Sun protection for preventing basal cell and squamous cell skin cancers

  • Review
  • Intervention

Authors


Abstract

Background

'Keratinocyte cancer' is now the preferred term for the most commonly identified skin cancers basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), which were previously commonly categorised as non-melanoma skin cancers (NMSC). Keratinocyte cancer (KC) represents about 95% of malignant skin tumours. Lifestyle changes have led to increased exposure to the sun, which has, in turn, led to a significant increase of new cases of KC, with a worldwide annual incidence of between 3% and 8%. The successful use of preventive measures could mean a significant reduction in the resources used by health systems, compared with the high cost of the treatment of these conditions. At present, there is no information about the quality of the evidence for the use of these sun protection strategies with an assessment of their benefits and risks.

Objectives

To assess the effects of sun protection strategies (i.e. sunscreen and barrier methods) for preventing keratinocyte cancer (that is, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) of the skin) in the general population.

Search methods

We searched the following databases up to May 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trial registries and the bibliographies of included studies for further references to relevant trials.

Selection criteria

We included randomised controlled clinical trials (RCTs) of preventive strategies for keratinocyte cancer, such as physical barriers and sunscreens, in the general population (children and adults), which may provide information about benefits and adverse events related to the use of solar protection measures. We did not include trials focused on educational strategies to prevent KC or preventive strategies in high-risk groups. Our prespecified primary outcomes were BCC or cSCC confirmed clinically or by histopathology at any follow-up and adverse events.

Data collection and analysis

Two review authors independently selected studies for eligibility using Early Review Organizing Software (EROS). Similarly, two review authors independently used predesigned data collection forms to extract information from the original study reports about the participants, methods of randomisation, blinding, comparisons of interest, number of participants originally randomised by arm, follow-up losses, and outcomes, and they assessed the risk of bias. We resolved any disagreement by consulting a third author and contacted trial investigators of identified trials to obtain additional information. We used standard methodological procedures expected by Cochrane.

Main results

We included one RCT (factorial design) that randomised 1621 participants.

This study compared the daily application of sunscreen compared with discretionary use of sunscreen, with or without beta-carotene administration, in the general population. The study was undertaken in Australia; 55.2% of participants had fair skin, and they were monitored for 4.5 years for new cases of BCC or cSCC assessed by histopathology. We found this study to be at low risk of bias for domains such as allocation, blinding, and incomplete outcome data. However, we found multiple unclear risks related to other biases, including an unclear assessment of possible interactions between the effects of the different interventions evaluated (that is, sunscreen and beta-carotene). We found no difference in terms of the number of participants developing BCC (n = 1621; risk ratio (RR) 1.03, 95% confidence interval (CI) 0.74 to 1.43) or cSCC (n = 1621; RR 0.88, 95% CI 0.50 to 1.54) when comparing daily application of sunscreen with discretionary use, even when analyses were restricted to groups without beta-carotene supplementation. This evidence was of low quality, which means that there is some certainty that future studies may alter our confidence in this evidence.

We reported adverse events in a narrative way and included skin irritation or contact allergy.

We identified no studies that evaluated other sun protection measures, such as the use of sun-protective clothing, sunglasses, or hats, or seeking the shade when outdoors.

Authors' conclusions

In this review, we assessed the effect of solar protection in preventing the occurrence of new cases of keratinocyte cancer. We only found one study that was suitable for inclusion. This was a study of sunscreens, so we were unable to assess any other forms of sun protection. The study addressed our prespecified primary outcomes, but not most of our secondary outcomes. We were unable to demonstrate from the available evidence whether sunscreen was effective for the prevention of basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC).

Our certainty in the evidence was low because there was a lack of histopathological confirmation of BCC or cSCC in a significant percentage of cases. Amongst other sources of bias, it was not clear whether the study authors had assessed any interaction effects between the sunscreen and beta-carotene interventions. We think that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Resumen

Protección contra el sol para prevención del cáncer de piel escamocelular y basocelular

Antecedentes

"Cáncer de queratinocitos" es actualmente el término preferido para los cánceres cutáneos identificados con más frecuencia, el carcinoma basocelular (CBC) y el carcinoma escamocelular cutáneo (CEC), que con anterioridad se categorizaron habitualmente como cánceres cutáneos no melanoma (CCNM). El cáncer de queratinocitos (CK) representa cerca del 95% de los tumores malignos de la piel. Los cambios en el estilo de vida han provocado una mayor exposición al sol, lo que a la vez ha dado lugar a un aumento significativo de nuevos casos de CK, con una incidencia global anual entre el 3% y el 8%. El uso exitoso de medidas preventivas podría dar lugar a una reducción significativa de los recursos utilizados por los sistemas de salud, en comparación con el costo elevado del tratamiento de estas afecciones. Actualmente no existe información acerca de la calidad de las pruebas del uso de estas estrategias de protección contra el sol con una evaluación de los efectos beneficiosos y los riesgos.

Objetivos

Evaluar los efectos de las estrategias de protección contra el sol (es decir, filtro solar y métodos de barrera) para prevenir el cáncer de queratinocitos (o sea, el carcinoma basocelular [CBC] y el carcinoma escamocelular cutáneo [CEC]) en la población general.

Métodos de búsqueda

Se hicieron búsquedas en las siguientes bases de datos hasta mayo de 2016: registro especializado del Grupo Cochrane de Piel (Cochrane Skin Group), CENTRAL, MEDLINE, Embase y en LILACS. También se buscó en cinco registros de ensayos y en las bibliografías de estudios incluidos para obtener referencias adicionales de ensayos relevantes.

Criterios de selección

Se incluyeron los ensayos clínicos controlados aleatorios (ECA) de estrategias preventivas para el cáncer de queratinocitos, como las barreras físicas y los filtros solares, en la población general (niños y adultos), que pudieran proporcionar información acerca de los efectos beneficiosos y los eventos adversos relacionados con el uso de medidas de protección solar. No se incluyeron los ensayos centrados en estrategias educacionales para prevenir el CK o en estrategias preventivas en grupos de alto riesgo. Los resultados primarios preespecificados fueron CBC o CEC confirmado clínicamente o por histopatología a cualquier seguimiento y eventos adversos.

Obtención y análisis de los datos

Dos autores de la revisión, de forma independiente, seleccionaron la elegibilidad de los estudios utilizando el programa Early Review Organizing Software (EROS). De igual manera, dos autores de la revisión de forma independiente utilizaron formularios prediseñados para la obtención de datos para extraer información de los informes originales de los estudios acerca de los participantes, los métodos de asignación al azar, el cegamiento, las comparaciones de interés, el número de participantes originalmente asignados al azar por brazo, las pérdidas durante el seguimiento y los resultados, y además evaluaron el riesgo de sesgo. Los desacuerdos se resolvieron mediante consulta con un tercer autor y contacto con los investigadores de los ensayos identificados para obtener información adicional. Se utilizaron los procedimientos metodológicos estándar previstos por la Colaboración Cochrane.

Resultados principales

Se incluyó un ECA (diseño factorial) que asignó al azar a 1621 participantes.

Este estudio comparó la aplicación diaria de filtro solar con el uso discrecional de filtro solar, con o sin la administración de beta-caroteno, en la población general. El estudio se realizó en Australia; el 55,2% de los participantes tenían la piel clara y se monitorizaron por 4,5 años para la detección de nuevos casos de CBC o CEC evaluado por histopatología. Se encontró que este estudio tuvo bajo riesgo de sesgo en dominios como asignación, cegamiento y los datos incompletos de los resultados. Sin embargo, se encontraron múltiples riesgos inciertos relacionados con otros sesgos, que incluyó una evaluación poco clara de las posibles interacciones entre los efectos de las diferentes intervenciones evaluadas (o sea, filtro solar y beta-caroteno). No se encontraron diferencias en cuanto al número de participantes que desarrollaron CBC (n = 1621; cociente de riesgos [CR] 1,03; intervalo de confianza [IC] del 95%: 0,74 a 1,43) o CEC (n = 1621; CR 0,88; IC del 95%: 0,50 a 1,54) al comparar la aplicación diaria del filtro solar con el uso discrecional, aun cuando los análisis estuvieron limitados a los grupos sin suplementos de beta-caroteno. Estas pruebas fueron de calidad baja, lo que significa que hay alguna seguridad de que los estudios futuros puedan alterar la confianza en estas pruebas.

Los eventos adversos se informaron de una manera narrativa e incluyeron la irritación de la piel o la alergia de contacto.

No se identificaron estudios que evaluaran otras medidas de protección contra el sol como el uso de ropa protectora contra el sol, gafas de sol o sombreros, o buscar la sombra cuando se está al aire libre.

Conclusiones de los autores

En esta revisión se evaluó el efecto de la protección solar en la prevención de la aparición de nuevos casos de cáncer de queratinocitos. Sólo se encontró un estudio adecuado para su inclusión. Este estudio fue de filtros solares, de manera que no fue posible evaluar otras formas de protección contra el sol. El estudio analizó los resultados primarios preespecificados, pero no la mayoría de los resultados secundarios. No fue posible demostrar a partir de las pruebas disponibles si el filtro solar fue efectivo para la prevención del carcinoma basocelular (CBC) o el carcinoma escamocelular cutáneo (CEC).

La seguridad en las pruebas fue baja porque en un porcentaje significativo de los casos hubo una falta de confirmación histopatológica del CBC o el CEC. Entre otras fuentes de sesgo, no estuvo claro si los autores del estudio evaluaron cualquier efecto de la interacción entre el filtro solar y las intervenciones con beta-caroteno. Se piensa que es probable que la realización de más investigaciones tenga una marcada repercusión sobre la confianza en la estimación del efecto y pueda cambiarla.

Plain language summary

Sun protection (including sunscreens) to prevent basal cell carcinoma and cutaneous squamous cell carcinoma of the skin

What is the aim of this review?

The aim of this Cochrane Review was to find out if using topical sunscreen and physical barrier methods (such as sun-protective clothing, hats, sunglasses, and the active search for shade when outdoors) compared with no specific precautionary activity prevented the development of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) of the skin in adults and children.

What was studied in this review?

Keratinocyte cancer (BCC and cSCC of the skin) is the most commonly identified type of skin cancer. The main risk is exposure to ultraviolet radiation, which is a component of sunlight. Prevention has become an important way to manage this cancer, so it is important to assess the effectiveness of methods used to prevent keratinocyte cancer in the general population. In this review, we assessed the effects of using topical sunscreen and physical barrier methods (such as sun-protective clothing, hats, sunglasses, and the active search for shade when outdoors) compared with no specific precautionary interventions aimed at preventing the development of BCC and cSCC in adults and children.

We searched the medical literature up to May 2016 for randomised controlled trials that evaluated preventive strategies. We found only one study suitable for inclusion. This study compared the daily application of sunscreen (with or without beta-carotene, which is a precursor of vitamin A) compared with the occasional use of sunscreen (with or without beta-carotene) in the general population, without restriction by gender or age. The study was undertaken in Australia, where 1621 participants, 55% of them with fair skin, were monitored for 4.5 years for new cases of BCC or cSCC assessed by histopathology (which is a method used to detect cancerous cells under the microscope).

What are the main results of this review?

We found no difference between the number of people who developed BCC or cSCC in the two groups over the time period of the trial. So, there did not seem to be a difference in applying sunscreen daily compared with using it occasionally.

Key messages

Our one included study was a study of sunscreens, so we were unable to assess any other forms of sun protection.

We identified no studies that evaluated other sun protection measures, such as the use of sun-protective clothing, sunglasses, or hats, or seeking the shade when outdoors.

We did not find evidence for the effectiveness of daily sunscreen for preventing BCC or cSCC compared with the occasional use of sunscreen. The certainty of the evidence was low, which means that future studies may alter this result.

Side effects from the sunscreen used with or without the addition of beta-carotene included a low percentage of cases of contact allergy and skin irritation.

How up to date is this review?

This review included studies identified up to May 2016.

Laički sažetak

Zaštita od sunca (uključujući zaštitne kreme za sunčanje) za sprječavanje karcinoma bazalnih i pločastih stanica kože (bazocelularni i planocelularni karcinom)

Što je cilj ovog pregleda?

