576465 research-article2015

CMSXXX10.1177/1203475415576465Journal of Cutaneous Medicine & SurgeryBarber et al

Special Section

Non-melanoma Skin Cancer in Canada Chapter 2: Primary Prevention of Non-melanoma Skin Cancer

Journal of Cutaneous Medicine and Surgery 1­–11 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1203475415576465 jcms.sagepub.com

Kirk Barber1,2, Gordon E. Searles3, Ronald Vender4,5, Hwee Teoh6, and John Ashkenas6 for the Canadian Non-melanoma Skin Cancer Guidelines Committee* Abstract Background: Non-melanoma skin cancer (NMSC), including basal and squamous cell carcinoma (BCC and SCC), represents the most common malignancy. Objective: To provide guidance to Canadian health care practitioners regarding primary prevention of NMSC. Methods: Structured literature searches were conducted, using search terms including prevention, sunscreen, and sun prevention factor. All recommendations concern guidance that physicians should regularly discuss with their patients to help establish photoprotection habits. The GRADE system was used to assign strength to each recommendation. Results: Ultraviolet exposure is the major modifiable risk factor for NMSC. Aspects of photoprotection, including effective sunscreen use and avoidance of both the midday sun and artificial tanning, are discussed. Several widespread misunderstandings that undermine responsible public health measures related to sun safety are addressed. Conclusions: Photoprotection represents both an individual priority and a public health imperative. By providing accurate information during routine patient visits, physicians reinforce the need for ongoing skin cancer prevention. Résumé Contexte : De tous les cancers, le carcinome cutané (non-mélanome), y compris le carcinome basocellulaire et le carcinome spinocellulaire, est le plus fréquent. Objectif : Fournir des conseils aux professionnels canadiens de la santé au sujet de la prévention du carcinome cutané. Méthodologie : On a effectué des recherches documentaires structurées à l’aide de divers mots clés, dont « prévention », « écran solaire » et « facteur de protection solaire ». Toutes les recommandations que nous avons repérées portent sur des conseils dont les médecins devraient régulièrement discuter avec leurs patients pour les aider à adopter des habitudes de photoprotection. On a utilisé l’échelle GRADE pour évaluer la pertinence de chacune des recommandations. Résultats : L’exposition aux rayons UV est le plus important facteur de risque modifiable du carcinome cutané. Certains aspects de la photoprotection, entre autres l’utilisation efficace d’un écran solaire, l’évitement du soleil de mi-journée et l’évitement du bronzage artificiel, sont examinés. Plusieurs croyances erronées répandues nuisent aux mesures de santé publique en matière de protection contre le soleil. Conclusions : La photoprotection constitue autant une priorité personnelle qu’un impératif de santé publique. En fournissant des renseignements précis aux patients lors des visites de routine, les médecins insistent sur la nécessité d’une prévention continue du cancer de la peau. Keywords photodamage, photoprotection, sunscreen, artificial tanning

Introduction Non-melanoma skin cancer (NMSC) is eminently preventable. The occurrence of basal and squamous cell carcinomas (BCC and SCC; the 2 predominant forms of NMSC) on sunexposed sites and areas of photodamage provided the first evidence of a causal relationship with solar radiation.1 This conclusion has since been validated both by interventional

studies and by epidemiology. Specifically, studies in Canada,2 Australia,3 and Italy4 and a large international study of southern Europe5 documented a strong correlation between BCC risk with intermittent ultraviolet (UV) exposure before the age of 20 years.6 By contrast, SCC risk appears to increase with cumulative lifetime exposure to UV.2,5,7 UV exposure is the major modifiable risk factor for NMSC, and strict, ongoing adherence to principles of photoprotection

2 would largely prevent the genetic and structural changes in the epidermis that lead to these malignancies. Because this effort must be lifelong, it represents both an individual priority, to be reinforced by physicians in their interactions with their patients, and a public health imperative. In Canada and elsewhere, much effort has aimed to educate the public on the hazards of unprotected exposure to both natural and artificial UV radiation. Educational campaigns urge the public to limit UV exposure and wear sunprotective clothing outdoors whenever possible, avoid the midday sun, eliminate indoor tanning, and routinely apply and reapply sunscreen properly (Figure 1). Various myths and misunderstandings about skin cancer risk, some with a shaky basis in clinical science, continue to frustrate public education efforts. It is important for physicians to have accurate information in order to combat misunderstandings and reinforce the need for ongoing, effective UV protection.

