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kin cancer is one of the most common malignan- epidemiological studies have yielded conflicting informa-
cies in the world and is an important public health tion about the relationship between risk of skin cancer
concern. The incidence of both melanoma and non- and use of sunscreen. Some studies [7-11] show that reg-
melanoma skin cancer has increased over the past decades ular sunscreen use could significantly reduce the risk of
[1, 2]. Globally, around 350,000 melanomas and 13 mil- skin cancer while other studies [12-20] report an increased
lion non-melanoma skin cancers occur each year leading risk of skin cancer related to sunscreen application. Four
to approximately 81,000 deaths [3,4]. In the Unites States, previous systematic reviews have assessed the associa-
the average annual number of adults treated for skin cancer tion between risk of melanoma and sunscreen use [21-24].
increased from 3.4 million in 2002-2006 to 4.9 million in Despite the differences in the number of included studies
2007-2011 [5]. During the same period, the average annual and some inconsistencies in data extraction, all four reviews
total cost for skin cancer increased from $3.6 billion to $8.1 show no significant overall association between risk of
billion. melanoma and use of sunscreen. However, non-melanoma
Exposure to ultraviolet (UV) radiation from sunlight is skin cancer, which represents more than 90% of all cases
considered a major modifiable environmental risk factor of skin cancer [4, 25], has not been addressed in previous
doi:10.1684/ejd.2018.3251
To cite this article: Silva Esd, Tavares R, Paulitsch Fds, Zhang L. Use of sunscreen and risk of melanoma and non-melanoma skin cancer: a systematic review and
meta-analysis. Eur J Dermatol 2018; 28(2): 186-201 doi:10.1684/ejd.2018.3251
performed cumulative meta-analysis to track how the body of the first author, year of publication, country and set-
of evidence has shifted over time. We also explored the ting of study and study sponsor; (2) Participants: age,
possible reasons for conflicting results across studies. We gender, inclusion and exclusion criteria, type of sampling
hypothesized that the strength and direction of the associ- and sample size; (3) Methods: study design, classifica-
ation between risk of skin cancer and sunscreen use may tion of exposure (sunscreen use), definition of outcomes
have changed significantly over the last three decades. (melanoma, basal cell carcinoma, and squamous cell car-
cinoma), instruments for data collection or data source,
potential confounders, and statistical analysis methods; and
(4) Results: for case-control studies: the number of cases,
Methods number of controls, number of exposed and non-exposed in
each group, crude and/or adjusted odds ratio (OR), and 95%
We followed the PRISMA (Preferred Reporting Items for confidence intervals (95% CI); for cross-sectional studies
Systematic Reviews and Meta-Analyses) guidelines [26] and cohort studies: the total number of participants, number
to conduct and report this review. The review protocol was of participants in exposed and non-exposed groups, num-
completed in 2015 and approved by a panel of experts, ber of persons with skin cancer in each group, crude and/or
consisting of two epidemiologists and one dermatologist. adjusted relative risk (RR) and 95% CI; for randomized
controlled trials: the number of participants in the interven-
tion and control groups, number of persons with skin cancer
Databases and search strategy in each group, RR, and 95% CI.
We searched PubMed, Google Scholar, and the Virtual We obtained the altitude (meters from sea level) and lati-
Health Library of the Latin American and Caribbean Center tude (degrees from the equator) of the study setting from
on Health Sciences Information (BIREME), which con- MyGeoPosition.com (http://mygeoposition.com). For mul-
tains Medline, LILACS, and more than 20 other databases ticentre studies, we used only geographical data from the
(http://bvsalud.org). All databases were initially searched coordinating centre.
from inception until November 30, 2015, with no language
restrictions. We updated the literature search on May 17,
2017. We used the following search terms for PubMed: Study quality assessment
(sunscreen OR sunblock OR “suntan lotion” OR “sunburn Two review authors independently assessed the quality of
cream” OR “sun cream” OR “block out” OR “solar pro- each study according to the criteria of the National Institutes
tector”) AND (“skin cancer” OR “skin tumor” OR “skin of Health (NIH) [27, 28]. The study quality was rated good,
neoplasm” OR melanoma OR “basal cell carcinoma” OR fair or poor, mainly based on the potential risk of selection
“squamous cell carcinoma”). We used “human species” as a bias, information bias, measurement bias, and confounding
search limit. For Google Scholar and BIREME, we used the factors.