Cilj ovog Cochrane sustavnog pregleda literature bio je istražiti može li korištenje lokalnih krema za zaštitu od sunca i fizičke zapreke (kao što je odjeća koja štiti kožu od sunca, šeširi, naočale za sunce i aktivno traženje hlada u vanjskom prostoru) u usporedbi s nikakvim mjerama zaštite protiv sunca spriječiti razvoj karcinoma bazalnih stanica kože (bazocelularni karcinom) i karcinoma pločastih stanica kože (planocelularni karcinom) u djece i odraslih.

Što je istraženo u ovom pregledu literature?

Bazocelularni i planocelularni karcinomi su najčešći karcinomi kože. Glavni rizik za njihov nastanak je ultraljubičasto zračenje, koje je dio sunčevog svjetla. Sprječavanje tih karcinoma vrlo je važna mjera. Stoga je važno procijeniti djelotvornost mjera za prevenciju tih karcinoma u općoj populaciji. U ovom Cochrane sustavnom pregledu analizirana je uporaba lokalnih krema za zaštitu od sunca, metode fizičke zapreke (kao što je odjeća koja štiti od sunca, šeširi, sunčane naočale i aktivno traženje hlada u vanjskom prostoru) u usporedbi s nikakvim specifičnim zaštitnim mjerama, a sve s ciljem sprječavanja nastanka bazocelularnog i planocelularnog karcinoma kože u djece i odraslih.

Pretražena je medicinska literatura objavljena do svibnja 2016. Traženi su isključivo randomizirani kontrolirani pokusi koji su ispitali preventivne mjere. Pronađena je samo jedna studija koja je odgovarala kriterijima uključenja. Ta je studija usporedila dnevnu primjenu kreme za zaštitu od sunca (s ili bez beta-karotena, koji je preteča vitamina A) u usporedbi s povremenom uporabom takve kreme (s ili bez beta-karotena) u općoj populaciji, bez ograničenja prema dobi i spolu. Studija je provedena u Australiji i u njoj je sudjelovalo 1621 ispitanika, od kojiih je 55% bilo svijetle kože. Ispitanici su praćeni 4,5 godine i tijekom tog razdoblja se analizirala pojava novih slučajeva bazocelularnog i planocelularnog karcinoma temeljem histopatološke procjene (metoda analize karcinomskih stanica pod mikroskopom).

Koji su glavni rezultati pregleda literature?

Nije utvrđena razlika među skupinama u broju osoba koje su razvile bazocelularni ili planocelularni karcinom kroz analizirano razdoblje. Stoga se čini da nema razlike ako se krema za zaštitu od sunca nanosi svakodnevno ili povremeno.

Ključne poruke

Uključena je samo jedna studija, u kojoj je analizirano korištenje zaštitene kreme, tako da nije bilo moguće analizirati djelotvornost drugih preventivnih mjera za zaštitu od sunca.

Nisu pronađene studije koje su ispitale druge vrste preventivnih mjera.

Nisu pronađeni dokazi o djelotvornosti svakodnevne uporabe zaštitne kreme za sprječavanje bazocelularnog ili planocelularnog karcinoma u usporedbi s povremenim korištenjem kreme. Pouzdanost tih dokaza je niska, što znači da buduće studije na tu temu mogu promijeniti taj rezultat.

Nuspojave korištenja zaštitne kreme za sunce koja sadrži ili ne sadrži beta-karoten uključuju malen broj slučajeva kontaktne alergije i nadražaja (iritacije) kože.

Koliko su ažurni ovi dokazi?

Ovaj pregled uključuje studije objavljene do svibnja 2016.

Bilješke prijevoda

Hrvatski Cochrane
Prevela: Livia Puljak
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr

Streszczenie prostym językiem

Ochrona przed słońcem (w tym filtry przeciwsłoneczne) w celu zapobiegania rakowi podstawnokomórkowemu i płaskonabłonkowemu skóry

Jaki jest cel przeglądu?

Celem przeglądu Cochrane było sprawdzenie czy miejscowe stosowanie kremów z filtrem przeciwsłonecznym oraz innych środków ochrony (takich jak ubranie chroniące przed słońcem, nakrycia głowy, okulary przeciwsłoneczne oraz poszukiwanie schronienia w cieniu w czasie przebywania na zewnątrz) w porównaniu do niestosowania konkretnych środków ochrony przed promieniami słonecznymi zapobiega rozwojowi raka podstawnokomórkowego (BCC) i płaskonabłonkowego (cSCC) skóry u dorosłych i dzieci.

Co analizowano w przeglądzie?

Nowotwór wywodzący się z keratynocytów (BCC i cSCC skóry) jest jednym z najczęściej rozpoznawanych nowotworów skóry. Głównym czynnikiem ryzyka jest ekspozycja na promieniowanie ultrafioletowe, które jest składową promieni słonecznych. Profilaktyka jest najlepszą metodą zapobiegania nowotworowi, dlatego istotna jest ocena skuteczności metod stosowanych w zapobieganiu nowotworom skóry w populacji ogólnej. W przeglądzie tym oceniliśmy skuteczność stosowania miejscowych kremów z filtrem przeciwsłonecznym oraz innych środków ochronnych (takich jak ubranie chroniące przed słońcem, nakrycia głowy, okulary przeciwsłoneczne oraz poszukiwanie schronienia w cieniu w czasie przebywania na zewnątrz) w porównaniu do niestosowania konkretnych środków ochronnych przed promieniowaniem słonecznym w celu zapobiega rozwojowi raka skóry (BCC i cSCC) u dorosłych i dzieci.

Przeprowadziliśmy wyszukiwanie literatury medycznej do maja 2016 r. w poszukiwaniu badań z grupą kontrolną i randomizacją oceniających metody profilaktyki. Odnaleźliśmy tylko jedno badanie spełniające kryteria włączenia. W badaniu tym porównywano codzienne stosowanie kremów z filtrem przeciwsłonecznym (z lub bez beta-karotenu, który jest prekursorem witaminy A) z okazjonalnym stosowaniem takich kremów (z lub bez beta-karotenu), w populacji ogólnej, bez ograniczeń w odniesieniu do płci i wieku. Badanie przeprowadzono w Australii, uczestniczyło w nim 1621 osób, 55% spośród nich miało jasną karnację. Obserwowano ich przez okres 4,5 roku pod kątem wystąpienia nowych przypadków raka skóry (BCC lub cSCC), potwierdzonych w badaniu histopatologicznym (metoda wykrywania komórek nowotworowych pod mikroskopem).

Jakie były główne wyniki przeglądu?

W okresie obserwacji nie stwierdziliśmy żadnych różnic w obu grupach w liczbie osób, u których rozwinął się rak skóry (BCC lub cSCC). W związku z powyższym wydaje się, że nie ma różnicy pomiędzy stosowaniem kremu z filtrem przeciwsłonecznym codziennie a stosowaniem takiego kremu okazjonalnie.

Kluczowe informacje

Nasze jedno włączone badanie, dotyczyło tylko kremów z filtrem przeciwsłonecznym, dlatego nie mogliśmy ocenić innych sposobów ochrony przed słońcem.

Nie zidentyfikowaliśmy żadnego badania, w którym oceniano inne metody, takie jak ubrania chroniące przed słońcem, okulary słoneczne, nakrycia głowy lub poszukiwanie schronienia w cieniu, gdy przebywa się na zewnątrz.

Nie odnaleźliśmy danych dotyczących skuteczności codziennego stosowania kremów z filtrem przeciwsłonecznym w zapobieganiu rakom skóry (BCC lub cSCC) w porównaniu ze sporadycznym stosowaniem kremów ochronnych. Dane były niepewne, dlatego przyszłe badania mogą zmienić obecne wyniki.

Efekty uboczne związane ze stosowaniem kremów z filtrem przeciwsłonecznym zawierających beta-karoten lub bez jego dodatku obejmowały alergię kontaktową i podrażnienia skóry i wystąpiły u niewielkiego odsetka przypadków.

Jak aktualny jest ten przegląd?

Przegląd zawiera badania odnalezione do maja 2016 r.

Uwagi do tłumaczenia

Tłumaczenie Magdalena Koperny Redakcja Joanna Zając

Резюме на простом языке

Защита от солнца (включая солнцезащитные средства) для предупреждения базальноклеточной карциномы и плоскоклеточной карциномы кожи

Какова цель этого обзора?

Целью этого Кокрейновского обзора было выяснить, предотвращает ли использование местных солнцезащитных средств и физических барьерных методов (таких, как солнцезащитная одежда, шляпы, солнцезащитные очки и активный поиск тени при пребывании на открытом воздухе), по сравнению с отсутствием специфических мер предосторожности, развитие базальноклеточной карциномы (БКК) и плоскоклеточной карциномы (ПКК) кожи у взрослых и детей.

Что было изучено в этом обзоре?

Кератиноцитарный рак (БКК и ПКК кожи) - это наиболее часто выявляемый тип рака кожи. Основным фактором риска является воздействие ультрафиолетового излучения, которое является компонентом солнечного света. Профилактика является одним из важных способов контроля этого рака, поэтому важно оценить эффективность методов, используемых для предупреждения кератиноцитарного рака у населения, в целом. В этом обзоре мы оценили эффекты использования местных солнцезащитных средств и физических барьерных методов (таких, как солнцезащитная одежда, шляпы, солнцезащитные очки и активный поиск тени при пребывании на открытом воздухе) в сравнении с отсутствием специфических предупредительных мер, направленных на предотвращение развития БКК и ПКК кожи у взрослых и детей.

Мы провели поиск медицинской литературы по май 2016 года на предмет рандомизированных контролируемых испытаний, в которых оценивали превентивные (профилактические) стратегии. Мы нашли только одно подходящее исследование для включения в этот обзор. В этом исследовании сравнивали ежедневное нанесение солнцезащитного средства (с бета-каротином, который является предшественником витамина А, или без него) с применением солнцезащитного средства по случаю (с бета-каротином или без него) в общей популяции, без ограничений по полу и возрасту. Это исследование было проведено в Австралии, включало 1621 участника, 55% которых были со светлой кожей, наблюдаемых в течение 4,5 лет для выявления новых случаев БКК и ПКК кожи, определяемых гистопатологическими исследованиями (методами, используемыми для выявления раковых клеток под микроскопом).

Каковы главные результаты этого обзора?

Мы обнаружили отсутствие различий между числом людей, у которых развилась БКК или ПКК кожи, в двух группах за время проведения этого клинического испытания. Таким образом, различий между ежедневным нанесением солнцезащитного средства и использованием его по случаю не оказалось.

Ключевая информация

Наше единственное включенное исследование было исследованием солнцезащитных средств, поэтому мы не смогли оценить другие формы защиты от солнца.

Мы не выявили исследований, в которых оценивали другие меры защиты от солнца, такие как использование солнцезащитной одежды, солнцезащитные очки, шляпы или поиск тени при пребывании на открытом воздухе.

Мы не нашли доказательств эффективности ежедневного применения солнцезащитного средства для профилактики БКК и ПКК кожи, в сравнении с применением его по случаю. Уверенность в доказательствах была низкой, и это означает, что будущие исследования могут изменить этот результат.

Побочные эффекты от применения солнцезащитного средства (с добавлением бета-каротина или без него) включили низкий процент случаев контактной аллергии и раздражения кожи.

Насколько актуален этот обзор?

Этот обзор включает исследования, выявленные по май 2016 года.

Заметки по переводу

Перевод: Змиевская Екатерина Анатолькевна. Редактирование: Юдина Екатерина Викторовна. Координация проекта по переводу на русский язык: Cochrane Russia - Кокрейн Россия (филиал Северного Кокрейновского Центра на базе Казанского федерального университета). По вопросам, связанным с этим переводом, пожалуйста, обращайтесь к нам по адресу: cochrane.russia.kpfu@gmail.com; cochranerussia@kpfu.ru

Laienverständliche Zusammenfassung

Sonnenschutz (einschließlich Sonnencremes) zur Vorbeugung von Basalzellkarzinomen und kutanen Plattenepithelkarzinomen der Haut

Was ist das Ziel dieses Reviews?

Das Ziel dieses Cochrane Reviews war es herauszufinden, ob die Anwendung von topischem Sonnenschutz und physikalischen Barrieremethoden (wie z.B. Sonnenschutzkleidung, Hüte, Sonnenbrillen, und die aktive Suche nach Schatten im Freien) im Vergleich zu keiner speziellen Vorsichtsmaßnahme der Entstehung von Basalzellkarzinomen (BBC) und kutanen Plattenepithelkarzinomen (cSCC) der Haut bei Erwachsenen und Kindern vorbeugt.

