ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Epidemiology, natural history, and diagnosis of actinic keratosis

Epidemiology, natural history, and diagnosis of actinic keratosis
Author:
R Steven Padilla, MD
Section Editor:
June K Robinson, MD
Deputy Editor:
Rosamaria Corona, MD, DSc
Literature review current through: Sep 2022. | This topic last updated: Jan 04, 2022.

INTRODUCTION — Actinic keratosis (AK; also known as solar keratosis) is a cutaneous lesion that results from the proliferation of atypical epidermal keratinocytes. AKs represent early lesions on a continuum with squamous cell carcinoma (SCC) and occasionally progress to SCC.

AKs often present as erythematous and scaly macules or papules; lesions are most commonly detected in adults with fair skin. Chronic sun exposure is a major risk factor for the development of these lesions, which accounts for the usual detection of AKs in frequently sun-exposed areas (eg, balding scalp, face, lateral neck, and distal upper or lower extremities).

The epidemiology, clinical features, natural history, and diagnosis of AK will be discussed here. The management of AK and SCC is reviewed elsewhere. (See "Treatment of actinic keratosis" and "Cutaneous squamous cell carcinoma: Epidemiology and risk factors" and "Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis" and "Treatment and prognosis of low-risk cutaneous squamous cell carcinoma (cSCC)".)

EPIDEMIOLOGY AND RISK FACTORS — In the United States, AKs are among the most common reasons for visits to dermatologists [1-4]. It is estimated that between 1990 and 1999, 14 percent of dermatology visits in the United States were related to AKs [3].

Individuals with fair skin are most likely to develop AKs, and many of the data on the epidemiology and risk factors for AK are derived from studies in Australia, northern Europe, and the United States. Factors such as the extent of exposure to ultraviolet light and certain phenotypic features have been associated with risk for developing these lesions. AK is a risk factor for the development of cutaneous squamous cell carcinoma (SCC) [5].

Ultraviolet radiation — Ultraviolet radiation is known to contribute to the development of AK through the induction of mutations in epidermal keratinocytes that lead to increased survival and proliferation of atypical cells [6]. Mutations in the p53 tumor suppressor gene, a gene involved in cell cycle regulation, apoptosis, and DNA repair, have been detected in 30 to 50 percent of lesional skin samples from patients with AKs [7,8]. In addition, many genetic and epigenetic alterations have been identified that impact divergent oncogenic pathways leading to AK and SCC [9,10].

Extent of sun exposure — Individuals with extensive sun exposure, such as those with outdoor occupations, are at increased risk for AK [11-14]. In a population-based study of 20,637 people in the United States, AKs were present in 55 percent of White males and 37 percent of White females between the ages of 65 and 74 years and who were classified as having high cumulative sun exposure [15]. In contrast, among a similar demographic population composed of subjects with low cumulative exposure to the sun, AKs were present in only 19 percent of males and 12 percent of females.

History of sunburn — A history of sunburn increases the risk for AK [11-13]. In an Australian study of 2045 residents of Queensland, Australia (aged 20 to 69 years), six or more painful sunburns over the course of life were associated with an increased likelihood for AK (prevalence odds ratio [OR] 1.47, 95% CI 1.01-2.14) [12]. A separate cohort study of 197 residents of the same Australian state found that even a single episode of sunburn in childhood elevated the risk for AK [13]. (See "Sunburn".)

Impact of sun protection — The stimulatory role of sun exposure on the development of AKs is supported by evidence that use of sunscreens reduces the development of these lesions [16,17]. In a seven-month, randomized trial, 588 residents (aged 40 or older) of Victoria, Australia, who had between 1 and 30 AKs were instructed to apply either a broad-spectrum sunscreen with a sun protection factor (SPF) of 17 or a vehicle cream to the head, neck, and forearms daily. Patients in the sunscreen group developed significantly fewer new AKs (mean number of new lesions 1.6 versus 2.3) and had significantly more spontaneous remissions of AKs (mean percentage of resolved lesions 28 versus 20 percent) [16]. The 157 subjects who withdrew from the study prior to completion were not included in the study analysis. (See "Cutaneous squamous cell carcinoma: Primary and secondary prevention", section on 'Sun protection'.)