following search strategy: sunscreen AND (“skin cancer”
OR melanoma OR “basal cell carcinoma” OR “squamous
cell carcinoma”). Different types of articles (case-control,
cross-sectional, cohort and controlled trial) were used as Statistical analysis
search limits on BIREME. Given the excessive number of We used the random-effects model for conventional and
records on Google Scholar, we searched only the titles of cumulative meta-analysis. The association between risk of
articles. We examined the reference lists of retrieved pri- skin cancer and sunscreen use was assessed by pooled OR
mary studies and systematic reviews to identify additional and 95% CI. When RR and 95% CI were used as the mea-
relevant studies. sures of association in the primary studies, we estimated
the OR and 95% CI by reconstructing a 2 × 2 contingency
Selection of studies table. If there were no available data for reconstruction, we
used the RR and 95% CI for the meta-analysis given that
To be included in this review, studies had to meet all of the the RR is close to the OR when the outcome is a relatively
following criteria: (1) Study design: observational studies uncommon event such as skin cancer. For the overall meta-
(case-control, cross-sectional or cohort) or controlled tri- analysis, we combined two or more categories of sunscreen
als; (2) Participants: adults, children or both; (3) Exposure use as a single category “sunscreen use”, compared to the
of interest: use of sunscreen classified into two or more reference category “no or rare use.
categories according to frequency of use; (4) Outcomes: We assessed the heterogeneity of results between studies
any type of skin cancer (melanoma, basal cell carcinoma or using I2 statistic that ranges from 0% to 100%, with values
squamous cell carcinoma). of 25%, 50%, and 75% corresponding to low, moderate,
Three review authors independently assessed the titles and and high heterogeneity, respectively [29].
abstracts of all citations identified by the searches. The To investigate the possible sources of heterogeneity, we
definitive inclusion of studies was made after reviewing conducted a prior subgroup analyses based on type of skin
the full-text articles. cancer, study design, sampling method, control for con-
founding factors, age group, date of data collection, latitude
of study location, and comparison of the frequency of sun-
Data extraction screen use. We also conducted a post-hoc subgroup analysis
Two review authors independently extracted the data from according to study quality. We conducted meta-regression
each study using a standardized data extraction form. We to assess the influence of geographical factors (altitude and
extracted the following data: (1) Study characteristics: name latitude) of study location on the sunscreen effects.
Excluded on basis of
titles and abstracts
(n = 1619)
Figure 1. PRISMA flow diagram of study selection showing the process of identification, screening, assessment for eligibility,
and inclusion of studies.
We assessed publication bias using a funnel plot and The subgroup “non-melanoma skin cancer” included five
Egger’s test. All meta-analyses were performed using Stata studies [11, 30, 32, 37, 40] involving 110,914 participants
version 11.0 (Stata-Corp, College Station, TX, USA). (857 cases). Four studies showed no significant associa-
tion, but one study revealed a protective effect of sunscreen
against squamous cell carcinoma. The pooled results of
five studies showed no significant association between
Results the risk of non-melanoma skin cancer and sunscreen use
(OR = 0.99; 95% CI: 0.62-1.57; I2 = 87.3%). In the sub-
The search strategy identified 1,736 records from PubMed, group analysis according to latitude of study location, the
BIREME and Google Scholar, and 29 articles met the pooled OR was 1.54 (95% CI: 1.23-1.92, I2 = 90%) for
inclusion criteria. One additional paper was found through 10 studies [13, 14, 16, 18-20, 30, 36, 39, 43] (3,933 cases)
reviewing the reference lists of systematic reviews. Thus, a conducted at latitude ≥450 from the equator, whereas it
total of 30 papers [7-20, 30-45] reporting 29 studies were was 0.89 (95% CI: 0.71-1.10, I2 = 79%) for 19 studies
included in the review (figure 1). Table 1 summarizes the [7-12, 15, 17, 31-35, 37, 38, 40-42, 44, 45] (6,737 cases)
characteristics of the 29 included studies, of which 28 were conducted at latitude <450 (p = 0.001 for subgroup differ-
observational studies (25 case-control, two cohort, and one ence). There were no significant differences in the effect
cross-sectional) and one was a randomized controlled trial. size of sunscreen between other subgroups. The substantial
A total of 313,717 participants (10,670 cases of skin cancer) heterogeneity remained in all subgroups.