Some Misguided Notions “I Rarely Bother With Sunscreen” Skin damage from UV exposure accumulates in a roughly linear fashion over time, with 23% of photodamage occurring by age 18, 46% by age 40, and 74% by age 59 (Figure 2).8 These findings underscore the importance of early and lifelong sun protection to prevent new UV-induced skin damage. Unfortunately, only 56% of Caucasian North Americans report moderate or frequent use of sunscreen when outside on a sunny day.9 Routine use of sunscreen significantly reduces the incidence of SCC and actinic keratoses (AKs), a class of premalignant lesions that are common precursors of SCCs.10-12 Some of the clearest data on the benefits of UV protection can be found in studies of organ transplant recipients (OTRs), who experience long-term immunosuppression and are particularly susceptible to NMSCs, which can be highly aggressive in these patients.13 The risks for SCCs, BCCs, and AKs in OTRs are 65- to 250-fold, 10- to 16-fold, and 250-fold, respectively, greater than in controls.14,15 In OTRs, regular sunscreen use for 24 months was associated with significant reductions in new SCC and AK occurrences.16 In addition, habitual use of sunscreens and other photoprotection decreased the rate of subsequent SCCs after a first SCC in OTRs.17

Journal of Cutaneous Medicine and Surgery  UV protection is therefore essential for both primary10-12 and secondary prevention of NMSC, and this behaviour should be reinforced in healthy patients as well as in OTRs and others at elevated risk of skin cancer.

“A Tan Will Protect Me From Skin Cancer” While skin pigmentation18,19 and ethnicity19-22 substantially influence susceptibility to UV-induced skin damage, it is difficult to establish the protective effect of tanning (ie, facultative pigmentation). It has been suggested that facultative pigmentation can yield modest protection, the equivalent of using a sunscreen with a sun protection factor (SPF) of 2 to 3.23 However, this is not an appropriate strategy for sun safety. Tanning following suberythemal UV exposure has several components, with different implications for the skin’s response to later UV challenge.24 As shown in Figure 3, UV radiation is classified according to wavelength into UVC (200-290 nm), UVB (290-320 nm), and UVA (320-400 nm).25-27 UVC from sunlight is virtually all filtered out at the ozone layer. UVB radiation, too, is mostly screened out at the stratosphere, but the 1% to 10% that reaches us has profound effects on human skin. For instance, UVB stimulates vitamin D synthesis28 and induces morphological changes (increased epidermal thickness and keratinocyte height).29 UVB also alters skin lipid composition and enzyme metabolism,30,31 increasing transepidermal water loss.31,32 These events culminate in premature aging of the skin, such as actinic elastosis. UVA transits the atmosphere more readily than the shorterwavelength UV, and it penetrates the skin to the level of the upper dermis. UVB, more energetic but less penetrating than UVA, causes DNA damage in epidermal keratinocytes, including mutations in the tumour suppressor gene P53.33 Both UVA and UVB can stimulate high-level expression of p53 protein in sun-exposed keratinocytes, and both must be blocked to prevent the formation of p53 overexpressing clonally expanded keratinocytes.34 As discussed in Chapter 1, formation of such regions, carrying 1 or more mutations in P53, may explain the formation and recurrence of AKs and SCCs in the photodamaged epidermis. Because UVA and UVB also induce cutaneous immunosuppression, premalignant and malignant cells that would ordinarily be eliminated may persist and proliferate in these photodamaged areas.35

1

Kirk Barber Research, Calgary, AB, Canada University of Calgary, Calgary, AB, Canada 3 Searles Dermatology and Aesthetics, Edmonton, AB, Canada 4 Dermatrials Research, Hamilton, ON, Canada 5 McMaster University, Hamilton, ON, Canada 6 SCRIPT, Toronto, ON, Canada *The Canadian Non-melanoma Skin Cancer Guidelines Committee: Kirk Barber, MD, FRCPC (Co-Chair), Charles W. Lynde, MD, FRCPC (Co-Chair), Marc Bourcier, MD, FRCPC, Joël Claveau, MD, CSPQ, FRCPC, FABD, Lyn C. Guenther, MD, FRCPC, Yves Poulin, MD, FRCPC, Mariusz Sapijaszko, MD, FRCPC, Gordon E. Searles, MD, FRCPC, Ronald Vender, MD, FRCPC, and David Zloty, MD, FRCPC 2