Phenotype — Skin color contributes to the risk for AK, as the majority of AKs are detected in individuals with fair skin [11-13,15,18,19]. Epidermal melanin absorbs ultraviolet radiation and shields keratinocytes against damage from ultraviolet light, resulting in a reduced risk for AK with darkening skin pigmentation.

The importance of skin color is supported by a study of 197 residents of Queensland, Australia [13]. Compared with olive-skinned individuals, people with fair or medium-toned (between fair and olive) skin were significantly more likely to develop AKs (age and sex adjusted odds ratios [OR] of 14.1, 95% CI 2.9-69.6 and 6.5, 95% CI 1.2-34.7, respectively) [13]. In addition, AKs are uncommon in African Americans [15]. Freckling, light hair color, a propensity to sunburn easily, and an inability to tan, which are more often seen in people with fair skin, are additional features that have been associated with increased risk for AK [1,15].

The balding scalp is a common site for AK in males and may represent a risk factor for lesion development. In a Dutch, population-based, cohort study of 2061 individuals over the age of 50, severe baldness was associated with increased risk for AK when compared with minimal or no baldness [20]. In particular, males with severe baldness were approximately seven times more likely to have 10 or more AKs than males with minimal or absent baldness (adjusted OR 7.0, 95% CI 3.8-13.1).

Sex, age, and geographic location — Sex and age influence the risk for AK. Males are more likely than females to develop these lesions, and the prevalence of AK rises with age [12,18,20-23]. The magnitude of these effects is illustrated by the following observations:

In a study in Queensland, Australia, that evaluated the prevalence of AK in 2045 adults between the ages of 20 and 69 years, AKs were detected in 40 percent [12]. Lesions were present in 79 percent of males and 68 percent of females between the ages of 60 and 69 compared with only 10 percent of males and 5 percent of females aged 20 to 29 years.

A cohort study of 1040 people over the age of 40 in North Central Victoria, Australia, also detected a high prevalence of AK that increased with age. Fifty-nine percent of study participants had at least one AK, and the mean age of individuals with AK was significantly higher than in those without AK (62 versus 54 years) [22].

Compared with Australia, AKs are less prevalent in the United States and northern Europe, where there is generally less sun exposure. Estimates of the proportion of adults with AKs in these locations range from 11 to 26 percent [1,21,23,24]. In a Dutch population-based study limited to individuals over the age of 50 years, physical examination revealed AK in 38 percent [20].

The impact of geographic location was illustrated in a cohort study that compared the prevalence of AKs in Australian-born adults with that in British immigrants to Australia. All subjects were age 40 years or older. The prevalence of AKs in those who immigrated to Australia before the age of 20 became similar to Aboriginal Australians in late adulthood, while those who immigrated after the age of 20 had fewer AKs than Aboriginal Australians in all age groups [25]. These results suggest that living in a location associated with greater exposure to ultraviolet light early in life may increase the risk for AK.

Other

Genetic disorders — Individuals with genetic disorders that interfere with effective DNA repair after exposure to ultraviolet radiation are at increased risk for AK. Examples include xeroderma pigmentosum, Bloom syndrome, and Rothmund-Thompson syndrome. (See "The genodermatoses: An overview", section on 'Xeroderma pigmentosum' and "Bloom syndrome".)

Human papillomavirus — Betapapillomavirus types of human papillomavirus (HPV) have been detected in AKs, SCCs, and basal cell carcinomas (BCCs) [18,26-30]. However, HPV is also detected in normal skin [28], and an etiologic relationship between HPV and these lesions is uncertain. A cohort study of 291 adults (ages 36 to 86 years) in Queensland, Australia, who were tested for the presence of Betapapillomavirus in eyebrow hairs in 1996 did not identify an independent association of Betapapillomavirus infection with the detection of AK in 2003 [18]. However, when combined with risk factors for AKs (eg, fair skin, male sex, age over 60), Betapapillomavirus infection appeared to increase the likelihood for the development of AK. Additional studies are necessary to explore the role of HPV in this disorder.