were recruited from 13 countries across three continents Figure 2 shows the results of cumulative meta-analysis.
(11 studies from America, 12 studies from Europe, and six A relatively strong positive association between risk of
studies from Asia-Pacific). melanoma and sunscreen use (cumulative OR = 2.35;
The overall meta-analysis including all 29 studies showed 95% CI: 1.66-3.33) was observed when the analysis
no significant association between the risk of skin can- included only three studies [12,15,16] conducted before the
cer and sunscreen use (OR = 1.08; 95% CI: 0.91-1.28; 1980s, involving a total of 1,364 participants (619 cases of
I2 = 89.4%). The pooled OR was 1.11 (95% CI: 0.93-1.33; melanoma). The strength of the association between risk
I2 = 90.2%) for 28 observational studies. of skin cancer and sunscreen use has constantly reduced
Table 2 shows the results of subgroup analyses. The since the early 1980s, but the association remained sta-
subgroup “melanoma” included 25 studies [7-10, 12- tistically significant until the analysis included 13 studies
20, 31, 33-36, 38, 39, 41-45] involving a total of 203,948 [8, 10, 12-16, 18, 19, 30-33] with data collection com-
participants (9,813 cases). Ten studies showed an increased pleted until the early 1990s (119,756 participants, 4,841
risk of melanoma related to sunscreen use while five stud- cases of skin cancer; cumulative OR = 1.25; 95% CI: 1.0-
ies reported a protective effect of sunscreen use against 1.56; p = 0.05). From then on, the association was no longer
melanoma. The pooled results of 25 studies revealed that statistically significant, and the cumulative point estimate
the risk of melanoma was not significantly associated with of OR has continued to move towards the null hypothe-
sunscreen use (OR = 1.10; 95% CI: 0.92-1.33; I2 = 89.4%). sis value (OR = 1). The cumulative OR and 95% CI have
Source, location Type of cancer Study design and Cases/sample Overall Association between Confounding Study
sampling size (n) association skin cancer and factors controlled quality
Age range (yr) between skin frequency of sunscreen rating
cancer and use (OR/RR*/HR**,
“sunscreen use” 95% CI)
(OR, 95% CI)
Autier et al., Melanoma Hospital-based 418/856 1.50, 1.09-2.06 Never: 1.0 Age, sex, hair Fair
189
Table 1. (Continued)
190
Source, location Type of cancer Study design and Cases/sample Overall Association Confounding Study quality
sampling size (n) association between skin factors controlled rating
Age range (yr) between skin cancer and
cancer and frequency of
“sunscreen use” sunscreen use
(OR, 95% CI) (OR/RR*/HR**,
95% CI)
Espinosa Arranz Melanoma Hospital-based 116/351 0.47, 0.34-0.71 Use of sunscreen Age, skin type, Fair
et al., 1999 [9], case-control 21-87 (with OR Yes: 1.0 naevi count
Madrid, Spain converted to “no No: 2.1, 1.4-2.9
sunscreen use”)
Fargnoli et al., Melanoma Hospital-based 100/300 0.92, 0.55-1.56 Use of sunscreen Age, gender, Fair
2004 [45], case-control 18-74 No: 1.0 ethnicity, hair
L’Aquila, Italy Yes: 0.92, colour, eye
0.55-1.56 colour, skin type,
number of
melanocytic
naevi
Ghiasvand et al., Melanoma Population-based 543/109,886 1.25, 0.97-1.6 (2 Sunscreen use in Age, hair colour, Good
2016 [43], Oslo, cohort 40-75 x 2 contingency high/low freckling,
Norway table latitudes reported ambient UV
