Australian Dental Journal

Transcription

1 Australian Dental Journal The official journal of the Australian Dental Association Australian Dental Journal 2010; 55:(1 Suppl): doi: /j x NW Savage,* C McKay, C Faulknerà *School of Dentistry, The University of Queensland and Maxillofacial Unit, The Royal Brisbane and Women s Hospital. St John s Institute of Dermatology, Guy s and St Thomas Hospital, London, United Kingdom. àdepartment of Dermatology, The Royal Brisbane and Women s Hospital. ABSTRACT Actinic cheilitis is a potentially premalignant condition involving predominantly the vermilion of the lower lip. The aim of the current paper was to review the clinical presentation of actinic cheilitis and demonstrate the development of management plans using a series of cases. These are designed to provide immediate treatment where required but also to address the medium and long-term requirements of the patient. The authors suggest that the clinical examination of lips and the assessment of actinic cheilitis and other lip pathology become a regular part of the routine soft tissue examination undertaken as a part of the periodic examination of dental patients. Early recognition of actinic cheilitis can allow the development of strategies for individual patients that prevent progression. These are based on past sun exposure, future lifestyle changes and the daily use of emollient sunscreens, broad-brimmed hats and avoidance of sun exposure during the middle of the day. This is a service that is not undertaken as a matter of routine in general medical practice as patients are not seen with the regularity of dental patients and generally not under the ideal examination conditions available in the dental surgery. Keywords: Actinic cheilitis, lips, sun damage. INTRODUCTION This paper looks specifically at lip disease related to sunlight exposure. In doing so it extends the scope of routine examination in general dental practice and expands the responsibility encompassed within the professional examination. The current authors believe that dental practitioners are in an ideal professional position to provide this service. Not only are dental practitioners familiar with the normal appearance of the lips but this is an area that is difficult to ignore when examining the adjacent soft and hard tissues of the mouth. Dental practitioners are an appropriate professional group to undertake this screening as they provide a regular frequency of examination at general practice level not usually seen in any other area of health care, see a patient cohort over an extended period of their lives and have the clinical requirements for a rapid, routine and comprehensive soft tissue examination of the lips and visible facial skin. The intent is not to extend the detailed diagnostic skills of dental practitioners but to provide a patient service that can rapidly recognize abnormality, irrespective of the specific diagnosis, and allow early referral to the patient s medical practitioner, dermatologist or specialist in oral medicine or oral and maxillofacial surgery. It focuses specifically on early recognition and the support of the patient s well-being. The level of anticipated demand and benefit that might justify and drive this practice initiative is defined by the community disease load. Current lip cancer statistics in Australia 1 indicate 1000 new cases per year over the 10-year period from 1996 to Lip cancer is now within the list of top 10 malignancies in males. There are two further characteristics of malignant disease of the lips. Firstly, it is almost exclusively related to squamous epithelial lesions which may have a 20- to 30-year development time and, secondly, actinic cheilitis cheilosis should be regarded as a premalignant condition. Clearly an opportunity exists for early recognition of lip changes and interceptive strategies to prevent further progression. Normal anatomy The action of actinic radiation is restricted to the skin and vermilion (lip-stick surface) of the lip and the interactions and boundaries of these are important in clinical assessment. The vermilion is bounded on the 78 ª 2010 Australian Dental Association