Was wurde in diesem Review untersucht?

Keratinozyten Krebs (BCC und cSCC der Haut) ist die am häufigsten identifizierte Krebsart. Das Hauptrisiko ist ultraviolette Strahlung, die ein Bestandteil des Sonnenlichts ist. Vorbeugung ist zu einer wichtigen Strategie gegen diesen Krebs geworden, weshalb es wichtig ist, die Alltagswirksamkeit von Methoden zur Vorbeugung von Keratinozyten Krebs in der Allgemeinbevölkerung zu bewerten. In diesem Review bewerteten wir die Wirkung der Anwendung von topischem Sonnenschutz und physikalischen Barrieremethoden (wie Sonnenschutzkleidung, Hüte, Sonnenbrillen, und die aktive Suche nach Schatten im Freien) im Vergleich zu keinen speziellen Vorsichtsmaßnahmen zur Vorbeugung der Entstehung von BCC und cSCC bei Erwachsenen und Kindern.

Wir suchten in der medizinische Literatur bis Mai 2016 nach randomisierten, kontrollierten Studien, die vorbeugende Strategien auswerteten. Wir fanden nur eine Studie, die zum Einschluss geeignet war. Diese Studie verglich die tägliche Anwendung von Sonnencreme (mit oder ohne Beta-Karotin, das ein Vorläufer von Vitamin A ist) mit der gelegentlichen Anwendung von Sonnencreme (mit oder ohne Beta-Karotin) in der Allgemeinbevölkerung, ohne Beschränkung von Geschlecht oder Alter. Die Studie wurde in Australien durchgeführt, wo 1621 Teilnehmer, 55% von ihnen mit heller Haut, für 4,5 Jahre auf neuen Fälle von BCC oder cSCC untersucht wurden, ermittelt durch Histopathologie (eine Methode, die angewendet wird, um Krebszellen unter dem Mikroskop nachzuweisen).

Was sind die wesentlichen Ergebnisse dieses Reviews?

Wir fanden keinen Unterschied zwischen der Anzahl der Personen in den beiden Gruppen, die BCC oder cSCC im Zeitraum der Studie entwickelten. Also schien es keinen Unterschied zwischen der täglichen Anwendung von Sonnencreme und der gelegentlichen Anwendung zu geben.

Hauptaussagen:

Unsere einzige eingeschlossene Studie war eine Studie zu Sonnencremes, weshalb wir nicht in der Lage waren, andere Formen von Sonnenschutz zu bewerten.

Wir identifizierten keine Studien, die andere Sonnenschutzmaßnahmen auswerteten, wie die Verwendung von Sonnenschutzkleidung, Sonnenbrillen oder Hüten, oder der Suche nach Schatten im Freien.

Wir fanden keine Evidenz für die Wirksamkeit der täglichen Anwendung von Sonnencreme zur Vorbeugung gegen BCC oder cSCC im Vergleich zur gelegentlichen Anwendung von Sonnencreme. Die Sicherheit der Evidenz war niedrig, was bedeutet, dass künftige Studien dieses Ergebnis ändern könnten.

Nebenwirkungen der angewandten Sonnencremes mit oder ohne Zusatz von Beta-Karotin umfassten einen niedrigen Prozentsatz von Fällen der Kontaktallergie und Hautirritation.

Wie aktuell ist dieser Review?

Dieser Review schloss Studien ein, die bis Mai 2016 identifiziert wurden.

Anmerkungen zur Übersetzung

C. Zollbrecht, freigegeben durch Cochrane Deutschland.

Resumen en términos sencillos

Protección contra el sol (que incluye los filtros solares) para prevenir el cáncer de piel escamocelular y basocelular

¿Cuál es el objetivo de esta revisión?

El objetivo de esta revisión Cochrane fue determinar si el uso tópico de filtro solar y métodos físicos de barrera (como ropa protectora contra el sol, sombreros, gafas de sol y la búsqueda activa de sombra cuando se está al aire libre) en comparación con ninguna actividad preventiva específica previene la aparición del carcinoma basocelular (CBC) y el carcinoma escamocelular cutáneo (CEC) en adultos y niños.

¿Qué se estudió en esta revisión?

El cáncer de queratinocitos (CBC y CEC) es el tipo de cáncer de piel identificado con más frecuencia. El riesgo principal es la exposición a la radiación ultravioleta, que es un componente de la luz solar. La prevención se ha convertido en una forma importante de controlar este cáncer, de manera que es importante evaluar la efectividad de los métodos utilizados para prevenir el cáncer de queratinocitos en la población general. En esta revisión se evaluaron los efectos del uso tópico de filtro solar y métodos físicos de barrera (como ropa protectora contra el sol, sombreros, gafas de sol y la búsqueda activa de sombra cuando se está al aire libre) en comparación con ninguna intervención preventiva específica encaminada a prevenir el desarrollo de CBC y CEC en adultos y niños.

Se realizaron búsquedas de ensayos controlados aleatorios en la literatura médica hasta mayo de 2016 que evaluaron las estrategias preventivas. Sólo se encontró un estudio adecuado para la inclusión. Este estudio comparó la aplicación diaria de filtro solar (con o sin beta-caroteno, que es un precursor de la vitamina A) en comparación con el uso ocasional del filtro solar (con o sin beta-caroteno) en la población general, sin restricción por sexo o edad. El estudio se realizó en Australia, donde 1621 participantes, el 55% con piel clara se monitorizaron por 4,5 años para la detección de nuevos casos de CBC o CEC evaluado por histopatología (que es un método utilizado para detectar células cancerosas bajo el microscopio).

¿Cuáles son los principales resultados de esta revisión?

No se encontraron diferencias entre el número de personas que desarrollaron CBC o CEC en los dos grupos durante el período del ensayo. Por lo tanto, no pareció haber una diferencia al aplicar el filtro solar diariamente en comparación con utilizarlo de forma ocasional.

Mensajes clave

El único estudio incluido fue un estudio de filtros solares, de manera que no fue posible evaluar otras formas de protección contra el sol.

No se identificaron estudios que evaluaran otras medidas de protección contra el sol como el uso de ropa protectora contra el sol, gafas de sol o sombreros, o buscar la sombra cuando se está al aire libre.

No se encontraron pruebas de la efectividad del filtro solar diario para prevenir el CBC o el CEC en comparación con el uso ocasional del filtro solar. La certeza de las pruebas fue baja, lo que significa que los estudios futuros podrían alterar este resultado.

Los efectos secundarios del uso del filtro solar con o sin el agregado de beta-caroteno incluyeron un porcentaje bajo de casos de alergia por contacto e irritación de la piel.

¿Qué grado de actualización tiene esta revisión?

Esta revisión incluyó estudios identificados hasta mayo de 2016.

Notas de traducción

La traducción y edición de las revisiones Cochrane han sido realizadas bajo la responsabilidad del Centro Cochrane Iberoamericano, gracias a la suscripción efectuada por el Ministerio de Sanidad, Servicios Sociales e Igualdad del Gobierno español. Si detecta algún problema con la traducción, por favor, contacte con Infoglobal Suport, cochrane@infoglobal-suport.com.

Summary of findings(Explanation)

Summary of findings for the main comparison. Daily application of sunscreen compared with discretionary use for preventing basal cell and cutaneous squamous cell skin cancers
  1. ¹Downgraded by one level due to other potential sources of bias, including an unclear assessment of interaction between the effects of the different interventions evaluated (that is, sunscreen and beta-carotene).
    ²Downgraded by one level due to indirectness because it is not clear whether these results are applicable to the wider population. Also, these results included cases not confirmed histologically (by clinical examination only).

Daily application of sunscreen compared with discretionary use (including beta-carotene use) for preventing basal cell and cutaneous squamous cell skin cancers
Patient or population: general participants
Settings: outpatient
Intervention: daily application of sunscreen (including beta-carotene use)
Comparison: discretionary use (including beta-carotene use)
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
Number of participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
Discretionary use (including beta-carotene use) Daily application of sunscreen (including beta-carotene use)
Basal cell carcinoma
Confirmed clinically or by histopathology
Follow-up: 4.5 years
78 per 1000

80 per 1000

(58 to 111)

RR 1.03 (95% CI 0.74 to 1.43)1621
(1 study)
⊕⊕⊝⊝
Low¹,²
The study authors reported narratively that the incidence was similar, even when analysis was restricted to cases of BCC diagnosed histologically. Also, the study authors reported a similar risk when groups receiving beta-carotene were excluded (IDR 0.96, 95% CI 0.59 to 1.57).
Cutaneous squamous cell carcinoma
Confirmed clinically or by histopathology
Follow-up: 4.5 years
31 per 1000

27 per 1000

(15 to 48)

RR 0.88 (95% CI 0.50 to 1.54)1621
(1 study)
⊕⊕⊝⊝
Low¹,²
The study authors reported an IDR of 0.74 (95% CI 0.39 to 1.38) when the analyses were restricted to histologically diagnosed cSCC. Also, the study authors reported a similar risk when groups receiving beta-carotene were excluded (IDR 0.74, 95% CI 0.31 to 1.77).
Adverse events
Number of participants with adverse events
Follow-up: 4.5 years
See commentSee comment-1621
(1 study)
⊕⊕⊝⊝
Low¹,²
This was reported narratively for the daily sunscreen use group only. The most frequent adverse events were contact allergy or skin irritation (25 participants), skin greasiness (10 participants), and interference with perspiration or stinging eyes after facial perspiration (6 participants).
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
BCC: basal cell carcinoma; CI: confidence interval; cSCC: cutaneous squamous cell carcinoma; IDR: incidence density ratio; RR: risk ratio.
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Background

Description of the condition

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) were previously commonly categorised as non-melanoma skin cancers (NMSC), but now the preferred term 'keratinocyte cancer' is used (Albert 2003). Throughout the review, we have used this term when we refer to BCC and cSCC collectively.

Keratinocyte cancer (KC) is a term that includes BCC and cSCC of the skin. Together, KC represents about 95% of all skin cancers (Dubas 2013). Since 1960, changes in lifestyle have led to increased exposure to the sun, which has in turn led to a significant increase of new cases of KC, with a worldwide annual incidence of between 3% and 8% (Glass 1989; Ricotti 2009). Around 1.2 million keratinocyte cancers are diagnosed per year in the USA (Ricotti 2009). In Australia, the estimated incidence is 400 cases per 100,000 inhabitants (Johnson 1992; Stern 2010). In Colombia, an equatorial country with a predominant population of phototype III (skin type), a significant increase in KC figures has been documented, rising from 23 cases per 100,000 inhabitants in 2003 to 41 cases per 100,000 in 2007 (Sánchez 2011). In Europe, there is an increasing trend in the incidence of keratinocyte cancer, with exceptional cases such as Switzerland where the highest rate of cSCC has been documented in the whole continent, rising from 14.2 cases per 100,000 inhabitants in 1978 to 28.9 cases per 100,000 inhabitants in 1997 (Lomas 2012).

The action of ultraviolet radiation on the keratinocyte layer of cells in the epidermis is the common site of the development of cSCC and BCC lesions (Preston 1992). The mechanism involves damage to DNA and its repair system, specifically the formation of pyrimidine dimers (the bases that are part of the structure of DNA), as well as mutations of p53 tumour suppressor genes (Preston 1992). Basal cell carcinoma is characterised by a slow rate of growth and extremely low probability of metastasis; however, this condition can compromise wide areas of tissue, cartilage, and bone and produce local damage (Rubin 2005). By contrast, the potential for distant metastasis of cSCC is greater, with up to 5% of lesions metastasising within five years (Miller 2010).

