Slavomir Obalek

Cutaneous warts clinical, histologic, and virologic correlations☆

Abstract Human-papillomavirus (HPV)-induced cutaneous lesions differ considerably in their clinical morphology. This was thought to depend mainly on anatomic location and other factors related to the host and to the age of the lesions. It was long-assumed that a single virus was responsible for all of these lesions. 1 Disclosure of the plurality of HPV types associated with skin warts 2–9 raised the problem of the relation of clinical morphology to the distinct types of HPV. This was first suggested by the characterization of distinct HPVs from different types of lesions: HPV1 from deep plantar warts, 3 HPV2 from common hand warts, 3 and HPV3 from plane warts and flat wart-like lesions of patients with epidermodysplasia verruciformis (EV). 5 At present, 39 types of HPVs are recognized, with several subtypes for many of them. 10 Some HPV types are specifically associated with cutaneous warts: HPV1, 2, 3, 4, 7, 10, 26–28, and a great number of them are associated with EV. 10,11 The problem of specific or preferential association of distinct HPVs with warts differing in morphology and/or location is still controversial, since only a limited number of cases were studied, 2–17 and no widely accepted clinical and histologic criteria are available for the differentiation between wart types. 18–21 For instance, myrmecia warts are often not distinguished from common or mosaic warts in spite of their very precise histologic and clinical description by Lyell and Miles. 22 Our aim is to present the available data on the association of different types of cutaneous warts with distinct HPVs, and to find out whether it is possible to evaluate the type of infecting HPV on the basis of clinical and histologic features. Such recognition might be important because of the differences in clinical course, contagiousness, and response to treatment of lesions associated with different HPVs.

Condylomata acuminata in children: Frequent association with human papillomaviruses responsible for cutaneous warts

To identify the papillomavirus types associated with condylomata acuminata in children and to evaluate their mode of transmission, we studied 32 children with anogenital warts. External condylomata were found in 12 of their mothers and in 10 of their fathers. Ten mothers, including two without external lesions, had cervical condylomata. Blot hybridization studies disclosed a genital human papillomavirus (HPV) in 14 of 27 children (HPV-6 in 12 and HPV-11 in two) and in 8 of 14 patients (HPV-6 in all). HPV-6 was found in another child by the polymerase chain reaction technique. Infection occurred most likely at birth or from nonsexual contact, but sexual abuse could not be excluded in one 11-year-old girl. Cutaneous HPV-2 was found in seven children and as yet uncharacterized papillomaviruses were found in two children. Three mothers of HPV-2-infected children had common hand warts, and two children had subungual warts. This study shows the frequent nonsexual transmission of genital papillomaviruses in children and the unexpectedly high association of childrens condylomata with papillomaviruses responsible for skin warts, possibly transmitted by heteroinoculation or autoinoculation.

Plurality of genital human papillomaviruses: characterization of two new types with distinct biological properties

The genomes of two new genital human papillomavirus (HPV) types, tentatively named HPVs 39 and 42, have been cloned from biopsy specimens of penile Bowenoid papules and vulvar papillomas, respectively. Blot hybridization experiments, performed under stringent conditions (Tm -10 degrees), have revealed no cross-hybridization between the DNAs of HPVs 39 and 42, and between these DNAs and those of other genital and cutaneous HPVs. A significant cross-hybridization has been observed between the DNA of HPV42 and that of HPV32, the latter being associated with oral focal epithelial hyperplasia. The fraction of HPV32 and HPV42 hybrid molecules resistant to nuclease S1 treatment after hybridization in liquid phase at saturation has been evaluated to 20%, supporting the view that these HPVs constitute distinct types. In addition to HPV42 DNA, a 6.8-kb BamHI fragment, cross-hybridizing with HPV39 DNA, has been cloned from the vulvar papilloma DNA preparation. The cross-hybridization has been evaluated to 16%, pointing to the existence of an additional HPV39-related type. Electron microscope analysis of heteroduplex molecules formed between HPV32 and HPV42 DNAs showed paired regions over about 60 and 87% of their genome lenghts under stringent (Tm -18 degrees) and nonstringent (Tm -42 degrees) conditions, respectively. The 6.8-kb HPV DNA and HPV39 DNA formed paired regions over about 63 and 95% of the 6.8-kb fragment length at Tm -18 degrees and Tm -26 degrees, respectively. These data point to greater DNA sequence homologies than anticipated from the percentages of nuclease S1 resistance. Heteroduplex mapping has allowed the alignment of the physical maps of HPV39 and 42 DNAs and of the 6.8-kb HPV DNA with the map of the open reading frames of the HPV16 genome. So far, HPV42 has been detected only in benign genital lesions showing usually no cell atypia. HPV39 has been detected in a few cases of intraepithelial neoplasias and invasive carcinomas of the uterine cervix. The viral DNA sequences have been found integrated into the cell genome in all four HPV39-associated cervical cancers of our series. It seems most likely that HPV42 belongs to the low-risk group of genital HPVs, while HPV39 represents a potentially oncogenic genital HPV type.

HPV-associated intraepithelial neoplasia of external genitalia

Abstract Intraepithelial neoplasia of the external genitalia with the histologic features, but not the clinical characteristics, of Bowens disease, has been described under several names: bowenoid papulosis (BP) of the penis or genitalia, 1,2 pigmented penile papules with carcinoma in situ changes, 3 multicentric pigmented Bowens disease (MPBD), 4,5 multicentric Bowens disease of the genitalia, 6 reversible vulvar atypia, 7 bowenoid atypia of the vulva, 8 bowenoid dysplasia of the vulva, 9 early vulvar carcinoma, 10 vulvar neoplasia in the young, 11 vulvar intraepithelial neoplasia (VIN), 12 penile intraepithelial neoplasia, 13 carcinoma in situ of the vulva, 14 multicentric vulvar carcinoma in situ , 15 and intraepithelial carcinoma of the vulva. 16 The term bowenoid papulosis of the penis is adequate, since it stresses the multifocal and papular type of the lesions, their localization, and histologic pattern. The term multicentric pigmented Bowens disease is suitable for the confluent, usually heavily pigmented, and somewhat proliferative lesions in women. The relationship between BP or MPBD and Bowens disease is currently substantiated by the detection of the same type of human papillomavirus (HPV) in lesions recognized as BP or MPBD, and in typical cases of genital Bowens disease 17 (Obalek S, et al. unpublished observations).

Characterization of a new type of human papillomavirus (HPV) related to HPV5 from a case of actinic keratosis

Human papillomavirus (HPV) DNA sequences, related to the genomes of HPVs associated with epidermodysplasia verruciformis (EV), were detected in DNA samples extracted from biopsied lesions in 2 of 24 cases of actinic keratosis found in the general population. An HPV DNA was molecularly cloned from one of these samples. Blot hybridization experiments, performed under stringent conditions, revealed a significant cross-hybridization only between this HPV DNA and the DNAs of HPV5 and of the HPV5-related types. The extent of homology between them ranged from 7 to 30%, as evaluated by hybridization in liquid phase at saturation followed by nuclease S1 analysis. This showed that the cloned HPV represented a new type, tentatively named HPV36. HPV36 was not found in the other 22 cases of actinic keratosis, but was detected in scrapings of benign lesions of 7 of 18 (39%) EV patients.