Corresponding Author: Kirk Barber, Calgary Dermatology, Kirk Barber Research, University of Calgary, 1100 1st St SE Suite #510, Calgary, AB, T2G 1B1, Canada. Email: [email protected]

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Figure 2.  Average cumulative percentages of an individual’s lifetime ultraviolet dose for different ages. Calculated on the basis of averaged US data. Reproduced with permission from Godar et al.8

Figure 1.  Some Canadian initiatives to promote ultraviolet (UV) awareness. (A) “Sun Safety for Daycares” is one arm of the “UV Index Sun Awareness Program,” an annual campaign championed by Health Canada and Environment Canada. The goal of this initiative is to educate Canadian children about UV radiation, the harmful effects of overexposure, and how to protect themselves with the aid of the UV index. From http://www.hc-sc.gc.ca/hl-vs/ sun-sol/uv-prog/daycares-garderi-eng.php. Accessed February 2013. Reprinted with permission. (B) “The Big Burn” is an interactive Web site developed by Alberta Health Services that educates visitors on the health risks associated with indoor tanning. From http://www.thebigburn.ca, accessed February 2013. (C) The “Indoor Tanning Isn’t Pretty” video created by the Canadian Dermatology Association uses comedy and social media to discourage individuals from using indoor tanning beds. The video capture shows a young woman “tanning” her face with a waffle maker. Available on YouTube at http://youtu.be/ sfzn_PlRskk. Viewed February 2013.

Both UVA and UVB are mutagenic in the skin, although by somewhat distinct mechanisms. UVA promotes the buildup of reactive oxygen and nitrogen species (ROS and RNS), both of which trigger DNA fragmentation.36,37 UVA exposure produces a characteristic class of DNA lesions

(single nucleotide transversions) that can be found in the P53 gene of NMSC and in premalignant, photodamaged areas of the skin.33 Both UVA and UVB cross-link adjacent pyrimidines in the DNA, leading to single- or double-nucleotide transition mutations.38-40 Such mutations can be detected in the P53 gene in AKs, SCCs, and BCCs.38-43 UVA exposure leads to immediate pigment darkening,44 in which pigment granules redistribute within the melanocytes, and existing pigment (melanin) undergoes photo-oxidation to a darker form, although no new melanin is formed in this process.24 In a careful study of UVA or UVB pretreatment, prior to challenge with erythema-inducing broad-spectrum UV, UVA caused tanning but did not induce melanin production. This UVA pretreatment did not protect subjects’ skin from suffering DNA damage during a subsequent UV challenge. Conversely, UVB caused facultative pigmentation by inducing melanin biosynthesis. With this form of tanning, there was a modest protective effect of prior exposure to suberythemal doses of UVB-containing light. Unfortunately, however, the suberythemal UVB dose was mutagenic in itself.24 Hence, tanning, either with the full UV spectrum or with the UVA or UVB spectra alone, cannot be recommended as a means to prevent mutations or skin cancer.

“Indoor Tanning Is Safer Than the Sun” The implication that a bronze tan symbolizes a healthy body has contributed to a persistent obsession with tanning.45,46 Tanning devices, which can be designed to provide only part of the UV spectrum, are sometimes thought of as a safer means than direct sun exposure to achieve a tan, in part because of a misunderstanding of the mutagenic potential of UVA (see above). However, UV-emitting tanning devices are now classified as Class 1 carcinogens.47 There is great variability in UV outputs from tanning beds. A recent study examining 402 tanning beds in England showed a >10-fold range (between 0.10 and 1.32 W/m2) in measured UV emissions.48 Tanning beds predominantly

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Figure 3.  Ultraviolet and the human skin. RNS, reactive nitrogen species; ROS, reactive oxygen species. UV radiation is divided based on wavelength into 3 subclasses: UVA, UVB, and UVC. UVC and most UVB rays are filtered out at the stratosphere. The UVB rays that penetrate the stratosphere can travel as deep as the epidermis, where they trigger vitamin D synthesis and can initiate DNA damage, elevate oxidative stress, cause sunburn, and elicit morphological and biomechanical modifications that can compromise the integrity and function of the skin. UVA rays can reach as far as the dermis, where they increase oxidative stress and directly and indirectly instigate DNA damage. UVA radiation is responsible for causing immediate pigment darkening, whereas UVB-initiated tanning occurs via increased melanin biosynthesis.