Immunosuppression — Immunosuppression has been associated with an increased risk for SCC and may also increase the risk for AK [31-33]. In a study of 94 renal transplant recipients in England (mean age 38 years and mean duration from transplant 4.5 years) and their matched controls, AKs developed in seven of the transplant recipients (7.4 percent) and in none of the controls [32]. All patients with AKs had a history of high sun exposure, defined as more than three months in a tropical or subtropical climate or more than five years in an outdoor occupation. The risk for AK may rise as the time interval after transplant increases [31,33].

CLINICAL FEATURES — AKs typically develop as solitary or multiple lesions on highly sun exposed areas, such as the balding scalp, neck, dorsal hands, and dorsal forearms. The lower extremities are an additional common site for AKs in females. Skin adjacent to AKs usually shows signs of solar damage, such as a yellow or pale color, spotty hyperpigmentation, scattered telangiectasias, or xerosis. AKs are generally asymptomatic, but some patients experience local tenderness or a stinging sensation.

AKs present as several clinical variants, including:

Classic (common) – The classic form of AK presents as an erythematous, scaly macule, papule, or plaque (picture 1A-B). Lesions typically range from a few millimeters to 2 cm in diameter. Occasionally, lesions are larger.

Hypertrophic – Hypertrophic AKs are characterized by the presence of thick, adherent scale on an erythematous base (picture 2A-B).

Atrophic – Scale is absent in atrophic AKs. Lesions are smooth, red macules.

Actinic keratosis with cutaneous horn – A cutaneous horn is a keratotic projection the height of which is at least one-half of the largest diameter (picture 3) [34]. The mound of compact keratin often resembles a spicule or cone. Several other skin lesions can present with cutaneous horns. (See 'Differential diagnosis' below.)

Pigmented – Pigmented actinic keratoses usually present as scaly, hyperpigmented macules or patches. Lesions may be large, exceeding 1.5 cm in some cases [19]. Pigmented AKs can be difficult to distinguish from lentigo maligna. (See 'Differential diagnosis' below and 'Dermoscopy' below.)

Actinic cheilitis – "Actinic cheilitis" (also known as solar cheilosis) is a term that is used to refer to lesions analogous to AKs that occur on the lip [35]. This disorder typically presents on the lower lip as a persistent rough or scaly area (picture 4A-C). Patients often complain of a constantly dry lip. Actinic cheilitis may involve only a small portion of the lip or the entire lower lip. Fissuring or ulceration may also occur. (See "Actinic cheilitis".)

CLINICAL COURSE — AKs are considered lesions that are on a continuum with squamous cell carcinoma (SCC) rather than lesions that are distinct from SCC [9,10,36]. This viewpoint recognizes the potential for AKs to progress to invasive skin cancer.

Progression to skin cancer — The likelihood of progression of an individual AK to SCC is low. Estimates of annual rates of transformation have ranged from 0.03 to 20 percent [37-40]. The following data come from two of the largest studies:

An Australian study that evaluated 1689 adults over the age of 40 who had more than 20,000 AKs found the risk for transformation of an individual AK to SCC within one year to be less than 0.1 percent [37].

Analysis of data from a cohort of patients in a United States trial designed to investigate the use of topical tretinoin for skin cancer prevention in patients with at least two prior keratinocyte carcinomas revealed a rate of transformation to invasive or in situ SCC of 0.6 percent in 6015 AKs followed for one year and a rate of 2.6 percent in 1480 lesions followed for four years [38].

Progression of AKs to basal cell carcinoma (BCC) occurred in 0.5 percent of AKs within one year and in 1.6 percent within four years. However, it is unclear whether this finding was related the misdiagnosis of early BCCs as AKs or was true disease progression.