The diagnosis of KC is based on clinical examination of the lesion and confirmation by histopathology (Motley 2003; Telfer 2008), and is classified into two large groups: basal cell carcinomas and cutaneous squamous cell carcinomas (Gloster 1996). The American Cancer Society reports that around 50% to 65% of KCs are classified as BCC, and 20% to 25%, as cSCC (Kornek 2013). Basal cell carcinoma is a tumour of epithelial (outer layer of the skin) origin, which rarely metastasises (ranging from an incidence of 0.0028% to 0.1%) (Glass 1989), but has significant disease burden and considerable costs (Green 2010; Sánchez 2011; Stern 2010). The main risk factor for developing BCC is exposure to ultraviolet radiation (UV) (Corona 2001). Other factors, such as sun exposure during work, skin cancer family history, personal history of sunburn, presence of actinic keratoses, and having skin phototypes I to III, have also been associated with its onset (Lear 1997; Sánchez 2012). By contrast, cSCC is a locally invasive malignant tumour with a great potential to spread to distant parts of the body (Lansbury 2010). Presence of cSCC has been associated with different factors, such as chronic exposure to UV radiation, history of burns and occupational exposure, inherited skin conditions (albinism or xeroderma pigmentosum), and human papilloma virus infection, among other factors (Green 2010; Sánchez 2013).

Description of the intervention

Prevention is an important component in the management of KC and includes measures to avoid and reduce the consequences of exposure to the sun (Kornek 2013). These measures are broadly divided into sunscreens and physical barriers.

Sunscreen agents include all the products designed to reduce contact between the skin and UV radiation (Mulliken 2012). The ability of sunscreens to prevent the damage related to UV radiation is measured by the sun protection factor (SPF) (Mulliken 2012). Briefly, the SPF is defined as the time needed to produce sunburn when the sunscreen is applied to the skin, divided by the time needed to cause sunburn when nothing is applied to the skin (Schalka 2011). The sun protection factor is accepted as the worldwide standard for the assessment of protection against the erythemogenic (reddening) effects of UVB and UVA radiation (Schalka 2011). The effectiveness of a sunscreen is dependent on such characteristics as specific ingredients, general formulation, water-resistance, time over which the solar filter has been exposed to the sun, and the quantity of sunscreen applied (Saki 2012). Similarly, numerous studies have confirmed that instances of sunburn throughout life increase the risk of developing skin cancer (Sánchez 2012; Sánchez 2013; Zanetti 1996). UVB generates direct changes in DNA (Ravanat 2001). So, sunscreens that block UVB radiation would potentially increase the time of sun exposure without sunburn and, in theory, reduce the risk of developing skin cancer. The level of protection against UVB can be quantified by measuring the MDE (minimum dose of radiation that can produce erythema, which is reddening of the skin) and the SPF. The SPF is the result of the relationship between the minimal erythema dose (MED) with and without protection (MDE with sunscreen/MDE without sunscreen) (Jansen 2013a). Then, the question is to define the SPF that is able to decrease the risk of DNA damage resulting from sunburn and thus prevent the occurrence of new cases of KC.

Physical barriers can also help in preventing and minimising the harmful effects of UV radiation (Gasparro 1998; Latha 2013). Some authors have proposed that such measures could be more effective than sunscreen to prevent skin cancer (Linos 2011). Physical barriers include photoprotection with special clothes made of different materials, which provide protection against both UVB and UVA radiation (Diaz 2013). Polyester is the material with the highest ultraviolet light absorption capacity, while cotton has the lowest capacity (Diaz 2013). Hats can provide protection to the head and neck depending on their size and shape and the materials from which they are made (Klostermann 2013). Sunglasses, depending on their size, shape, and ability to block UV radiation, are effective in protecting the periorbital region, usually on the lower eyelid and inner edge, which are both areas highly exposed to solar radiation (Klostermann 2013). Finally, the active search for shade may be from a physical barrier, such as from a roof or the use of an umbrella when outdoors. These could provide significant protection against UV radiation without modifying exposure to visible light (Burnett 2012; Cooley 2013).

How the intervention might work

Sun protection strategies, such as those previously mentioned, act by blocking or diminishing the contact of UVA and UVB radiation with the skin, thus, avoiding DNA damage and the development of keratinocyte cancer (Sambandan 2011). Although there is a larger proportion of UVA (wavelength = 320 nm to 400 nm) radiation in the solar spectrum, UVB radiation (290 nm to 320 nm) causes most of the acute and chronic biological damage to the skin (Cole 2001). Any strategy suitable for wide implementation should protect against both types of radiation (Latha 2013). An intervention, such as beta-carotene supplementation, has been evaluated in its role as a protective agent of the skin, for example, in the prevention of sunburn (Kopcke 2008).

Why it is important to do this review

Ultraviolet radiation is a risk factor in the development of KC (Lucas 2006), which has an effect on the quality of life of those with the condition, as well as having serious cost consequences for countries' health systems. The use of preventive measures could mean a significant reduction of the resources used by health systems compared with the high cost that the treatment of KCs and their aftermath entails. At present, there is no information about the evidence for the use of these sun protection strategies with an assessment of their benefits and harms.

Our review aims to systematically assess the effectiveness and related adverse events of these protective elements, providing information on the possible routes for controlling the increasing incidence of keratinocyte cancer in the general population.

The plans for this review were published as a protocol 'Sun protection for preventing basal cell and squamous cell skin cancers' (Sánchez 2014).

Objectives

To assess the effects of sun protection strategies (i.e. sunscreen and barrier methods) for preventing keratinocyte cancer (that is, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) of the skin) in the general population.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled clinical trials that may provide information about benefits and adverse events related to the use of solar protection elements, such as physical barriers and sunscreens, as preventive strategies for keratinocyte cancer.

We did not include trials focused on educational strategies to prevent KC (Langbecker 2014), nor preventive strategies in high-risk groups (for example, people with actinic keratoses, organ transplant recipients, etc.), because there are other Cochrane Reviews published or in development that focus on these specific issues (Bath-Hextall 2007; Morales-Sánchez 2016).

Types of participants

We included trials focused on the general population (children and adults) without restriction by gender or age. We did not include trials focusing on special populations (for example, people with actinic keratoses, organ transplant recipients, etc.).

Types of interventions

Studies included one or more of the following interventions versus no intervention, placebo, or other interventions.

  1. Sunscreens with any sun protection factor (SPF).

  2. Wearing hats, sunglasses, and special clothing outdoors.

  3. Staying out of the sun (e.g. use of shady places, roofs, and umbrellas outdoors, etc.).

Types of outcome measures

Primary outcomes
  1. Basal cell carcinoma (BCC) confirmed clinically or histopathologically at any follow-up.

  2. Cutaneous squamous cell carcinoma (cSCC) confirmed clinically or histopathologically at any follow-up.

  3. Adverse events (e.g. dermatitis from sunscreens, acne secondary to the use of sunscreens, dermatitis from the use of hats and clothes, vitamin D deficiency from lack of exposure to the sun, etc.) reported by a number of participants or individually.

We have explained our reason for the addition of 'clinical' to our two primary outcomes in the Differences between protocol and review section.

Secondary outcomes
  1. Number of self-reported sunburns or skin lesions, defined by each study, at the end of follow-up.

  2. Actinic or solar keratoses at any follow-up.

  3. Total hours of ultraviolet radiation exposure at the end of follow-up.

  4. Total hours outdoors in peak exposure times at the end of follow-up.

  5. Minimal erythema dose (MED) at the end of follow-up.

  6. Participant's compliance with preventive strategies at the end of the trial.

Search methods for identification of studies

We aimed to identify all relevant randomised controlled trials (RCTs) regardless of language or publication status (published, unpublished, in press, or in progress).

Electronic searches

We searched the following databases up to 10 May 2016:

  • the Cochrane Skin Group Specialised Register using the search strategy in Appendix 1;

  • the Cochrane Central Register of Controlled Trials (CENTRAL) 2016, Issue 5, in the Cochrane Library using the strategy in Appendix 2;

  • MEDLINE via Ovid (from 1946) using the strategy in Appendix 3;

  • Embase via Ovid (from 1974) using the strategy in Appendix 4; and

  • LILACS (Latin American and Caribbean Health Science Information database, from 1982) using the strategy in Appendix 5.

Trial registries

We searched the following trials registries and portals up to 10 May 2016:

We used the terms "non melanoma skin cancer", "basal cell carcinoma", "squamous cell carcinoma", "bowen disease", and "actinic keratosis".

Searching other resources

References from included studies

We checked the bibliographies of included studies for further references to relevant trials.

Adverse effects

We did not perform a separate search for adverse effects of the target intervention, but we examined data on adverse effects from the included study that we identified.

Data collection and analysis

Due to the lack of studies, we were unable to carry out analyses that we had planned in our protocol. We have explained this in the Differences between protocol and review section.

Selection of studies

Two review authors (MO and GS) independently selected studies for eligibility with Early Review Organizing Software (EROS) (Ciapponi 2011; Glujovsky 2010; Glujovsky 2011). We checked the titles and abstracts of all of the retrieved studies to determine if they fulfilled the inclusion criteria previously proposed. We assessed the full texts of identified studies to confirm their final inclusion. We resolved all disagreements by involving a third author (IA-R). We were not blinded to characteristics such as the authors' names, institutions, or the journal of publication at any stage of the review. We recorded the reasons for our exclusion of potential studies in the 'Characteristics of excluded studies' tables (Higgins 2011).

Data extraction and management

Two review authors (CS and JG) used predesigned data collection forms to retrieve information, such as randomisation methods, blinding of participants and personnel, comparisons, number of participants by arm, and follow-up losses, from the original study in an independent way (Higgins 2011). We tested this format prior to extended use. We resolved any disagreement by discussion with a third review author (JN). We entered extracted data into Review Manager 5 for further analyses (Review Manager 2012).

Assessment of risk of bias in included studies

Two authors (ARH and IA-R) used the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions to independently assess the risk of bias of the included trial (Higgins 2011). We took six domains into consideration: random sequence generation; allocation concealment; blinding of participants, personnel, and outcome assessment; incomplete outcome data; selective reporting; and other biases. We resolved any disagreement by discussion with a third author (GS). We assessed the likely magnitude and direction of the bias and whether we considered it likely to impact on the findings (Higgins 2011). We summarised the information in a 'Risk of bias' table, which is an extension of the 'Characteristics of included studies' table. We planned to explore the impact of the level of bias through undertaking sensitivity analyses (see the Sensitivity analysis section), but we did not perform this analysis because of the number of studies included.

Measures of treatment effect

We presented results of dichotomous outcomes (such as BCC and cSCC) as summary risk ratios (RR) with 95% confidence intervals (CIs), as well as the number needed to treat for an additional harmful outcome (NNTH) as an absolute measure of harm, and NNTH as the reciprocal of risk differences (RD) (McQuay 1998). We also planned that for continuous outcomes (such as the number of sunburns and total hours of ultraviolet radiation exposure), we would report the mean difference (MD) with its corresponding 95% CI, but these outcomes were not reported (see Differences between protocol and review section).

Unit of analysis issues

We did not expect to find any unit of analysis issues as we did not expect to find cross-over studies. In the case of within-participant trials (e.g. split face) related to the effectiveness of the sunscreen, we planned to report the results in a narrative way and not include this information in planned meta-analyses. However, we found that information about these kinds of tumours can be expressed as number of participants affected, as well as total number of tumours by groups.

Dealing with missing data

We planned to retrieve levels of attrition of information if possible. We planned to explore, by using sensitivity analyses, the impact of trials with high levels of attrition in the assessment of treatment effects. If possible, we carried out analyses, as far as possible on an intention-to-treat (ITT) basis (i.e. we attempted to include in the analyses all randomised participants in the denominator of the assessed groups).

Assessment of heterogeneity

We planned to investigate heterogeneity in the first instance through visual examination of measures of treatment effect forest plots. Main sources of heterogeneity could include skin phototype, duration of follow-up, and gender and age groups. We planned to evaluate statistical heterogeneity by means of the I² statistic. This statistic estimates the percentage of total variation across included trials due to heterogeneity rather than sampling error (Higgins 2003; Higgins 2011). We planned to explore heterogeneity if the I² statistic was greater than 30%, and in cases where the I² statistic was more than 80%, we did not plan to present pooled results.

Assessment of reporting biases

We planned to create funnel plots of the primary outcomes to provide a visual assessment of reporting bias if at least 10 trials were available (Higgins 2011; Sterne 2011). Also, we planned to use two tests to assess asymmetry in the corresponding funnel plot: the regression asymmetry test (Egger 1997) and the adjusted rank correlation test (Begg 1994). However, we did not perform this analysis because of the number of studies included.