produce UVA radiation but may emit UVB as well.49 UVA emissions from tanning beds can exceed that from the sun by as much as 10-fold.50 With newer, high-pressure tanning lamps, a single tanning session may expose the user to approximately 10% of a typical annual solar UVA dose.51 A population-based, case-control study found that tanning devices elevate the risk of BCC and SCC by 1.5- and 2.5fold, respectively.52 A recent meta-analysis of 12 studies determined that exposure to indoor tanning increased the risk for SCC by 67% and BCC by 29%.53 This coincides with another report noting that approximately 25% of early-onset BCC can be avoided if an individual never tanned indoors.54 BCC risk is increased by 10% and 73% with 1 and 6 indoor tanning sessions per year, respectively, in high school or college.55 Meta-analysis of 3 studies further revealed a relative risk of 2.0 and 1.4 for SCC and BCC, respectively, if indoor tanning took place prior to age 25.53 There is widespread support for limiting indoor tanning and prohibiting use of tanning devices for cosmetic purposes, at least in young people.56-58 In Australia59 and the United Kingdom,60 minors are prohibited from indoor tanning. In more than half of the US states,61 indoor tanning is either

prohibited or restricted to adults or older teenagers. In May 2011, Nova Scotia became the first Canadian province to formally limit tanning bed access.62 Since then, similar regulations have been enacted in British Columbia,63 Manitoba,64 New Brunswick,65 Prince Edward Island,66 and Quebec,67 as well as in Ontario and Newfoundland and Labrador.68

“With Sunscreen, I Can Stay out All Day” There is substantial basis for concern that regular sunscreen users will increase their exposure to UV, offsetting or eliminating the benefits of this one protective measure. In observational studies, use of sunscreen was associated with sun exposure that was 13% to 39% longer than if no sunscreen was applied.69 Furthermore, subjects using sunscreen products with SPF 30 (see text box) remained in the sun 19% to 25% longer than subjects provided with SPF 10 sunscreen.70,71 Overreliance on sunscreen, which may be unevenly applied, used in inadequate quantities or reapplied too infrequently, may lead to a false sense of security. In fact, the most basic photoprotective tools are avoidance of midday sun and wearing UV-blocking clothing.

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Barber et al Text Box 1.  Sun Protection Factor (SPF).

•• SPF is a measure of how much longer it takes sunscreen-protected skin (applied at 2 mg/cm2) to produce a minimal erythema (redness) response to UVB exposure, compared with unprotected skin. •• The relationship with UVB deflection is not linear. A product with an SPF of 15, under laboratory-controlled conditions, blocks 93% of UVB rays, while another with an SPF of 30 will block 97% of UVB rays. •• SPF provides only a crude estimate of how much protection a sunscreen product can provide against UVB-induced damage, since the strength of UV rays can alter with environmental changes. •• SPF does not indicate efficacy in blocking UVA, which can also be damaging and carcinogenic to the skin.

The UV index72,73 was developed by Environment Canada to provide details on the intensity of UVB radiation. It spans a range of 0 to >11, with 5 subcategories of exposure (Figure 4). Because UV radiation is most intense when the sun is highest in the sky, outdoor activities in the full sun should be avoided during this period.56-58,74 The UV index is typically highest at 12 noon but is enhanced with altitude, reflective surfaces (eg, snow, sand, and water), reduced cloud cover, and decreasing ozone density. Physicians should regularly remind patients to minimize sun exposure when the UV index is ≥3. Depending on locale and other factors, this may be from 11 am to as late as 4 pm). Coverage provided by appropriate clothing can significantly reduce the risk of UV exposure.56,57,74 UV protection factor (UPF) is a term used with sun-protective textiles and clothing, indicating the amount of UV radiation that is blocked (Table 1). The endpoint of fabric protection assessments is the erythema,75 and the results reflect how well a fabric can protect the underlying skin from sunburn. Fabrics are provided with a UPF designation only if they have successfully undergone testing to assess residual UV protection at the end of the fabric’s 2-year life cycle.76-78 Clothing items that provide optimal coverage include wide-brimmed hats, sunglasses, gloves, long sleeves, pants, and skirts.56-58,74 Ideally, clothing should be lightweight, stretchy, and/or loose fitting and made of tightly woven fabric with a high UPF rating and good wicking properties.56-58,74 Ordinary clothing that adequately covers sun-exposed skin is also likely to provide significant photoprotection. Unfortunately, this simple and effective approach to photoprotection is underrated by the public, and its use may be at odds with fashion trends favouring low-cut necklines, lowrise bottoms, miniskirts, and other items that leave large areas of the skin exposed to the sun.