Although few AKs progress to SCC, data from these studies suggest that approximately 60 percent of cutaneous SCCs arise from pre-existing AKs [37,38]. However, in an Australian cohort of immunosuppressed renal transplant recipients, the presence of an AK >1 cm2 (AK patch) was predictive of invasive or in situ SCC development in sun-exposed sites within 18 months [41]. This observation supports a close relationship between these lesions. Molecular studies support the hypothesis that the coexpression of putative pathogenetic genes in AK and SCC underlie the progression of AK to cutaneous SCC [36,42-45].

Spontaneous resolution — Lesions that do not progress to SCC may regress or persist as AKs [22,38,46]. Reported rates of AK regression generally range between 20 to 30 percent per year, though a regression rate up to 63 percent per year has been reported [47]. Lesions that regress may subsequently reappear; studies with limited follow-up suggest that 15 to 53 percent of spontaneously regressed AKs recur within one year [47].

Risk for skin cancer in other sites — Although the majority of AKs do not progress to SCC, the presence of AKs serves as a marker of chronic sun damage and, therefore, of an increased risk for the development of both SCC and BCC [48-51]. Increasing age and the presence of AKs are correlated with an increased risk of developing SCC and BCC in addition to malignant melanoma [52,53].

DIAGNOSIS — AK is frequently diagnosed clinically through a combination of touch and visual inspection. Some macular lesions lack erythema and are more easily identified through the detection of rough texture. Lesion biopsy is performed if the diagnosis is uncertain. A common indication for biopsy is the differentiation of AK from squamous cell carcinoma (SCC).

Differential diagnosis — Distinguishing AK from SCC can be challenging, as both disorders commonly present as erythematous, scaly papules on sun exposed areas. Lesions with underlying substance, or that are tender, ulcerated, or rapidly growing, are particularly suspicious for SCC. Such lesions should be biopsied for definitive diagnosis. (See "Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis".)

In addition to SCC, multiple other lesions may resemble AKs. Classic (common) AKs may resemble:

SCC (picture 5)

Benign lichenoid keratoses (picture 6)

Superficial basal cell carcinoma (BCC) (picture 7)

Inflamed seborrheic keratosis (picture 8)

Porokeratosis (picture 9A-B)

Inflammatory dermatoses (psoriasis, seborrheic dermatitis) (picture 10A-C)

Hypertrophic AKs or AK with cutaneous horn may resemble:

SCC (picture 11)

Viral wart

Seborrheic keratosis (picture 12)

Pigmented AKs share clinical features with:

Seborrheic keratosis (often distinguished by a "stuck on" appearance) (picture 13)

Solar lentigo (picture 14)

Lentigo maligna melanoma (picture 15)

Biopsy — The decision of whether to perform a biopsy is determined by certainty of diagnosis. In particular, biopsy to rule out SCC should be considered for:

Lesions greater than 1 cm in diameter

Lesions with underlying substance/induration

Rapidly growing lesions

Ulcerated lesions

Tender lesions

Lesions that fail to respond to appropriate therapy (eg, AK that persists 8 to 12 weeks after treatment with liquid nitrogen)

Technique — Biopsies of lesions suspicious for AK are most commonly performed with a shave or punch biopsy technique. If only a portion of the lesion can be removed due to size or concern for scarring, the thickest area of the lesion should be biopsied as SCC arising in an AK is most likely to be detected in this area.

Shave biopsies should extend into the dermis, and preferably at least into the mid-reticular dermis for lesions that are suspicious for SCC. An insufficient biopsy depth will compromise the pathologist's ability to rule out an invasive SCC. Punch biopsies performed with the full length of the punch blade usually reach the subcutaneous fat. (See "Skin biopsy techniques", section on 'Biopsy techniques'.)

