Human papilloma virus type 16-associated verruca vulgaris on the digits with multiple cancerous anogenital lesions

ARTICLE

ejd.2012.1682

Auteur(s) : Chieko Ibusuki, Makoto Kunisada, Kanako Ogura, Tetsuya Ikeda, Yoshiko Oda, Chikako Nishigori chikako@med.kobe-u.ac.jp

Division of Dermatology, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan

Bowen disease (BD) usually manifests as a solitary erythematous macule and plaque, typically on the extremities and trunk; it is histologically characterised by proliferation of atypical mitotic cells throughout the epidermis. Bowenoid papulosis has the same diagnostic criteria as BD, featuring multiple verrucous lesions in the genital area of sexually active adults and frequently associated with human papillomavirus (HPV) type 16/18. Various high-risk HPV types, particularly HPV-16/18, have also been linked to BD [1]. In contrast to BD, verruca vulgaris typically develops on the digits of young people and is frequently associated with HPV 1, 2, 4, 27 and 57 [2]. We report a case of multiple verruca vulgaris lesions on the fingers and toes, coincident with HPV 16 infection but histologically benign, associated with multiple BD in the anogenital area. A 58-year-old woman presented with a history (more than 30 years) of multiple verrucous warts on her fingers and toes. She had a past history of cervical cancer, for which she underwent a hysterectomy 14 years earlier. We clinically diagnosed the lesions as verruca vulgaris and initiated liquid nitrogen treatment. Physical examination showed 7 brown, slightly elevated, verrucous papules of miliary size distributed around the nails of the fingers and toes (figure 1A). As she was undergoing liquid nitrogen therapy for her lesions, she revealed that she had been experiencing genital itching for several years. Physical examination showed erythematous, spotty, black, relatively hard plaques around the entire vaginal and perianal area (figure 1B). We biopsied the verrucous lesions of the toes with sterile single-used instruments to avoid the risk of other sample contamination and found epidermal hyperplasia without atypicality and abundant koilocytes in the granular layer (figure 1C). Histopathology of the vaginal lesions revealed the proliferation of atypical cells throughout the epidermis. Individual cells with multiple mitotic figures and dyskeratotic cells were also present. Vacuolated koilocyte proliferation was also seen in the granular layer (figure 1D). Immunohistochemical study for p16^INK4a showed small numbers of positive cells in the toe lesions and strong expression in vaginal lesions (figures 1E-F). Polymerase chain reaction of HPV-DNA revealed the presence of only HPV type 16 in all samples from the anogenital area and toes (figure 1G). We diagnosed the patient with HPV-16-associated BD in the anogenital region and verruca vulgaris on the toes and performed wide surgical resections for anogenital BD. Liquid nitrogen therapy for the toe lesions was continued. There have been more than 20 reports of multiple BD with HPV-16 accompanied by anogenital BD [3]. BD lesions associated with HPV-16 at non-anogenital sites are often located on the soles, fingers and toes, without any background such as epidermodysplasia verruciformis. The individual tumour manifests as verrucous and hyperkeratotic warty plaques with histological features typical of BD [4]. HPV-16/18 carries a high risk of cancer development, as viral overexpression of E6/E7 oncoproteins in the HPV-infected cells causes uncontrolled proliferation via p53 inactivation [5]. HPV-16 has also been detected in the verruca vulgaris of an immunocompetent patient [6]. To the best of our knowledge, this is the first report of 2 HPV-16 infection features appearing in the same individual; one, histologically benign and longstanding verruca vulgaris of the fingers and toes and the other, typical anogenital BD with high atypicality. Given our results showing positive cells for p16^INK4a in the toe sample, we speculate that HPV-16 was playing some role in the development of common warts but there may exist a mechanism where cancer initiation does not occur in the toe. Non-genetic factors such as local inflammation might drive neoplastic processes in the development of HPV-16-associated BD.

Disclosure

Conflicts of interest: none. Financial support: none.

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