“I Choose a Sunscreen by Its SPF” Sunscreen products remain the most popular form of daily and vacation sun protection. The first commercial sun protection product, marketed in the United States in 1928, was an emulsion with benzyl salicylate and benzyl cinnamate. Today, sunscreen products are available in many formats, and the ingredients used reflect the evolving understanding of how broad-spectrum UV radiation effects skin damage.

The goal of all sunscreen formulations is to attenuate UVA and UVB radiation before they exert their harmful effects. SPF value has traditionally been synonymous with the efficacy of a sunscreen product. However, SPF measures only UVB protection. Historically, sunscreen products consisted of UV absorbers and a vehicle. Unlike their predecessors, newer UV absorbers cover the entire UV spectrum. UV absorbers can be divided into 2 groups: organic filters and inorganic blockers. Organic filters are chromophores that absorb UV radiation,79 whereas inorganic blockers (zinc oxide and titanium dioxide) can both absorb and reflect or scatter UV radiation.80,81 The growing appreciation of the role of ROS in UV-induced lesions has inspired the inclusion of a third class of sunscreen components, antioxidants such as vitamins C and E,82 the clinical value of which remains to be demonstrated. In 2012, the United States approved new legislation on how nonprescription sunscreen products should henceforth be labelled (Table 2). Specifically, sunscreen products can be labelled “broad spectrum” only if they effectively protect against both UVA and UVB. Only broad-spectrum products with an SPF of 15 or more can claim to retard/reduce the incidence of skin aging and skin cancer. Broad-spectrum products with an SPF of less than 15, and those that do not provide broad-spectrum protection, must carry a warning indicting that they are effective only against sunburns. Products with SPF values greater than 50 will be labelled as 50+. Products can claim only to be “water-resistant” (rather than “waterproof”) and must display the duration of effectiveness (either 40 minutes or 80 minutes) while exposed to water or sweat. In July 2013, Health Canada released a guidance document on sunscreen products.84 Most of the proposed recommendations mirror those of the US Food and Drug Administration.

“Everyone Knows How to Use Sunscreen” In a large, randomized trial, daily use of sunscreens reduced the development of SCCs by 39% over 4.5 years11 and by 35% after an additional 8 years of follow-up.12 Development of AKs was also reduced by 24% in the routine sunscreen group.10 Another randomized study, focusing on individuals with 1 to 30 AKs, established that daily use of sunscreen over

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Figure 4.  Ultraviolet (UV) radiation index and recommended actions. The UV index is a simple measure of the intensity of UVB radiation and varies according to the time of day and outdoor conditions, providing a quick indication of the potential for skin damage. The higher the UV index, the more harmful the sun’s rays and therefore the more critical it is to implement photoprotection. Reprinted with permission from Environment Canada.72,73 Table 1.  Ultraviolet Protection Factor (UPF) Ratings and Protection Categories.a UPF Rating

Protection Category

% of UV Radiation Blocked

15-24 25-39 40-50+

Good Very good Excellent

93.3-95.9 96.0-97.4 97.5-99+

a UPF is an indication of how much UV radiation a fabric is able to block. UPF designations are based on the residual UV protection status of the fabric at the end of a 2-year life cycle.77 This system has been adopted by the Canadian Dermatology Association.

7 months significantly reduced the emergence of new AKs and also promoted the regression of lesions that were evident at baseline, relative to subjects using a vehicle control.85

These findings are consistent with studies in OTRs, where AKs and SCCs occur reliably and at a greatly elevated rate, compared with the general population.16 While routine sunscreen use in the same cohorts did not significantly protect subjects from BCCs,11,12,16 it appears that sunscreens delay the recurrence of this malignancy in patients with a prior history of BCCs.86 However, there is often a mismatch between the expected and delivered photoprotection. Manufacturers recommend that sunscreens be applied at an even thickness of 2 mg/cm2, because SPF values are determined under those laboratory conditions. Yet the amount of sunscreen used is typically less than half that recommended,87 decreasing UV protection by 2- to 4-fold.88,89 Furthermore, sunscreen application is also typically not homogenous, with many areas (eg, ears, neck, back of hands, and temples) often left unprotected.90,91

