Epidemiology of basal and cutaneous squamous cell carcinoma in the U.K. 2013-15: a cohort study.

BACKGROUND: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together known as keratinocyte cancers (KCs), are the commonest cancer in white ethnic populations. Recent improvements to registry data collection in England has allowed more accurate analysis of the epidemiology of BCC and cSCC and for the first time we are able to provide an accurate (representative) tumour burden for KC in the U.K. OBJECTIVES: To estimate the incidence of BCC and cSCC in the U.K. METHODS: A cohort of patients with KCs between 2013 and 2015 were identified using linkage to diagnostic codes derived from pathology reports collected into the national cancer registry. Data from England's cancer registry were combined with data from Scotland, Northern Ireland and Wales. European age-standardized incidence rates (EASRs) of the first BCC and cSCC per patient per annum (PPPA) were calculated. RESULTS: In the U.K, the EASR of the first BCC and cSCC PPPA in 2013-15 were 285 and 77 per 100 000 person years, respectively (211 120 KCs total in 2015). The mean annual percentage increase was 5% between 2013 and 2015 for both BCC and cSCC. By counting the first KC PPPA, we include an additional 51% KCs compared with the previous reporting technique which counts only the first BCC and cSCC in a patient's lifetime, yet it represents a probable underestimation of 5-11% of the true tumour count. CONCLUSIONS: Based on an improved methodology, a more representative incidence of KC is presented, which is essential to healthcare planning and will lead to improved understanding of the epidemiology of KC. What's already known about this topic? Keratinocyte cancers (KCs) are the most common cancers affecting white ethnic populations. The incidence of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) is increasing worldwide including the U.K., most commonly in elderly male Caucasian patients. These cancers are traditionally substantially underreported and frequently excluded from national cancer statistics. What does this study add? Using improved data collection methods in England and validated tumour-reporting techniques, we report the most accurate BCC and cSCC incidence data for the U.K. ever published. Identifying the first BCC and cSCC per patient per annum, the incidence of BCC and cSCC in the U.K. (excluding Wales) was 285 and 77 per 100 000 person years, respectively, between 2013 and 2015, with more than 210 000 KCs in the U.K. in 2015.

Epidemiological evidence of carcinogenicity of sunbed use and of efficacy of preventive measures.

The International Agency for Research on Cancer classified, in July 2009, exposure to artificial tanning devices (sunbeds) as carcinogenic to humans. This classification was based on evidence from epidemiological and experimental animal studies. The present chapter will review these epidemiological evidences. The summary risk estimates from 27 epidemiological studies obtained through a meta-analysis showed an increased risk of melanoma: summary relative risk (SRR) = 1.20 [95% confidence interval (CI) 1.08-1.34]. The risk was higher when exposure took place at younger age (SRR = 1.59; 95% CI 1.36-1.85). The risk was independent of skin sensitivity or population and a dose response was evident. A meta-analysis of 12 studies was conducted for non-melanoma skin cancers and showed a significantly increased risk for basal cell carcinoma (SRR = 1.29; 95% CI 1.08-1.53) and for squamous cell carcinoma (SRR = 1.67; 95% CI 1.29-2.17). As for melanoma, the risk for other skin cancers increased for first exposures at young age. Epidemiological studies have gradually strengthened the evidence for a causal relationship between indoor tanning and skin cancer and they fit with prior knowledge on relationship between UV exposure and skin cancer. Additionally, several case-control studies provided consistent evidence of a positive association between use of sunbed and ocular melanoma, also with greater risk for first exposures at younger age. Preventive measures based on information on risk or by requiring parental authorization for young users proved to be inefficient in several studies. The significant impact of strong actions or total ban, such as performed in Iceland, or a total ban of sunbed use, as in Brazil or Australian states, needs to be further assessed.

MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project.

