Skin cancer in Europe today and challenges for tomorrow.

One in every three cancers diagnosed is a skin cancer. Europe has the global lead in the number of UV-attributable cancer cases with the highest number of melanoma cases worldwide and the second highest number of keratinocyte cancers (KC). Further increases are expected in Europe for the coming decades. Projected increases are highest for KC with increases in incidence around 40% and increases in mortality around 50%, with KC mortality in males approximating melanoma mortality in females. The two main drivers for this skin cancer epidemic are ageing of the population but especially UV exposure. In conclusion, skin cancer represents a major challenge in the cancer field in Europe today and will continue to do so in the coming decades. This calls for a European skin cancer action plan intended to reduce avoidable UV exposure and to prepare the healthcare system to safeguard early diagnosis and treatment of skin cancer.

Knockdown of Simulated-Solar-Radiation-Sensitive miR-205-5p Does Not Induce Progression of Cutaneous Squamous Cell Carcinoma In Vitro.

Solar radiation is the main risk factor for cSCC development, yet it is unclear whether the progression of cSCC is promoted by solar radiation in the same way as initial tumorigenesis. Additionally, the role of miRNAs, which exert crucial functions in various tumors, needs to be further elucidated in the context of cSCC progression and connection to solar radiation. Thus, we chronically irradiated five cSCC cell lines (Met-1, Met-4, SCC-12, SCC-13, SCL-II) with a custom-built irradiation device mimicking the solar spectrum (UVB, UVA, visible light (VIS), and near-infrared (IRA)). Subsequently, miRNA expression of 51 cancer-associated miRNAs was scrutinized using a flow cytometric multiplex quantification assay (FirePlex®, Abcam). In total, nine miRNAs were differentially expressed in cell-type-specific as well as universal manners. miR-205-5p was the only miRNA downregulated after SSR-irradiation in agreement with previously gathered data in tissue samples. However, inhibition of miR-205-5p with an antagomir did not affect cell cycle, cell growth, apoptosis, or migration in vitro despite transient upregulation of oncogenic target genes after miR-205-5p knockdown. These results render miR-205-5p an unlikely intracellular effector in cSCC progression. Thus, effects on intercellular communication in cSCC or the simultaneous examination of complementary miRNA sets should be investigated.

S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" - update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

CD74 and CD44 Expression on CTCs in Cancer Patients with Brain Metastasis.

Up to 40% of advance lung, melanoma and breast cancer patients suffer from brain metastases (BM) with increasing incidence. Here, we assessed whether circulating tumor cells (CTCs) in peripheral blood can serve as a disease surrogate, focusing on CD44 and CD74 expression as prognostic markers for BM. We show that a size-based microfluidic approach in combination with a semi-automated cell recognition system are well suited for CTC detection in BM patients and allow further characterization of tumor cells potentially derived from BM. CTCs were found in 50% (7/14) of breast cancer, 50% (9/18) of non-small cell lung cancer (NSCLC) and 36% (4/11) of melanoma patients. The next-generation sequencing (NGS) analysis of nine single CTCs from one breast cancer patient revealed three different CNV profile groups as well as a resistance causing ERS1 mutation. CD44 and CD74 were expressed on most CTCs and their expression was strongly correlated, whereas matched breast cancer BM tissues were much less frequently expressing CD44 and CD74 (negative in 46% and 54%, respectively). Thus, plasticity of CD44 and CD74 expression during trafficking of CTCs in the circulation might be the result of adaptation strategies.

Who Are the Nonusers of Sunscreen, and What Are Their Reasons? Development of a New Item Set.

Sunscreen use is an important aspect of sun protective behavior. Previous studies revealed deficits in sunscreen use. Our aim was to quantify sunscreen use in a nationwide representative study in Germany as well as to develop and test an item battery on reasons for none use of sunscreen. We analyzed data of the National Cancer Aid Monitoring (NCAM; wave 4; n = 3000, aged 14-45). To describe those who only use sunscreen rarely or never, we used chi2 statistics and logistic regression analysis. In addition, we utilized a newly developed item battery on barriers to sunscreen use. Here, we used Cronbach's alpha to investigate reliability. In total, 20.7% reported using sunscreen rarely or never. Infrequent or none use of sunscreen was associated with male sex, immigrant background, none or rare sunbathing in summer, and current or past use of sunbeds. Participants with higher skin cancer risk (e.g., pale skin) were less likely to use sunscreen infrequently or never. The major reasons for not using sunscreen were inconvenience and no perceived need for applying sunscreen. Overall, internal consistency of the item battery on potential barriers to sunscreen use was very good (Cronbach's alpha = 0.865). We found deficits in sunscreen use especially in sunbed users, men, and individuals with immigrant background. Our results give important implications for future prevention and health promotion campaigns on sunscreen use.

