A review of sunscreen in the prevention of skin cancer

Introduction

Skin cancer is the most commonly occurring malignancy in the United States, with over 400,00 cases diagnosed annually. ¹ Basal-and squamous-cell carcinomas primarily manifest themselves in the basal and squamous layers of the skin, respectively, and are considered relatively indolent.^2–4 Conversely, melanoma originates in the melanocytes and albeit less common than non-melanoma skin cancers, the neoplasm accounted for 7990 deaths in the United States during 2024.^1,5

Skin cancer is primarily attributed to ultraviolet A (UVA) or B (UVB) radiation, for which the varying UV subtypes confer specific, deleterious outcomes. ⁶ UVA light primarily comprises the UV rays that damage the skin, thereby harming the inherent collagen and elastin, engendering the manifestation of wrinkles, and accelerating the aging process.^6–8 Alternatively, UVB rays encompass nearly 5% of the UV radiation, but they are more intense and induce DNA impairment, the precipitant of most skin cancers.^9–11 UVC rays, the most pernicious of the UV variants, are absorbed by the ozone layer and not a predominant risk factor for skin cancer, cases ascribed to persistent exposure to UV bulbs and suntanning beds excepted.^10–12

Despite the assertion that sunscreen reduces the incidence of skin cancer, the evidence is controversial. ¹³ Hence, the purpose of this review is to edify clinicians regarding the safety and efficacy of chemical and physical sunscreen in the prevention of skin cancer.

Search strategy and data resources

We conducted an extensive PubMed search primarily comprising select observational, case-control studies, cohort studies, review articles and randomized controlled trials (RCTs) from approximately 2003–2024, with specific terms that included sunscreen, skin cancer prevention, and sunscreen-related side effects. Prima facie, our review incorporates aspects of systematic reviews and meta-analyses but the scope was ultimately narrowed to address practical and concisely-applied issues regarding sunscreen use and the prevention of skin cancers.

Sunscreen mechanism of action

UV light filters are active ingredients in sunscreen products that afford a protective effect by absorbing, reflecting, and/or scattering UV radiation.^14,15 A shorter wavelength (i.e. UVB) corresponds with an increased proclivity for dermal injury. For example, sunscreen filters prevent UV A1 wavelengths (UVA1; 340–400 nm), UV A2 wavelengths (UVA2; 320–340 nm) and UVB wavelengths (290 to 320 nm).^7,15

Chemical filter sunscreens (e.g. oxybenzone, avobenzone) absorb high-intensity UV rays and engender catalysis, for which a lower-energy wavelength is ultimately actuated. ⁷ Alternatively, physical sunscreens (e.g. titanium dioxide, zinc oxide) primarily reflect or refract UV rays, thereby diminishing their effect.^15–17 Physical sunscreen confers immediate protection, whereas chemical sunscreen requires a period of absorption time prior to becoming effective; ultimately, the efficacy associated with the two sunscreen subtypes reflects the inherent sun protection factor. ¹⁸

Sun protection factor

Fundamentally, sunscreen efficacy or protection is measured via the sun protection factor (SPF; dose of UV radiation without sunscreen/ dose of UV radiation with sunscreen) insofar as the degree that solar energy (i.e. UV radiation) can produce a sunburn. Accordingly, the effectiveness of sunscreen corresponds to the higher SPF value (i.e. SPF 10 permits 10% of the photons to reach the skin, whereas SPF 20 product reduces the photon skin penetration to 5%). ¹⁹ Currently, the American Academy of Dermatology recommends regular sunscreen use with a SPF of 30 or higher for people of all skin types. ²⁰

Sunscreen should be applied uniformly, the amount of which should encompass 2 mg/m² to the various areas of interest (e.g. head, neck, face). ²¹ Nevertheless, the propensity for developing a sunburn is increased by longer duration and timing of sun exposure and thus, reapplication of sunscreen is indicated under these circumstances. For example, at midday, the sun exposure intensifies, in contrast to the early morning or late evening, wherein the risk from UV rays is attenuated. ²² Geographically higher altitudes are further associated with increased solar intensity, and in cases of an overcast sky, the exposure is relatively mitigated.

Sunscreen efficacy in melanoma and non-melanoma skin cancers

Observational, case-control and cohort studies have reported a reduced incidence of skin cancer associated with the use of sunscreen.^23,24 In a RCT, van der Pols et al. ²⁵ reported on the effect of sunscreen (broad-spectrum SPF 16) in preventing basal-cell and squamous-cell carcinoma with 1621 subjects who either used daily or discretionary sunscreen (Table 1). After 8 years of follow-up, the incidence of squamous-cell carcinoma was 35% lower for the regular users (hazard ratio (HR), 0.65; 95% CI (0.43–0.98); there was also a 25% reduction in the incidence of basal-cell carcinoma for routine users, although the difference was non-significant compared to the discretionary users (HR, 0.75; 95% confidence interval (CI), 0.49–1.14).

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Table 1.

Sunscreen and cancer-associated benefits.