Pathology — The histopathologic findings of AKs are dependent upon the clinical variant and specific lesion characteristics. Unlike invasive SCCs, atypical keratinocytes do not invade into the dermis. Common histopathologic features of AK include:

A collection of atypical keratinocytes with hyperchromatic and pleomorphic nuclei that extends from the basal layer of the epidermis upward; the full thickness of the epidermis is spared (picture 16A-B). Mitoses are not uncommon, and acanthosis (epidermal thickening) may be present.

A hyperkeratotic stratum corneum with alternating areas of orthokeratosis and parakeratosis ("flag sign"), particularly in hypertrophic AKs.

A variable lymphocytic dermal infiltrate.

Dermal changes consistent with solar elastosis.

In addition to the above, pigmented AKs demonstrate increased melanin in the lower epidermis and dermal melanophages. Clinically atrophic lesions demonstrate a thin epidermis with atypia that predominantly involves the basal layer.

Histologic variants of AK include bowenoid, lichenoid, and acantholytic subtypes. The existence of the histologic bowenoid variant of AK is controversial. Bowenoid AKs are characterized by full-thickness epidermal dysplasia that is indistinguishable from SCC in situ; notably, keratinocytes in the acrosyringium are spared. Lichenoid lesions feature vacuolization of the basal layer of the epidermis and a band-like chronic inflammatory infiltrate in the superficial dermis. Acantholytic AKs exhibit detachment of keratinocytes due to loss of intercellular bridges; this results in the formation of clefts or lacunae immediately above the basal layer.

A histologic grading system analogous to that used for cervical intraepithelial neoplasia in gynecology has been proposed for AKs [54]. In this system, the term "keratinocytic intraepidermal neoplasia," divided into grades of I, II, and III, is used to describe the progression of AK to in situ SCC. This grading system has not been widely adopted.

Biopsy specimens should be sent to a dermatopathologist when feasible. If pathology results fail to correlate with the clinical findings, consultation with the dermatopathologist may be beneficial. Additional pathologic sections may aid in identifying an invasive SCC, particularly in cases in which clinical suspicion for SCC is high [55].

Dermoscopy — Dermoscopy is a noninvasive procedure that involves use of a handheld tool that combines magnification and a transilluminating light source to aid in the diagnosis of many cutaneous lesions. Dermoscopy is widely used for the evaluation of melanocytic nevi and lesions suspicious for melanoma.

Common dermoscopic features of nonpigmented AKs include a strawberry pattern (picture 17 and picture 18) (background erythema or a red pseudonetwork that consists of unfocused large vessels between hair follicles and prominent follicular openings surrounded by white halos) or a vascular pattern with linear, wavy vessels [56]. Pigmented AKs commonly demonstrate slate-gray to brown dots and globules around follicular ostia and annular-granular and rhomboidal structures (picture 19) [51].

In clinical practice, distinguishing between pigmented AKs and lentigo maligna can be challenging. Dermoscopy may not be reliable for distinguishing between these lesions [51], but helpful clues suggestive of an AK are white and clearly defined follicles, scale, and red color (picture 19). Intense pigmentation, gray rhomboid lines, and loss of identifiable follicles are suggestive of lentigo maligna. However, histopathologic examination remains the gold standard for such cases. (See "Dermoscopic evaluation of skin lesions" and "Dermoscopy of facial lesions", section on 'Actinic keratosis'.)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Actinic keratosis (The Basics)")

SUMMARY AND RECOMMENDATIONS

Actinic keratoses (AKs) are common cutaneous lesions that result from the proliferation of atypical epidermal keratinocytes. Major risk factors for the development of AKs include chronic sun exposure, fair skin, advancing age, and male sex. (See 'Introduction' above and 'Epidemiology and risk factors' above.)

AKs most commonly present as scaly, erythematous macules or papules on sites of chronic sun exposure (picture 1A-B). Lesions may also be pigmented, nonerythematous, or free of scale. Typical locations for AKs include the scalp, face, lateral neck, dorsal forearms, and dorsal hands. Actinic cheilitis is a variant of AK that involves the lip (picture 4A-C). (See 'Clinical features' above.)