reconstructed; at both baseline radiation of
consistently SPF and follow-up, residence,
<15, SPF ≥15 HR, 95% CI cumulative
on at least one SPF: <15/SPF < number of weeks
occasion, 15 (consistently sunbathing,
none/SPF <15-, SPF<15: 1.0 cumulative
SPF <15/none; SPF ≥15 on at number of
combined as least one sunburns, indoor
“sunscreen use”) occasion: 0.69, tanning
0.55-0.88
None/SPF <15,
SPF <15/none:
0.92, 0.75-1.14
None/none: 0.63,
0.46- 0.86
Gon et al., 2011 Basal cell Hospital-based 127/407 1.69, 0.82-3.49 Sunscreen use Age, sex, eye Fair
[40], Londrina, carcinoma case-control 18-80 (with OR, Frequently: 1.0 colour, hair
Brazil converted to Never or rarely: colour, skin type,
“never”) 0.59, 0.29-1.21 family history of
skin cancer,
presence of
actinic keratosis
Graham et al., Melanoma Hospital-based 218/419 2.20, 1.2-4.1 Sun screening No Poor
1985 [15], New case-control All lotion
York, United No use: 1.0
States Use: 2.20,
1.20-4.10
Source, location Type of cancer Study design and Cases/sample Overall Association Confounding Study quality
sampling size (n) association between skin factors controlled rating
Age range (yr) between skin cancer and
cancer and frequency of
“sunscreen use” sunscreen use
(OR, 95% CI) (OR/RR*/HR**,
191
192
Table 1. (Continued)
Source, location Type of cancer Study design and Cases/sample Overall Association Confounding Study quality
sampling size (n) association between skin factors controlled rating
Age range (yr) between skin cancer and
cancer and frequency of
“sunscreen use” sunscreen use
(OR, 95% CI) (OR/RR*/HR**,
95% CI)
Holly et al., 1995 Melanoma Population-based 452/1,382 0.47, 0.36-0.59 Sunscreen use Age, ethnicity, Fair
[10], San case-control 25-59 (3 groups Cutaneous hair colour, skin
Francisco, combined; with malignant colour, history of
United States OR, converted to melanoma skin cancer,
“never”) Almost always: sunburns up to 12
1.0 yr, skin reaction
Sometimes: 1.50, to sun, number of
1.10-2.20 large nevi
Never: 2.10,
1.50-3.0
Superficial
spreading
melanoma
Almost always:
1.0
Sometimes: 1.70,
1.20-2.60
Never: 2.20,
1.50-3.2
Nodular
melanoma
Almost always:
1.0
Sometimes: 0.8,
0.33-1.90
Never: 2.0,
1.0-4.0
Holman et Melanoma Population-based 511/1,022 1.10, 0.83-1.45 Duration of use Age, sex, Fair
al., 1986 [31], case-control <80 (2 groups < 10 yr residence, hair
Perth, Australia combined as Never: 1.0 colour, ethnicity,
“sunscreen use”) Sunscreen use: skin reaction to
1.06, 0.71-1.57 sunlight, age at
Duration of use arrival in
≥ 10 yr Australia
Never: 1.0
Sunscreen use:
1.15, 0.78-1.68
Source, location Type of cancer Study design and Cases/sample Overall Association Confounding Study quality
sampling size (n) association between skin factors controlled rating
Age range (yr) between skin cancer and
cancer and frequency of
“sunscreen use” sunscreen use
(OR, 95% CI) (OR/RR*/HR**,
95% CI)
Klepp et Melanoma Hospital-based 77/206 2.26, 1.25-4.09 Sun lotion/oil, No Poor
al., 1979 [16], case-control ≥ 20 (2 x 2 RR
193
194
Table 1. (Continued)
Source, location Type of cancer Study design and Cases/sample Overall Association Confounding Study quality
sampling size (n) association between skin factors controlled rating
Age range (yr) between skin cancer and
cancer and frequency of
“sunscreen use” sunscreen use