BACKGROUND: The melanocortin-1-receptor (MC1R) gene regulates human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between MC1R variants and the risk of non-melanoma skin cancer (NMSC), and to investigate whether risk estimates differed by phenotypic characteristics. METHODS: Data on 3527 NMSC cases and 9391 controls were gathered through the M-SKIP Project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. We calculated summary odds ratios (SOR) with random-effect models, and performed stratified analyses. RESULTS: Subjects carrying at least one MC1R variant had an increased risk of NMSC overall, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC): SOR (95%CI) were 1.48 (1.24-1.76), 1.39 (1.15-1.69) and 1.61 (1.35-1.91), respectively. All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19-1.70) for V60L to 2.66 (1.06-6.65) for D84E variant. In stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair. CONCLUSIONS: Our pooled-analysis highlighted a role of MC1R variants in NMSC development and suggested an effect modification by red hair colour phenotype.

Diabetes and breast cancer risk: a meta-analysis.

BACKGROUND: The potential of an increased risk of breast cancer in women with diabetes has been the subject of a great deal of recent research. METHODS: A meta-analysis was undertaken using a random effects model to investigate the association between diabetes and breast cancer risk. RESULTS: Thirty-nine independent risk estimates were available from observational epidemiological studies. The summary relative risk (SRR) for breast cancer in women with diabetes was 1.27 (95% confidence interval (CI), 1.16-1.39) with no evidence of publication bias. Prospective studies showed a lower risk (SRR 1.23 (95% CI, 1.12-1.35)) than retrospective studies (SRR 1.36 (95% CI, 1.13-1.63)). Type 1 diabetes, or diabetes in pre-menopausal women, were not associated with risk of breast cancer (SRR 1.00 (95% CI, 0.74-1.35) and SRR 0.86 (95% CI, 0.66-1.12), respectively). Studies adjusting for body mass index (BMI) showed lower estimates (SRR 1.16 (95% CI, 1.08-1.24)) as compared with those studies that were not adjusted for BMI (SRR 1.33 (95% CI, 1.18-1.51)). CONCLUSION: The risk of breast cancer in women with type 2 diabetes is increased by 27%, a figure that decreased to 16% after adjustment for BMI. No increased risk was seen for women at pre-menopausal ages or with type 1 diabetes.

Mammography screening and breast cancer mortality in Sweden.

BACKGROUND: Swedish women aged 40-69 years were gradually offered regular mammography screening since 1974, and nationwide coverage was achieved in 1997. We hypothesized that this gradual implementation of breast cancer screening would be reflected in county-specific mortality patterns during the last 20 years. METHODS: Using data from the Swedish Board of Health and Welfare from 1960 to 2009, we used joinpoint regression to analyze breast cancer mortality trends in women aged 40 years and older (1,286,000 women in 1995-1996). Poisson regression models were used to compare observed mortality trends with expected trends if screening had resulted in breast cancer mortality reductions of 10%, 20%, or 30% among women screened during 18 years of follow-up after the introduction of screening. All statistical tests were two-sided. RESULTS: From 1972 to 2009, breast cancer mortality rates in Swedish women aged 40 years and older declined by 0.98% annually, from 68.4 to 42.8 per 100,000, and it continuously declined in 14 of the 21 Swedish counties. In three counties, breast cancer mortality declined sharply during or soon after the implementation of screening; in two counties, a steep decline started at least 5 years after screening was introduced; and in two counties, breast cancer mortality increased after screening started. In counties in which screening started in 1974-1978, mortality trends during the next 18 years were similar to those before screening started, and in counties in which screening started in 1986-1987, mortality increased by approximately 12% (P = .007) after the introduction of screening compared with previous trends. In counties in which screening started in 1987-1988 and in 1989-1990, mortality declined by approximately 5% (P = .001) and 8% (P < .001), respectively, after the introduction of screening. Conclusion County-specific mortality statistics in Sweden are consistent with studies that have reported limited or no impact of screening on mortality from breast cancer.

