Clinical aspects of epidermodysplasia verruciformis

Abstract

Thirteen patients with epidermodysplasia verruciformis (EV) were studied over a period of 7 years. EV is a rare genodermatosis characterized by a generalized infection with a specific group of human papilloma virus (HPV) and a propensity for developing skin malignant tumours in 30%-50% of patients. The diagnosis of EV was confirmed by histopathological and immunohistochemical findings. Three of our patients had the benign form of EV, which is characterized by monomorphous lesions and no malignant changes, whereas 10 had the malignant form, which is characterized by polymorphic lesions and development of cutaneous malignant tumours. All EV patients with the malignant form developed multiple skin tumours (77%). They started to appear at age 20, predominantly on the forehead (50%). Most were squamous cell carcinoma, extremely aggressive and invasive, which provoked metastasis and death in two patients.

The E6 Oncoproteins from Human Betapapillomaviruses Differentially Activate Telomerase through an E6AP-Dependent Mechanism and Prolong the Lifespan of Primary Keratinocytes

“…More recently, human betapapillomaviruses (beta-HPVs; such as HPV types 5, 8, and 38) have been implicated in skin cancer progression, yet the molecular mechanisms of cancer development are still largely unknown. BetaHPVs were first isolated from patients with the rare genetic disorder epidermodysplasia verruciformis, who suffer from life-long development of benign lesions such as warts but are also at greatly increased risk for development of squamous cell skin carcinomas (6)(7)(8). Cancers from patients with epidermodysplasia verruciformis led to the original isolation and identification of HPV type 5 (HPV5) and HPV8, whereas benign lesions from these patients contained dozens of different beta-HPV types (8).…”

Role of Zn 2+ Ions in Host-Virus Interactions

“…It is tempting to speculate that this biological effect of HPV E5 action could be related to its influence on EVER/ZnT-1 function and in turn on cellular zinc homeostasis. Remarkably, a similar, highly penetrating and invasive mode of tumor growth with a propensity to metastasize in many cases has been observed in EV patients (9). We hypothesize that breaking the EVER barrier, regardless of whether it is due to a mutation in either of the EVER genes or to the effect of E5, could constitute a tumorpromoting factor, which changes the natural evolution of the developing cancer.…”

Genetic Predisposition to Cutaneous Squamous Cell Carcinoma

“…Mutations in EVER1 and EVER2 genes result in susceptibility to beta-human papillomavirus (β-HPV) infection and a high risk of skin cancer -about 50% of the patients eventually develop cSCC (Ramoz et al, 2002). Onset of lesions usually appears within the first decade, with cSCCs appearing at an average age of 20 at sun-exposed areas (de Oliveira et al, 2003;Gul et al, 2007). Although the tumours are generally localized, aggressive metastatic cSCCs resulting in mortality have been reported (Kaspar et al, 1991;de Oliveira et al, 2003;Gul et al, 2007).…”

“…Onset of lesions usually appears within the first decade, with cSCCs appearing at an average age of 20 at sun-exposed areas (de Oliveira et al, 2003;Gul et al, 2007). Although the tumours are generally localized, aggressive metastatic cSCCs resulting in mortality have been reported (Kaspar et al, 1991;de Oliveira et al, 2003;Gul et al, 2007). Due to the high incidence of cSCC in transplant patients it has long been postulated that a viral etiology exists.…”