Actinic, or solar, keratoses (AKs) are commonly encountered intraepidermal, sun-induced skin lesions. (1,2) AKs are markers of cumulative ultraviolet (UV) skin exposure and should be considered the precursors of at least 60% of invasive squamous cell carcinoma (SCC) of the skin (3-6); up to 40% of SCC are estimated to rise de novo. As part of a disease continuum, it is not surprising that AK and SCC share the same genetic alterations, morphology, and are frequently contiguous (FIGURE 1).
A growing body of histologic evidence suggests that AK should be regarded as early SCC in situ, (7-9) since AK is frequently the initial lesion in the sequence of tumor progression leading to SCC. (8) Biopsy sampling of sun-damaged skin, AK lesions, and SCC provides evidence of histologic similarities and shows the cellular progression of AK to SCC. (9) One study used step-wise biopsy sections to determine the presence of cutaneous malignant tumors in patients who were initially diagnosed by biopsy sampling as having AK. (8) On further analysis, histologic findings of deeper sections showed that 20% of patients were found to have malignant lesions (SCC or basal cell carcinoma [BCC]). BCC and SCC, both nonmelanoma skin cancers (NMSCs), are the most common skin cancers in the world. (10)
It is impossible to determine which AK lesions may progress to SCC, (11) and predictions on the progression vary considerably. Two well designed, prospective longitudinal studies suggest that the yearly rate of progression of an AK lesion to invasive SCC in an average-risk person in Australia is between 8 and 24 per 10,000, (3,12) while a study with data from Arizona found a rate of progression of 12% over 5 years. (13) Additionally, about 25% of AK lesions spontaneously recede without treatment, and some SCC arise de novo.
EPIDEMIOLOGY
Actinic keratosis is likely underdiagnosed and underreported, partially because separating AK from SCC is a challenge and partially because it is difficult to track, since reports of AK diagnosis are not included in cancer registries. In northern hemisphere populations, 11% to 25% of adults have at least one AK, compared with 40% to 60% of adult Australians, who live closer to the equator. (10) Epidemiologic studies from Australia, Wales, Sweden, and the northern United States demonstrate that the incidence of AK and NMSC is increasing in both men and women, with an average increase of 3% to 8% since the 1960s. (14-16) Perhaps more alarming is that the incidence is increasing in persons younger than 40 years of age. (16)
RISK FACTORS
Risk factors for NMSC are also risk factors for AK because of the direct relationship of AK to SCC. The majority of all skin cancers are thought to be caused by high intensity or cumulative exposure to UV radiation. (10,15) There are no "safe" UV rays: UV-B is the primary carcinogen, while UV-A is synergistic. (14)
General risk factors
A culture that promotes tanning, as well as clothing styles that expose skin, increased outdoor activities, and increased longevity, contribute to UV...