Public primary and secondary skin cancer prevention, perceptions and knowledge: an international cross-sectional survey.

BACKGROUND: The incidence of melanoma and non-melanoma skin cancer is continuing to increase worldwide, with sun exposure serving as the primary external aetiologic force in its development. Despite noticeable public health efforts, there continue to be gaps in public awareness and primary and secondary prevention mechanisms. This survey study sought to investigate preventative behaviours regarding sun exposure and skin cancer detection at an international scale. METHODS: A questionnaire was submitted, both online and by telephone, to a representative sample (based on official demographic statistics on gender, age and region) of people aged from 15 to 65 originating from 23 countries. Questions dealt with demographics, sun exposure and protection, risk knowledge, self-examination, medical advice seeking. Data were then gathered and analysed at different levels. RESULTS: A total of 19 569 respondents were recruited. Overall, sunscreen and sunglasses were the most used measures for sun protection. There were however difference between countries and geographical areas. Some high-risk countries in terms of sun exposure (according to their location to Equator) exhibited higher rates of primary preventative behaviours, in particular Australia, Chile and Greece. There were also discrepancies between countries regarding secondary prevention through self-examination and medical advice seeking. Young people, men, individuals belonging to a lower socio-economic class or having a lower education level were all least likely to know or follow primary and secondary preventive measures. CONCLUSION: We found imperfections and geographical inequality both regarding primary and secondary prevention of skin cancer. Our study provides insights that could help to target populations more effectively through information campaigns embedded into the global needed endeavour aiming to reduce mid- and long-term development of skin cancer.

Oxidization of squalene, a human skin lipid: a new and reliable marker of environmental pollution studies.

A review of the oxidization of squalene, a specific human compound produced by the sebaceous gland, is proposed. Such chemical transformation induces important consequences at various levels. Squalene by-products, mostly under peroxidized forms, lead to comedogenesis, contribute to the development of inflammatory acne and possibly modify the skin relief (wrinkling). Experimental conditions of oxidation and/or photo-oxidation mechanisms are exposed, suggesting that they could possibly be bio-markers of atmospheric pollution upon skin. Ozone, long UVA rays, cigarette smoke… are shown powerful oxidizing agents of squalene. Some in vitro, ex vivo and in vivo testings are proposed as examples, aiming at studying ingredients or products capable of boosting or counteracting such chemical changes that, globally, bring adverse effects to various cutaneous compartments.

The revised COLIPA in vitro UVA method.

A multicentred study derived from the COLIPA in vitro UVA method was performed to assess the influence of test conditions on UVA protection factor (UVAPF) values in terms of amplitude, reproducibility between laboratories and correlation with in vivo UVA results. Eight products with a range of in vivo UVAPF from three to 29 were used. Two different types of plates, namely high-roughness (5 µm) and low-roughness (2 µm) plates, were used with a different application rate for each (1.3 mg cm(-2) and 0.75 mg cm(-2) respectively). The UVR dose applied to both plate types followed the same principle as the original test (1.2 J. cm(-2)  × UVAPF0). Strong, significant correlations between in vitro and in vivo UVAPF values were observed for both plate types (Pearson correlation > 0.9, P ≤ 0.01). The correlation and slope obtained with the low-roughness plates confirmed the previous results obtained by COLIPA. Across all laboratories, higher UVAPF values were obtained on the high-roughness plates (P < 0.01). Reproducibility of UVAPF values between laboratories was comparable between the two plate roughness values (low roughness, COV = 8%; high roughness, COV = 12%). Considering the in vitro/in vivo comparisons, a regression slope of 0.83 was observed for the low-roughness plates, in comparison with a value of 1.05 for the high-roughness plates. The accuracy of the method was improved, therefore, with the use of the high-roughness plates. With a constraint to recommend the use of only one plate type in the COLIPA UVA in vitro Test, the high-roughness plate was selected on an on-going basis to limit variability of results and to provide better accuracy with in vivo data.

UVA filters in sun-protection products: regulatory and biological aspects.

This review of published in vitro and in vivo studies concerning the biological effects of ultraviolet A (UVA; 320-400 nm) radiation illustrates the evidence for combining UVA and UVB filters in sun-protection products. These data have led to the development of new sunscreens as well as methods to evaluate their efficacy. After listing the UVA filters available and briefly noting the requirements for a high SPF, broad-spectrum sunscreen, the methods for evaluating the level of UVA protection will be described. This article also summarizes several studies looking at the prevention of erythema, pigmentation, DNA damage, photoimmunosuppression, photoaging and photodermatoses. These data demonstrate in vitro and in vivo that only well-balanced UVA-UVB sunscreens, absorbing over the entire UV spectrum are able to prevent or significantly reduce the associated biological damage.