Data synthesis

We planned to summarise the findings using random-effects models with the DerSimonian and Laird method and carry out statistical analyses using Review Manager 5 (Review Manager 2012). We planned not to present a pooled result if we identified substantial heterogeneity (I² statistic was greater than 80%). Also, we planned to conduct a trial sequential analysis (TSA), which combines an information size calculation (cumulated sample sizes of included trials) for meta-analysis with the threshold of statistical significance. We planned to conduct a TSA using the TSA software on binary outcomes (Brok 2009; Pogue 1997; Pogue 1998; Thorlund 2009; Wetterslev 2008) and apply trial sequential monitoring boundaries according to a heterogeneity-adjusted required information size, based on an a priori 10% relative risk reduction (RRR) employing alpha = 0.05 and beta = 0.20 (CTU 2011; Thorlund 2011). However, we did not perform these analyses due to the number of studies included, and we present the results in a narrative way, with figures to illustrate the main information.

Subgroup analysis and investigation of heterogeneity

We planned to undertake subgroup analysis and perform interaction tests to check for subgroup differences where this assessment would be meaningful. For the primary outcomes, we planned to consider subgroup analyses for the following factors, as appropriate:

  • gender;

  • age groups (i.e. less than 18 years, 18 to 40 years, 41 to 60 years, greater than 60 years);

  • skin phototype (i.e. I, II, III, IV, V, VI);

  • hair colour phenotype (i.e. redhead, blonde, black, etc.);

  • eye colour phenotype (i.e. blue, green, black, brown, etc.);

  • duration at follow-up (less than one year, between one to two years, between two to five years, more than five years); and

  • history of skin cancer or precancerous lesions (personal and family).

However, we did not perform these analyses because of the number of studies included (see Differences between protocol and review section).

Sensitivity analysis

We planned to perform a sensitivity analysis using those trials classified as having a low risk of bias (Higgins 2011) in three core domains: allocation concealment, incomplete outcome data, and blinding of outcome assessment. However, we did not perform this analysis because of the number of studies included (see Differences between protocol and review section).

'Summary of findings' tables

We used the guidelines of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group (Guyatt 2008) to assess the quality of the evidence related to primary outcomes, and developed a 'Summary of findings' table with the GRADE profiler software. The GRADE system assesses the quality of evidence based on the extent to which users can be confident that an association reflects the item being evaluated (Guyatt 2008). Assessment of the quality of evidence included consideration of the risk of bias, heterogeneity, directness of the evidence, risk of publication bias, and precision of effect estimates (Guyatt 2011; Guyatt 2011a; Guyatt 2011b; Guyatt 2011c; Guyatt 2011d; Guyatt 2011e; Guyatt 2011f; Guyatt 2011g).

Results

Description of studies

See Characteristics of included studies and Characteristics of excluded studies.

Results of the search

We identified 482 records from the database searches after removal of duplicates. We excluded 452 records based on titles and abstracts and identified 30 records for further evaluation in full text. We excluded a further 21 records (See Characteristics of excluded studies). We included one trial, Green 1999, with data reported in nine different references (Figure 1). We did not find additional references from trial registers or other sources of information.

Figure 1.

Study flow diagram

Included studies

We included one study, which compared daily application of sunscreen versus discretionary use (mostly for recreational use). We did not find studies of children or studies comparing sunscreen at any sun protection factor (SPF) with no intervention or placebo. Also, we did not identify studies about interventions such as wearing hats, sunglasses, or sun-protective clothing outdoors, or staying out of the sun (use of shady places, roofs, umbrellas, etc.).

Design

We included one study that randomly assigned 1621 people and included 1383 with full skin examination in the analysis (see the Characteristics of included studies section). This study was a randomised 2x2 factorial trial developed in Australia, which evaluated the following four interventions: daily sunscreen and beta-carotene supplementation (30 mg beta-carotene tablet each day); daily sunscreen and placebo; discretionary sunscreen and beta-carotene supplementation (30 mg beta-carotene tablet each day); and discretionary sunscreen and placebo. The use of placebo cream alone was considered "unethical"; thus, the daily application of sunscreen was compared with the discretionary use of sunscreen. However, the study authors effectively reduced the comparisons to two by combining the groups (see below).

Participants

Adult participants were selected from a population-based prevalence survey of skin cancer conducted in 1986, with 43.7% being men; the average age was 48.77 years. Fifty-two per cent of the participants were fair skinned; 18.7% had an occupation that they carried out mainly outdoors; and 27% had a previous diagnosis of skin cancer.

Sample size and setting

One thousand two hundred and one eligible residents of Nambour were randomised to the different groups of this trial. The study authors presented analysis based on 1383 trial participants who had full skin examination during the follow-up period. The study authors estimated that a minimum of 1600 participants needed to be enrolled to detect a 36% reduction of basal cell carcinoma (BCC) and a 59% reduction of cutaneous squamous cell carcinoma (cSCC).

Interventions

Four groups were evaluated.

  • Participants in group one received instructions for daily use of SPF 16 sunscreen and a 30 mg beta-carotene tablet to be taken each day.

  • Participants in group two received instructions for daily use of SPF 16 sunscreen and a 30 mg placebo tablet each day.

The study authors added groups one and two together to obtain results for all participants with daily administration of SPF 16 sunscreen (daily sunscreen group: number of participants randomised = 812).

  • Participants in group three received a 30 mg beta-carotene tablet each day and received instructions to use sunscreen on a discretionary basis.

  • Participants in group four received a 30 mg placebo tablet each day and received instructions to use sunscreen on a discretionary basis.

The study authors added groups three and four together to obtain results for all participants with discretionary administration of SPF 16 sunscreen (non-daily sunscreen group: number of participants randomised = 809).

One thousand three hundred and eighty-three participants completed the full follow-up period of 4.5 years (85.3%). We included the 1621 participants originally allocated to our analysis (intention-to-treat analysis). Losses by group ranged from 12.3% to 17.1%. The administration of sunscreen on a daily basis involved the application of a layer of sunscreen to all exposed sites of the head, neck, arms, and hands every morning.

Outcomes

The primary outcome of our sole included study was the number of new cases of BCC and cSCC (Green 1999). Secondary outcomes were change in the prevalence of solar keratosis (as full body counts and per sunscreen site counts), adverse events (main reported complaints), and the degree of photoageing. The researchers assessed the participants' compliance with sunscreen use every three months by comparing the weight of the sunscreen provided with the average rate of consumption for a group of non-participants. Likewise, the use of sunscreen in the control group was measured through a standard questionnaire delivered annually. Two follow-up clinics in 1994 (two years after the beginning of the study) and 1996 (at the end of the study) assessed the participants, and all lesions identified at those times were evaluated by histopathology. Local doctors documented the rest of the lesions on prespecified cards.

Excluded studies

We excluded 21 studies for reasons reported in the 'Characteristics of excluded studies' tables after assessment of the full text of the report and most frequently because they did not evaluate the effectiveness of sun protection strategies in the prevention of keratinocyte cancer.

Risk of bias in included studies

We assessed the one included study for risk of bias and reported the judgments for the individual domains in the 'Risk of bias' table (see Figure 2).

Figure 2.

'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study

Allocation

Regarding randomisation issues, Green 1999 declared, "A customized randomization computer program was used to assign all attending the baseline study clinics to one of four treatment groups." Likewise, regarding allocation concealment, they added, "The treatment code was known only to the investigator who generated it and the two people who packaged the tablets for distribution. None of these people had contact with participants." We therefore judged these two domains to be at low risk of bias.

Blinding

Regarding blinding of participants, personnel, and assessment of outcomes, the authors of Green 1999 reported that the treatment code was known only to the investigator who generated it and to the two people who packaged the tablets for distribution. None of these people had contact with participants. Likewise, a single dermatopathologist histologically examined all clinically diagnosed skin cancers during these follow-up surveys. Dermatologists involved in the study survey were unaware of the treatment allocation. We judged these domains at low risk of bias.

Incomplete outcome data

Regarding attrition bias for our primary outcomes, Green 1999 declared: "At the end of the study in year 5, 238 (15%) participants had withdrawn without a complete skin examination by a dermatologist in the follow-up period." The percentage of losses to follow-up was similar for all groups, and it was the same for all primary outcomes (group one: 12.37%; group two: 17.15%; group three: 14.1%; group four: 15.01%). We judged this domain at low risk of bias.

By contrast, the number of participants lost to follow up was bigger for actinic keratosis (ranging from 28% to 36%), and the risk was considered high for this outcome. One thousand three hundred and eighty-three participants completed the full follow-up period of 4.5 years, but we included the 1621 participants originally randomised under intention-to-treat (ITT) analysis.

Selective reporting

In a secondary reference, Green 1999 reported the association between possible predictors of sunscreen use and frequency of sunscreen application, including general information on variables such as time outdoors on weekdays in summer and burns during the trial, but this information was not reported in a sufficient way to enable analysis. So, we judged this domain to be at unclear risk of bias.

Other potential sources of bias

We identified other potential sources of bias in the study, including an unclear assessment of the interaction between the effects of the different interventions evaluated (that is, sunscreen and beta-carotene), an unclear impact of multiple posthoc analyses not planned a priori (repeated significance testing), and an unclear impact of clinical versus histological diagnosis of keratinocyte cancer. We did not consider funding as a source of bias as the Public Health Research and Development Committee of the National Health and Medical Research Council of Australia provided funding.

Effects of interventions

See: Summary of findings for the main comparison Daily application of sunscreen compared with discretionary use for preventing basal cell and cutaneous squamous cell skin cancers

We only found information from one study comparing the daily application of sunscreen (in which participants applied a layer of sunscreen themselves every morning to all uncovered areas on the head, neck, arms, and hands, reapplying after substantial sweating, bathing, or extended sun exposure) versus discretionary use (mostly for recreational use).

For the main analyses, Green 1999 included all participants in the trial, including those who received beta-carotene tablets. They combined groups one and two to obtain results for all participants with daily administration of SPF 16 sunscreen (i.e. those participants who received instructions for daily use of SPF 16 sunscreen and a 30 mg beta-carotene tablet to be taken each day, plus those participants who received instructions for daily use of SPF 16 sunscreen and a 30 mg placebo tablet each day). These were compared to all participants (groups three and four) with discretionary administration of SPF sunscreen (i.e. those participants who received a 30 mg beta-carotene tablet each day and received instructions to use sunscreen on a discretionary basis, plus those participants who received a 30 mg placebo tablet each day and received instructions to use sunscreen on a discretionary basis).

For BCC and cSCC, the trial authors provided information for cases confirmed histopathologically in terms of incidence density ratios (IDR); these estimates are provided below as supplementary information. For actinic keratosis (AK), authors combined all lesions on the whole body at each examination (full body counts) and also added all lesions on the sites to which sunscreen was applied (sunscreen site counts). Also, Green 1999 provided supplementary analyses for BCC and cSCC excluding participants assigned to beta-carotene tablets (i.e. groups one and three). However, there was not enough information about the number of cases per arm to estimate risk ratios (RR). Information about IDR (which was the effect measure reported by the study authors) is provided as supplementary information.

We present the quality of the evidence in Summary of findings for the main comparison.

Primary outcomes

Basal cell carcinoma (BCC) confirmed clinically or histopathologically at any follow-up

The incidence of new BCC was similar in the daily-application group (812 participants randomly assigned) compared with the discretionary-use group (809 participants randomly assigned) (RR 1.03, 95% confidence interval (CI) 0.74 to 1.43; Analysis 1.1). This evidence was of low quality, which means that there is some certainty that future studies may alter our confidence in this evidence.

It was reported in a narrative way that the incidence was similar, even when authors restricted analysis to cases of BCC "that had been diagnosed histologically". The study authors also provided information in terms of IDR when they excluded groups receiving beta-carotene (that is, the authors excluded groups one and three), but they did not find differences between groups (IDR 0.96, 95% CI 0.59 to 1.56).

Cutaneous squamous cell carcinoma (cSCC) confirmed clinically or histopathologically at any follow-up

The incidence of new cSCC was similar in the daily-application group (812 participants randomly assigned) compared with the discretionary-use group (809 participants randomly assigned) (RR 0.88, 95% CI 0.50 to 1.54; Analysis 1.2). This evidence was of low quality, which means that there is some certainty that future studies may alter our confidence in this evidence.

