Skin cancer in general practice: know the risk factors by Devon Phillips

Clinical Focus on
Actinic Keratosis
Skin cancer in general practice:
know the risk factors
by Devon Phillips
Skin cancer continuum: AK to SCC
SCC and previous AK status
Actinic keratosis (AK) has been demonstrated as the initial lesion in
the disease continuum that progresses to invasive squamous cell carcinoma (SCC) with the potential for significant morbidity and death.1
Similar to the value of the fecal occult blood test for colorectal cancer
and the PAP test for cervical cancer in saving thousands of lives,2
the prevention, screening and early treatment of AK has been recommended to reduce the potential for progression to nonmelanoma
skin cancer (NMSC).3,4
Different studies have shown an estimated 40–80% of SSCs arose
from lesions previously diagnosed on AKs.11,12 In defined high-risk
populations (older males), about 65% of all primary SCCs diagnosed
arose in lesions that were previously defined as AKs.13
Increased rates of nonmelanoma skin cancer
The incidence of NMSC (the most frequent family of skin cancers) in
Canada is projected to increase over the next several decades due to
a growing and aging population, from an estimated annual average
of 75,953 cases between 2000 and 2004 to 147,000 cases in 2031,
representing a significant burden of treatment costs and lost productivity.5 It’s estimated that 81,300 new cases of NMSC will be diagnosed
in Canada in 2012 alone6 and that 320 deaths will result from this
disease in 2012.6
Redefining actinic keratosis
AKs are dysplastic keratinocytic skin lesions that are caused by chronic
exposure to ultraviolet (UV) radiation. The clinical significance of AK
relates to the risk of malignant transformation to NMSC. Although
NMSC is treatable, some lesions, particularly SCC, may become
invasive and lead to death.3
Current consensus in some jurisdictions is that AK can be considered the earliest clinically recognizable manifestation of malignancy1 or
an early in situ SCC.7
AK demonstrates cytologic and molecular features of malignancy.
AK and SCC share genetic tumour markers and identical p53 gene
mutations, are considered to be on the same disease continuum1 and
share the same risk factors.8
Risk of progression from AK to NMSC
In a review of 5 clinical studies, the risk of progression of AK to invasive
SCC ranged between 0.025% and 16% per year for individual lesions.9
Extrapolation from these studies suggests a rate of risk of progression
of AK to SCC of approximately 8%.9
Relative risk of transformation depends on a number of factors relating
to the AK itself including thicknesss, grade of inflammation, degree of
photo-damage in the surrounding area, as well as individual patient
factors such as immune status and degree of pigmentation.10
Clinical appearance of AKs
AKs appear as rough or scaly, often hyperkeratotic, flesh-coloured
macules, papules, patches or plaques with discrete or diffuse borders.
They can also be pigmented or erythematous and can present as
plaques. The key to clinical diagnoses is often the sandpapery-like “People at increased
sensation when touched.7
risk for actinic
Lesions are typically 1–3 mm
keratosis have fair
in diameter but can be several
skin, blue eyes, light
centimetres in size and numerous as well as blended together. hair, tend to burn in
The scaliness can often be felt
the sun and not tan,
before it is seen.1
and they have spent
AK lesions occur on areas of
a great deal of time
chronically sun-exposed skin,
including hands, forearms, face, out in the sun. Those
bald scalp/forehead and rim of the
at most risk include
ears. If the patient has a history
outdoor workers.”
of significant tanning bed use,
­– Cheryl F. Rosen, MD, FRCPC,
lesions could appear anywhere.
Canadian Dermatology Association
AK: scalp
Squamous cell carcinoma
AK: chest
AK: forearm and hand
All images have been acquired from DermNetNZ and images are published with permission from
the New Zealand Dermatological Society Incorporated.
Sponsorship of this Clinical Focus in Parkhurst Exchange is funded by Leo Pharma Inc.
Risk factors for actinic keratosis (AK)
and squamous cell carcinoma (SCC)1
Skin type
Fair-skinned phenotype (with light-coloured
eyes, red or blonde hair, inability to tan,
tendency to sunburn, and the ability to form
freckles, especially nonfacial freckles)
UV light exposure
Excessive or cumulative overexposure
to UV radiation
*Age
Advancing age
Occupation
Outdoor vocation or hobbies
Place of residence
Sunbelt latitudes
*History
Presence of AKs or previous NMSC
Gender
Male, especially in early decades of life;
in advanced age, gender risk is equal
Anatomic
distribution
AK: often appears on back of hands,
forearms, head, neck; SCC: frequently
on head and neck
Other
Immunosuppression or predisposing genetic
diseases such as xeroderma pigmentosum
* The highest risk factors for developing AK and SCC are advancing age and
the presence of AKs or a previous NMSC.
Treatment
The goals of treatment are to eradicate AKs and minimize their risk
of progression to invasive SCC. This reduces the potential to metastasize and cause death, while achieving the best cosmetic outcome and
reducing symptoms such as tenderness.14
Lesion-directed therapy (e.g. cryotherapy and other surgical therapies
such as excision, laser therapy, derma­brasion, electrodessication and
curettage) are used to treat single
lesions but they don’t address “There are not enough
dermatologists in
the problem of actinic changes
in the surrounding sun-damaged
Canada. We need to
area. To treat the whole area of
enlist the help of
field damage (i.e. obvious AK
family physicians to
as well as subclinical disease/
diagnose and treat
invisible lesions), topical treatactinic keratoses.”
ment or photodynamic therapy
­– Cheryl F. Rosen, MD, FRCPC, Canadian
is recommended.10
Dermatology Association
Follow-up and prevention
A 5-minute skin examination by physicians (perhaps as part of the
annual physical checkup) to screen and monitor for the development
of AKs is vital, especially in high-risk patients.8 In addition, primary
care physicians should educate patients about skin self-examination
to detect the signs of malignant transformation and to report any
suspicious moles or plaques.14
NMSC prevention strategies 6,14
Field cancerization
AKs may present on a patient as a few detectable lesions. In addition to
these, there are subclinical (invisible) AKs that are estimated to occur up to
10 times more often than visible AKs because all unprotected skin receives
UV radiation from the sun.14 The phenomenon of clinical and subclinical
AK lesions occurring in photo-damaged skin is called field cancerization.
