Skin Cancer and UVB Phototherapy

What is the risk of skin cancer with UVB phototherapy?

Unlike ultraviolet radiation from natural sunlight and
cosmetic tanning lamps, many decades of use in dermatology
has shown that UVB/UVB-Narrowband phototherapy (which has
UVA substantially excluded) is not a major risk for skin cancer;
including basal cell carcinoma (BCC), squamous cell carcinoma (SCC)  and cutaneous malignant melanoma (CMM).

To support this statement, please consider
the following study excerpts, and the discussion that follows:
 

"No increased risk of skin cancer was evidenced in the four studies specifically assessing the potential carcinogenic risk of NB-UVB."

To read the full study, follow this link:

Carcinogenic risks of psoralen UV-A therapy and narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review.

Archier E1, Devaux S, Castela E, Gallini A, Aubin F, Le Maître M, Aractingi S, Bachelez H, Cribier B, Joly P, Jullien D, Misery L, Paul C, Ortonne JP, Richard MA. 2012

“Reviews of studies on UVB, both narrowband and broadband, do not indicate any increased risk of nonmelanoma skin cancer or melanoma.”

To read the full study, follow this link:

Treatments for psoriasis and the risk of malignancy.

Patel RV1, Clark LN, Lebwohl M, Weinberg JM.

“In this large study, with follow-up of up to 22 years from first treatment with NB-UVB, we did not find any definite association between NB-UVB treatment and BCC, SCC or melanoma skin cancer.” 

To read the full study, follow this link:
Incidence of skin cancers in 3867 patients treated with Narrow-Band UVB Phototherapy
Hearn RMKerr ACRahim KFFerguson JDawe RS.

“No increased risk of skin cancer was evidenced in the four studies specifically assessing the potential carcinogenic risk of NB-UVB.”

To read the full study, follow this link:
Carcinogenic risks of psoralen UV-A therapy and narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review.

Archier E1, Devaux S, Castela E, Gallini A, Aubin F, Le Maître M, Aractingi S, Bachelez H, Cribier B, Joly P, Jullien D, Misery L, Paul C, Ortonne JP, Richard MA.

“There were no statistically significant differences between the nbUVB and control groups. Thus, nbUVB phototherapy using TL-01 lamps seems to be a safe therapeutic modality for patients with skin phototypes III-V.”

To read the full study, follow this link:
No evidence for increased skin cancer risk in Koreans with skin phototypes III-V treated with narrowband UVB phototherapy.

Jo SJ1, Kwon HH, Choi MR, Youn JI.

“Dr. Lebwohl says. “At least so far, it appears that narrowband UVB does not contribute to skin cancer. Nonetheless, in patients who are cancer prone, we are cautious about the use of phototherapy.”

To read the full study, follow this link:
Common psoriasis therapies
influence chances of patients developing skin cancer Dermatology Times May-2017

“Thus, the present study does not provide evidence for an increased skin cancer risk for patients treated with either broadband or narrowband UVB phototherapy” 


To read the full study, follow this link:
No evidence for increased skin cancer risk in psoriasis patients treated with broadband or narrowband UVB phototherapy: a first retrospective study.

Weischer M1, Blum A, Eberhard F, Röcken M, Berneburg M.

“(UVB-Narrowband) Phototherapy is safe and easy to perform. Although complications can include sunburn, we are not seeing any skin cancers, melanoma or non-melanoma. Vitiligo is probably protective for melanoma.” 

To read the full study, follow this link:
New thoughts, therapies for vitiligo – Pearl Grimes – Dermatology Times Aug-2016

“Despite concerns over the carcinogenic potential of ultraviolet radiation, most studies have not found an increased risk of non-melanoma or melanoma skin cancer in patients treated with ultraviolet B (broadband and narrowband) and ultraviolet A1 phototherapy.”

To read the full study, follow this link:
The dark side of the light: Phototherapy adverse effects.

Valejo Coelho MM1, Apetato M2.

Discussion

Ultraviolet radiation (UVR) from natural sunlight
“is regarded as the main causative factor
in the induction of skin cancer”

UVR is subdivided into:

UVA
320-400nm
The tanning wavelengths

UVB
280-320nm
The burning wavelengths

UVC
100-280nm
Filtered out by the earth’s atmosphere

Hence, for the purposes of this discussion, UVR=UVA+UVB.

Each different wavelength of light induces a variety of different biological effects in human skin. The longer wavelengths of UVA penetrate into the dermis, whereas UVB penetrates only to the epidermis.

There are three major types of skin cancers:

BCC

basal cell carcinoma

SCC

squamous cell carcinoma

CMM

cutaneous malignant melanoma

BCC and SCC are grouped together as non-melanoma skin cancers (NMSC), and are UVB cumulative lifetime dose dependent. Skin areas that have had received large lifetime doses of UVR are the most susceptible, such as possibly the head, neck, chest, and forearms. NMSC is readily treatable if diagnosed early.