Likewise, the incidence rate of histologically diagnosed cSCC, based on 40 participants with pathological confirmation, was similar in both groups (IDR 0.74, 95% CI 0.39 to 1.38). The study authors also provided information in terms of IDR when they excluded groups receiving beta-carotene (that is, the authors excluded groups one and three), but they found no differences between groups (IDR 0.74, 95% CI 0.31 to 1.77).

Adverse events

In a narrative report, Green 1999 stated that the main complaints made by the daily sunscreen use group were related to skin irritation or contact allergy (25 participants out of 812) and skin oiliness (10 participants out of 812). This evidence was of low quality, which means that there is some certainty that future studies may alter our confidence in this evidence. Adverse events related to the discretionary-use group were not reported.

Secondary outcomes

We did not find information about the number of self-reported sunburns or skin lesions, total hours of ultraviolet radiation exposure, total hours outdoors in peak exposure times, or minimal erythema dose (MED). Our sole included study only reported the following secondary outcomes.

Actinic or solar keratoses at any follow-up

The rate of change in the total number (full body count) of prevalent actinic keratoses between 1994 and 1996 was similar in the daily-application group (n = 812 participants randomly assigned) and in the discretionary-use group (n = 809 participants randomly assigned; 559 participants analysed) (RR 0.95, 95% CI 0.75 to 1.20; Analysis 1.3).

Participant's compliance with preventive strategies at the end of the trial

In a narrative report, Green 1999 stated, "75% of participants assigned to daily sunscreen use were applying sunscreen to their neck, arms and hands at least 3 to 4 days a week and those people not assigned to the sunscreen group were applying sunscreen to head, neck and arms not at all or no more than 1 or 2 days a week." For the daily use group, the median daily weight of sunscreen applied on average throughout the trial was 1.5 g/d (range 0 to 7.4 g/d), but the median decreased as the trial progressed (1992 = 1.67 g and 1996 = 1.22 g).

Discussion

We have summarised the evidence in Summary of findings for the main comparison.

Summary of main results

In this review, we only identified one study, which evaluated whether regular daily use of sunscreen in comparison with discretionary or occasional use prevented new cases of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and our secondary outcome actinic keratoses at follow-up (Green 1999). The study was undertaken in Nambour in South East Queensland (Australia); the researchers also studied adverse events and adherence related to the use of sunscreen. They found that sun protection factor (SPF) 16 sunscreen applied on exposed sites of the body, such as the head, neck, and upper limbs, every morning and repeated after heavy sweating or bathing made no difference in terms of reducing the occurrence of new cases of BCC and cSCC confirmed or not by histopathology at 4.5 years, in comparison with discretionary use (low-quality evidence; see Summary of findings for the main comparison). We did not identify studies comparing the use of sunscreen against no use of sunscreen.

Adverse events associated with the use of sunscreen in the daily sunscreen use group, such as occasional local reactions, like contact dermatitis; the feeling of oily skin; and interference with perspiration, were documented.

We identified no studies that evaluated other sun protection measures or regimens, such as wearing sun-protective clothing, glasses, or hats, or seeking the shade when outdoors.

Overall completeness and applicability of evidence

Although we searched for randomised controlled trials (RCTs) of sun protection strategies aimed at preventing the development of cutaneous squamous cell carcinoma, basal cell carcinoma, and actinic keratoses, we found only one study, which was on the use of sunscreen. Limitations of this study were that it was restricted to only one SPF (SPF 16); it was in a population at higher risk of keratinocyte cancer due to the majority of participants having fair skin (55.2% were fair) and therefore a higher risk of sun damage and developing keratinocyte cancer (KC); and it did not address several of the prespecified secondary outcomes planned in our review.

Our review did not find differences between two sunscreen regimens (daily use versus discretionary use) in terms of the number of participants with new cases of BCC or cSCC, so to date, available evidence regarding the effectiveness and safety of preventive strategies for cSCC and BCC is scarce. This result could be attributed to a short period of exposure to sunscreen (4.5 years) and a limited tracking time. Given the above, it is possible that the clinical assessment did not last long enough to demonstrate that a protective effect can reduce the occurrence of BCC.

Cutaneous squamous cell carcinoma lesions are strongly related to sun exposure. It is estimated that 90% of these occur in body sites that are usually exposed to the sun (Miller 2010). Preventing early stages of carcinogenesis would indicate the benefit of performing preventive procedures from childhood with a longer follow-up period (Zelen 1988). The pattern of BCC-causing sun exposure seems to be different from that of cSCC, because although it is accepted that ultraviolet exposure (UV) is the main causal factor, the accurate relationship between the amount, timing, and pattern of exposure is unknown (i.e. exposure age, number of years, intensity of exposure, etc.) (Roewert-Huber 2007). Although cSCC lesions show a higher metastatic profile in comparison with basal cell carcinoma lesions, there are BCC histologic patterns that might be locally aggressive without correlation with its metastatic risk (Roewert-Huber 2007). However, reduced sunlight exposure can be deleterious for some populations, producing long-term harms such as vitamin D deficiency and depression, which is a reason for not recommending reduced exposure to sunlight as a general measure (Maslin 2014).

The results of this study highlight that there are peculiarities in populations that could change the estimate of the effect, among which, phototype, type of radiation, geographic location (altitude above sea level, ozone layer, and latitude), and the number of hours spent outdoors are worth noting (Holman 1984). Thus, the benefits of using sunscreen may vary from one population to another. Finally, we must emphasise that Green 1999 conducted an evaluation of effectiveness with only one sun protection factor (SPF 16) and a once a day application scheme, which today would be considered inadequate (Pissavini 2013).

Quality of the evidence

The results of this single study suggest that using sunscreen on a daily basis, compared with discretionary use, does not reduce the onset of new cases of basal cell or cutaneous squamous cell carcinoma. This evidence was of low quality, which means that there is some certainty that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. We downgraded the risk of bias due to a number of potential risks that had an unclear impact on the results, including an unclear assessment of interaction between the effects of the different interventions evaluated (that is, sunscreen and beta-carotene), an unclear impact of multiple posthoc analyses not planned a priori (repeated significance testing), and an unclear impact of clinical versus histological diagnosis of keratinocyte cancer. We deemed other considerations such as inconsistency, imprecision, and publication bias as not serious, but readers should consider these issues when considering the main results of this trial.

Potential biases in the review process

This review was comprehensive in aiming to identify clinical trials addressing the issue of the effectiveness and safety of sun protection measures for the prevention of cSCC and BCC. In general, we followed most of the strategies recommended by the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) regarding identification of relevant studies. However, the number of references identified was low, demonstrating the poor level of research at trial level in this area. This is understandable given the difficulty of long-term population experiments, which are needed to adequately identify incident cases of KC. Also, the effectiveness of sun protection measures is often studied in conjunction with educational strategies to maximise adherence to preventive strategies, but this review did not address the educational aspect.

In this review, we made some changes from the protocol, which may be sources of bias. We expanded the criteria for confirmation of BCC and cSCC lesions, because histopathological confirmation of keratinocyte cancer could be a difficulty in population-based studies with large sample sizes, and then, clinical confirmation is more likely to be used. Despite expanding our criteria, we considered that there was a lack of applicability of our results to a wider population, so we downgraded for indirectness. This change could be considered a source of bias in this review.

Agreements and disagreements with other studies or reviews

van der Pols 2006 contained the results of a follow-up study of the cohort of people participating in the Nambour study eight years after the cessation of the trial. Including the time of the trial, a 12-year follow-up was completed. Comparing the group of participants originally assigned to daily sunscreen use with the group not assigned to daily sunscreen use, the author found that sunscreen significantly reduced the incidence of cSCC in both the number of people affected (RR 0.65, 95% CI 0.45 to 0.94) and the number of tumours diagnosed (RR 0.59, 95% CI 0.38 to 0.90). However, it was not possible to demonstrate, even during this monitoring period, that the regular application of sunscreen could reduce the occurrence of new cases of BCC, which may take many years to develop (van der Pols 2006). Although our plan was to assess the development of BCC or cSCC at any follow-up period, it was clear to us (because of the participants' compliance with the preventive strategies) that the information reported in this study was a follow-up of a cohort of participants who did not necessarily use sunscreen as planned in the trial.

Bimczok 2007 found that the minimum dose of sunscreen to be effective was SPF 15, and the minimum amount should be 2 mg/cm². However, subsequent studies have reported that the general population applies close to 1 mg/cm², which would affect the effectiveness of the intervention (Jansen 2013a; Jansen 2013b). In 2011, the U.S. Food and Drug Administration (FDA) recommended the use of sunscreen with a SPF higher than 15, and that same year, the National Institute for Health and Care Excellence (NICE) in the UK published a guide for the prevention of skin cancer in which it too recommended the use of sunscreen with a SPF higher than 15 (NICE 2011). Pissavini and collaborators, who after studying the population's patterns of sunscreen use and ultraviolet (UV) exposure, recommended the use of SPF 30, have recently supplemented these results, given that the effectiveness of this measure is related to frequency of use and the dose used (Pissavini 2013).

Authors' conclusions

Implications for practice

In different countries, it has been documented that there has been a progressive increase in the rates of skin cancer (Lomas 2012; Sánchez 2011), driving the implementation of strategies that may help to control this growing phenomenon. The present systematic review explored the evidence related to the effect of sun protection measures against the occurrence of new cases of keratinocyte cancer, but was unable to find evidence for the effectiveness of sunscreen to prevent the development of basal cell carcinoma lesions (BCC) or cutaneous squamous cell carcinoma (cSCC) in the participants (Green 1999).

Implications for research

Despite the fact that well-planned studies need to be performed to address the main objective of this review, the widespread use of sunscreen may make it more difficult to run clinical trials where placebo creams are used as the control. However, other important questions remain, such as the optimal application frequency and minimum sun protection factor for the adequate prevention of cSCC and BCC, as well as the safety of the different sunscreen brands and their effects when applied to the skin. Future studies should also include histological confirmation of keratinocyte cancer (KC) cases, in order to obtain an accurate estimation of incident cases of cSCC or BCC, as well as the harms and possible adverse effects related to reduced sun exposure, such as vitamin D deficiency and depression.

Another difficulty is the proper monitoring of participants, with sufficient time to fully identify incident cases, which in the case of BCC could be longer than for cSCC. Population studies should be designed to assess follow-up periods longer than 10 years to establish the effectiveness of sunscreen in preventing KC, because current studies have had short follow-up periods. Although these short-term outcome variables could be assumed as "proxy" in the incidence of KC, they do not allow for the generation of definitive conclusions given that they provide insufficient evidence. In addition, it would be worthwhile to evaluate the effect of multiple barrier measures combined with the use of sunscreen. It is important to remark that the design and conduct of these interventions need to be delivered within a suitable behavioural change framework. Such complex interventions require understanding the lessons learned from existing educational campaigns and behavioural motivation studies in these areas.

With regard to other protective measures (such as wearing sun-protective clothing, glasses, or hats, or seeking the shade when outdoors), clinical studies need to be developed to evaluate their effectiveness and safety. These could be carried out in combination with the use of sunscreens and also in special groups, such as children or those with predominant skin phototypes I to III who have a higher risk of developing skin cancers.

The design of future studies in sun protection might be improved with the following suggestions.

  1. Evaluating different sun protection factors and different application regimens in order to establish what is the best sunscreen regimen to avoid onset of KC.

  2. Combining different sun protection strategies compared with sunscreen use in order to assess their effectiveness and safety.

  3. Comparing other sun protection strategies (such as wearing sun-protective clothing, glasses, or hats, and seeking the shade when outdoors) versus sunscreen in order to assess whether there are differences between these interventions in terms of effectiveness and safety.

  4. Running campaigns to prevent skin cancer in different populations, especially those including the predominant skin phototypes I to III who have a higher risk of developing it.

  5. Adding adverse events as an important endpoint in the assessment of all of these preventive strategies.

Acknowledgements

We are grateful to Hywel Williams, Finola Delamere, Elizabeth Doney, Helen Scott, and Laura Prescott from the Cochrane Skin Group for their assistance and advice in writing this review. We and the Cochrane Skin Group editorial base wish to thank Luigi Naldi, who was the Cochrane Dermatology Editor for this review; Thomas Chu, who was the statistical editor; Ching-Chi Chi, who was the methods editor; the clinical referees, Eleni Linos and An-Wen Chan; and the consumer referee, Jack Tweed.

