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Actinic Cheilosis: Etiology, Epidemiology, Clinical Manifestations, Diagnosis, and Treatment

Course Number: 400

Etiology and Epidemiology

The etiologic factors associated with SC are the same as those associated with AK and cutaneous SCC, namely the cumulative effect of exposure to ultraviolet radiation (UVR), skin phenotype, genetic predisposition, increasing age, male gender, outdoor occupation and leisure activities, geographic latitude of residence, failure to use lip-protective agents, and host immune status. 1,4 The risk associated with smoking, alcohol consumption, and poor oral hygiene is unclear.1

Chronic exposure to UVR is the most important cause of SC.1,5-10 UVR is generally divided into 3 categories: UV-A (wavelength 315-400 nm), UV-B (wavelength 280-315 nm), and UVC (wavelength 100-280 nm). The atmosphere efficiently filters out most UVR and only about 5% of solar radiation reaches the earth’s surface (96.65% UV-A, 3.35% UV-B, insignificant UV-C).8 UV-B radiation reaches the epidermal cell layer to induce very specific mutational changes which serve to both initiate and promote dysplastic changes in the epidermis. UV-B radiation is principally responsible for carcinogenic risk, but UV-A radiation penetrates to reach the underlying dermis to also contribute to the risk.7,8,11,12 AK and SC serve as clinical dose-meters for chronic UVR exposure.13

UV-B directly damages the DNA at adjacent pyrimidines resulting in double cytosine (CC) to double thymidine transition mutations.6,8,14 This mutation is so specific that it is referred to as the “UV signature” or “UV fingerprint.”6,14‑16 The characteristic UV-B mutations target tumor suppressor genes, the most notable being p53.8,10,11,17 Normal p53 acts to allow repair of damaged DNA or induce apoptosis (controlled cell death) when the DNA damage is nonrepairable.6,8,11,16

UVR-induced mutations to the p53 gene lead to impaired tumor suppressor activity. Other UVR-induced molecular alterations affect the normal activity of cyclooxygenases, signal transducer and activator of transcription proteins, fibroblast growth factor, cytokeratin, and cytotoxic killer cells.1 While these effects contribute to the molecular evolution of SC to SCC, their reliability as clinical markers with predictive or staging value remains unclear.1,11

Since SC occurs more frequently in light-complected than darker-complected individuals, skin phenotype (Table 1) is an important predisposing factor determining the risk for SC.4,8,12,13,18,19 The increased melanin in the lip vermilion of dark-complected individuals appears to provide increased protection from the harmful effects of UVR.4,11 It is of note that SCC of the lower lip occurs 30 times more frequently in white than in black individuals.4

Table 1. Skin Phenotypes.18

Skin type I: burns easily, never tans

Skin type II: burns easily, tans minimally

Skin type III: burns moderately, tans gradually

Skin type IV: burns minimally, tans well

Skin type V: rarely burns, tans profusely

Skin type VI: deeply pigmented, never burns

Individuals whose poor sun exposure habits began early in life are at greatest risk for developing SC.13,20 Persons with SC tend to be over the age of 45 years and men are afflicted more frequently than women by a 2.8 to 1 ratio.21 It has been postulated that women are at lesser risk because they experience less chronic sun exposure and are more likely to use a lip protective agent such as lipstick or sunblock.1

While the association between tobacco use and SC is unclear, the habit of leaving a cigarette on the lip has been reported to increase the risk of labial SCC.10,22 Immune competency, specifically scenarios of immunosuppression, appears to profoundly increase the risk of developing AK and SCC of the lip.22-26

The true incidence of SC is unknown; however, the likelihood that SC will progress to SCC of the lip vermilion is 2.5 times higher than the risk of AK progressing to cutaneous SCC.27-28 SCC of the lip tends to be more severe in those patients who develop SC at a younger age and in those with severe clinical and histologic evidence of inflammatory infiltrates at the time of diagnosis.1 The progression of SC to SCC of the lip may take 2 to 3 decades.29

The incidence of SCC of the lip in the United States has declined from 1.4 per 100,000 in 1992 to stabilize at 0.7 per 100,000 in 2008."21 This represents approximately 7% of all oral cavity and pharynx cancers. The 5 years survival rate for lip cancer is 90.9%. It should be noted, that approximately 15% of the patients with SCC of the lower lip will develop a second primary on the lip vermilion.28,30