(OR, 95% CI) (OR/RR*/HR**,
95% CI)
Luiz et al., 2012 Melanoma Hospital-based 202/424 0.32, 0.11-0.97 Lifetime Age, sex, Fair
[42], São Paulo, case-control 15-79 (with OR, sunscreen use educational level,
Brazil converted to Often: 1.0 ethnicity, eye
“never/almost Occasionally: colour, sunburn
never”) 3.53, 0.59-21.21 at 15-19 yr,
Never/almost lifetime severe
never: 3.08, sunburn
1.03-9.22
Naldi et al., 2000 Melanoma Hospital-based 542/1,080 0.89, 0.69-1.15 Never: 1.0 Age, sex, Fair
[36], Milan, Italy case-control ? (Sometimes, Sometimes: 0.97, geographic area,
often, combined 0.69-1.35 education, skin,
as “sunscreen Often: 0.80, eye, and hair
use”) 0.54-1.17 colour, number
of freckles, large
nevi, history of
sunburns,
tanning pattern,
sunny holidays
Olsen et al., 2015 Melanoma Population-based 1433/40,172 1.56, 1.41-1.73 Prevalence Age, sex, Fair
[17], cross-sectional 40-69 (2 x 2 proportion ratio educational level
Queensland, contingency table No regular
Australia reconstructed) sunscreen use:
1.0
Regular
sunscreen use:
1.77, 1.59-1.97
Osterlind et Melanoma Population-based 474/1,400 1.22, 1.01-1.47 RR, 95% CI Constitutional Fair
al., 1988 [18], case-control 20-79 (Occasional/always Never: 1.0 factors, sex, age
Copenhagen, used, combined Occasional use:
Denmark as “sunscreen 1.30, 0.99 = 1.60
use”) Always: 1.10,
0.8-1.50
Source, location Type of cancer Study design and Cases/sample Overall Association Confounding Study quality
sampling size (n) association between skin factors controlled rating
Age range (yr) between skin cancer and
cancer and frequency of
“sunscreen use” sunscreen use
195
Table 1. (Continued)
196
Source, location Type of cancer Study design and Cases/sample Overall Association Confounding Study quality
sampling size (n) association between skin factors controlled rating
Age range (yr) between skin cancer and
cancer and frequency of
“sunscreen use” sunscreen use
(OR, 95% CI) (OR/RR*/HR**,
95% CI)
Whiteman et Melanoma Population-based 52/208 1.21, 0,69-2.14 Sunscreen use Sex, school, Fair
al., 1997 [34], case-control ≤15 (Sunscreen on on holiday grade, tanning
Queensland, holiday and at Never/rarely: 1.0 ability, freckles,
Australia school; Sometimes: 1.50, number of nevi
sometimes, 0.30-8.20
often, always; Often: 1.50,
combined as 0.30-7.4
“sunscreen use”) Always: 2.20,
0.40-11.6
Sunscreen use at
school
Never/rarely: 1.0
Sometimes: 0.80,
0.30-2.10
Often: 1.60,
0.50-5.50
Always 0.70,
0.10-6.0
Wolf et al., 1998 Melanoma Hospital-based 193/512 3.47, 1.81-6.64 Never: 1.0 Age, sex, hair Fair
[20], Graz, case-control 15-89 (Often vs. never) Rarely: 1.30, and skin colour,
Austria 0.70-2.39 skin phototype,
Often: 3.47, sun sensitivity,
1.81-6.64 sunbathing,
sunburns
Youl et al., 2002 Melanoma Population-based 201/406 0.97, 0.71-1.34 Lifetime Age, sex, Fair
[35], case-control 15-19 (2 x 2 sunscreen use at residency
Queensland, contingency table home
Australia reconstructed; Often/always: 1.0
sunscreen use at Sometimes: 0.90,
home and on 0.50-1.70
holiday; Never/rarely:
often/always, 0.90, 0.50-1.70
sometimes; Lifetime
combined as sunscreen use
“sunscreen use”) on holidays
Often/always: 1.0
Sometimes: 1.30,
0.80-2.00
Never/rarely: 1.0,
0.50-1.80
* RR: relative risk (risk ratio, rate ratio, relative risk); **HR: hazard ratio; SPF: sun protection factor.
