lesion, usually within the first year after stopping. Alcohol Although the synergistic effect of alcohol with smoking in the development of oral cancer is beyond doubt, there is no clear evidence that alcohol is involved in the development of leukoplakia, but it does appear to have some influence. Excessive use of a high alcohol-containing mouth wash (> 25%) may cause a grey plaque to form on the buccal mucosa, but these lesions are not considered true leukoplakia. Sanguinaria Sanguinaria (Bloodroot) is a herbal extract that is included in some toothpastes and mouthwashes. Its use is strongly associated with development of leukoplakia, usually in the buccal sulcus. This type of leukoplakia has been termed "sanguinaria associated keratosis" and more than 80% of people with leukoplakia in the vestibule of the mouth have used this substance. Upon stopping contact with the causative substance, the lesions may persist for many years. Although this type of leukoplakia may show dysplasia, the potential for malignant transformation is unknown. Ultraviolet radiation Ultraviolet radiation is believed to be a factor in the development of some leukoplakia lesions of the lower lip, usually in association with actinic cheilitis. Micro-organisms Candida in its pathogenic hyphal form is occasionally seen in biopsies of idiopathic leukoplakia. It is debated whether candida infection is a primary cause of leukoplakia with or without dysplasia, or a superimposed (secondary) infection that occurs after the development of the lesion. It is known that Candida species thrive in altered tissues. Some leukoplakias with dysplasia reduce or disappear entirely following use of antifungal medication. Smoking, which as discussed above can lead to the development of leukoplakia, can also promote oral candidiasis. Candida in association with leukoplakia should not be confused with white patches which are primarily caused by candida infection, such as chronic hyperplastic candidiasis ("candidal leukoplakia"). The involvement of viruses in the formation of some oral white lesions is well established, e.g. Epstein-Barr virus in oral hairy leukoplakia (which is not a true leukoplakia). Human papilloma virus (HPV), especially HPV 16 and 18, is sometimes found in areas of leukoplakia, however, since this virus can be coincidentally found on normal, healthy mucosal surfaces in the mouth, it is unknown if this virus is involved in the development of some leukoplakias. In vitro experimentation has demonstrated that HPV 16 is capable of inducing dysplastic changes in previously normal squamous epithelium. Epithelial atrophy Leukoplakia is more likely to