Dose limits for occupational exposure to ionising radiation and genotoxic carcinogens: a German perspective.

This paper summarises the view of the German Commission on Radiological Protection ("Strahlenschutzkommission", SSK) on the rationale behind the currently valid dose limits and dose constraints for workers recommended by the International Commission on Radiological Protection (ICRP). The paper includes a discussion of the reasoning behind current dose limits followed by a discussion of the detriment used by ICRP as a measure for stochastic health effects. Studies on radiation-induced cancer are reviewed because this endpoint represents the most important contribution to detriment. Recent findings on radiation-induced circulatory disease that are currently not included in detriment calculation are also reviewed. It appeared that for detriment calculations the contribution of circulatory diseases plays only a secondary role, although the uncertainties involved in their risk estimates are considerable. These discussions are complemented by a review of the procedures currently in use in Germany, or in discussion elsewhere, to define limits for genotoxic carcinogens. To put these concepts in perspective, actual occupational radiation exposures are exemplified with data from Germany, for the year 2012, and regulations in Germany are compared to the recommendations issued by ICRP. Conclusions include, among others, considerations on radiation protection concepts currently in use and recommendations of the SSK on the limitation of annual effective dose and effective dose cumulated over a whole working life.

S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma (cSCC) - short version, part 2: epidemiology, surgical and systemic treatment of cSCC, follow-up, prevention and occupational disease.

Actinic keratoses (AKs) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guidelines for actinic keratosis and cutaneous squamous cell carcinoma were developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guidelines are aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AKs and cSCC. The guidelines are also aimed at affected patients, their relatives, policy makers and insurance funds. In the second part, we will address aspects relating to epidemiology, etiology, surgical and systemic treatment of cSCC, follow-up and disease prevention, and discuss AKs and cSCC in the context of occupational disease regulations.

S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma - short version, part 1: diagnosis, interventions for actinic keratoses, care structures and quality-of-care indicators.

Actinic keratoses (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guideline is aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AK and cSCC. The guideline is also aimed at affected patients, their relatives, policy makers and insurance funds. In the first part, we will address aspects relating to diagnosis, interventions for AK, care structures and quality-of-care indicators.

Profile of sunless tanning product users: Results from a nationwide representative survey.

BACKGROUND: Sunless tanning products (STPs) are often seen as "healthy alternative" to sunbathing and indoor tanning. However, STP use may entail indirect risks such as overestimating an individual's natural skin type, resulting in risky (natural and artificial) tanning behavior. We aimed to explore STP use in combination with other health-related risk behaviors (eg, smoking), skin cancer risk, risk awareness of ultraviolet radiation, and preventive behavior. METHODS: We used data from the NCAM, a nationwide representative cross-sectional sample (n = 3000, aged 14-45, 48.6% female) interviewed via telephone. Differences between STP users and nonusers regarding the abovementioned aspects were identified using chi²-test. RESULTS: The 1-year prevalence of STP use was 7.5%. Tanning bed users showed a higher prevalence of STP use than past and never users (16.1% vs 9.6% vs 5.8%, P < 0.05). Although STP users had a higher skin cancer risk based on individual characteristics, they were less likely to have participated in a skin cancer screen. CONCLUSION: The identified parallel use of STPs and tanning beds can have severe health consequences, since the "fake tan" of STPs may lead to an overestimation of the individual's skin type, which may result in overdosed UV exposure. The lower risk awareness among STP users accompanied with their higher skin cancer risk calls for target group-specific prevention.

Optimistically biased perception of one's own skin cancer risk: Representative nationwide findings.

BACKGROUND: Previous research has shown that individuals tend to have unrealistic comparative optimism (UCO) for different diseases and health outcomes. Our aim was to analyze UCO in relation to skin cancer for the first time in a representative nationwide sample. The results will be important for planning future prevention. METHODS: The National Cancer Aid Monitoring on Sunbed Use (NCAM, wave 3) is a representative nationwide German survey (n = 3,000, 14-45 years). We assessed UCO in relation to skin cancer and analyzed its association with sociodemographics, tanning and health-related risk behaviors, skin cancer risk, and skin cancer risk awareness. RESULTS: Four out of ten (43.3 %) respondents believed themselves to have a lower risk of developing skin cancer than other people of the same age and sex. Younger individuals were more likely to be optimistic. Individuals with an increased risk of skin cancer were more likely to perceive this higher risk. CONCLUSION: While it is realistic for those who actually have a higher risk of skin cancer to perceive it that way, the findings for the general population (and specifically for younger individuals) are concerning. It seems important to explain to people that their perception of their own risk of skin cancer is unrealistic, as this may affect their individual screening and prevention behavior.

