High β-HPV DNA Loads and Strong Seroreactivity Are Present in Epidermodysplasia Verruciformis

Abstract

Epidermodysplasia verruciformis (EV) is a rare disease, characterized by cutaneous warts and associated with a strong predisposition to beta-genus human papillomavirus (HPV). Earlier studies reported high copy numbers of HPV-DNA in nearly all skin tumors from EV patients, but neither HPV replication status in non-lesional skin nor anti-HPV seroreactivity in these patients have been reported yet. We therefore performed a comprehensive viral load analysis for the more common beta-HPV types on skin samples and plucked eyebrow hairs from four EV patients treated at our dermatology department. The results clearly demonstrate that they carry a multiplicity (up to eighteen types) of beta-HPV genotypes in both skin sites. Worthy of note, a high intrapatient concordance for specific types between hair bulbs and skin biopsies was observed and the same beta-PV profile was maintained over time. Viral load analysis revealed a load range between less than one HPV-DNA copy per 100 cells to more than 400 HPV-DNA copies per cell in both eyebrow hairs and skin proliferative lesions. Evaluation of seroreactivity to beta-HPV types in the four EV patients revealed that antibodies against the 16 beta-HPV were significantly more prevalent and showed higher titers than in the controls.

Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients

“…In addition, we have also demonstrated, using fluorescent in situ hybridization (FISH), that the abundance of b-HPV seen in some lesions was a direct result of genome amplification within the carcinoma tissue. 34 Overall, our results indicated that E4 staining could be exploited as a marker of viral expression during b-HPVassociated skin cancer progression as reported in the HPV8 transgenic mouse model and in cervical disease for the a-genotypes. 33,[45][46][47] To extend the data obtained so far in epidermodysplasia verruciformis patients to other groups of patients at high risk of developing skin cancer, here we studied a series of skin lesions from kidney transplant recipients attending our University Hospital by systematically analyzing for the presence of b-HPV infection both at the DNA (PCR) and protein level.…”

“…[30][31][32] In these patients, HPV5 and 8 replicate very efficiently and reveal their full transforming potential, inducing multiple cutaneous neoplasia. 33,34 Emerging evidence also supports the role of b-HPV in skin cancer development in immunosuppressed individuals. Seroepidemiological studies have associated skin cancer in organ transplant recipients with the presence of anti-b-HPV antibodies, and PCR-based studies have identified b-HPV DNA in over 80% of skin tumors from these patients.…”

Human Papillomavirus Load in Eyebrow Hair Follicles and Risk of Cutaneous Squamous Cell Carcinoma

“…Exceptionally high loads of up to more than 400 viral DNA copies per cell were detected in eyebrow hair follicles of patients with epidermodysplasia verruciformis, who have a high risk of SCC development (19). The viral loads in eyebrow hair follicles from the general population and from OTR span 7 orders of magnitude and are mostly extremely low but OTR are more likely to have higher loads (20).…”

Genetics of Epidermodysplasia Verruciformis

“…In both their benign and malignant lesions, a broad spectrum of predominantly beta PV were found with a combined prevalence of 90% for HPV 5 and 8 in SCC [2,6] . In lesions of EV patients, the viral genome usually persists extrachromosomally and in high copy numbers (100-300 copies per cell equivalent) [45][46][47]. High viral loads have also been found in hair bulbs from plucked eyebrows of these patients [47].…”

“…In lesions of EV patients, the viral genome usually persists extrachromosomally and in high copy numbers (100-300 copies per cell equivalent) [45][46][47]. High viral loads have also been found in hair bulbs from plucked eyebrows of these patients [47]. In both immunocompetent and immunosuppressed non-EV patients these viruses are also frequently found; however, only very low copy numbers (usually below one copy per cell) were detected in actinic keratosis, SCC, basal cell carcinoma, and perilesional skin [48].…”