AKs may progress to squamous cell carcinoma (SCC). The risk that an individual AK will progress is low, but approximately 60 percent of cutaneous SCCs arise in sites of pre-existing AKs. In addition, patients with AKs are at an increased risk for the development of SCCs or basal cell carcinomas (BCCs) in other sites. (See 'Clinical course' above.)

The diagnosis of AK is often made based on visual and tactile clinical inspection. Biopsy is indicated if the diagnosis is uncertain; a common indication for biopsy is distinguishing AK from SCC. In particular, lesions that are greater than 1 cm in diameter, indurated, ulcerated, or rapidly growing and lesions that fail to respond to appropriate therapy should be considered for biopsy. (See 'Diagnosis' above.)

Pigmented AKs are often difficult to distinguish from lentigo maligna on clinical exam. Histopathologic examination is the gold standard for diagnosis. Dermoscopy may not reliably distinguish between these lesions. (See 'Dermoscopy' above.)

  1. Salasche SJ. Epidemiology of actinic keratoses and squamous cell carcinoma. J Am Acad Dermatol 2000; 42:4.
  2. Feldman SR, Fleischer AB Jr, McConnell RC. Most common dermatologic problems identified by internists, 1990-1994. Arch Intern Med 1998; 158:726.
  3. Gupta AK, Cooper EA, Feldman SR, Fleischer AB Jr. A survey of office visits for actinic keratosis as reported by NAMCS, 1990-1999. National Ambulatory Medical Care Survey. Cutis 2002; 70:8.
  4. Warino L, Tusa M, Camacho F, et al. Frequency and cost of actinic keratosis treatment. Dermatol Surg 2006; 32:1045.
  5. Madani S, Marwaha S, Dusendang JR, et al. Ten-Year Follow-up of Persons With Sun-Damaged Skin Associated With Subsequent Development of Cutaneous Squamous Cell Carcinoma. JAMA Dermatol 2021; 157:559.
  6. Leffell DJ. The scientific basis of skin cancer. J Am Acad Dermatol 2000; 42:18.
  7. Taguchi M, Watanabe S, Yashima K, et al. Aberrations of the tumor suppressor p53 gene and p53 protein in solar keratosis in human skin. J Invest Dermatol 1994; 103:500.
  8. Nelson MA, Einspahr JG, Alberts DS, et al. Analysis of the p53 gene in human precancerous actinic keratosis lesions and squamous cell cancers. Cancer Lett 1994; 85:23.
  9. Thomson J, Bewicke-Copley F, Anene CA, et al. The Genomic Landscape of Actinic Keratosis. J Invest Dermatol 2021; 141:1664.
  10. Yao Q, Epstein CB, Banskota S, et al. Epigenetic Alterations in Keratinocyte Carcinoma. J Invest Dermatol 2021; 141:1207.
  11. Hensen P, Müller ML, Haschemi R, et al. Predisposing factors of actinic keratosis in a North-West German population. Eur J Dermatol 2009; 19:345.
  12. Green A, Beardmore G, Hart V, et al. Skin cancer in a Queensland population. J Am Acad Dermatol 1988; 19:1045.
  13. Frost CA, Green AC, Williams GM. The prevalence and determinants of solar keratoses at a subtropical latitude (Queensland, Australia). Br J Dermatol 1998; 139:1033.
  14. Trakatelli M, Barkitzi K, Apap C, et al. Skin cancer risk in outdoor workers: a European multicenter case-control study. J Eur Acad Dermatol Venereol 2016; 30 Suppl 3:5.
  15. Engel A, Johnson ML, Haynes SG. Health effects of sunlight exposure in the United States. Results from the first National Health and Nutrition Examination Survey, 1971-1974. Arch Dermatol 1988; 124:72.
  16. Thompson SC, Jolley D, Marks R. Reduction of solar keratoses by regular sunscreen use. N Engl J Med 1993; 329:1147.
