Purpose of This PDQ Summary
Summary of Evidence

Nonmelanoma Skin Cancer         Squamous cell carcinoma         Basal cell carcinoma Cutaneous Melanoma

Significance
Evidence of Benefit
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Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about skin cancer prevention. This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board ¹.

Information about the following is included in this summary:

• Skin cancer incidence and mortality statistics and information about skin cancer risk factors.
• Interventions for skin cancer prevention.
• Benefits and harms of interventions to prevent skin cancer.

This summary is intended as a resource to inform clinicians and other health professionals about the currently available information on skin cancer prevention. The PDQ Screening and Prevention Editorial Board uses a formal evidence ranking system ² in reporting the evidence of benefit and potential harms associated with specific interventions. It does not provide formal guidelines or recommendations for making health care decisions. Information in this summary should not be used as a basis for reimbursement determinations.

This summary is also available in a patient version ³, which is written in less technical language.

Summary of Evidence

Note: Separate PDQ summaries on Skin Cancer Screening ⁴, Skin Cancer Treatment ⁵, and Levels of Evidence for Cancer Screening and Prevention Studies ² are also available.

There is inadequate evidence to determine whether the use of sunscreen reduces the incidence of squamous cell carcinoma of the skin.[1]

Description of the Evidence

• Study Design: One randomized controlled trial (RCT) with tumor incidence as the outcome and one RCT with actinic keratosis as the outcome. Other study designs give inconsistent results.
• Internal Validity: Poor.
• Consistency: Good.
• Magnitude of Effects on Health Outcomes: 39% point estimate reduction in tumor incidence (from one study).
• External Validity: Poor.

There is inadequate evidence to determine whether the use of sunscreen reduces the incidence of basal cell carcinoma of the skin.

Description of the Evidence

• Study Design: Evidence of association obtained from cohort studies.
• Internal Validity: Not applicable (N/A).
• Consistency: N/A.
• Magnitude of Effects on Health Outcomes: N/A.
• External Validity: N/A.

There is inadequate evidence to determine whether the avoidance of sunburns alters the incidence of cutaneous melanoma.

Description of the Evidence

• Study Design: Evidence of association only obtained from cohort or case-control studies.
• Internal Validity: Inadequate.
• Consistency: Poor.
• Magnitude of Effects on Health Outcomes: N/A.
• External Validity: N/A.

References

1. Green A, Williams G, Neale R, et al.: Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial. Lancet 354 (9180): 723-9, 1999.  [PUBMED Abstract]
   
   

Significance

Skin cancer is the most commonly occurring cancer in the United States and accounts for about 4% of all cancer deaths.[1] In 2008, it is estimated that 62,480 individuals in the United States will develop melanoma and approximately 8,420 are expected to die of it.[2]

There are three main types of skin cancer: basal cell carcinoma, squamous cell carcinoma (together with basal cell carcinoma referred to as nonmelanoma skin cancer), and melanoma. Basal cell carcinoma and squamous cell carcinoma are the most common forms of skin cancer but have substantially better prognoses than the less common but generally more aggressive melanoma.

The incidence of melanoma and nonmelanoma skin cancer appears to be increasing,[3,4] though melanoma incidence rates may have stabilized in the 1990s.[5] Epidemiologic evidence suggests that exposure to ultraviolet (UV) radiation and the sensitivity of an individual’s skin to UV radiation are risk factors for skin cancer, though the type of exposure (high-intensity and short-duration vs. chronic exposure) and pattern of exposure (continuous vs. intermittent) may differ among the three main types of skin cancer.[3,4,6]

The visible evidence of susceptibility to skin cancer (skin type and precancerous lesions) and of sun-induced skin damage (sunburn and solar keratoses) and the ability of an individual to modify sun exposure provide the basis for implementation of programs for the primary prevention of skin cancer.

References

1. American Cancer Society.: Cancer Facts and Figures 2006. Atlanta, Ga: American Cancer Society, 2006. Also available online. ⁶ Last accessed January 18, 2008. 
   
   
2. American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. ⁷ Last accessed October 1, 2008. 
   
   
3. Koh HK: Cutaneous melanoma. N Engl J Med 325 (3): 171-82, 1991.  [PUBMED Abstract]
   
   
4. Preston DS, Stern RS: Nonmelanoma cancers of the skin. N Engl J Med 327 (23): 1649-62, 1992.  [PUBMED Abstract]
   
   
5. Hall HI, Miller DR, Rogers JD, et al.: Update on the incidence and mortality from melanoma in the United States. J Am Acad Dermatol 40 (1): 35-42, 1999.  [PUBMED Abstract]
   
   
6. English DR, Armstrong BK, Kricker A, et al.: Case-control study of sun exposure and squamous cell carcinoma of the skin. Int J Cancer 77 (3): 347-53, 1998.  [PUBMED Abstract]
   
   

