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Epidemiology and UV Exposure

      In the hierarchy of evidence that is used to support clinical and public health decisions, systematic reviews of randomized trials are at the top of the list, followed by individual randomized trials and multiple time series, and then other types of observational studies. For keratinocyte carcinomas (basal and squamous cell carcinomas of the skin), the most common malignancies in the developed world, evidence for prevention of these lesions had been relatively low on this hierarchy of evidence during the entire 20th century. At least for squamous cell carcinoma, a good animal model was well established, with a known action spectrum (
      • de Gruijl F.R.
      • Sterenborg H.J.C.M.
      • Forbes P.D.
      • et al.
      Wavelength dependence of skin cancer induction by ultraviolet irradiation of albino hairless mice.
      ), but rodents did not develop melanomas as readily, and a fish model of melanoma had suggested that UVA was most important in causing melanoma (
      • Setlow R.B.
      • Grist E.
      • Thompson K.
      • et al.
      Wavelengths effective in induction of malignant melanoma.
      ). Debates raged over whether sunscreens were of any benefit; some argued that they may just serve to increase the amount of time that users spend in the sun, hence ultimately increasing skin cancer risk.
      This last argument was supported by a frequently cited study of University students who increased their time in the sun during a spring vacation while using a sunscreen with a higher SPF (Sun Protection Factor;
      • Autier P.
      • Doré J.F.
      • Négrier S.
      • et al.
      Sunscreen use and duration of sun exposure: a double-blind, randomized trial.
      ). Some other studies did not find this association (
      • Dupuy A.
      • Dunant A.
      • Grob J.J.
      D’Epidemiologie en Dermatologie. Randomized controlled trial testing the impact of high-protection sunscreens on sun-exposure behavior.
      ). However, there were numerous case-control studies that failed to observe an association between sunscreen use history and melanoma, or that found that greater sunscreen use was associated with greater melanoma risk.
      A key weakness in these case-control studies was confounding, and particularly confounding by indication:those participants with the greatest skin cancer risk were particularly likely to use sunscreen because of that strong risk. Hence, a case-control study would be likely to observe a direct association between sunscreen use and subsequent skin cancer, not because the sunscreens cause the cancer but because sunscreen use was the best available measure of skin cancer risk. This artifact is notoriously difficult to disentangle from true biological causeand-effect associations without a randomized experimental intervention.
      Twenty years ago, even though UV radiation was thought to be a key cause of the common skin cancers based on many lines of evidence, the quality of the evidence to support the use of sunscreens for the prevention of these cancers was lacking strong empirical validation. Yet this issue was of substantial public health importance; authorities needed stronger evidence to devote the needed resources to encourage sunscreen use. Hence, a landmark randomized trial was launched to gather a higher level of evidence. It was conducted by a team in Queensland, Australia, the area with the highest incidence of skin cancer in the world. A general population sample of 1621 residents (aged 20–69 years) of Nambour, a town in southwest Queensland, was randomized either to continue their usual pattern of sunscreen use or to apply an SPF 16 sunscreen every morning to the exposed areas of the head, neck, arms, and hands. During 4.5 years of follow-up, the sunscreen group developed 39% fewer squamous cell carcinomas on the head, neck, arms, and hands than the control group (
      • Green A.
      • Williams G.
      • Neale R.
      • et al.
      Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomized controlled trial.
      ).
      An additional 8 years of follow-up was obtained on this cohort, and the nearly 40% reduction in squamous cell carcinomas persisted (
      • Van der Pols J.C.
      • Williams G.M.
      • Pandeya N.
      • et al.
      Prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use.
      ). Most recently, a 50% reduction in melanomas was noted after a total of nearly 15 years of followup (
      • Green A.C.
      • Williams G.M.
      • Logan V.
      • et al.
      Reduced melanoma after regular sunscreen use: randomized trial follow-up.
      ). No other adequately powered randomized trials of sunscreen use for skin cancer prevention have been published.
      The United States Food and Drug Administration (FDA) has heard extensive arguments regarding labeling of sunscreens, including a major focus on allowing manufacturers to claim that sunscreen use can reduce the risk of some skin cancers. These arguments relied heavily on the findings of the Nambour study, and the FDA has now promulgated regulations that explicitly allow marketing of sunscreens with an SPF greater than 15 to claim that appropriate use can lead to reduction in skin cancer risk. Sunscreens have improved in multiple respects over the past 20 years. In particular, higher SPFs are now quite commonly used. Nevertheless, to this day, this remarkable data from Nambour provide the highest-level evidence that the use of sunscreens of adequate SPF, when applied consistently, leads to reduction in skin cancer risk, and important public health action has followed.

      Conflict of Interest

      The author states no conflict of interest

      To Cite This Article

      Weinstock MA (2013) Epidemiology and UV exposure. J Invest Dermatol 133: E11-E12.

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