Are tanning salons in compliance with German law? An evaluation based on a nationwide representative survey.

BACKGROUND: Given the evidence for increased skin cancer risk due to the sunbed use, a regulation of hazardous artificial ultraviolet radiation (UVR regulation) was passed in Germany in 2012. The aim of this study was to explore the advisory services in tanning studios as reported by sunbed users and to evaluate the information provided by the personnel of tanning salons after the UVR regulation was enacted. METHODS: The first wave of the representative National Cancer Aid Monitoring on Sunbed Use included a subgroup of 357 German citizens between 14 and 45 years who had used sunbeds since the UVR regulation was implemented. The participants provided data on sunbed use and related issues in telephone interviews. RESULTS: Although sunbed operators are mandated to offer their customers certain services at least once since the implementation of the UVR regulation, 15.4% of sunbed users were never advised to use protective eyewear during tanning and 13.1% were not provided with eyewear during their last sunbed use. Overall, 66.0% were never offered to develop a tanning schedule, 56.9% were never advised on the risks of UVR, 43.4% were never offered a determination of their skin type and 40.0% of users were never advised on how to use a sunbed safely. CONCLUSIONS: The data showed that 3 years after the UVR regulation was enacted, compliance with this legislation is still not optimal. Binding wording in the legal text and making them applicable to unsupervised sunbeds as well is necessary to extend the impact of this legislation.

"Lost in the sun"-The key role of perceived workplace support for sun-protective behavior in outdoor workers.

BACKGROUND: Previous studies show that workplace support for sun-protective behaviors plays an important role in the actual sun-protective behavior of outdoor workers. Therefore, our aim was to examine perceived workplace support (organizational and social support) in relation to different sun-protective behaviors. METHODS: A Germany-wide sample of outdoor workers (n = 485) was surveyed via telephone. We analyzed associations of workplace support with sun-protective behaviors, sociodemographic, and occupational characteristics, occupational sun exposure, and concerns about sun. RESULTS: A large number of outdoor workers perceived no workplace support for sun protection (eg, 17.8% agreed that sun protection is enforced at their workplace). We found that those who do not get any support are less likely to show sun-protective behaviors. CONCLUSIONS: A starting point for a better organizational support is the implementation of mandatory sun protection policies in the workplace. Social support for protection against solar UV exposure can be promoted through safety training and education.

Energetic ultrafast fiber laser sources tunable in 1030-1215 nm for deep tissue multi-photon microscopy.

We demonstrate an energy scalable approach to implement ultrafast fiber laser sources suitable for deep tissue multi-photon microscopy imaging. Enabled by fiber-optic nonlinearities (dominated by self-phase modulation), these unique ultrafast sources produce nearly transform-limited pulses of 50-90 fs in duration with the center wavelength tunable in the wavelength range of 1030-1215 nm. The resulting pulse energy can be scaled up to 20 nJ by optimizing fiber dispersion, shortening fiber length, and using large-mode-area fibers. We applied such an energetic source to a proof-of-principle study of ex vivo human skin based on harmonics (i.e., second-harmonic generation and third-harmonic generation) imaging. This new type of fiber-format energetic ultrafast source provides a robust solution for multiphoton microscopy applications.

German "National Cancer Aid Monitoring" 2015-2019 - study protocol and initial results.

BACKGROUND AND OBJECTIVES: The National Cancer Aid Monitoring of Tanning Bed Use (NCAM) project is a major German study that aims to observe the most significant risk factors for skin cancer: natural sunlight and artificial UV radiation. PARTICIPANTS AND METHODS: NCAM is a nationwide cross-sectional survey that will initially involve four rounds of data collection (so-called waves) between 2015 and 2018. Every year, a representative nationwide sample consisting of 3,000 individuals aged between 14 and 45 years will be surveyed. The cross-sectional survey will be complemented by a panel of n  =  450 current tanning bed users. RESULTS: The initial wave in 2015 shows an overall prevalence of tanning bed use of 29.5 %. Eleven percent of all participants had used a tanning bed within the past twelve months. Determinants of current tanning bed use included younger age, female gender, and full-time/part-time employment. The main motivations for tanning bed use reported were relaxation and increased attractiveness. CONCLUSIONS: NCAM is the first study worldwide to monitor skin cancer risk factors at one-year intervals using a large, nationally representative sample. Initial results indicate that, despite WHO warnings, millions of Germans use tanning beds, and that many of these users are adolescents despite legal restrictions aimed at preventing minors from using tanning beds.