Evidence of Benefit

Most evidence about ultraviolet (UV) radiation exposure and the prevention of skin cancer comes from observational and analytic epidemiologic studies, not from experimental studies in humans. Such studies have consistently shown that increased cumulative sun exposure is a risk factor for nonmelanoma skin cancer.[1,2] Individuals whose skin tans poorly or burns easily after sun exposure are particularly susceptible.[1]

It is not known, however, if reduction of exposure to UV radiation through the use of sunscreens and/or protective clothing or through limitation of exposure time can reduce the incidence of nonmelanoma skin cancer in humans. One study has shown that regular sunscreen use can reduce the incidence of solar keratoses (precursors of squamous cell carcinoma) and increase remissions of existing lesions.[3] In Australia, 588 persons aged 40 years and older who attended a free skin cancer screening clinic and had one to 30 solar keratoses were enrolled in a randomized, controlled trial assessing the effect that the regular use of sunscreen (sun protection factor 17) could have on solar keratoses; 431 persons completed the study. Persons in the sunscreen group developed significantly fewer new lesions and had significantly more remissions of existing lesions than persons in the base-cream group. Furthermore, the amount of sunscreen used was related to development of new lesions and remission of existing lesions in the sunscreen group; no such effect was observed in the base-cream group. A different Australian randomized study, however, showed that after 4.5 years of follow-up, there was no significant difference in incidence of squamous cell carcinomas after regular sunscreen use. Although a post hoc subgroup analysis showed a reduction in the frequency of carcinomas on the sites of daily sunscreen application, the validity of that finding is questionable because of the possible effects of multiple testing.[4] An 8-year post-trial observational follow-up demonstrated statistically significant reductions in both the frequency and the overall incidence of squamous cell carcinomas in the regular sunscreen-use arm, but the reliability of these findings is uncertain given their occurrence outside of the controlled-trial environment.[5]

The relationship between UV radiation exposure and cutaneous melanoma is less clear. Rather than cumulative sun exposure, it is intermittent acute sun exposure leading to sunburn that seems to be more damaging;[6] such exposures in childhood or adolescence may be particularly important.[7] Results from a collaborative European case-control study and one animal study, however, suggest that sunscreens that protect against sunburn may not protect against UV radiation-associated cutaneous melanoma.[8,9] Nonmodifiable host factors, such as propensity to burn, a large number of benign melanocytic nevi, and atypical nevi may also increase the risk of developing cutaneous melanoma.[7] A meta-analysis of 18 studies that explored the association between melanoma risk and previous sunscreen use illustrates widely differing study qualities and suggests an absence of an association.[10]

Several groups have conducted studies to learn more about possible intervention strategies for reduction of exposure to UV radiation. The best approach seems to be education about the risks associated with sun exposure and sunburn and education about sun protection strategies.[11,12] Although long-term reminders regarding recommendations for sun protection may have had some impact on reducing sun exposure in individuals who had been treated for nonmelanoma skin cancer, it was the educational intervention at the time of treatment—a time when an individual may have recognized his or her susceptibility to skin cancer—that seemed to have had the greatest impact.[11] Even in this high-risk group, it was difficult for many individuals to maintain sun-protective behaviors. A community skin cancer screening study found that although regular use of sunscreens was not related to personal or family history of skin cancer, it was more common among persons who perceived themselves to be at moderate or high risk of developing melanoma.[12] Sun-protective strategies may include avoiding sun exposure at times of the day when the exposure is more intense and wearing clothing that protects skin from sun exposure.

Self-examination for skin pigmentary characteristics associated with melanoma (e.g., freckling status) may be a useful way to identify individuals at increased risk of developing melanoma.[13] Skin type (propensity to burn after sun exposure, tanning ability), alone or with other physical characteristics such as hair color, has been used as a measure of sun sensitivity in epidemiologic studies.[14]

The efficacy of chemopreventive agents (isotretinoin, beta carotene) has been assessed in individuals at increased risk of developing nonmelanoma skin cancer. High-dose isotretinoin was found to prevent new skin cancers in individuals with xeroderma pigmentosum.[15] A randomized clinical trial of long-term treatment with isotretinoin in individuals previously treated for basal cell carcinoma, however, showed that such treatment did not prevent the occurrence of new basal cell carcinomas but did produce side effects characteristic of isotretinoin treatment.[16,17] Randomized clinical trials of long-term treatment with beta carotene in individuals previously treated for nonmelanoma skin cancer showed no benefit in preventing the occurrence of new nonmelanoma skin cancers.[4,18] For all of these trials, it is not known whether treatment would benefit individuals at high-risk (sun-damaged skin) who have not yet developed skin cancer or if longer follow-up would show a long-term effect in the prevention of subsequent skin cancers.

