplified by a lack of skin cancer awareness. Alarming elements were noted in participants' sun exposure history (>65% reported a history of sunburns, >50% previously used a tanning bed, and >75% recently tanned for pleasure), beliefs and attitudes (>50% believe that they look better/healthier with a tan, and >40% believe that having a base tan is protective against further sun damage), and sun protection efforts (sun protective clothing was used <60% of the time, sunscreen was used by <50%, and there was a lack of knowledge about sunscreen characteristics in ~30% of respondents), in addition to significant differences being established between demographic subgroups (based on gender, age, skin phototype, income, and education attained). This study provides worrisome insight onto the grim landscape of sun protective behaviors and attitudes in Manitoba, which will inevitably translate into higher skin cancer rates and should serve as a call to action to promote targeted public health messaging in this jurisdiction and beyond.

Understanding the Perceived Relationship between Sun Exposure and Melanoma in Atlantic Canada: A Consensual Qualitative Study Highlighting a "Sunscreen Paradox".

Globally, cutaneous melanoma (CM) incidence is increasing, with sun exposure identified as a key modifiable risk factor. The Atlantic provinces of Canada display varied CM incidence rates: New Brunswick aligns with the national average, while Nova Scotia and Prince Edward Island exceed it, and Newfoundland and Labrador fall below this benchmark. We investigated the relationship between sun exposure and CM in these provinces. Twenty-two focus groups encompassing 95 Atlantic Canada residents were conducted and transcribed. A thematic analysis was conducted in MAXQDA using the social-ecological model as a framework. Residents of high-CM incidence provinces demonstrated greater sun exposure awareness, consulting UV indices, and using sunscreen and sun-protective clothing. However, they received greater UV exposure due to warmer climates and outdoor work and cultural activities. Conversely, those in low-incidence provinces used sunscreen and sun-protective clothing less often, engaged in occupations and hobbies affording less sun exposure, and lived in cooler climates. Our data supports a possible "sunscreen paradox", whereby increased sunscreen use is correlated with augmented sun exposure, leading to a deceptive sense of security. Public health initiatives in Atlantic Canada promoting sun safety must address this paradox while integrating community-specific behaviors and norms in order to develop tailored campaigns.