  17. Ulrich C, Jürgensen JS, Degen A, et al. Prevention of non-melanoma skin cancer in organ transplant patients by regular use of a sunscreen: a 24 months, prospective, case-control study. Br J Dermatol 2009; 161 Suppl 3:78.
  18. McBride P, Neale R, Pandeya N, Green A. Sun-related factors, betapapillomavirus, and actinic keratoses: a prospective study. Arch Dermatol 2007; 143:862.
  19. Goldberg LH, Mamelak AJ. Review ofactinic keratosis. Part I: etiology, epidemiology and clinical presentation. J Drugs Dermatol 2010; 9:1125.
  20. Flohil SC, van der Leest RJ, Dowlatshahi EA, et al. Prevalence of actinic keratosis and its risk factors in the general population: the Rotterdam Study. J Invest Dermatol 2013; 133:1971.
  21. Memon AA, Tomenson JA, Bothwell J, Friedmann PS. Prevalence of solar damage and actinic keratosis in a Merseyside population. Br J Dermatol 2000; 142:1154.
  22. Marks R, Foley P, Goodman G, et al. Spontaneous remission of solar keratoses: the case for conservative management. Br J Dermatol 1986; 115:649.
  23. Zagula-Mally ZW, Rosenberg EW, Kashgarian M. Frequency of skin cancer and solar keratoses in a rural southern county as determined by population sampling. Cancer 1974; 34:345.
  24. Frost CA, Green AC. Epidemiology of solar keratoses. Br J Dermatol 1994; 131:455.
  25. Marks R, Jolley D, Lectsas S, Foley P. The role of childhood exposure to sunlight in the development of solar keratoses and non-melanocytic skin cancer. Med J Aust 1990; 152:62.
  26. Pfister H, Fuchs PG, Majewski S, et al. High prevalence of epidermodysplasia verruciformis-associated human papillomavirus DNA in actinic keratoses of the immunocompetent population. Arch Dermatol Res 2003; 295:273.
  27. Astori G, Lavergne D, Benton C, et al. Human papillomaviruses are commonly found in normal skin of immunocompetent hosts. J Invest Dermatol 1998; 110:752.
  28. Forslund O, Ly H, Reid C, Higgins G. A broad spectrum of human papillomavirus types is present in the skin of Australian patients with non-melanoma skin cancers and solar keratosis. Br J Dermatol 2003; 149:64.
  29. Weissenborn SJ, Nindl I, Purdie K, et al. Human papillomavirus-DNA loads in actinic keratoses exceed those in non-melanoma skin cancers. J Invest Dermatol 2005; 125:93.
  30. Forslund O, Lindelöf B, Hradil E, et al. High prevalence of cutaneous human papillomavirus DNA on the top of skin tumors but not in "Stripped" biopsies from the same tumors. J Invest Dermatol 2004; 123:388.
  31. Keller B, Braathen LR, Marti HP, Hunger RE. Skin cancers in renal transplant recipients: a description of the renal transplant cohort in Bern. Swiss Med Wkly 2010; 140:w13036.
  32. Boyle J, MacKie RM, Briggs JD, et al. Cancer, warts, and sunshine in renal transplant patients. A case-control study. Lancet 1984; 1:702.
  33. Chen QP, Aw DC. Epidemiology of skin diseases in renal transplant recipients in a tertiary hospital. Ann Acad Med Singapore 2010; 39:904.
  34. Duncan KO, Geisse JK, Leffell DJ. Epithelial precancerous lesions. In: Fitzpatrick's Dermatology in General Medicine, 7th ed, Wolff K, Goldsmith LA, Katz SI, et al. (Eds), McGraw-Hill, New York 2008. Vol 1, p.1007.
  35. Jadotte YT, Schwartz RA. Solar cheilosis: an ominous precursor: part I. Diagnostic insights. J Am Acad Dermatol 2012; 66:173.
  36. Padilla RS, Sebastian S, Jiang Z, et al. Gene expression patterns of normal human skin, actinic keratosis, and squamous cell carcinoma: a spectrum of disease progression. Arch Dermatol 2010; 146:288.