While UVB is responsible for skin burning (erythema) and NMSC, it is paradoxically also the waveband that makes Vitamin D in the skin and is the most effective for the treatment of a wide range of skin diseases.

To minimize erythema and NMSC while still providing effective skin disease treatment, UVB-Narrowband (311nm peak, /01) was developed by Philips Lighting in the 1980’s and it now dominates medical phototherapy worldwide. For more information see: Understanding Narrowband UVB Phototherapy.

Melanoma is the most dangerous skin cancer as it can spread cancer to other areas of the body. “It’s likely that a combination of factors, including environmental and genetic factors, causes melanoma. Still, doctors believe exposure to ultraviolet (UV) radiation from the sun and from tanning lamps and beds is the leading cause of melanoma.”17

UV light doesn’t cause all melanomas, especially those that occur in places on your body that don’t receive exposure to sunlight. This indicates that other factors may contribute to your risk of melanoma. Melanoma can be caused by both UVA and UVB, but there is some evidence that UVA may play a dominant role.3

Melanoma risk factors include: moles (melanocytic nevi), skin type (fair-skinned individuals are at much greater risk than those with darker skins), and repeated sunburn, especially in childhood. “Intermittent exposure to intense sunlight is more strongly associated with the development of melanoma than continuous daily sun exposure.6

Yet to be explained is the fact that “Melanoma is more frequent among people with indoor occupations than among people getting large accumulated environmental UV exposures (farmers, fishermen, etc.).”

The vast majority of skin cancer scientific literature is related to the effects of natural sunlight (UVR, which consists of mostly UVA, with a declining percent of UVB as latitude increases),

But what about when only UVB is used (with UVA excluded), as in medical UVB / UVB-Narrowband phototherapy?

Despite the fact that the action spectrum for NMSC is almost entirely in the UVB range, the above studies indicate that UVB/UVB-Narrowband phototherapy is not a major risk factor for skin cancer; including basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous malignant melanoma (CMM).

The absence of potentially harmful UVA likely plays a role, and “Overall, there is some evidence that vitamin D may play a role in nonmelanoma skin cancer (NMSC) and melanoma prevention, although as of yet there is no direct evidence to show a protective effect.14,15 Several studies have suggested that vitamin D plays a protective role in a variety of internal malignancies. With regard to skin cancer, epidemiologic and laboratory studies suggest that vitamin D and its metabolites may have a similar protective effect.13

To address the concern with UVB induced NMSC, because it is lifetime cumulative dose dependent, especially for fair-skinned individuals, it is sensible to exclude from treatment the areas of skin that do not need treatment and have had considerable UVR in the patient’s lifetime, and to also protect those areas from additional UVR from natural sunlight. Those with a history and/or family history of skin cancer should consult their physician before taking UV phototherapy. They should also have a “skin check” at least annually to detect skin cancer; as should anyone exposed to ultraviolet light, be it from medical UV phototherapy, cosmetic tanning equipment, or natural sunlight.

Furthermore, UVR from natural sunlight is mostly received from above the person (for example sun shining from above on the forehead, ears and shoulders), whereas full-body UVB phototherapy is almost always delivered from the side (patients typically stand for treatment from a vertically mounted device), so there is some geometric exposure reduction to the most at risk skin areas. The initial UVB “clearing” phase typically involves increasingly larger doses UVB phototherapy over several months, followed by long-term “maintenance” treatments at reduced doses and frequency.

UVB phototherapy does not require that the patient get sunburn, and UVB doses less than the maximum are effective for long-term maintenance Are Narrow-band Ultraviolet B Home Units a Viable Option for Continuous or Maintenance Therapy of Photoresponsive Skin Diseases?” ,18 and to maintain Vitamin D sufficiency. 09,11,12 

All SolRx UVB-Narrowband devices are Health Canada compliant for “Vitamin-D Deficiency” as an “indication for use”, which means they have been determined to be safe and effective, and thus can be legally marketed for that purpose in Canada. 10

Regarding Home phototherapy, the inherently boring process of taking treatments and human nature guides the patient to take only the amount of UVB necessary to maintain clear or nearly-clear skin. Home phototherapy patients typically become quite expert at how much UVB to take and when, with smaller, more frequent doses being preferred by many.

Home phototherapy also makes it less likely that treatments are missed and subsequent treatments produce unwanted sunburn. To wit, “Ultraviolet B phototherapy at home is equally effective for treating psoriasis as ultraviolet B phototherapy in an outpatient setting and implies no additional safety hazards in a setting precluding possible non-prescribed irradiations. Furthermore, home treatment poses a lower burden, is better appreciated, and gives similar improvements in quality of life. Most of the patients said that they would prefer future ultraviolet B treatment at home over phototherapy in an outpatient setting.” 16

Solarc Systems welcomes any suggestions to improve this public information article.