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Barber et al Table 2.  New Labelling Regulations for Over-the-Counter Sunscreen Products in the United States83 and, More Recently, Canada.84 Prior Labelling Some sunscreen products claim to be “broad spectrum” and have “anti-aging” and “skin cancer protection” properties    

Some sunscreen products are labelled with SPF values that are higher than 50  Some sunscreen products claim to be “waterproof,” “sweatproof,” and “sun block” or to provide protection for more than 2 h     

Current Labelling Standards The “broad-spectrum” label is for sunscreen products that demonstrate effective protection against UVA and UVB radiation during mandatory tests administered by the US Food and Drug Administration. Only sunscreen products that qualify as being “broad spectrum” and also have an SPF ≥15 may assert skin cancer and early skin-aging reduction properties when used as per the manufacturer’s instructions. Sunscreen products that do not meet the “broad-spectrum” requirements or are of “broad-spectrum” grade with an SPF between 2 and 14 must have a warning that reads “Skin Cancer/Skin Aging Alert: Spending time in the sun increases your risk of skin cancer and early skin aging. This product has been shown to help prevent only sunburn, not skin cancer or early skin aging.” The highest SPF rating is set at 50+ There is insufficient evidence to indicate that sunscreen products with SPF >50 offer appreciably greater protection than those with SPF 50. These claims are inaccurate and are no longer permitted. Effectiveness of sunscreen products decreases with exposure to water; reapplication is necessary for continual protection. Reapplication, sometimes more frequently than every 2 h, is necessary for continual protection. “Water resistance” claims are allowed but must clearly specify if the sunscreen product remains active for 40 or 80 min while swimming or sweating.

Abbreviations: SPF, sun protection factor; UV, ultraviolet.

A significant amount of sunscreen is removed and degraded following exposure to water (eg, swimming and sweating) and friction (eg, sand abrasion and towelling).92,93 With normal bathing, physical activity, and towelling, the SPF of a single application of sunscreen at 2 mg/cm2 was reduced by 40% and 55% after 4 and 8 hours, respectively.94 Hence, sunscreen must be reapplied frequently, especially under more active conditions.95 The ban on “waterproof,” “sweatproof,” and “protection for more than 2 hours” claims in the United States and Canada, coupled with the coincident requirements to specify how long “water-resistant” sunscreen products remain effective, should help promote frequent reapplication of sunscreen. Still, the message must be reinforced, particularly for individuals with a history of NMSC.96-98 Considering that most people do not apply sunscreen at the recommended thickness and likely do not routinely reapply sunscreen, use of sunscreen products with high SPF factors may be warranted to achieve the necessary protective effect.98-100

Methods In developing this chapter, the PubMed database was searched with no publication date restriction, using a combination of MeSH subject headings and text words, including “actinic keratosis,” “age,” “basal cell carcinoma,” “squamous cell carcinoma,” “non-melanoma skin cancer,” “photodamage,” “race,” “sun protection factor,” “ prevention,” and

“sunscreen.” These searches were independent from the searches used to research the treatment chapters in these guidelines (Chapters 3, 4, and 5).101-103 Reference lists from recent review articles were examined to identify additional studies. Clinical trials with the highest level of evidence were included. In the absence of data from controlled studies, findings from observational trials were included. The quality of the papers reviewed were scored, where appropriate, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, as discussed in Chapter 1.104

Conclusions Risk and progression of NMSCs are closely associated with UV exposure. Prevention strategies are warranted, aimed at better educating people of all ages about the immediate and long-term dangers of natural and artificial UV exposure. Because misunderstandings regarding risk abound, physicians will often encounter patients needing clear guidance on the need for ongoing UV protection and the practical means to reduce risk of photodamage and NMSC. All patients should be reminded to avoid the midday sun, to wear appropriate protective clothing when outside, and to refrain from indoor tanning. Sunscreen products are likely to remain a mainstay for UV protection for many people, and the improved labelling standards should help the public use these products effectively. However, physicians should