  37. Marks R, Rennie G, Selwood TS. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet 1988; 1:795.
  38. Criscione VD, Weinstock MA, Naylor MF, et al. Actinic keratoses: Natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer 2009; 115:2523.
  39. Quaedvlieg PJ, Tirsi E, Thissen MR, Krekels GA. Actinic keratosis: how to differentiate the good from the bad ones? Eur J Dermatol 2006; 16:335.
  40. Fuchs A, Marmur E. The kinetics of skin cancer: progression of actinic keratosis to squamous cell carcinoma. Dermatol Surg 2007; 33:1099.
  41. Jiyad Z, O'Rourke P, Soyer HP, Green AC. Actinic keratosis-related signs predictive of squamous cell carcinoma in renal transplant recipients: a nested case-control study. Br J Dermatol 2017; 176:965.
  42. Zhang L, Qin H, Wu Z, et al. Pathogenic genes related to the progression of actinic keratoses to cutaneous squamous cell carcinoma. Int J Dermatol 2018; 57:1208.
  43. Hameetman L, Commandeur S, Bavinck JN, et al. Molecular profiling of cutaneous squamous cell carcinomas and actinic keratoses from organ transplant recipients. BMC Cancer 2013; 13:58.
  44. Lambert SR, Mladkova N, Gulati A, et al. Key differences identified between actinic keratosis and cutaneous squamous cell carcinoma by transcriptome profiling. Br J Cancer 2014; 110:520.
  45. Schmitz L, Grinblat B, Novak B, et al. Somatic mutations in kinetochore gene KNSTRN are associated with basal proliferating actinic keratoses and cutaneous squamous cell carcinoma. J Eur Acad Dermatol Venereol 2019; 33:1535.
  46. Harvey I, Frankel S, Marks R, et al. Non-melanoma skin cancer and solar keratoses. I. Methods and descriptive results of the South Wales Skin Cancer Study. Br J Cancer 1996; 74:1302.
  47. Werner RN, Sammain A, Erdmann R, et al. The natural history of actinic keratosis: a systematic review. Br J Dermatol 2013; 169:502.
  48. Green A, Battistutta D. Incidence and determinants of skin cancer in a high-risk Australian population. Int J Cancer 1990; 46:356.
  49. Marks R, Rennie G, Selwood T. The relationship of basal cell carcinomas and squamous cell carcinomas to solar keratoses. Arch Dermatol 1988; 124:1039.
  50. Kwa RE, Campana K, Moy RL. Biology of cutaneous squamous cell carcinoma. J Am Acad Dermatol 1992; 26:1.
  51. Akay BN, Kocyigit P, Heper AO, Erdem C. Dermatoscopy of flat pigmented facial lesions: diagnostic challenge between pigmented actinic keratosis and lentigo maligna. Br J Dermatol 2010; 163:1212.
  52. Chen GJ, Feldman SR, Williford PM, et al. Clinical diagnosis of actinic keratosis identifies an elderly population at high risk of developing skin cancer. Dermatol Surg 2005; 31:43.
  53. Lee JH, Kim YH, Han KD, et al. Incidence of Actinic Keratosis and Risk of Skin Cancer in Subjects with Actinic Keratosis: A Population-based Cohort Study. Acta Derm Venereol 2018; 98:382.
  54. Cockerell CJ. Histopathology of incipient intraepidermal squamous cell carcinoma ("actinic keratosis"). J Am Acad Dermatol 2000; 42:11.
  55. Carag HR, Prieto VG, Yballe LS, Shea CR. Utility of step sections: demonstration of additional pathological findings in biopsy samples initially diagnosed as actinic keratosis. Arch Dermatol 2000; 136:471.
  56. Peris K, Micantonio T, Piccolo D, Fargnoli MC. Dermoscopic features of actinic keratosis. J Dtsch Dermatol Ges 2007; 5:970.
Topic 13712 Version 15.0

References