Differential diagnosis of adnexal masses: sequential use of the risk of malignancy index and HistoScanning, a novel computer-aided diagnostic tool.

OBJECTIVE: To assess the value of ovarian Histo-Scanning(™) , a novel computerized technique for interpreting ultrasound data, in combination with the risk of malignancy index (RMI) in improving triage for women with adnexal masses. METHODS: RMI indices were assessed in 199 women enrolled in a prospective study to investigate the use of HistoScanning. Ultrasound scores were obtained by blinded analysis of archived images. The following sequential test was developed: HistoScanning was modeled as a second-line test for RMI between a lower cut-off and an upper cut-off. The optimal combination of these cut-offs that together maximized the Youden index (Sensitivity + Specificity - 1) was determined. RESULTS: Using RMI at the standard cut-off value of 250 resulted in a sensitivity of 74% and a specificity of 86%. When RMI was combined with HistoScanning, the highest accuracy was achieved by using HistoScanning as a sequential second-line test for patients with RMI values between 105 and 2100. At these cut-off values, sequential use of RMI and HistoScanning resulted in mean sensitivity and specificity estimates of 88% and 95%, respectively. CONCLUSIONS: Our data suggest that HistoScanning may have the potential to improve the diagnostic accuracy of RMI, which could result in better triage for women with adnexal masses. Further prospective validation is warranted.

The impact of the process of clinical research on health service outcomes.

Chapter 1 introduces the key questions and context for the work described in the supplement, on the impact of the process of clinical research on healthcare outcomes. The distinction between the influence of research activity on the outcomes for individual patients involved in clinical trials and other well-designed studies when compared to similar individuals cared for within similar healthcare institutions are considered. The evidence is reviewed and broadly the conclusion is that there is little evidence to support the hypothesis that individuals included in randomized trials do better than individuals with the same clinical characteristics in such trials within the same institution. However, the more important question of the influence of research activity on the outcomes of healthcare institutions is identified and clarified. There are less research data which address this question and it is harder to study. However, the existing data are encouraging and suggest that the hypothesis that research- intensive healthcare institutions provide improved outcomes is worthy of further study. There is a pressing need for additional high-quality, methodologically robust studies of this question.

Advanced breast cancer incidence following population-based mammographic screening.

BACKGROUND: Breast cancer mortality is declining in many Western countries. If mammography screening contributed to decreases in mortality, then decreases in advanced breast cancer incidence should also be noticeable. PATIENTS AND METHODS: We assessed incidence trends of advanced breast cancer in areas where mammography screening is practiced for at least 7 years with 60% minimum participation and where population-based registration of advanced breast cancer existed. Through a systematic Medline search, we identified relevant published data for Australia, Italy, Norway, Switzerland, The Netherlands, U.K. and the U.S.A. Data from cancer registries in Northern Ireland, Scotland, the U.S.A. (Surveillance, Epidemiology and End Results (SEER), and Connecticut), and Tasmania (Australia) were available for the study. Criterion for advanced cancer was the tumour size, and if not available, spread to regional/distant sites. RESULTS: Age-adjusted annual percent changes (APCs) were stable or increasing in ten areas (APCs of -0.5% to 1.7%). In four areas (Firenze, the Netherlands, SEER and Connecticut) there were transient downward trends followed by increases back to pre-screening rates. CONCLUSIONS: In areas with widespread sustained mammographic screening, trends in advanced breast cancer incidence do not support a substantial role for screening in the decrease in mortality.

Impact of PSA testing and prostatic biopsy on cancer incidence and mortality: comparative study between the Republic of Ireland and Northern Ireland.