2 inner aspect by the mucocutaneous junction which tends to be a narrow zone but showing progressive change from the keratinized vermilion to the nonkeratinized mucosal aspect of the lip. Minor mucous glands are often present on the vermilion adjacent to the mucocutaneous junction. These become prominent as scattered red dots representing the inflamed pores of the glands during cheilitis glandularis, a condition with reduced flow from the glands and reduced clearance of the ducts and hence peri-ductal inflammation. This often occurs in actinic cheilitis. The position of the mucocutaneous junction may also change with both cosmetic treatment to the lips and repositioning of the support provided for the lips by the anterior maxillary and mandibular teeth. The exposed mucosal surface may undergo metaplasia to a keratinized epithelium and this represents a reactive response of the tissues and a change to the position of the mucocutaneous junction. This metaplastic potential is exploited following a vermilionectomy (lip shave) and advancement of the mucosa to replace the vermilion where it is sutured to the skin. This change identifies a difference in reactivity of the two surfaces which almost certainly relates in large part to the anatomical exposure to sunlight. The outer margin to the vermilion is the vermilion border itself. This is a sharp dividing line between the keratinized vermilion without adnexal structures (pilosebaceous units and sweat glands) to the thin skin of the lip. This line is an important boundary and its loss is one defining feature of actinic cheilitis. Understanding the geographic variation of the lip is the first step in identifying change. The second is recognition that the lips will often undergo a rapid and permanent change with disease. A consideration of normal anatomy shows that the affected lips will have a reduced protective and functional capacity. Moreover, between individuals there is not only a variable response to the same level of actinic exposure but a variable return to the premorbid status. Patients will often relate clinically apparent sun damage to lips to a single significant exposure with sunburn whilst others seem resistant to the same apparent exposure. It is also important in this section of discussion to identify the issue of co-morbidities. This is not uncommon on the lip and an example is actinic cheilitis and angular cheilitis. These are very different conditions, often contributed to but not primarily caused by similar factors, e.g., lip anatomy, but treated clinically in a very different manner. It is also appropriate at this early stage in the discussion to remove the often used term of photo-ageing. There must be a recognition of agerelated change but the use of photo-ageing dilutes the significance of sun-induced change. This is not suggesting that photo-ageing does not occur as it is well characterized and certainly involves the lips. However, genotoxic stresses such as ultraviolet radiation exposure can only be responded to by activation of DNA damage responses 2,3 at a reasonable and individual level. Senescence (permanent cell cycle arrest) and carcinogenesis (decreased expression of DNA damage response genes) are frequent accompaniments of high exposure to ultraviolet radiation and hence the emphasis taken in this paper on the spectrum of change that may present under the term actinic cheilitis and downstream sequelae. Actinic cheilitis cheilosis Actinic cheilitis attracts a number of clinical definitions varying from premalignant to relatively bland descriptors of the sun-damaged lip. Histologically, however, it is seen as a premalignant condition 4 and this is the position favoured in the current paper. It does not predict progression to malignancy but raises the very real risk in a small number of patients who do in fact present with squamous cell carcinoma on the lip each year. Conversely, almost all lip carcinomas are associated with pre-existing actinic cheilitis and the particular histological type of actinic cheilitis does not correlate with progression to squamous cell carcinoma. 5,6 The expected demographic of a patient with actinic cheilitis is usually fair skinned, middle aged and with a history of accumulated sun exposure to the lower lip where the vermilion receives a high dose of ultraviolet radiation because it lies at right angles to the midday sun. It is also poorly protected by melanocytes or keratin. The upper lip is rarely affected. 7 This same demographic also describes the typical patient with general skin changes from sun exposure, so it is important not to view actinic cheilitis in isolation but as part of the spectrum of skin change in an individual. Actinic cheilitis develops slowly over an extended period and with a greater prevalence in outdoors workers. This is also the group most likely to be regular cigarette users and the coincident application of radiation and chemical carcinogens to the one site is of concern with a synergistic effect amplifying the summed individual effects of ultraviolet radiation and cigarette use. It is relevant that the majority of squamous cell carcinomas on the vermilion of the lip seem to favour the right side, and this is the recognized site for habitually holding a cigarette. A recent study 8 has detailed the clinical findings and frequency of clinical signs of actinic cheilitis in a group of patients. These are detailed in Table 1. Although patient numbers are limited in this study, the results correlate with the authors practices and allow an understanding of the development of actinic cheilitis. Hyperkeratosis is often cited as the dominant finding and a diagnostic feature of actinic cheilitis but in fact dryness and atrophy are a more frequent clinical finding. The early presence of atrophy is significant as ª 2010 Australian Dental Association 79