Photodamage to human skin by suberythemal exposure to solar ultraviolet radiation can be attenuated by sunscreens: a review.

The effects of acute or repeated suberythemal solar ultraviolet radiation (UVR) exposure on human skin have been insufficiently investigated. Such exposure almost certainly has important long-term consequences that include skin ageing and skin cancer. This review summarizes the published data on the biological effects of suberythemal exposure using a wide range of clinical, cellular and molecular endpoints, some of which may be considered as biomarkers for skin cancer and photoageing. We also include some recent unpublished results from our laboratories. The effects of UVA (320-400 nm), UVB (290-320 nm) and total solar UVR (290-400 nm) are compared. We demonstrate that avoiding sunburn does not prevent many indicators of cutaneous biological damage and that use of low sun protection factor (SPF) sunscreen can inhibit much of the damages induced by suberythemal exposure to UVR. However, even when applied correctly, sunscreen use will result in suberythemal exposure. The degree and spectral quality of such exposure will depend on the SPF and absorption spectrum of the sunscreen, but nonetheless it may contribute to cumulative photodamage. This review may help to determine the level of photoprotection required in sunscreens and daily use products, as well as the ideal ratio of UVB/UVA protection, to improve long-term photoprotection outcomes.

The COLIPA in vitro UVA method: a standard and reproducible measure of sunscreen UVA protection.

There is a continuing need to measure and communicate reliably the UVA protection offered by commercial sunscreens. To that end, the COLIPA (European Cosmetics Trade Association) 'In Vitro Sun Protection Methods' group has developed a new in vitro method for measuring UVA protection in a standardized, reproducible manner. The method is based on in vitro UV substrate spectrophotometry and convolution of resulting absorbance data with the action spectrum for the in vivo Persistent Pigment Darkening (PPD) endpoint to provide an in vitro UVA protection factor (UVAPF) which is correlated with an in vivo measure. This method has been published as a COLIPA guideline, used currently in European geographies for testing and labelling sunscreen products. This article summarizes two 'ring' studies, involving eight separate testing laboratories, which both defined critical parameters for the method and validated it. In Ring Study 1, eight laboratories tested the in vitro UV transmission of a total of 24 sunscreens and, from the data, a unit dose of UVA (D(0) of 1.2 J cm(-2)) was defined to provide a single irradiation step which, by taking into account potential sunscreen photo-instability, gave the closest agreement with in vivo UVAPF values. In Ring Study 2, eight laboratories tested the in vitro UV transmission of a total of 13 sunscreens using this single irradiation step and established a very good correlation (r(2) = 0.83; slope = 0.84, P < 0.0001) between resulting in vitro UVAPF values and corresponding values derived from the in vivo PPD method. This new method, therefore, can be used to provide a reliable in vitro metric to describe and label UVA efficacy in sunscreen products, in line with the EU Commission recommendation 2006/247/EC.

Importance of sunscreen products spreading protocol and substrate roughness for in vitro sun protection factor assessment.

The purpose of this study was to evaluate the impact of substrate roughness and of product spreading method on in vitro sun protection factor (SPF) measurement and to define the experimental conditions most appropriate to reach the best level of correlation to in vivo SPF. In vitro SPF assessment was carried out on 13 products (including different formulation types with SPF from 20 to 75) using various in vitro SPF protocols and comparing related predictive potential regarding in vivo SPF. In the first part, two spreading methods were compared on two types of PMMA (Polymethyl methacrylate plate with different roughness. The impact of a second spreading step after product drying was also evaluated. From the various investigated parameters, it was shown that (i) a higher roughness (Ra = 4, 5 microm) was preferred for O/W formulations (ii) using a defined sequence of light linear and circular strokes was more adequate than monitoring product spreading in terms of time and pressure (iii) both correlation to in vivo SPF and results variability were improved when a second spreading step was added. The altered protocol showed a good predictive potential regarding in vivo SPF values for O/W formulations (correlation coefficient 0.92, correlation curve slope 0.98) and coefficient of variation of in vitro results (14% of the mean SPF value) close to what is usually obtained in vivo. The repeatability of the protocol was also demonstrated. In the second part, we evaluated the impact of PMMA plate pre-treatment with paraffinum liquidum before spreading the product to get a better correlation between in vivo and in vitro SPF values for W/O formulations. This allowed us to define a protocol suitable for both O/W and W/O formulations.