NOTE

It is important that UVB and UVB-Narrowband phototherapy is not confused with PUVA (psoralen + UVA light), as ” the role of PUVA therapy in skin carcinogenesis in humans with psoriasis has been clearly demonstrated” [Carcinogenic risks of PUVA and nbUVB in chronic plaque psoriasis_ a systematic literature review 2012] PUVA is thus often limited to 200 to 300 treatments, and only for the most serious cases that have failed UVB or UVB-Narrowband phototherapy.   

References:

1 Brenner, Michaela, and Vincent J. Hearing. “The Protective Role of Melanin Against UV Damage in Human Skin.” Photochemistry and Photobiology, vol. 84, no. 3, 2007, pp. 539–549., doi:10.1111/j.1751-1097.2007.00226.x.

2 “Skin Cancer / Melanoma Center: Signs, Treatments, Symptoms, Types, Causes, and Tests.”  WebMD

3 Setlow, R. B., et al. “Wavelengths Effective in Induction of Malignant Melanoma.” Proceedings of the National Academy of Sciences, vol. 90, no. 14, 1993, pp. 6666–6670., doi:10.1073/pnas.90.14.6666.

4 Berneburg, Mark, and Lena Krieger. “Faculty of 1000 Evaluation for Melanoma Induction by Ultraviolet A but Not Ultraviolet B Radiation Requires Melanin Pigment.” F1000 – Post-Publication Peer Review of the Biomedical Literature, 2012, doi:10.3410/f.717952967.793458514.

5 Brenner, Michaela, and Vincent J. Hearing. “The Protective Role of Melanin Against UV Damage in Human Skin.” Photochemistry and Photobiology, vol. 84, no. 3, 2007, pp. 539–549., doi:10.1111/j.1751-1097.2007.00226.x.

6 Rhodes, A. “Melanoma Risk Factors.” AIM at Melanoma, Fitzpatrick’s Dermatology in General Medicine

7 Juzeniene, Asta, and Johan Moan. “Beneficial Effects of UV Radiation Other than via Vitamin D Production.” Dermato-Endocrinology, vol. 4, no. 2, 2012, pp. 109–117., doi:10.4161/derm.20013.

8 Maverakis, Emanual, et al. “Light, Including Ultraviolet.” National Institute of Health, May 2010, doi:10.1016/j.jaut.2009.11.011.

9 United States, Congress, National Toxicology Program. “Broad-SpectrumUltraviolet (UV) RadiationandUVA, and UVB, and UVC.” Broad-SpectrumUltraviolet (UV) RadiationandUVA, and UVB, and UVC, Technology Planning and Management Corporation, 2000.

10 “Regulatory Information.” Solarc Systems Inc.

11 Bogh, M.k.b., et al. “Narrowband Ultraviolet B Three Times per Week Is More Effective in Treating Vitamin D Deficiency than 1600IU Oral Vitamin D3 per Day: A Randomized Clinical Trial.” British Journal of Dermatology, vol. 167, no. 3, 2012, pp. 625–630., doi:10.1111/j.1365-2133.2012.11069.x.

12 Ala-Houhala, M.j., et al. “Comparison of Narrowband Ultraviolet B Exposure and Oral Vitamin D Substitution on Serum 25-Hydroxyvitamin D Concentration.” British Journal of Dermatology, vol. 167, no. 1, 2012, pp. 160–164., doi:10.1111/j.1365-2133.2012.10990.x

13 Tang, Jean Y., et al. “Vitamin D in Cutaneous Carcinogenesis: Part I.” National Institute of Health, Nov. 2012, doi:10.1016/j.jaad.2012.05.044.

14 Tang, Jean Y., et al. “Vitamin D in Cutaneous Carcinogenesis: Part II.” National Institute of Health, Nov. 2012, doi:10.1016/j.jaad.2012.05.044.

15 Navarrete-Dechent, Cristián, et al. “Circulating Vitamin-D Binding Protein and Free 25-Hydroxyvitamin D Concentrations in Patients with Melanoma: A Case-Control Study.Journal of the American Academy of Dermatology, vol. 77, no. 3, 2017, pp. 575–577., doi:10.1016/j.jaad.2017.03.035.

16 Koek, M. B G, et al. “Home versus Outpatient Ultraviolet B Phototherapy for Mild to Severe Psoriasis: Pragmatic Multicentre Randomised Controlled Non-Inferiority Trial (PLUTO Study).” Bmj, vol. 338, no. may07 2, July 2009, doi:10.1136/bmj.b1542.

17 https://www.mayoclinic.org/diseases-conditions/melanoma/symptoms-causes/syc-20374884

18 Are Narrow-band Ultraviolet B Home Units a Viable Option for Continuous or Maintenance Therapy of Photoresponsive Skin Diseases?” 

Summary