Does lichen sclerosus play a central role in the pathogenesis of human papillomavirus negative vulvar squamous cell carcinoma? The itch-scratch-lichen sclerosus hypothesis

In the past decade, two types of vulvar squamous cell carcinoma (SCC) have been delineated, Human papillomavirus (HPV) positive and negative. Clinicop athologic, virologic, cytomorphometric, and genetic differences support the view that these two types of carcinoma are fundamentally different and tha t HPV-negative carcinoma is not simply carcinoma where viral DNA has not be en able to be identified. The traditional view of HPV-negative carcinoma is that it is caused by chronic tissue damage from itching and scratching. Ho wever, itching and scratching alone do not explain the close association of carcinoma with lichen sclerosus, nor the absence of such an association wi th other itchy conditions such as eczema or psoriasis. These observations p oint to a role for lichen sclerosus in the pathogenesis of vulvar carcinoma . Most observations about the etiology of lichen sclerosus can be grouped i nto its immunogenetic or genital predisposition, or the Kobner phenomenon. In the itch-scratch-lichen sclerosus hypothesis, lichen sclerosus is postul ated to occur as a Kobner phenomenon in women with the susceptible immunoph enotype who scratch because of genital irritants such as urine, vaginal sec retions and smegma, and psychological factors. Lichen sclerosus, itself a v ery itchy condition, contributes to a vicious cycle of itching and scratchi ng which leads to superimposed lichen simplex chronicus, squamous cell hype rplasia, and ultimately carcinoma. The itch-scratch-lichen sclerosus hypoth esis reconciles the traditional itch-scratch hypothesis with the strong cli nicopathologic association of lichen sclerosus with carcinoma.