3 NW Savage et al. Table 1. Clinical signs associated with actinic cheilitis 8 Sign % of patients Dryness 100 Atrophy 72 Scaly sites 65 Swelling 62 Erythema 59 Ulceration 59 Vermilion border indistinct 59 Transverse fissures 48 White plaques 41 Crusting 34 Blotchiness 28 Tissue pallor 17 it identifies the earliest sign the clinician should be aware of and explains the significance of allowing actinic cheilitis to develop. A typical description of actinic cheilitis is a white lip plaque but this is a late reactive change occurring after atrophy and, given the tissue fragility inherent in atrophy, it is potentially useful for the integrity of the lip epithelium. Such hyperkeratotic plaques however, are frequently progressive and the early homogeneity often changes to an opaque non-homogeneous plaque requiring at least biopsy and histological assessment. A review of the histological features of actinic cheilitis 9 shows negligible hyperkeratosis in 14% of cases and the authors speculate that this indicates initial damage at the level of the basal cell layer. This is in keeping with the current premise that the initial damage is epithelial with early atrophy. This is amplified by reflected radiation from the subsequent development of solar elastosis with the progression of further epithelial damage and a reduced capacity of the lip to repair. Actinic cheilitis is a persistent chronic condition that is present in all seasons of the year, not just summer where acute sun exposure can cause congestion, erythema, vesicles, bullae, desquamation and even ulceration. The vermilion edge loses its plasticity which can be noted by the formation of wrinkles perpendicular to the long axis of the lip. Although squamous cell carcinoma may develop without ulcer formation, it should always be considered if an ulcer develops within an area of actinic cheilitis. Other clinical signs that may indicate malignant change include: recurrent ulceration and failure to heal; red and white blotchy appearance with loss of the vermilion border; persistent crusting and flaking; generalized atrophic appearance with focal areas of opaque white thickening; 7 and focal induration or nodule formation. The difficulty with clinical descriptors is that whilst they can be of assistance they do not consider the often atypical presentation of lip pathology. To focus on a textbook description of a lip squamous cell carcinoma as an indurated, granular, exophytic and probably ulcerated lesion excludes the numerous lip lesions that do not fulfil these criteria. The dominant clinical rule is to identify any abnormality and achieve an early and accurate diagnosis. In many cases this will involve referral of lesions with a bland clinical presentation but these are just the lesions that respond to early intervention and management and have very low metastatic potential. A detailed patient history will usually reveal recurrent crusting restricted to one or two sites with very slow resolution, often over a period of months. Consideration of the primary atrophic change stresses the tissue fragility of actinic cheilitis and introduces the involvement of the superficial dermis. This latter zone undergoes a change referred to as solar elastosis in 100% of reported cases. 4,8 This term refers to a loss of both cellularity and distinction of the normal fibrillar elastin composition of the dermis. The upper dermis is replaced by accumulations of thickened, curled and serpiginous fibres forming tangled masses. 4 The tissues have in effect lost their normal microanatomy and, along with it, the normal healing process and hence the prolonged resolution time of crusted ulcerations on the vermilion. Table 2 details a number of histological findings seen commonly in actinic cheilitis and their frequency of occurrence. There is almost certainly some bias in these findings as the sites selected for histology are inevitably clinically significant in so far as their clinical presentation introduces an element of uncertainty that requires histology for a definitive diagnosis. Notwithstanding this, the presence of dysplasia and solar elastosis in 100% of cases is worrying as an immediate histological diagnosis and in the progression of the actinic cheilitis. Solar elastosis reflects solar radiation and may well amplify damage to the superficial tissues. Considering that only 5 to 10% of ultraviolet radiation is reflected from the skin and up to 70% is absorbed, 10 solar elastosis may provide some protection to deeper tissue levels but the surface vulnerability is increased. Dysplasia in actinic cheilitis is usually reported as mild but the presence of inflammation is associated with epithelial atypia and may be predictive of an adjacent squamous cell carcinoma. 6 Reviewing the histological features in Table 2, the top four, with an incidence of 100%, are worrying with respect to the future progression of actinic cheilitis. Table 2. Histological features of actinic cheilitis 8 Feature % of cases Dysplasia 100 Solar elastosis 100 Inflammation 100 Vasodilatation 100 Hyperplasia 86 Hyperkeratosis 59 Epithelial atrophy ª 2010 Australian Dental Association