In vivo persistent pigment darkening method: proposal of a new standard product for UVA protection factor determination.

The European Commission (EC) has recommended assessing the level of ultraviolet A (UVA) protection afforded by sunscreen products using the in vivo persistent pigment darkening (PPD) method or other methods giving equivalent results. In this context, the reproducibility of the in vivo PPD method is of importance. To check the validity of the UVA protection factor (UVAPF) tests, the Japanese Cosmetic Industry Association (JCIA) recommends using a standard product (JCIA standard) with an expected UVAPF 3.75 (SD 1.01). However, considering the increase in UVA efficacy of the new sunscreen products available in the market, with UVAPF up to 30, it seemed useful to develop a new standard product to be used when testing products with expected UVAPF > or =10. The PPD method was used in six centres to determine the UVAPF of the two products. Reproducibility of results was also studied by testing two batches of the new product at two different times. There was no statistical difference between the six centres with regard to the JCIA standard. The ring study showed that the mean value of UVAPF (4.3) was higher than that given by JCIA (3.75). These data enable the proposal of a new acceptance range for the JCIA standard product (3.4-5.2) derived from actual results from European laboratories. Whereas this range is different from that proposed by JCIA (2.74-4.76), there is an overlapping of the values. Data on the new standard product show that reproducibility is not influenced by the batches of this product. The mean UVAPF value obtained is 12.1. An acceptance range (9.6-14.6) is proposed for the new standard. Data presented here demonstrate that if an identical protocol is used, reproducible results can be expected and that the PPD method is reproducible and reliable.

Broad-spectrum sunscreens provide better protection from the suppression of the elicitation phase of delayed-type hypersensitivity response in humans.

It is well established that ultraviolet radiation has immunomodulatory effects that may be involved in skin cancer. Recent studies have shown that ultraviolet A radiation (320-400 nm) as well as ultraviolet B (290-320 nm) is immunosuppressive. This means sunscreens that mainly absorb ultraviolet B (protection against erythema) may be less effective in preventing ultraviolet radiation-induced immunosuppression than broad-spectrum products. We have studied the effects of ultraviolet A exposure on the human delayed-type hypersensitivity response and compared the efficacy of sunscreens having different levels of ultraviolet A protection under both solar-simulated radiation and outdoor real-life solar exposure conditions. Delayed-type hypersensitivity was assessed using recall antigens. In a first study, two groups of volunteers were exposed to ultraviolet A (either full spectrum ultraviolet A or ultraviolet A1) without prior application of sunscreen and they were shown to exhibit significantly reduced delayed-type hypersensitivity responses. In order to compare the efficacy of sunscreens in preventing photoimmunosuppression, three groups of subjects received 10 cumulative exposures to solar-simulated radiation; one group was exposed unprotected and the other two were exposed after being applied either a ultraviolet B or a broad-spectrum sunscreen, each with the same sun protection factor 9, but with different ultraviolet A protection factors 9 and 2. Then, an outdoor study was conducted in which delayed-type hypersensitivity was assessed before and after six daily exposures. Two different groups of subjects were treated with one of two sunscreens having the same sun protection factor 25 but different ultraviolet A-protection factors. In unprotected volunteers, responses to delayed-type hypersensitivity tests were significantly reduced irrespective of ultraviolet exposure conditions (full spectrum ultraviolet A, ultraviolet A1, solar-simulated radiation). The ultraviolet B sunscreen failed to protect from solar- simulated radiation-induced immunosuppression. In contrast, the broad-spectrum sunscreen having the same sun protection factor but providing high protection in the ultraviolet A range significantly reduced local ultraviolet-induced immunosuppression and prevented the distal effects. In the outdoor study, as compared with delayed-type hypersensitivity responses obtained before sun exposure, no alteration of immune response was detected when the skin was protected by broad-spectrum sunscreen sun protection factor 25 and ultraviolet A-protection factor 14. Conversely, a broad-spectrum sunscreen sun protection factor 25 ultraviolet A-protection factor 6 failed to protect against the sun-impaired response. The above studies clearly demonstrate the role of ultraviolet A in the induction of photoimmunosuppression together with the need for sunscreen products providing efficient photoprotection throughout the entire ultraviolet spectrum.