Deutsches "Nationales Krebshilfe-Monitoring" 2015-2019 - Studienprotokoll und erste Ergebnisse.

HINTERGRUND UND ZIELE: Das Projekt "Nationales Krebshilfe-Monitoring zur Solariennutzung" (National Cancer Aid Monitoring of Tanning Bed Use, NCAM) ist eine deutsche Großstudie mit dem Ziel, die wichtigsten Risikofaktoren für Hautkrebs zu beobachten: natürliches Sonnenlicht und künstliche UV-Strahlung. TEILNEHMER UND METHODEN: NCAM ist eine bundesweite Querschnittstudie mit zunächst vier Runden der Datenerfassung (sogenannten Wellen) zwischen 2015 und 2018. Jedes Jahr wird eine bundesweit repräsentative Stichprobe aus 3.000 Personen im Alter von 14 bis 45 Jahren befragt. Die Querschnittsbefragung wird durch eine Kohorte von n = 450 aktuellen Solariennutzern ergänzt. ERGEBNISSE: Die erste Welle im Jahr 2015 ergab eine Gesamtprävalenz der Solariennutzung von 29,5 %. Elf Prozent aller Teilnehmer hatten in den vergangenen zwölf Monaten ein Solarium genutzt. Zu den Determinanten der aktuellen Solariennutzung gehörten jüngeres Alter, weibliches Geschlecht und Vollzeit-/Teilzeitbeschäftigung. Die hauptsächlichen Beweggründe, die für die Nutzung eines Solariums genannt wurden, waren Entspannung und Attraktivitätssteigerung. SCHLUSSFOLGERUNGEN: NCAM ist weltweit die erste Studie zur Überwachung der Risikofaktoren für Hautkrebs in jährlichen Intervallen anhand einer großen, landesweit repräsentativen Stichprobe. Erste Ergebnisse deuten darauf hin, dass Millionen Deutsche trotz Warnungen der WHO Solarien nutzen, und dass viele dieser Nutzer Jugendliche sind - trotz gesetzlicher Beschränkungen, die das Ziel haben, die Nutzung von Solarien durch Minderjährige zu verhindern.

Casting shadows on the prevalence of tanning dependence: an assessment of mCAGE criteria.

Recently more and more studies have reported high prevalence rates for a 'tanning dependence' among tanning bed users. The authors of these studies base their argumentation on a modified (m) version of the CAGE (Cut-down, Annoyed, Guilty and Eye-opener) Criteria, initially used for alcohol addiction. By means of cognitive interviews and a large population survey, we tested the validity of the mCAGE Criteria and the above-mentioned prevalence that was deduced on the basis of rather small collectives. Firstly, it seems that the mCAGE Criteria wording used so far is inconsistent, misleading and intrinsically invalid. Secondly, our population-based data show a much lower percentage (15%) of current sunbed users with potential dependence symptoms than the above-mentioned previously published studies. Thirdly, the usage parameters for most of the supposed 'addicts' do not indicate a substance addiction: 38% of the users with positive scores reported not having visited a tanning studio at all in the previous month, 39% did not use sunbeds regularly and 89% did not show signs of tolerance to UV radiation. The mCAGE Criteria do not seem suitable for assessing tanning dependence.

The German SCREEN project--design and evaluation of the communication strategy.

BACKGROUND: Skin cancer is the most common cancer in light-skinned populations worldwide. Primary and secondary preventive activities such as skin cancer screening are intended to reduce skin cancer burden. In 2003, a population-based skin cancer screening project [SCREEN (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany)] was conducted in Northern Germany with more than 360,000 people screened. SCREEN was supported by a communication intervention that was aimed at informing the population about skin cancer, its risk factors and the screening intervention as well as preparing the health professionals for the project. Within SCREEN both physicians and practice nurses were educated in counselling. The aim of the present article is to describe and evaluate the communication strategy accompanying SCREEN. METHODS: Two computer-assisted telephone interview surveys were performed in April/May 2003 and May 2004. Participants had to be members of the statutory health insurance and be aged 20 years. They were asked about knowledge of skin cancer, perception of physicians' performance and skin cancer screening in general. Data are mainly presented in a descriptive manner. For statistical analyses, Mann-Whitney U test and Pearson's chi-square test were used. RESULTS: Knowledge about sunburn in childhood and high ultraviolet exposure as skin cancer risk factors increased during SCREEN. Simultaneously, the awareness for early detection of skin cancer increased significantly from 41.3 to 74.0% (P < 0.001). A total of 21.5% of the interviewees participated in the skin cancer screening project, similar to the population-based participation rate reached. CONCLUSION: A comprehensive communication strategy accompanying a screening intervention improves the knowledge of potential screenees and may additionally increase the participation rate.