SUNSCREENS AND SKIN CANCER PREVENTION 193 Those allocated to daily sunscreen received unlimited free supplies of the study sunscreen, a water-resistant, broad-spectrum, sun protection factor (SPF) 16 sunscreen (Ross Cosmet- ics, Melbourne, Australia). They were asked to apply it every morning to all exposed skin on the head, neck, arms, and hands, with reapplication after heavy sweating, bathing, or prolonged sun exposure. To estimate compliance with trial protocol, participants answered questionnaires in 1994 and at the end of the trial about frequency of sunscreen use on average each week and attended study clinics quarterly when they returned sunscreen bottles for weighing. Incident skin cancers were monitored in several ways to ensure complete capture. At the quarterly study clinics, participants reported new skin cancers they carried wallet-sized treatment cards which doctors completed if a skin cancer was treated, and they had full skin examinations by dermatologists in 1994 and 1996. Histological confi rmation was sought for all clinically diagnosed skin cancers. The Nambour Trial ceased in 1996, and the participants were followed up for another decade with regular questionnaires about habits of sun exposure and protection and about treatment of new skin cancers, all of which were confi rmed by review of medical records. All major regional and state pathology laboratories provided pathology reports for any skin cancers diagnosed among trial participants resulting in virtually complete ascertain- ment of all skin cancers confi rmed histologically (9,10). A priori, all new cancers diag- nosed in the fi rst year of the trial were excluded from analyses of the preventive effect of sunscreen (8). At the end of the trial, 75% of those allocated to daily sunscreen use were regular users (defi ned as applying sunscreen 3–4 d per week), and 74% of those allocated to discre- tionary sunscreen were either not using it at all or applying it at most 1–2 d per week (8). Sun exposure among those in the daily and discretionary sunscreen groups remained similar throughout the trial, as shown by measured UVB radiation exposure in a sub- sample, and by 79% and 77%, respectively, reporting that in the previous summer, they had spent 50% of their time outdoors in the sun on weekends at the trial’s end propor- tions of hat-wearing and shade-seeking people were also similar in each treatment group (11). After trial cessation, a large proportion of those allocated to daily sunscreen use continued to apply sunscreen to their skin regularly: 35% of pretrial regular users and 20% of those who were irregular or never users before the trial (12). B CC The incidence of BCC was not reduced by daily sunscreen use during the trial period [rate ratio (RR) = 1.03] (8) or at the end of the follow-up in 2004 (RR = 1.02) compared with controls (9). However, there was evidence that sunscreen application delayed the appear- ance of subsequent BCCs in those who developed multiple BCCs during follow-up (13). S CC At the end of the trial, new SCC tumors diagnosed clinically or histologically were re- duced by 40% in the intervention group (RR = 0.61 95% confi dence interval (CI) 0.46– 0.81) and by more than 50% based on only histologically confi rmed SCCs (RR = 0.48 95% CI 0.35–0.64) (8). By 2004, incidence rates of SCC were signifi cantly reduced in

JOURNAL OF COSMETIC SCIENCE 194 terms of both people newly affected (RR = 0.65 95% CI 0.45–0.94) and new SCC tumor development (RR = 0.62 95% CI 0.38–0.90) in those allocated to daily sunscreen versus discretionary users (9). MELANOMA The effect of regular application of sunscreen in the trial on subsequent occurrence of primary melanoma was evaluated 15 years post-trial. Diagnostic pathology slides of all fi rst primary melanomas (in situ and invasive) that occurred (confi rmed in the Queensland Cancer Registry) in participants between 1993 and 2006 were obtained and were re- viewed by two expert dermatopathologists who were unaware of sunscreen allocation status of the 33 persons affected (19 in situ, 14 invasive, and 0 metastatic). A borderline- signifi cant 50% reduction in risk of melanoma across all sites was observed in people who had been randomly assigned to the sunscreen intervention compared with controls [hazard ratio (HR) = 0.50 95% CI 0.24–1.02], with the estimated risk reduction slightly more on the head, neck, and upper limbs although this was not statistically signifi cant because of the small number of cases involved (HR = 0.46, 95% CI 0.17–1.20) (10). There was no difference between treatment groups in the risk of in situ melanomas (HR = 0.73 95% CI 0.29–1.81), but the risk of invasive melanoma in the intervention group was reduced by more than 70% (HR = 0.27 95% CI = 0.08–0.97) (10). SAFETY In the short-term, some in the intervention group complained of skin irritation (n = 25), skin greasiness (n = 10), and stinging eyes on facial perspiration (n = 6), and most of these were resolved by switching to another sunscreen of similar SPF (8). At the end of the trial, there was no difference in serum vitamin D status between those randomized to daily sunscreen versus discretionary use (14). On long-term follow-up in 2014, there was no difference in deaths in the sunscreen intervention group (n = 160, 59 of which were due to cardiovascular disease) and the control group (n = 170, 76 of which were due to cardio- vascular disease) with an overall HR = 0.94 and 0.77, respectively, for deaths from car- diovascular disease (15). LIMITATIONS Evidence about sunscreen’s ability to protect against skin cancer is limited to this single Nambour Trial conducted in a subtropical population, so there is uncertainty about both the repeatability of the fi ndings and their applicability in populations living in temperate climates. Trial participants in the intervention group applied the sunscreen too thinly on average i.e., at far less that the thickness of 2 mg/cm2 recommended for maximum effec- tiveness (16). In addition, the intervention sunscreen had an SPF 16 rating, whereas many sunscreens today have higher SPF ratings, so the size of protective effects may have been underestimated. Finally, the actual trial period was only 5 years, which is relatively short for the assessment of cancer prevention, and moreover it was conducted among adults, so the effectiveness of a sunscreen intervention earlier in life, carried out for longer, is un- known but potentially greater. The longer term effects of the trial were estimated by in- tention-to-treat analyses (9,10), so although post-trial sunscreen use lessened after the