4 There is an acknowledgement among clinicians that lip squamous cell carcinoma is often reported alone with no coincident diagnosis of actinic cheilitis. There is also the possibility that lip squamous cell carcinoma is reported as non-melanoma skin cancer and so the registry numbers for this condition are likely to be under-reported. The translation of the above information to the clinical setting is not only the expected professional responsibility of a high index of suspicion of any lip change, irrespective of the type, but also the enhanced responsibility to recognize early actinic cheilitis at a stage when interception may be possible. In addition it emphasizes the role of histology in clinical assessment and particularly the significance of the hallmark change of solar elastosis and its possible impact on progression. Assessment and recording clinical information An unfortunate clinical fact is that most treatment is interceptive. This need not be the case with actinic cheilitis but it does require the early identification of atrisk individuals and their cooperation in ongoing surveillance. This group will usually have a fair skin type (compare with a skin area not exposed to sun) and have either regular occupational exposure or recreational exposure to ultraviolet radiation which is likely to be cumulative over a 5- to 20-year period. Actinic cheilitis is more often seen in men in their fourth to eighth decade of life. The patient may have a past history of actinic keratoses on the skin, non-melanoma skin cancer or malignant melanoma. The clinical record becomes as important for this early group to record development of atrophic change as it is for patients with recognized actinic cheilitis. In the former group, the success of education and interceptive strategies is readily monitored and a clinically useful indicator. In the latter group, the detailed clinical description is critical to allow an accurate assessment of change and possible progression. The main current recording instruments are: (1) a detailed clinical description; (2) clinical measurement with a ruler; (3) precise diagrams; (4) clinical photography. Digital clinical photography has revolutionized the recording of dermatological records. It accurately localizes lesions anatomically, provides an embedded clinical description of the status at any one examination and allows a ready identification of either progression or regression of lesions. The latter is important as skin changes resulting from ultraviolet exposure often follow a cyclical clinical presentation and it is important not to underestimate a change simply because the lesion is less clinically obvious at one point in time. Clinical assessment is important and provides an immediate statement of the lip presentation. It is important to carry out this assessment with adequate lighting, magnification if available, and with gloves so the lip surface can be palpated. In a balanced assessment, this clinical examination must be combined with a range of other factors including: patient age; skin type; past sun exposure; immune status; anticipated sun exposure; lifestyle factors (tobacco and alcohol); current clinical presentation; dual or multiple pathoses; and immediate, medium and long-term management. The five cases to be detailed are examples of the type of clinical presentations, examinations and the development of short, medium and long-term plans which will deal with sites of concern and management of the lip in the medium and longer time frames. The multifocal and variable tissue changes in actinic cheilitis are shown clearly and this stresses the care required in assessment of not only the entire lip but each individual site. Figure 1 shows an adolescent patient with a broad exposed vermilion on the lower lip and clear evidence of dryness and tissue fragility from heavy sun exposure. He has a transverse midline fissure that has ulcerated on a number of occasions and currently presents a very fragile zone highly likely to continue to break down in the future. There is a recent presentation of a melanotic macule on the right vermilion and, as a coincidental finding, shallow commissural pits. His pale freckled skin, outdoor lifestyle and active participation in sport provides a challenge both in immediate clinical decision-making and particularly in the medium to long term. He currently presents as a mild actinic cheilitis and the potential in this patient for significant progression is very concerning. The overall changes cover genetic, developmental and acquired causes and a prescribed programme for this patient must identify any sites requiring early active management and introduce a plan to improve the current presentation of the lip epithelium as well as provide long-term protection from further ultraviolet damage. A suggested plan might include: (1) initial discussion with the patient and family about the Fig 1. Early presentation of actinic cheilitis in a young patient. The vermilion presents generalized changes with a midline transverse fissure and melanotic macule. ª 2010 Australian Dental Association 81