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Table 3.  Recommendations for the Prevention of Non-melanoma Skin Cancer. Recommendation Physicians should regularly counsel patients that: •• They should protect their skin from the sun by wearing appropriate clothing, avoiding exposure to the midday sun, and using sunscreen •• They should use broad-spectrum sunscreen products with a SPF ≥30 or equivalent •• They should apply sunscreen liberally (2 mg/cm2; about 35 mL or 2 tablespoons of sunscreen for an average-sized adult) and in an even fashion to all parts of the skin that are not protected by clothing, ideally at least 15 min before going outside •• They should ideally reapply sunscreen at least once during the day and more frequently if swimming or sweating and after towelling •• Use of sunscreen should not be a reason for extending the duration of sun exposure •• Indoor tanning should be avoided at all times

Level of Evidencea

Strength of Recommendationb

High10-12

Strong

Low34

Strong

NA

Strong

NA

Strong

NA

Strong

High52,53

Strong

Abbreviation: SPF, sun protection factor. a Level of evidence (LoE) is evaluated as high, moderate, low, or very low, corresponding to the likelihood that the benefits of the therapeutic approach will stand up to further testing. Therapeutic approaches supported by meta-analyses or multiple randomized controlled trials (RCTs) that are free from significant bias have a high LoE. Studies based on intraindividual comparisons may also have a high LoE. Options supported by methodologically weaker (non-RCT) studies, and those with weak effects or inconsistent data across studies, have a low or very low LoE. Statements that are based on biological plausibility or other indirect arguments are listed as NA, indicating that direct support for the claim is not available. (See Chapter 1 for general methods.) b Strength of recommendation is evaluated as strong or weak, depending on the confidence that the treatment is more helpful than the alternative(s), including nontreatment. Hence, therapies with a high LoE regarding efficacy may receive a weak recommendation if the risk of adverse response is high or if this risk is not well known. Conversely, approaches with no likelihood of doing harm may receive a strong recommendation, even if they are supported by limited evidence. (See Chapter 1 for general methods.)

remind their patients not to rely exclusively on this one mode of photoprotection. Recommendations for prevention of NMSC are shown in Table 3. All of these strategies should be implemented with the goal of establishing lifelong, healthy sun-safety habits and practices.

Canadian NMSC Guidelines Committee gratefully acknowledges the unrestricted financial support of these sponsor companies: Leo Pharma, Inc, Galderma Canada Inc, Valeant Canada Ltd, Hoffman-La Roche Limited, La Roche-Posay, Inc. Sponsors played no part in the research, development, or writing of these guidelines.

Acknowledgments

1. Roelandts R. History of human photobiology. In: Lim H, Hönigsmann H, Hawk J, eds. Photodermatology. New York, NY: Informa Healthcare USA; 2007. 2. Gallagher RP, Hill GB, Bajdik CD, et al. Sunlight exposure, pigmentation factors, and risk of nonmelanocytic skin cancer. II. Squamous cell carcinoma. Arch Dermatol. 1995;131(2):164-169. 3. Kricker A, Armstrong BK, English DR, Heenan PJ. Does intermittent sun exposure cause basal cell carcinoma? A case-control study in Western Australia. Int J Cancer. 1995;60(4):489-494. 4. Naldi L, DiLandro A, D’Avanzo B, Parazzini F. Host-related and environmental risk factors for cutaneous basal cell carcinoma: evidence from an Italian case-control study. J Am Acad Dermatol. 2000;42(3):446-452. 5. Rosso S, Zanetti R, Martinez C, et al. The multicentre south European study ‘Helios’. II: Different sun exposure patterns in the aetiology of basal cell and squamous cell carcinomas of the skin. Br J Cancer. 1996;73(11):1447-1454. 6. Gallagher RP, Lee TK. Adverse effects of ultraviolet radiation: a brief review. Prog Biophys Mol Biol. 2006;92(1):119-131.

The Canadian NMSC Guidelines Committee gratefully acknowledges the unrestricted financial support of these sponsor companies: Leo Pharma, Inc, Galderma Canada Inc, Valeant Canada Ltd, Hoffman-La Roche Limited, La Roche-Posay, Inc. Sponsors played no part in the research, development, or writing of these guidelines. The authors also thank Nancy Richardson, BA, BSc, and Helen Leask, PhD, both of SCRIPT, Toronto, ON, for helping launch this project and providing organizational support. The Canadian NMSC Guidelines are officially recognized by the Canadian Dermatology Association and the Canadian Society for Dermatologic Surgery and endorsed by the Canadian Skin Patient Alliance.

Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The

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