A field of change can be up to 7 cm around the primary lesions, resulting in lesions that are genetically similar.10
The presence of whole actinically damaged fields demands treatment modalities that are able to target and clear all lesions within the
affected area, in order to reduce the risk of developing local recurrence,
further AK and second tumours. 10,15
No technology or tests exist to determine which individual AK
lesions will resolve spontaneously, remain stable or progress to invasive
skin cancer.1 In one study, 82.4% of SCC cases were found to have
concomitant AK giving rise to and/or in close proximity to SCC.16
ŠŠ Avoid excessive sun exposure (particularly between 11 a.m. and
2 p.m.), or any time of day the UV index is ≥ 3.
ŠŠ Wear protective clothing (e.g. wide-brimmed hats) and sunglasses
(wraparound is best) with 100% UV protection.
ŠŠ Avoid artificial UV light such as tanning beds and sun lamps.
ŠŠ Apply generous amounts of sunscreen with at least 30 SPF 3 or 4
times a day (if outdoors).
ŠŠ Take extra care to practise good sun protection technique when
participating in outdoor sports (e.g. swimming, skiing, snowboarding) because UV rays from the sun can be reflected by water, sand,
pavement, snow and ice.
ŠŠ Check “hard-to-see” places such as the back, back of the neck, legs
and ears for any change in a birthmark or a mole that changes shape,
colour, size or surface, or any new growth on the skin — pale, pearly
nodules that may grow larger and crust, or red, scaly, sharply defined patches, any sore that doesn’t heal, and any patch of skin that
bleeds, oozes, swells, itches or becomes red and bumpy.
References
1. Oppel T, Korting HC. Actinic keratosis: the key event in the evolution from photoaged skin to squamous cell carcinoma. Skin Pharmacol Physiol 2004;17:67-76.
2. Canada Cancer Statistics 2012. www.cancer.ca/Canada-wide/About%20us/
Media%20centre/CW-Media%20releases/CW-2012/Canadian%20Cancer%20
Statistics%202012.aspx?sc_lang=en#ixzz1uPEMbjMS. Accessed May 9, 2012.
3. Cohen JL. Actinic keratosis treatment as a key component of preventive strategies
for nonmelanoma skin cancer. J Clin Aesthet Dermatol 2010;3:39-44.
4. Carpenter PM, Linden KG, McLaren CE, et al. Nuclear morphometry and molecular
biomarkers of actinic keratosis, sun-damaged and nonexposed skin. Cancer Epidemiol
Biomakers Prev 2004;13:1996-2002.
5. National Skin Cancer Prevention Committee. The economic burden of skin cancer
in Canada: current and projected. February 26, 2012, pages 1, 42. www.partnership
againstcancer.ca/wp-content/uploads/Economic-Burden-of-Skin-Cancer-in-CanadaReport-Final1.pdf
6. Canadian Cancer Society. Non-melanoma skin cancer overview (http://info.cancer.
ca/cce-ecc/default.aspx?Lang=E&toc=47). Accessed May 9, 2012.
7. Anwar J, Wrone DA, Kimiyai-Asadi A, Alam M. The development of actinic
keratosis into invasive squamous cell carcinoma: evidence and evolving classification
schemes. Clinics Dermatol 2004;22:189-196.
8. Berman B, Bienstock L, Kuritzky L et al. Actinic keratosis: sequelae and treatments.
Recommendations from a consensus panel. Supplement to the Journal of Family Practice
2006: 1-8. www.jfponline.com/uploadedFiles/Journal_Site_Files/Journal_of_Family_
Practice/supplement_archive/Suppl_AK.pdf. Accessed May 6, 2012.
9. Glogau RG. The risk of progression to invasive disease. J Am Acad Dermatol 2000;42
(1) Suppl 1:S23-24.
10. Valve M, Ortonne J-P, Birch-Machine MA, Gupta G. Management of field change
in actinic keratosis. British J Derm 2007;157 (suppl 2):21-24.
11. Marks R, Rennie G, Selwood TS. Malignant transformation of solar keratosis to
squamous cell carcinoma. Lancet 1988;33 (8589):795-797.
12. Feldman SR, Fleischer AB. Progression of actinic keratosis to squamous cell carcinoma
revisited: clinical and treatment implications. Cutis 2011;Apr;87(4):201-7.
13. Criscione VD et al. Actinic keratosis. Natural history of malignant transformation in
the veterans affairs topical tretinoin chemoprevention trial. Cancer 2009;115:2523-30.
14. Berman B, Amini S, Valins W, Block S. Pharmacotherapy of actinic keratosis. Expert
Opin Pharmacother 2009:10(18):3015-3031.
15. Ulrich M, Drecoll U, Stockfleth E. Emerging drugs for actinic keratosis. Expert
Opin Emerging Drugs 2010;15(4):545-555.
16. Mittelbronn MA, Mullins DL, Ramos-Caro FA, Flowers FP. Frequency of pre-exisiting
actinic keratosis in cutaneous squamous carcinoma. Int J Dermatol 1998;37:677-681.
Sponsorship of this Clinical Focus in Parkhurst Exchange is funded by Leo Pharma Inc.