Sunscreens with broad-spectrum absorption decrease the trans to cis photoisomerization of urocanic acid in the human stratum corneum after multiple UV light exposures.

The trans to cis photoisomerization of urocanic acid (UCA) in skin is considered to play an important role in the mechanism of immunosuppression. We have investigated the effects of skin type and various sunscreens with low sun protection factor (SPF) on the UV-induced cis-UCA formation in human skin after exposure to artificial UV light. The rate of cis-UCA formation depends little on the skin type and is reduced by topical application of sunscreens. The rate of cis-UCA formation decreases with increasing SPF and only broad-spectrum, highly protective sunscreens offer protection against the UV-induced formation of cis-UCA, which accumulates in the stratum corneum after multiple UV exposures. A theoretical approach to estimate the distribution of cis-UCA after irradiation indicates that this compound may diffuse into the deeper layers of the epidermis with D approximately 10(-17) m2/s, and that its elimination from the stratum corneum is mainly due to desquamation.

Mexoryl SX: a broad absorption UVA filter protects human skin from the effects of repeated suberythemal doses of UVA.

There is now considerable evidence that chronic UVA exposure induces damage in animal and human skin; however, little is known about UVA protection of human skin. The aim of this study is to evaluate the efficacy of Mexoryl SX, a broad UVA absorber (lamada max = 345 nm) against UVA-induced changes in human skin. The regimen of UVA exposure (13 weeks with increasing suberythemal doses) induces intense pigmentation with no erythema. Skin hydration and elasticity decrease, whereas total skin thickness, assessed by echography, remains unchanged. Irradiated epidermis reveals a significant thickening of the stratum corneum, an absence of hyperplasia and an increase in the expression of the protective iron-storage protein ferritin. No significant alterations are seen using antisera against type IV collagen or laminin, suggesting that the dermal-epidermal junction (DEJ) is mainly preserved. In dermis, enhanced expression of tenascin is seen just below the DEJ but type I procollagen, which is localized at the same site, is unaltered. Although we are unable to visualize any changes in elastic network organization using Luna staining or specific antiserum directed against human elastin, we notice an increased deposition of lysozyme or alpha-1 antitrypsin on elastin fibres. Mexoryl SX (5%) efficiently prevents these alterations. Thus, these results suggest that UVA photoprotection can prevent early putative alterations leading to photoageing.

Protection of skin biological targets by different types of sunscreens.

In vitro and in vivo studies provide a body of evidence that adequate protection of the skin against ultraviolet (UV)-induced damage requires photostable broad-spectrum sunscreens with a proper level of UVA protection. UVA alone and UV solar simulated radiation (SSR) induce DNA lesions in keratinocytes and melanocytes as reflected by the comet assay and p53 accumulation. UVA and SSR impair the immune system as shown by significant alteration of Langerhans cells and inhibition of contact hypersensitivity response to chemical allergens and delayed-type hypersensitivity response to recall antigens. Any of these detrimental effects is more efficiently prevented by sunscreens with a higher level of protection in the UVA range. The involvement of UVA (fibroblast alteration, increased metalloproteinase expression) and the pivotal need for well-balanced UVA/UVB sunscreens were further demonstrated using reconstructed three-dimensional skin models.

Determination of UVA protection factors using the persistent pigment darkening (PPD) as the end point. (Part 1). Calibration of the method.

BACKGROUND/AIMS: The accuracy and reliability of any method to assess the UVA protection effectiveness of sunscreens needs to be demonstrated. The aim of the present study was to calibrate the effectiveness of a biological end point (Persistent Pigment Darkening, PPD) to assess UVA photoprotection, METHODS: Persistent Pigment Darkening was selected as the end point because its action spectrum extends across the UVA. A broad UVA source was chosen to challenge all UVA wavelengths. Attenuation of UVA was performed with neutral density filters (equally absorbing at all wavelengths). Human subjects were tested with a series of UVA beams attenuated by the neutral density filters. The UVA protection effectiveness of a standard sunscreen was also tested with four panels of volunteers to assess the reproducibility of the method. RESULTS: The attenuation factors of the neutral density filters were found to correspond to the UVA protection factors arrived at with PPD as the end point. The repetitive tests showed a good internal consistency of the method. CONCLUSIONS: The calibration procedure proposed shows threshold PPD, used as an end point in a UVA-PF test method, to be a reliable endogenous dosimeter for UVA radiation that enters the skin.