Data and analyses

Download statistical data

Comparison 1. Daily application of sunscreen versus discretionary use (including beta-carotene use)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 BCC confirmed clinically or histopathologically at any follow-up1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
2 cSCC confirmed clinically or histopathologically at any follow-up1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
3 Actinic or solar keratoses at any follow-up1 Risk Ratio (Random, 95% CI)Totals not selected
Analysis 1.1.

Comparison 1 Daily application of sunscreen versus discretionary use (including beta-carotene use), Outcome 1 BCC confirmed clinically or histopathologically at any follow-up.

Analysis 1.2.

Comparison 1 Daily application of sunscreen versus discretionary use (including beta-carotene use), Outcome 2 cSCC confirmed clinically or histopathologically at any follow-up.

Analysis 1.3.

Comparison 1 Daily application of sunscreen versus discretionary use (including beta-carotene use), Outcome 3 Actinic or solar keratoses at any follow-up.

Appendices

Appendix 1. Cochrane Skin Group Specialised Regiser (CRS)

(basal cell carcinoma or squamous cell carcinoma or keratinocyte carcinoma or bowen* or actinic keratos*) and (sunblock* or sun tan lotion* or suntan lotion* or sun screen* or sunburn cream* or sun cream* or block out or sunscreen* or hat or hats or sunglasses or protective cloth* or protective garment* or umbrella* or parasol* or sunshade* or canop* or tree or trees or shade or shadow)

Appendix 2. CENTRAL (Cochrane Library) search strategy

#1 "non melanoma skin cancer":ti,ab
#2 nmsc:ti,ab
#3 ((keratinocyte next cancer*) or (basal next keratinocyte*) or "keratinocyte carcinoma"):ti,ab
#4 MeSH descriptor: [Skin Neoplasms] this term only
#5 MeSH descriptor: [Acanthoma] this term only
#6 MeSH descriptor: [Carcinoma, Basal Cell] this term only
#7 (basal next cell next carcinoma*):ti,ab
#8 bcc:ti,ab
#9 (basal next cell next cancer*):ti,ab
#10 ((jacob* or rodent) next ulcer*):ti,ab
#11 basolioma*:ti,ab
#12 {or #1-#11}
#13 ("squamous cell" next (carcinoma* or epithelioma*)):ti,ab
#14 epidermoid next carcinoma*:ti,ab
#15 scc:ti,ab
#16 MeSH descriptor: [Carcinoma, Squamous Cell] this term only
#17 {or #13-#16}
#18 (skin or epiderm* or cutaneous):ti,ab
#19 MeSH descriptor: [Skin] this term only
#20 MeSH descriptor: [Skin Neoplasms] this term only
#21 {or #18-#20}
#22 #17 and #21
#23 ((senile or solar or actinic) next keratos*):ti,ab
#24 MeSH descriptor: [Keratosis, Actinic] this term only
#25 MeSH descriptor: [Bowen's Disease] this term only
#26 Bowen* next disease:ti,ab
#27 "bowenoid papulosis":ti,ab
#28 "morbus bowen":ti,ab
#29 {or #23-#28}
#30 #12 or #22 or #29
#31 MeSH descriptor: [Sunscreening Agents] this term only
#32 MeSH descriptor: [Eye Protective Devices] explode all trees
#33 MeSH descriptor: [Protective Clothing] this term only
#34 (sunblock* or (sun next tan next lotion*) or (suntan next lotion*) or (sun next screen*) or (sunburn next cream*) or (sun next cream*) or "block out" or sunscreen*):ti,ab
#35 (sunglasses or (sun next glasses)):ti,ab
#36 shadow:ti,ab
#37 shade:ti,ab
#38 (hat or hats):ti,ab
#39 (umbrella* or parasol* or sunshade* or canopy or canopies or tree or trees):ti,ab
#40 (sun and protective and (cloth* or garment*)):ti,ab
#41 (photo protective and (garment* or cloth*)):ti,ab
#42 {or #31-#41}
#43 #30 and #42

Appendix 3. MEDLINE (Ovid) search strategy

1. nmsc.ti,ab.
2. non melanoma skin cancer$.ti,ab.
3. keratinocyte cancer$.ti,ab.
4. basal keratinocyte$.ti,ab.
5. skin neoplasms/ or acanthoma/
6. carcinoma, basal cell/ or neoplasms, basal cell/
7. basal cell carcinoma$.ti,ab.
8. bcc.ti,ab.
9. basal cell cancer$.ti,ab.
10. rodent ulcer$.ti,ab.
11. Jacob$ ulcer$.ti,ab.
12. basalioma$.ti,ab.
13. or/6-12
14. carcinoma, squamous cell/ or neoplasms, squamous cell/
15. squamous cell carcinoma$.ti,ab.
16. epidermoid carcinoma$.ti,ab.
17. squamous cell epithelioma$.ti,ab.
18. scc.ti,ab.
19. or/14-18
20. Skin/
21. (skin or epiderm$ or cutaneous).ti,ab.
22. Skin Neoplasms/
23. 20 or 21 or 22
24. 19 and 23
25. Keratosis, Actinic/
26. senile keratos?s.ti
27. solar keratos?s.ti,ab.
28. (actinic adj3 keratos?s).ti,ab.
29. or/25-28
30. Bowen's Disease/
31. Bowen$ disease.ti,ab.
32. bowenoid papulosis.ti,ab.
33. morbus bowen.ti,ab.
34. 30 or 31 or 32 or 33
35. 1 or 2 or 3 or 4 or 5 or 13 or 24 or 29 or 34
36. Sunscreening Agents/
37. (sunblock$ or sun tan lotion$ or suntan lotion$ or sun screen$ or sunburn cream$ or sun cream$ or block out or sunscreen$).ti,ab.
38. Eye Protective Devices/
39. (sunglasses or sun glasses).ti,ab.
40. Protective Clothing/
41. (sun protective and (cloth$ or garment$)).ti,ab.
42. (photo protective and (garment$ or cloth$)).ti,ab.
43. hat$1.ti,ab.
44. (umbrella$ or parasol$ or sunshade$ or canop$3 or tree$1).ti,ab.
45. shade.ti,ab.
46. shadow.ti,ab.
47. or/36-46
48. randomised controlled trial.pt.
49. controlled clinical trial.pt.
50. randomized.ab.
51. placebo.ab.
52. drug therapy.fs.
53. randomly.ab.
54. trial.ab.
55. groups.ab.
56. or/48-55
57. exp animals/ not humans.sh.
58. 56 not 57
59. 35 and 47 and 58

[Lines 48-58: Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE: sensitivity- and precision-maximizing version (2008 revision)]

Appendix 4. Embase (Ovid) search strategy

1. nmsc.ti,ab.
2. non melanoma skin cancer$.ti,ab.
3. keratinocyte cancer$.ti,ab.
4. basal keratinocyte$.ti,ab.
5. keratinocyte carcinoma/
6. acanthoma/
7. skin tumor/
8. basal cell carcinoma$.ti,ab.
9. basal cell carcinoma/
10. bcc.ti,ab.
11. basal cell cancer$.ti,ab.
12. rodent ulcer$.ti,ab.
13. Jacob$ ulcer$.ti,ab.
14. basalioma$.ti,ab.
15. or/1-14
16. squamous cell carcinoma$.ti,ab.
17. squamous cell carcinoma/
18. epidermoid carcinoma$.ti,ab.
19. squamous cell epithelioma$.ti,ab.
20. scc.ti,ab.
21. or/16-20
22. Skin/
23. (skin or epiderm$ or cutaneous).ti,ab.
24. skin tumor/
25. or/22-24
26. 21 and 25
27. senile keratos?s.ti,ab.
28. actinic keratosis/
29. solar keratos?s.ti,ab.
30. (actinic adj3 keratos?s).ti,ab.
31. Bowen$ disease.ti,ab.
32. Bowen disease/
33. bowenoid papulosis.ti,ab.
34. morbus bowen.ti,ab.
35. or/27-34
36. 15 or 26 or 35
37. (sunblock$ or sun tan lotion$ or suntan lotion$ or sun screen$ or sunburn cream$ or sun cream$ or block out or sunscreen$).ti,ab.
38. (sunglasses or sun glasses).ti,ab.
39. (sun protective and (cloth$ or garment$)).ti,ab.
40. (photo protective and (garment$ or cloth$)).ti,ab.
41. hat$1.ti,ab.
42. (umbrella$ or parasol$ or sunshade$ or canop$3 or tree$1).ti,ab.
43. shade.ti,ab.
44. shadow.ti,ab.
45. skin protection/
46. sunscreen/ or skin protective agent/
47. sunglasses/
48. protective clothing/
49. sunlight protection/
50. or/37-49
51. crossover procedure.sh.
52. double-blind procedure.sh.
53. single-blind procedure.sh.
54. (crossover$ or cross over$).tw.
55. placebo$.tw.
56. (doubl$ adj blind$).tw.
57. allocat$.tw.
58. trial.ti.
59. randomised controlled trial.sh.
60. random$.tw.
61. or/51-60
62. exp animal/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or animal cell/ or nonhuman/
63. human/ or normal human/
64. 62 and 63
65. 62 not 64
66. 61 not 65
67. 36 and 50 and 66

Appendix 5. LILACS search strategy

("basal cell carcinoma" or "carcinoma basocelular" or "epitelioma basocelular" or "squamous cell carcinoma" or "epitelioma espinocelular") and (sunblock$ or sun tan lotion$ or suntan lotion$ or sun screen$ or sunburn cream$ or sun cream$ or block out or sunscreen$ or filtro solar or hat or hats or sunglasses or protective cloth$)

In LILACS we searched using the Controlled clinical trials topic-specific query filter.

What's new

DateEventDescription
21 September 2016AmendedExternal source of support amended with more detail

Contributions of authors

IAR was the contact person with the editorial base.
GS, IAR, and RDM co-ordinated contributions from the co-authors and wrote the final draft of the review.
GS, JN, ARH, CSR, JG, MO, and IAR screened papers against eligibility criteria.
GS, JN, ARH, CSR, JG, MO, IAR, and RDM appraised the quality of papers.
GS, IAR, JN, and ARH extracted data for the review and sought additional information about papers.
IAR, RDM, and GS entered data into RevMan.
GS, JN, ARH, CSR, JG, MO, IAR, and RDM analysed and interpreted data.
GS, IAR, JN, and ARH worked on the methods sections.
JN, MO, JG, and CSR drafted the clinical sections of the background and responded to the clinical comments of the referees.
GS, IAR, JN, and ARH responded to the methodology and statistics comments of the referees.
KG was the consumer co-author and checked the review for readability and clarity, as well as ensuring outcomes are relevant to consumers.
GS is the guarantor of the update.

Disclaimer

This project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Skin Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.

Declarations of interest

Guillermo Sánchez: nothing to declare.
John Nova: nothing to declare.
Andrea Esperanza Rodriguez-Hernandez: nothing to declare.
Roger David Medina: nothing to declare.
Carolina Solorzano-Restrepo: nothing to declare.
Jenny Gonzalez: nothing to declare.
Miguel Olmos: nothing to declare.
Kathie Godfrey: nothing to declare.
Ingrid Arevalo-Rodriguez: nothing to declare.

Sources of support

Internal sources

  • Fundación Universitaria de Ciencias de la Salud, Colombia.

  • Centro Dermatológico Federico Lleras Acosta, Colombia.

External sources

  • Colombian Ministry of Health and Social Protection, Colombia.

    Programa Nacional de Ciencia, Tecnología e Innovación en Salud, Departamento Administrativo de Ciencia Tecnología e Innovación en Salud, Colciencias, Convocatoria 563/2012, Grant number 469-2012, Code 5007-563-35261

  • The National Institute for Health Research (NIHR), UK.

    The NIHR, UK, is the largest single funder of the Cochrane Skin Group.

Differences between protocol and review

  1. Due to scarcity and nature of data (one single study was identified and included in our review), we were not able to implement the following methods:

    1. sensitivity analysis of 'Risk of bias' results;

    2. analysis of heterogeneity;

    3. assessment of reporting biases;

    4. subgroup analyses; or

    5. trial sequence analysis and summarising the findings using random-effects models with the DerSimonian and Laird method to carry out statistical analyses using Review Manager 5 (Review Manager 2012).