remained almost unchanged since the early 2000s, even The funnel plot and Egger’s test did not reveal a significant
though seven studies [11, 17, 40-43, 45] involving a total publication bias (figure 3).
of 187,747 participants (3,738 cases of skin cancer) were
added to the analysis.
The meta-regression analysis showed an inverse relation-
ship between the OR (log scale) and the altitude of study Discussion
setting (coefficient of -0.0004; p = 0.02). However, the
results were not statistically significant after adjusting for This systematic review and meta-analysis of 28 obser-
covariates (p = 0.69). The meta-regression analysis revealed vational studies and one community-based randomized
a significant positive association between the OR (log trial, with a total of 313,717 participants (10,670 cases),
scale) and the latitude of study setting (coefficient of 0.02; showed no significant overall association between the risk
p = 0.003), i.e. the higher the absolute latitude from the of melanoma and non-melanoma skin cancers and use of
equator, the greater the odds ratio, and the less the pro- sunscreen. The geographical latitude seemed to influence
tective effect of sunscreen against skin cancer, or even the the effects of sunscreen, that is, the higher the latitude
higher the risk of skin cancer associated with sunscreen use. where people live, the less the protective effect of sunscreen
The results remained statistically significant after adjusting against skin cancer.
for altitude, type of cancer, study design, sampling method, The cumulative evidence before the 1980s revealed a rel-
control of confounding factors (skin type/colour and/or hair atively strong positive association between the risk of
colour), and date of data collection (coefficient of 0.023; melanoma and sunscreen use. However, the strength of the
p = 0.01). association between risk of skin cancer and sunscreen use
.1 1 5
Favours sunscreen use Favours no sunscreen use
Figure 2. Cumulative meta-analysis of the association between skin cancer and sunscreen use. The solid squares represent point
estimates of cumulative odds ratio and the horizontal lines represent 95% CIs.
has constantly reduced since the early 1980s, and the asso- the growing public awareness of the risk of excessive sun
ciation was no longer statistically significant from the early exposure. These results may alleviate public concern about
1990s. Several hypotheses have been proposed to explain the increased risk of skin cancer related to sunscreen use, as
the positive association between risk of skin cancer, espe- reported by earlier epidemiological studies. However, the
cially melanoma, and use of sunscreen, as shown by earlier expected protective benefits of sunscreen against skin can-
observational studies, including compensation hypothesis, cer were not revealed by the cumulative meta-analysis, even
inconsistent use, vitamin D deficiency, and lack of control though seven new studies conducted in the 2000s, involv-
for confounding factors [46-49]. The median Sun Protection ing a large number of participants and cases of skin cancer,
Factor (SPF) of commonly used sunscreens in the 1970s and were added to the analysis. This may raise the question as
1980s was 4-10 [48], and these sunscreens incorporated to whether the use of sunscreens really protects against skin
active UV filters, limited largely to the UVB waveband. cancer.
People who use low SPF/UVB sunscreens may stay longer A 4.5-year community-based randomized controlled trial
in the sun because of reduced risk of sunburn, and thus conducted at Nambour, Australia, has been widely cited
increase their exposure to UVA radiation which may lead to show the efficacy of daily use of a broad-spectrum
to an increased risk of carcinogenesis. SPF15+ sunscreen in protecting against skin cancers in
The constant shift of the cumulative point estimate of the adults [37, 38, 50]. However, caution should be taken when
association between skin cancer and sunscreen use towards extrapolating the results of this trial to the general popula-
the null hypothesis value through the 1990s may be partly tion. This trial was conducted in the low-latitude township
explained by the improved efficacy of sunscreens in protect- of Nambour, situated at 26◦ south latitude, where cumula-
ing against solar UV radiation, particularly UVA rays, and tive sun exposure may affect the risk of skin cancer. The
-1 -.5 0 .5 1 1.5
log odds ratio (OR)
Figure 3. Funnel plot with pseudo 95% confidence limits, with log odds ratio (OR) against its standard error. The circles represent
risk estimates for each study. The vertical line represents the pooled effect estimate expressed as a log OR. Dashed lines represent
pseudo-95% confidence limits. The Egger test (p = 0.53) suggests no small-study effects.