OBJECTIVES: To investigate the impact of different PSA testing policies and health-care systems on prostate cancer incidence and mortality in two countries with similar populations, the Republic of Ireland (RoI) and Northern Ireland (NI). METHODS: Population-level data on PSA tests, prostate biopsies and prostate cancer cases 1993-2005 and prostate cancer deaths 1979-2006 were compiled. Annual percentage change (APC) was estimated by joinpoint regression. RESULTS: Prostate cancer rates were similar in both areas in 1994 but increased rapidly in RoI compared to NI. The PSA testing rate increased sharply in RoI (APC = +23.3%), and to a lesser degree in NI (APC = +9.7%) to reach 412 and 177 tests per 1,000 men in 2004, respectively. Prostatic biopsy rates rose in both countries, but were twofold higher in RoI. Cancer incidence rates rose significantly, mirroring biopsy trends, in both countries reaching 440 per 100,000 men in RoI in 2004 compared to 294 in NI. Median age at diagnosis was lower in RoI (71 years) compared to NI (73 years) (p < 0.01) and decreased significantly over time in both countries. Mortality rates declined from 1995 in both countries (APC = -1.5% in RoI, -1.3% in NI) at a time when PSA testing was not widespread. CONCLUSIONS: Prostatic biopsy rates, rather than PSA testing per se, were the main driver of prostate cancer incidence. Because mortality decreases started before screening became widespread in RoI, and mortality remained low in NI, PSA testing is unlikely to be the explanation for declining mortality.

Decline in breast cancer incidence in the Flemish region of Belgium after a decline in hormonal replacement therapy.

BACKGROUND: Breast cancer incidence rate in Belgian women was as high as 152.7 for 100 000 in 2003 (adjusted on European population). We made an estimation of the contribution of hormone replacement therapy (HRT) on breast cancer incidence from 1999 to 2005 in women aged 50-69 years in Flanders. METHODS: Breast cancer data were extracted from the Belgium Cancer Registry. Drug consumption was computed from drug sales data. The fraction of breast cancers attributable to HRT was calculated by year, using the relative risks of the Million Women Study in the UK. RESULTS: The proportion of women aged 50-69 years using HRT in Flanders increased since 1992, peaked at 20% in 2001, then decreased to 8% in 2008. The incidence of breast cancer in 100 000 women aged 50-69 years in Flanders increased from 332.8 in 1999 to 407.9 in 2003, then decreased to 366.1 in 2005; the variations were mostly noticeable for tumors <20 mm in size. The fraction of breast cancers attributed to HRT peaked at 11% in 2001 and decreased afterward. CONCLUSION: The high level of breast cancer observed in the years 2001-2003 in Flanders can be partly attributed to the use of HRT. Since participation to mammography screening of Flemish women aged 50-69 years was still on the rise in 2003 and never exceeds 62%, the decrease in breast cancer incidence was likely to be due to the decrease in HRT use and not to screening saturation.

Sunscreen abuse for intentional sun exposure.

Skin cancer is caused by exposure to ultraviolet radiation (UV) and the sun is the main source of this radiation. Sunscreens were initially formulated to prevent sunburns; laboratory studies later revealed that in rodents they could reduce UV-induced skin cancer which resembles human squamous cell carcinoma. Three randomized trials in older adults showed the ability of sunscreens to moderately reduce the occurrence of solar keratoses and of squamous cell carcinoma. However, no effect was observed for basal cell carcinoma. There is no animal model for human melanoma and observational studies often found sunscreen use associated with a higher risk of nevus, melanoma and basal cell carcinoma. These higher risks were found when sun exposure appeared to be intentional, that is, with the desire to acquire a tan, a healthy look or simply to spend as long as possible in the sun with as much skin exposed as possible. Three randomized trials showed that sunscreen use by sun sensitive subjects engaging in intentional sun exposure could increase the duration of exposure without decreasing sunburn occurrence. This increased duration could be the reason why melanoma risk is increased when sunscreen is used. Hence, sunscreen abuse may extend sun exposure duration thus allowing sun exposure behaviours that would not be possible otherwise. Advertising for sunscreens and labeling of sunscreen bottles should inform consumers of the carcinogenic hazards associated with sunscreen abuse. It would be good to use a personal UV dosimeter which would give an alert when one's individual sunburn threshold in the absence of sunscreen use is nearing. The combination of sunscreen and a UV dosimeter may be an option for reducing the melanoma risk among sun worshippers.