5 NW Savage et al. (a) (b) Fig 2. (a) Actinic cheilitis in a young patient with generalized atrophy and a non-homogeneous keratotic plaque with the right lateral aspect showing a granular surface. (b) A second younger patient with bilateral keratotic plaques overlying the generalized atrophy of actinic cheilitis. diagnosis and the potential for development of neoplastic lesions in the future; (2) limiting sun exposure between 10 am and 2 pm (or 11 am and 3 pm in daylight saving time), wearing a protective broadbrimmed hat, using an SPF30+ broad spectrum and water resistant sunscreen lip balm applied generously and reapplied at least every two hours when outdoors; (3) the prescription of an emollient to moisturize the lip; (4) early review of the lip fissure to ensure progress is satisfactory; (5) a decision on the melanotic macule, review or excise. In such a young patient this range of decisions is difficult in general practice and benefit may be derived from specialist referral but maintaining surveillance within the general practice setting should always be continued. The involvement of the family is also of primary importance as it is unlikely that such a young sportsperson will apply the necessary care without family guidance. Any scepticism encountered with such young patients and their families is easily placed in perspective when facial photographs of some of our prominent sportspersons show advanced actinic cheilitis. Figures 2a and 2b show not uncommon initial presentations of actinic cheilitis. This does not equate to the early manifestations of actinic cheilitis but merely the time at which it was noted. Both patients are fair skinned, young and with a past history of significant sun exposure but relatively limited current exposure. The typical features of epithelial atrophy, hyperkeratotic plaques, blotchy erythema and indistinctness of the vermilion border are present and should be detailed in both text and photographically as the description given fits both cases but the clinical presentation is different. The essential decisions and treatment plans must recognize both the immediate assessment requirements and particularly the ongoing management to the anticipated lifespan of both patients which is likely to be a further 50 years. The initial clinical assessment of hyperkeratotic lip plaques should always result in a clear decision to review, biopsy or excise. The assessment criteria are simple but clinically demanding and focus on the determination of either homogeneity or non-homogeneity. Keratotic plaques that are homogeneous are consistent across the lesion in all clinical parameters. They do not show any variation in appearance, texture (induration) or tissue mobility on the underlying dermis (fixation compared with adjacent or contralateral normal tissues). Any doubt during the clinical examination places the lesion in the non-homogeneous category. Some lesions are visibly homogeneous but difficult to examine due to the thickness of keratin and again they should be regarded as non-homogeneous and addressed as such. Figure 2a shows an extensive keratotic plaque extending from the left of midline to involve over half of the right vermilion. The central zone carries a focal erosion but the overall presentation of this area is nonhomogeneous and any latitude given to this site should be limited with early review in two weeks. The lateral aspect of the keratotic area on the right vermilion is perhaps blander in presentation but of greater clinical concern. The surface presents a granular keratosis that is difficult to examine and requires histology for a confident diagnosis. Overall, this lip plaque is nonhomogeneous and the immediate requirement for histology should be discussed with the patient but in context with the medium to long-term value of vermilionectomy, either partial or total. This patient is an excellent example of the value of intervention providing a very favourable long-term outcome. The treatment must be supplemented with the ongoing requirement for limiting sun exposure, broad-brimmed hat and generous application of SPF30+ broad spectrum and water resistant sunscreen applied two hourly when outdoors. This is standard advice applicable to all patients with actinic cheilitis and sound advice in the prevention of this condition in those without actinic cheilitis, particularly outdoor workers and sportspersons. Figure 2b shows a not dissimilar presentation but with keratotic plaques on both sides of the vermilion. The keratin density on the right side made clinical examination difficult and the patient made an informed decision and underwent excision of this area with an 82 ª 2010 Australian Dental Association