practicality and the cost of daily application of sunscreen dependence of the effect of sunscreen on the risk of skin can-
should also be considered. cer remains after adjusting for several covariates, including
While randomized trials assess the efficacy of an interven- skin type and hair colour. We believe that the influence of
tion under “ideal” circumstances, epidemiological studies the latitude on the effect of sunscreen could be mediated
can provide valid insights into the effectiveness of the inter- by UV radiation levels. It has been reported that, within
vention in the “real” world. Why have most epidemiological some countries, the incidence rates of melanoma and non-
studies, even recently conducted ones, not demonstrated melanoma skin cancers increase with decreasing latitude,
the expected effects of sunscreens in protecting against i.e. higher UV radiation levels [55-58]. It seems reasonable
skin cancer in the general population? The inappropriate that regular sunscreen use would have a greater protective
application of sunscreen has been postulated as the major effect for persons at higher risk of skin cancer because they
cause for the lack of protective benefits of sunscreen, even live at lower latitudes and are exposed to higher levels of
broad-spectrum ones [48, 51, 52]. People usually do not UV radiation. In contrast, for people who live at higher
apply enough sunscreen to achieve the claimed SPF, and latitudes where UV radiation is weaker and less constant,
the actual SPF received may be only 20% to 50% of the regular sunscreen use may provide less protection against
labelled SPF marked on the bottle. Additionally, reappli- skin cancer, or even increase the risk of carcinogenesis.
cation is generally considered a key element for obtaining While the current evidence suggests no increased risk of
the most effective protection from sunscreen [52, 53], but skin cancer related to sunscreen, this systematic review and
many people do not regularly reapply sunscreen [54]. Vita- meta-analysis does not confirm the expected protective ben-
min D deficiency and confounding factors may also have efits of sunscreen use against skin cancer in the general
contributed to the lack of protective effects of sunscreen population. These results support a wide range of strategies
use, as shown by epidemiological studies. besides sunscreen use for primary prevention of skin can-
The meta-regression analysis revealed an inverse relation- cer. These strategies include wearing hats and protective
ship between protective effect of sunscreen against skin clothing, seeking shade, limiting exposure during peak sun
cancer and latitude of study location. Additionally, the hours, and avoiding tanning beds and other artificial UV
subgroup analysis showed that use of sunscreens was asso- radiation sources [59-61].
ciated with a non-significant decreased risk of skin cancer at Meta-analyses of observational studies are generally prone
latitude <45◦ from the equator, whereas use of sunscreens to heterogeneity and bias [62, 63]. In this study, there
could significantly increase the risk of skin cancer at latitude was substantial heterogeneity with regards to the over-
≥45◦ . The influence of latitude on the association between all meta-analysis and the heterogeneity remained high in
the risk of melanoma and sunscreen use has previously been subgroup analyses according to study design, study qual-
reported by Gorham et al. [23]. The authors hypothesized ity, sampling method, control for confounding factors, age
that the influence of latitude on the effect of sunscreen could group, frequency of sunscreen use, and date of data col-
be explained by differences in skin type, rather than geo- lection. As many of these factors could simultaneously
physical effects of ultraviolet radiation at higher latitudes. affect the study results, it is difficult to identify the inde-
However, the findings of the present systematic review do pendent contribution of each factor to the heterogeneity.
not totally support this hypothesis given that the latitudinal Moreover, other covariates may also influence the effects