A multicenter, double-blind, randomized, placebo-controlled trial of 1,312 patients with a history of basal cell or squamous cell skin cancer and a mean follow-up of 6.4 years showed that 200 µg selenium (in brewer’s yeast tablets) did not have a significant effect on the primary endpoint of the development of basal cell carcinoma of the skin and may increase the risk of squamous cell carcinoma and total nonmelanoma skin cancer.[19,20]

References

1. Preston DS, Stern RS: Nonmelanoma cancers of the skin. N Engl J Med 327 (23): 1649-62, 1992.  [PUBMED Abstract]
   
   
2. English DR, Armstrong BK, Kricker A, et al.: Case-control study of sun exposure and squamous cell carcinoma of the skin. Int J Cancer 77 (3): 347-53, 1998.  [PUBMED Abstract]
   
   
3. Thompson SC, Jolley D, Marks R: Reduction of solar keratoses by regular sunscreen use. N Engl J Med 329 (16): 1147-51, 1993.  [PUBMED Abstract]
   
   
4. Green A, Williams G, Neale R, et al.: Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial. Lancet 354 (9180): 723-9, 1999.  [PUBMED Abstract]
   
   
5. van der Pols JC, Williams GM, Pandeya N, et al.: Prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use. Cancer Epidemiol Biomarkers Prev 15 (12): 2546-8, 2006.  [PUBMED Abstract]
   
   
6. Gandini S, Sera F, Cattaruzza MS, et al.: Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure. Eur J Cancer 41 (1): 45-60, 2005.  [PUBMED Abstract]
   
   
7. Koh HK: Cutaneous melanoma. N Engl J Med 325 (3): 171-82, 1991.  [PUBMED Abstract]
   
   
8. Autier P, Doré JF, Schifflers E, et al.: Melanoma and use of sunscreens: an Eortc case-control study in Germany, Belgium and France. The EORTC Melanoma Cooperative Group. Int J Cancer 61 (6): 749-55, 1995.  [PUBMED Abstract]
   
   
9. Wolf P, Donawho CK, Kripke ML: Effect of sunscreens on UV radiation-induced enhancement of melanoma growth in mice. J Natl Cancer Inst 86 (2): 99-105, 1994.  [PUBMED Abstract]
   
   
10. Dennis LK, Beane Freeman LE, VanBeek MJ: Sunscreen use and the risk for melanoma: a quantitative review. Ann Intern Med 139 (12): 966-78, 2003.  [PUBMED Abstract]
    
    
11. Robinson JK: Compensation strategies in sun protection behaviors by a population with nonmelanoma skin cancer. Prev Med 21 (6): 754-65, 1992.  [PUBMED Abstract]
    
    
12. Berwick M, Fine JA, Bolognia JL: Sun exposure and sunscreen use following a community skin cancer screening. Prev Med 21 (3): 302-10, 1992.  [PUBMED Abstract]
    
    
13. Gruber SB, Roush GC, Barnhill RL: Sensitivity and specificity of self-examination for cutaneous malignant melanoma risk factors. Am J Prev Med 9 (1): 50-4, 1993 Jan-Feb.  [PUBMED Abstract]
    
    
14. Weinstock MA: Assessment of sun sensitivity by questionnaire: validity of items and formulation of a prediction rule. J Clin Epidemiol 45 (5): 547-52, 1992.  [PUBMED Abstract]
    
    
15. Kraemer KH, DiGiovanna JJ, Moshell AN, et al.: Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med 318 (25): 1633-7, 1988.  [PUBMED Abstract]
    
    
16. Tangrea JA, Edwards BK, Taylor PR, et al.: Long-term therapy with low-dose isotretinoin for prevention of basal cell carcinoma: a multicenter clinical trial. Isotretinoin-Basal Cell Carcinoma Study Group. J Natl Cancer Inst 84 (5): 328-32, 1992.  [PUBMED Abstract]
    
    
17. Tangrea JA, Adrianza E, Helsel WE, et al.: Clinical and laboratory adverse effects associated with long-term, low-dose isotretinoin: incidence and risk factors. The Isotretinoin-Basal Cell Carcinomas Study Group. Cancer Epidemiol Biomarkers Prev 2 (4): 375-80, 1993 Jul-Aug.  [PUBMED Abstract]
    
    
18. Greenberg ER, Baron JA, Stukel TA, et al.: A clinical trial of beta carotene to prevent basal-cell and squamous-cell cancers of the skin. The Skin Cancer Prevention Study Group. N Engl J Med 323 (12): 789-95, 1990.  [PUBMED Abstract]
    
    
19. Clark LC, Combs GF Jr, Turnbull BW, et al.: Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA 276 (24): 1957-63, 1996.  [PUBMED Abstract]
    
    
20. Duffield-Lillico AJ, Slate EH, Reid ME, et al.: Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. J Natl Cancer Inst 95 (19): 1477-81, 2003.  [PUBMED Abstract]
    
    

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Changes To This Summary (04/10/2008)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Significance ¹¹

Updated incidence and mortality estimates ¹² for 2008 (cited American Cancer Society as reference 2).

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