6 excellent cosmetic result. Her current level of sun exposure is virtually nil and she decided to continue review of the lip with daily attention with an emollient sunscreen and the routine sun hygiene steps listed above. In a cooperative and responsible patient this is an acceptable position and achieves the medium and longer-term goals of lip care. The excision of keratotic plaques requires experience and is an unsuitable procedure for general practice. The anticipated outcome from the patient s perspective will focus on aesthetics and it is important to achieve this but not compromise the reason for undertaking the procedure in the first place. In the current case, an unaltered surface contour without distortion of the vermilion border and the fine surface scar without extension onto adjacent skin readily achieved this. Very acceptably to the patient, the procedure is also very suitable for local anaesthesia. Figures 3a and 3b show cases with clearly nonhomogeneous keratotic plaques overlying an actinic cheilitis. They both require histology for a definitive diagnosis. The precise features of non-homogeneity require documentation in the patient records but it is the presence of non-homogeneity that demands histology rather than the specific features that make a lesion non-homogeneous, e.g., crusting, nodularity and surface contour. In addition, the physical examination to determine induration and fixation may override the visible features as they strongly suggest malignancy. The latter features are particularly important in site selection and operative biopsy technique. Both patients are in their sixties with life expectancy exceeding 20 years so management involves immediate assessment as well as a long-term plan. Biopsy of both keratotic sites seen in Fig 3a is required, preferably excisional with an anticipated diagnosis of dysplasia associated with the actinic cheilitis, which was confirmed. As a general rule small areas that can be managed with a single excisional procedure and where the anticipated histological diagnosis is not neoplastic, should be treated as such rather than re-visited with a final procedure. However, this may not be possible in many cases and incisional shave biopsies are useful in determining the degree of dysplasia or neoplasia and then allow a reasoned treatment protocol to be discussed with the patient. The case in Fig 3b has the additional complication that the patient is a cigarette user. Clinical examination of the keratotic plaque readily confirms the presence of induration (loss of normal tissue texture and hardness compared with adjacent or contralateral sites) and fixation (loss of normal tissue mobility due to an infiltrative process) and the clinical diagnosis of squamous cell carcinoma was confirmed histologically. An appropriate treatment for this patient focused on the urgent management of the squamous cell carcinoma with surgical excision. The medium-term options were also reviewed for the actinic cheilitis and the choices were to review or to include a vermilionectomy in the resection procedure. (a) (b) Fig 3. (a) Generalized actinic cheilitis in an older patient with advanced non-homogeneous plaque formation. (b) A second older patient and tobacco user with a small squamous cell carcinoma on the left vermilion in a background of actinic cheilitis. Treatment of actinic cheilitis The overall philosophy for treatment, as previously discussed, includes a thorough assessment of the patient. This is to ensure that any required short-term treatment is followed by a reasonable medium to longterm management plan. It is particularly important to remember that dysplasia at some level is an intrinsic component of most cases of actinic cheilitis. Dysplasia is an unpredictable tissue change in the progression from normal epithelium to malignancy and, whilst malignant transformation is not inevitable, it is an important consideration in treatment planning. It is also the reason why it is so important to gather comprehensive patient information encompassing previous sun exposure history, current status, anticipated lifestyle changes, and likely compliance with intervention and preventive strategies. The plans for an office worker with limited exposure will clearly be very different from that prepared for a professional outdoor sportsperson. Squamous cell carcinoma is the most common cancer of the oral cavity and this includes the lip. As with actinic keratoses, the exact rate of transition of actinic cheilitis to squamous cell carcinoma is not known. The ª 2010 Australian Dental Association 83