Second primary cancers in patients with skin cancer: a population-based study in Northern Ireland.

Among all 14,500 incident cases of basal cell carcinoma (BCC), 6405 squamous cell carcinomas (SCC) and 1839 melanomas reported to the Northern Ireland Cancer Registry between 1993 and 2002, compared with the general population, risk of new primaries after BCC or SCC was increased by 9 and 57%, respectively. The subsequent risk of cancer, overall, was more than double after melanoma.

The causes of cancer in France.

BACKGROUND: While external factors are responsible for many human cancers, precise estimates of the contribution of known carcinogens to the cancer burden in a given population have been scarce. METHODS: We estimated the proportion of cancer deaths which occurred in France in 2000 attributable to known risk factors, based on data on frequency of exposure around 1985. RESULTS: In 2000, tobacco smoking was responsible for 23.9% of cancer deaths (33.4% in men and 9.6% in women), alcohol drinking for 6.9% (9.4% in men and 3.0% in women) and chronic infections for 3.7%. Occupation is responsible for 3.7% of cancer deaths in men; lack of physical activity, overweight/obesity and use of exogenous hormones are responsible for 2%-3% of cancer deaths in women. Other risk factors, including pollutants, are responsible for <1% of cancer deaths. Thus, known risk factors explain 35.0% of cancer deaths, and 15.0% among never smokers. CONCLUSIONS: While cancer mortality is decreasing in France, known risk factors of cancer explain only a minority of cancers, with a predominant role of tobacco smoking.

Determinants of the number of mammography units in 31 countries with significant mammography screening.

In the 2000s, most of the female population of industrialised countries had access to mammography breast cancer screening, but with variable modalities among the countries. We assessed the number of mammography units (MUs) in 31 European, North American and Asian countries where significant mammography activity has existed for over 10 years, collecting data on the number of such units and of radiologists by contacting institutions in each country likely to provide the relevant information. Around 2004, there were 32,324 MU in 31 countries, the number per million women ranging from less than 25 in Turkey, Denmark, the Netherlands, the United Kingdom, Norway, Poland and Hungary to more than 80 in Cyprus, Italy, France, the United States and Austria. In a multivariate analysis, the number of MUs was positively associated with the number of radiologists (P=0.0081), the number of women (P=0.0023) and somewhat with the country surface area (P=0.077). There is considerable variation in the density of MU across countries and the number of MUs in service are often well above what would be necessary according to local screening recommendations. High number of MUs in some countries may have undesirable consequences, such as unnecessarily high screening frequency and decreased age at which screening is started.

Quantification of changes in breast cancer incidence and mortality since 1990 in 35 countries with Caucasian-majority populations.

BACKGROUND: Since 1985 considerable changes have taken place in the early detection and treatment of breast cancer. We quantified breast cancer trends for 35 countries with populations mainly of European ancestry. METHODS: Incidence data were extracted from cancer registries and mortality data from World Health Organization database. Overall percentage change from 1990 to 2002 was quantified for all ages and for three different age-groups (35-49, 50-69 and >/=70 years of age). RESULTS: The incidence percent change in women of all ages varied from 2.1% in Canada to 54.2% in Lithuania. Main increases in incidence were observed for women 50-69 years old, from 12.4% in Canada until 105.3% in Norway. Decreases in mortality of >20% were observed in nine countries. Mortality decreases were highest in women 35-49 years old and lowest in women >/=70 years. The magnitude of mortality decrease from 1990 to 2002 was not related to the mortality rate observed in 1990. CONCLUSIONS: While increases in breast cancer incidence mainly concerned women >/=50 years, decreases in mortality were more marked in women 35-49 years old. Large disparities in changes in mortality rates probably reflect differences in detection of and management of breast cancer.