Epidermodysplasia verruciformis-associated and genital-mucosal high-risk human papillomavirus DNA are prevalent in nevus sebaceus of Jadassohn
ABSTRACT The hamartoma nevus sebaceus (NS) presents at birth or early childhood as a yellowish plaque characterized histologically by variable acanthosis, papillomatosis, sebaceus hyperplasia, and proliferations of adnexal structures. Clinically apparent human papillomavirus (HPV) infection is also recognized by acanthosis and papillomatosis.
We sought to determine the prevalence and physical state of HPV DNA in NS.
DNA was retrieved from 44 formalin-fixed, paraffin-embedded samples of NS (22 with secondary tumors [eg, trichoblastoma, verruca, syringocystadenoma papilliferum] and two epidermal nevi [EN]). Nested polymerase chain reaction with multiple degenerate consensus and type-specific primers and direct sequencing of polymerase chain reaction products was performed. For selected cases, in situ hybridization using probes specific for HPV 5 and 8 and for high-risk genital-mucosal HPV types was performed.
HPV DNA was detected in 82% of NS and both EN, and consisted of genital-mucosal HPV types in 52% (HPV 6, 16, and 33) and a diverse variety of epidermodysplasia verruciformis-associated HPV types in 61%, including well-known epidermodysplasia verruciformis HPV types (5, 8, 15, 20, 22, 24, 36, 37, 38, and 80) and putatively novel epidermodysplasia verruciformis HPV types (DL285, DL287, DL436, and alb-1, -2, -3, -5, -6, -7, -8, -10, -11, -12, and -13). HPV coinfection was frequent, found in 48% (two HPV genotypes in 35% and 3 in 13%). Of NS and EN, 42% had HPV genotypes associated with cancer (ie, HPV 5, 8, 16, 20, 33, and 38); the two most commonly identified HPV types where HPV 16 (39%) and HPV 38 (18%). No differences were detected comparing frequency of HPV DNA detected with respect to age or presence of a secondary tumor. Histologically, all NS and EN showed HPV-associated cytopathic effects (ie, perinuclear halos, altered keratohyaline granules). By in situ hybridization, 64% (18/28) were positive, showing a low-intensity, punctate nuclear signal in epidermal and adnexal keratinocytes, indicating viral integration and low viral genome copy number.
Absence of adjacent, uninvolved normal-appearing skin control samples.
HPV DNA is prevalent in NS, and HPV 16, the most frequently detected genotype, appears to be integrated into the host genome. Whether HPV represents a commensal infection caused by localized cutaneous predisposition, or is an essential factor in the pathogenesis of NS is unknown. The high frequency of oncogenic HPV types implicates maternal transmission of HPV and infection of an ectodermal stem cell leading to an epigenetic mosaic and altered skin development manifested along Blaschko's lines.
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