  2. We were not able to identify numerical information about the following continuous outcomes:

    1. the number of self-reported sunburns or skin lesions;

    2. total hours of ultraviolet radiation exposure;

    3. total hours outdoors in peak exposure times; or

    4. minimal erythema dosis (MED).

  3. We expanded on our primary outcomes by adding confirmation by 'clinical' criteria of basal cell carcinoma (BCC) lesions and cutaneous squamous cell carcinoma (cSCC) lesions, because histopathological confirmation of keratinocyte cancer could be a difficulty in population-based studies with large sample sizes, and then, clinical confirmation is more likely to be used. However, we thought that this was a source of indirectness, and we downgraded the evidence related to these outcomes in the corresponding Summary of findings for the main comparison.

  4. We added a 'Summary of findings' table, which was not planned in the protocol. However, these are now recommended in Cochrane Reviews to assess the quality of evidence.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Green 1999

  1. a

    SD = standard deviation.
    SPF = sun protection factor.

Methods

Design: 2x2 factorial design

Country: Australia

Multisite: no

International: no

Treatment duration: 4.5 years

Follow-up: 4.5 years

Random unit: participants

Analysis unit: participants, tumours

Participants

Inclusion criteria

Residents of Nambour (South East Queensland), aged between 20 and 69 when they took part in a skin cancer survey in 1986. To be eligible for the current study, the original survey participants had to participate in a second survey in 1992, undergo a complete skin examination by a dermatologist with removal of all diagnosed skin cancers, and give written consent to take part in this randomised trial until 1996.

Exclusion criteria

Participants who were taking vitamin supplements containing beta-carotene and those who reported that they were already applying sunscreen on a strict daily basis were excluded.

Participant groups

1621 participants were randomised to 1 of 4 groups (Green 1994: the original protocol reported 1626 participants):

Basal cell carcinoma, cutaneous squamous cell carcinoma, adverse events

  • Group 1: 404 (50 participants lost to follow up = 12%); 354 participants analysed

  • Group 2: 408 (70 participants lost to follow up = 17%); 338 participants analysed

  • Group 3: 416 (59 participants lost to follow up = 14%); 357 participants analysed

  • Group 4: 393 (59 participants lost to follow up = 15%); 334 participants analysed

Actinic keratosis

  • Group 1: 404 (110 participants lost to follow up = 28%); 294 participants analysed

  • Group 2: 408 (145 participants lost to follow up = 36%); 263 participants analysed

  • Group 3: 416 (136 participants lost to follow up = 32%); 280 participants analysed

  • Group 4: 393 (114 participants lost to follow up = 29%); 279 participants analysed

Frequency of sunscreen used

  • Group 1 + 2 = 812 (48 participants lost to follow up = 5.9%); 764 participants analysed

Demographic characteristics

  • Group 1: mean age = 48.5 years (SD: 12.9); percentage of men = 44.3%; skin type: always burn = 21.8%; skin colour: fair = 54.6%; occupation type: mainly indoors = 42.6%; previous skin cancer = 27.7%

  • Group 2: mean age = 48.7 years (SD: 13.6); percentage of men = 42.9%; skin type: always burn = 20.3%; skin colour: fair = 57.1%; occupation type: mainly indoors = 46.8%; previous skin cancer = 25.2%

  • Group 3: mean age = 48.1 years (SD: 13.6); percentage of men = 40.9%; skin type: always burn = 22.1%; skin colour: fair = 57.5%; occupation type: mainly indoors = 42.1%; previous skin cancer = 25.8%

  • Group 4: mean age = 49.8 years (SD: 12.7); percentage of men = 46.8%; skin type: always burn = 19.6%; skin colour: fair = 51.6%; occupation type: mainly indoors = 45.2%; previous skin cancer = 29%

Interventions

4 groups:

  • Group 1: daily application* of SPF 16 cream + 1 30 mg beta-carotene tablet once a day with a meal

  • Group 2: daily application* of SPF 16 cream + 1 placebo tablet a day with a meal

  • Group 3: 1 30 mg beta-carotene tablet a day with a meal + discretionary use of sunscreen

  • Group 4: 1 placebo tablet a day with a meal + discretionary use of sunscreen

*Daily sunscreen: self-application of a layer to all exposed sites on the head, neck, arms, and hands every morning (reapplication was advised after heavy sweating, bathing, or long sun exposure)

Outcomes

Primary outcomes

  1. Basal cell carcinoma confirmed by histopathology at any follow-up.

  2. Squamous cell carcinoma confirmed by histopathology at any follow-up.

Secondary outcomes

  1. Adverse events (e.g. dermatitis from sunscreens, acne secondary to use of sunscreens, dermatitis from the use of hats and sun-protective clothing, vitamin D deficiency from lack of exposure to the sun, etc.) reported by a number of participants or individually.

  2. Actinic keratosis (Darlington 2003): counts were recorded as the number of defined actinic keratoses observed on each site, except where this number exceeded 50 or on sites where more than 50% of the skin surface area was confluent with keratosis.

Assessment of participants' compliance with preventive strategies at the end of the trial (Neale 2002) through a questionnaire: weight and frequency of sunscreen used

Notes
  1. Trial registration: no

  2. Funder: Public Health Research and Development Committee of the National Health and Medical Research Council of Australia

  3. Role of funder: not stated

  4. A priori sample size estimation: yes

  5. Declaration of interest: not stated

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "A customized randomization computer program was used to assign all attending the baseline study clinics to one of four treatment groups." (Page 516 - Green 1994)
Allocation concealment (selection bias)Low riskQuote: "The treatment code was known only to the investigator who generated it and the two people who packaged the tablets for distribution. None of these people had contact with participants." (Page 724 - Green 1999)
Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "The treatment code was known only to the investigator who generated it and the two people who packaged the tablets for distribution. None of these people had contact with participants." (Page 724 - Green 1999)
Blinding of outcome assessment: Histologically diagnosed basal cell carcinomaLow riskQuote: "At follow-up clinics in 1994 and 1996, [a] collaborating dermatologist, unaware of treatment allocation, re-examined active participants... All skin cancers clinically diagnosed during these follow-up surveys were examined histologically by a single dermatopathologist." (Page 724 - Green 1999)
Blinding of outcome assessment: Histologically diagnosed cutaneous squamous cell carcinomaLow riskQuote: "At follow-up clinics in 1994 and 1996, [a] collaborating dermatologist, unaware of treatment allocation, re-examined active participants... All skin cancers clinically diagnosed during these follow-up surveys were examined histologically by a single dermatopathologist." (Page 724 - Green 1999)
Blinding of outcome assessment: Adverse eventsLow riskQuote: "At follow-up clinics in 1994 and 1996, [a] collaborating dermatologist, unaware of treatment allocation, re-examined active participants." (Page 724 - Green 1999)
Blinding of outcome assessment: Actinic or solar keratosesLow riskQuote: "Complete skin examinations were carried out in February 1992, August 1994 and August 1996 by dermatologists involved in the study survey but unaware of treatment allocation." (Page 452 - Darlington 2003)
Blinding of outcome assessment: Participant's compliance with preventive strategiesLow risk

Quote: "Compliance is assessed on a 3-monthly basis when supplies of sunscreen and tablets are replenished. Compliance with the daily sunscreen regimen is measured by comparing the weight of sunscreen used to an empirical standard usage rate derived from average consumption of the sunscreen when used by a group of non participants according to the study protocol. Sunscreen used by people in the control group is monitored by responses to a standard questionnaire delivered annually to participants to obtain information about sun exposure habits including frequency of use of sunscreen in the previous 12 months." (Pages 516 to 517 - Green 1994)

Quote: "To estimate compliance with the sunscreen protocol, participants completed a questionnaire in the third and fifth years of the trial that asked about average frequency of sunscreen use in a normal week, and about outdoor behavior. In addition, the measured weights of all returned sunscreen bottles used by those in the daily sunscreen group were recorded every 3 months." (Page 724 - Green 1999)

Incomplete outcome data (attrition bias)
Basal cell carcinoma
Low riskQuote: "...at the end of the study in year 5, 238 (15%) participants had withdrawn without a complete skin examination by a dermatologist in the follow-up period." (Page 725 - Green 1999)
Incomplete outcome data (attrition bias)
Squamous cell carcinoma
Low riskQuote: "...at the end of the study in year 5, 238 (15%) participants had withdrawn without a complete skin examination by a dermatologist in the follow-up period." (Page 725 - Green 1999)
Incomplete outcome data (attrition bias)
Adverse events
Low riskQuote: "...at the end of the study in year 5, 238 (15%) participants had withdrawn without a complete skin examination by a dermatologist in the follow-up period." (Page 725 - Green 1999)
Incomplete outcome data (attrition bias)
Actinic keratoses
High risk
  • Group 1: 110 participants lost to follow up (28%)

  • Group 2: 145 participants lost to follow up (36%)

  • Group 3: 136 participants lost to follow up (32%)

  • Group 4: 114 participants lost to follow up (29%)

Selective reporting (reporting bias)Unclear risk Neale 2002 reported the association between possible predictors of sunscreen use and frequency of sunscreen application, including information on variables such as time outdoors on weekdays in summer and burns during the trial, but this information was not reported in a full way in other references.
Other biasUnclear risk

The impact of multiple posthoc analysis (repeated significance testing) was unclear.

The report of the number of participants randomised (1626 versus 1621) was unclear.

The impact of differences in sample size estimations and final sample obtained (different estimations in Green 1994 and Green 1999) was unclear.

The impact of clinical versus histologic diagnosis of skin cancer was unclear. Quote: "67% of all interim skin cancers were diagnosed histologically, and 33% were clinically diagnosed." (Page 725 - Green 1999)

The impact of missing data was unclear. Quote: "Analyses have been based on the 1383 trial participants (85%) who had outcome data based on at least one complete skin examination by a dermatologist in 1994 or 1996." (Page 725 - Green 1999)

The assessment of interaction between the effects of the different interventions (sunscreen and beta-carotene) was unclear.

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
  1. a

    SPF = sun protection factor.
    UV = ultraviolet.

Autier 1999This study assessed if the sun protection factor (SPF) had an influence on sun exposure duration.
Bauer 2005This study focused on the prevention of melanocytic nevi by means of an educational strategy plus free provision of sunscreen.
Bauer 2014This study assessed the acceptance and usability of sunscreens during outdoor work.
Buller 2011The study assessed the effectiveness of a programme at school for reducing sun exposure.
Carrera 2013The study evaluated the effectiveness of a topical sunscreen in preventing the different UV effects on nevi.
Dobbinson 2009The study assessed whether students use or avoid newly shaded areas installed at schools, without assessment of the prevention of basal or squamous cell carcinomas.
Duffy 2013The reference presented a trial protocol about educational sun protection strategies.
Dupuy 2005The trial assessed the influence of sun protection factor and the information about protection (label) on sun-exposure behaviour.
Giles-Corti 2004The study showed the implementation of sun protection policies at school.
Glanz 2010This study showed the effects of a mailed intervention on skin cancer prevention and skin self-examination behaviours of adults.
Gordon 2009This was an evaluation of the cost-effectiveness of a skin cancer prevention initiative based on regular sunscreen use, using primary data from a randomised controlled trial.
Hirst 2012This study focused on the lifetime health costs and benefits of sunscreen promotion in the primary prevention of skin cancers, including melanoma.
Janda 2014This study identified current practice of sun protection and factors associated with effective use in 4 outdoor worker industries in Queensland, Australia.
Lagerlund 2006This was a cross-sectional survey that assessed sun protection behaviours, including the use of sunglasses.
Manion 1997This was a survey about knowledge, attitudes, and actual behaviour related to sun safety.
Marks 1995The trial included participants with at least 1 solar keratosis.
Mayer 2007This trial assessed an intervention including educational strategies.
Schalka 2009This was an evaluation of the amount of 2 sunscreens applied, including the same ingredients at different concentrations.
Thompson 1993The trial included participants with at least 1 to 30 solar keratoses at the beginning.
Vuong 2014This study evaluated the feasibility and acceptability of an opportunistic skin cancer prevention intervention in general practice.
Wolf 2003The study focused on calculating human in vivo immune protection factors of 2 sunscreen preparations in a model of ultraviolet-induced local suppression of the induction of contact hypersensitivity to 2,4-dinitrochlorobenzene.

Ancillary