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. Clinicopathologic, virologic, cytomorphometric, and genetic differences support the view that these two types of carcinoma are fundamentally different and that HPV-negative carcinoma is not simply carcinoma where viral DNA has not been able to be identified. The traditional view of HPV-negative carcinoma is that it is caused by chronic tissue damage from itching and scratching. However, itching and scratching alone do not explain the close association of carcinoma with lichen sclerosus, nor the absence of such an association with other itchy conditions such as eczema or psoriasis. These observations point to a role for lichen sclerosus in the pathogenesis of vulvar carcinoma. Most observations about the etiology of lichen sclerosus can be grouped into its immunogenetic or genital predisposition, or the Köbner phenomenon. In the itch-scratch-lichen sclerosus hypothesis, lichen sclerosus is postulated to occur as a Köbner phenomenon in women with the susceptible immunophenotype who scratch because of genital irritants such as urine, vaginal secretions and smegma, and psychological factors. Lichen sclerosus, itself a very itchy condition, contributes to a vicious cycle of itching and scratching which leads to superimposed lichen simplex chronicus, squamous cell hyperplasia, and ultimately carcinoma. The itch-scratch-lichen sclerosus hypothesis reconciles the traditional itch-scratch hypothesis with the strong clinicopathologic association of lichen sclerosus with carcinoma.