7 NW Savage et al. five-year survival statistics are very favourable but this should be tempered with the knowledge that squamous cell carcinoma of the lip is estimated to metastasize in up to 11% of cases. 11 Various treatment methods have been used in the management of actinic cheilitis and these can be both surgical and non-surgical and include cryotherapy, electrosurgery, topical retinoids, 5-fluorouracil cream, imiquimod cream, photodynamic therapy, carbon dioxide laser ablation and surgical vermilionectomy. These treatments are mentioned for the completeness of this paper and it is the authors opinion that they are unsuitable for general practice and require specialist prescription. Actinic cheilitis is histologically and clinically analogous to actinic keratosis on non-labial skin. As such, the treatments are essentially similar. However, due to the specific location and anatomy of this site, some treatments that are used commonly on the skin are very difficult when used on the lip, with a much greater incidence of mild to severe localized side effects. Therefore, often in clinical practice, the treatment options are more limited than with non-labial skin. All patients with actinic cheilitis, whether mild, moderate or severe should be advised to limit further sun exposure especially between 10 am and 2 pm (or 11 am and 3 pm in daylight saving time), wear a protective broad-brimmed hat, use a SPF30+ broad spectrum sunscreen lip balm regularly (every morning) with re-application every two hours when outdoors. Further treatment choices will depend on the nature and extent of the disease and other patient considerations. Mild cases can be reviewed regularly and if there is any indication of clinical progression they should be referred to the patient s medical practitioner, dermatologist or specialist in oral medicine for further assessment, investigation and possible treatment. Any patient with more significant disease should be referred immediately. In summary, actinic cheilitis is a common and greatly under-recognized condition in Australia. Dental practitioners are in an ideal position to provide a regular screening service to patients as a routine part of the general soft tissue examination. 13 It adds minimally to a dental recall appointment and has the potential to provide a significant service to patients. There is also the opportunity to provide advice on managing sun exposure and this is a common thread throughout this paper. Unfortunately, this service and information is not provided in many medical consultations simply because of the nature of the consultation and less opportunity for full skin examination including the lips. Dental practitioners have an opportunity to support medical colleagues and whilst many currently undertake this responsibility with their patients, there remains a valuable opportunity for further expansion into dental practice. REFERENCES 1. Australian Institute of Health and Welfare. Australian Cancer Incidence and Mortality Books. Lips, oral cavity and pharynx, URL: acim. Accessed August Nakanishi M, Niida H, Murakami H, Shimada M. DNA damage responses in skin biology implications in tumour prevention and aging acceleration. J Dermatol Sci 2009;56: Martinez A, Brethauer U, Rojas IG, et al. Expression of apoptotic and cell proliferation regulatory proteins in actinic cheilitis. J Oral Pathol Med 2005;34: Weedon D. Weedon s skin pathology. 3rd edn. Edinburgh: Churchill Livingstone, 2010: , Main JH. Actinic cheilitis and carcinoma of the lip. J Can Dent Assoc 1994;60: Pimentel DRN, Michalany N, Alchorne M, Abreu M, Borra RC, Weckx L. Actinic cheilitis: histopathology and p53. J Cutan Pathol 2006;33: Picascia DD, Robinson JK. Actinic cheilitis: a review of the etiology, differential diagnosis, and treatment. J Am Acad Dermatol 1987;17: Cavalcante ASR, Anbinder AL, Carvalho YR. Actinic cheilitis: clinical and histological features. J Oral Maxillofac Surg 2008;66: Markopoulos A, Albanidou-Farmaki E, Kayavis I. Actinic cheilitis: clinical and pathological features in 65 cases. Oral Dis 2004;10: Lundeen RC, Langlais RP, Terezhalmy GT. Sunscreen protection for lip mucosa: a review and update. J Am Dent Assoc 1985;111: Lund HZ. How often does squamous cell carcinoma of the skin metastasize? Arch Dermatol 1965;92: Lundeen RC, Langlais RP, Terezhalmy GT. Sunscreen protection for lip mucosa: a review and update. J Am Dent Assoc 1985;111: Kutcher MJ, Rubenstein D. Fifteen inches from cancer: early recognition of facial lesions by the dentist. Compend Contin Educ Dent 1995;16: Address for correspondence: Dr Neil W Savage School of Dentistry The University of Queensland 200 Turbot Street Brisbane QLD n.savage@uq.edu.au 84 ª 2010 Australian Dental Association