Patient Population	Sunscreen Use	Benefits	References
Basal-cell and squamous-cell carcinoma	Discretionary or daily use	35% reduction in incidence of squamous cell carcinoma and 25% reduction in incidence of basal cell carcinoma	25
basal-cell and squamous-cell carcinoma	Sunscreen with or without betacarotene or placebo	The incidence of squamous-cell carcinoma was significantly lower, but not for basal-cell carcinoma (HR, 0.61 (0.46–0.81)	26
melanoma	ever- vs. never-use of sunscreen	ever- vs. never-use of sunscreen was inversely associated with melanoma (OR) = 0.57, 95% CI: 0.37 to 0.87, <0.001).	28
melanoma	daily vs periodic sunscreen use	daily sunscreen users had a reduced risk for invasive melanoma (HR, 0.27; 95% CI, 0.08 to 0.97).	30

Similarly, in another RCT evaluating the impact of daily sunscreen (SPF 15) use with or without betacarotene supplementation (30 mg/day) or placebo alone (no daily sunscreen) on the prevention of basal-cell and squamous-cell carcinomas of the skin, Green et al. ²⁶ did not identify a significantly decreased number of basal-cell carcinoma by sunscreen use or by betacarotene ²⁶ ; although, the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group compared to the no daily sunscreen group (HR, 0.61 (0.46–0.81). Perhaps, sunscreen had a more discernible impact in forestalling squamous-cell cancer because basal-cell carcinoma is a relatively more indolent subtype and the prophylactic benefits from sunscreen were not borne out the during study's duration. ²⁷

In a random-effects meta-analysis, Rueegg et al. examined 28 primarily case-controlled studies that incorporated 21,069 melanoma patients. ²⁸ They reported that ever- vs. never-use of sunscreen was inversely associated with melanoma (adjusted odds ratio (OR) = 0.57; 95% CI, 0.37–0.87; p value < 0.001). While the authors attributed an overall limited association between sunscreen use and melanoma to discrepancies in study-design heterogeneity among the observational studies, they acknowledged a beneficial effect from sunscreen use coinciding with the RCT data. Moreover, Dennis et al. compared ever-use and never-users of sunscreen and the attendant risk of melanoma in a pooled analysis ²⁹ ; they also recounted a decreased risk of melanoma in the ever-use group (OR = 0.8, 95% CI 0.6–1.0).

Green et al. documented a reduced risk of melanoma (HR, 0.50; p value = 0.051) in a RCT comparing the effect of daily sunscreen use vs periodic sunscreen use. ³⁰ After 15 years of surveillance, daily sunscreen users exhibited a further reduction in the risk for invasive melanoma (HR, 0.27; 95% CI, 0.08 to 0.97). Nonetheless, the study results were limited considering only 75% of the daily users were consistent sunscreen users, not to mention the periodic sunscreen use cohort disproportionately encompassed both non- and twice-weekly users.

Sunscreen safety

When evaluating the benefits derived from sunscreen, one should also concurrently scrutinize the side effect profile. ³¹ Commonly documented reactions attributed to sunscreen include dermal irritation and rash (Table 2), both of which are observed in approximately 1% of cases.^31–34 The side effects from sunscreen are primarily attributed to the organic UV filters (e.g. avobenzone and oxybenzone), which constitute specific lipophilic qualities and molecular size, characteristics that facilitate dermal permeation.^15,31,34,35

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Table 2.

Side effects from sunscreen.

Sunscreen Type	Side Effects	References
avobenzone and oxybenzone	rash, swelling, and pruritis	31–35
Benzophenone-3	Potentially linked to breast cancer	40

Patients with dermal conditions (e.g. psoriasis, eczema) may be susceptible to photoallergic contact dermatitis in response to wearing sunscreen and consider the use of steroids to address this condition.^36,37 Since benzophenones and dibenzoylmethanes are frequently implicated in photoallergic contact dermatitis, UV filters containing these ingredients should be avoided if this condition manifests itself. ³⁷ Since the potential for side effects (e.g. dermal irritation) from sunscreen is an issue for select sunscreen users, one may also elect to use hats, wear protective clothing, spend time in the shade and avoid the sun at peak hours. ³⁸

The use of sunscreen may also be associated with long-term adverse effects on thyroid functioning, testosterone levels, and kidney function, although a precise association has not been elucidated. ³⁹ Moreover, benzophenone-3 is another chemical filter that is easily absorbed by the skin and reportedly linked to breast cancer, albeit the data are equivocal.^40,41 Alternatively, zinc oxide and titanium dioxide are not systemically absorbed and do not purportedly confer an iatrogenic effect. ¹⁶

Discussion

The routine use of sunscreen is essential to averting skin cancer, especially melanoma, a malignancy that contributes to nearly 8000 deaths annually in the United States. ¹ This recommendation is substantiated by RCTs and case-control data, which have indicated a reduced incidence and risk for both squamous-cell carcinoma and melanoma in routine sunscreen users.^25,26,28,30 Nevertheless, case–control studies have documented inconsistent results vis-a’-vis reductions in the risk of melanoma,^29,42 some of which may be ascribed to study design, variation in sun exposure and sunscreen practice (i.e. inconsistent adherence) among the included subjects.^43,44 Moreover, the specific benefits derived from ever-use and periodic use of sunscreen are unclear insofar as the results from many studies are confounded by potential recall bias and limitations from survey questionnaires, not to mention varying surveillance data.^26,29

In the current study, we would also acknowledge that study heterogeneity and selection criteria may have limited our findings.

Conclusion

Skin cancer remains a major concern in the United States. Fortunately, strategies such as proper use of broad-spectrum sunscreen in combination with refraining from indoor tanning and limiting sun exposure are indicated to mitigate the risk of skin cancer. Additionally, organic sunscreen ingredients (e.g. Bis (diethylamino hydroxybenzoyl benzoyl) piperazine) may further confer improved protection when incorporated with traditional sunscreen. ⁴⁵

Ultimately, the effectiveness of sunscreen is contingent upon the frequency of use, duration, timing, and location of sun exposure, but clinical research gaps remain in establishing precise guidelines. Hence, clinicians should ponder these implications when counseling their patients on the type of sunscreen and frequency of use, ⁴⁶ especially black patients who reportedly are more susceptible to being diagnosed with advanced-stage melanoma compared to non-Hispanic white patients. ⁴⁷ Currently, RCTs are evaluating the impact of UV ray exposure, sunscreen protection and skin cancer detection in adolescents, ⁴⁸ the results of which may similarly apply to the general population.