Sporadic cases of Heck disease in two Polish girls: association with human papillomavirus type 13.

Two sporadic cases of Heck disease in Polish girls were associated with human papillomavirus 13. No other children and nobody from their surroundings had similar lesions. The course of the disease was chronic in both patients. The lesions regressed spontaneously in one girl within several years after some of the papules were excised. The second girl's warts persist after eight years.

Childhood condyloma acuminatum: association with genital and cutaneous human papillomaviruses.

We studied 25 children, age 7 months to 12 years 6 months, with anogenital warts, and their parents. In most children the warts were localized in the anal area, in 3 of 18 girls perianally and on the vulva, and in 4 girls exclusively on the vulva. Southern blot hybridization studies disclosed an association of condylomata with human papillomaviruses (HPV) 6 and 11 in 74% and HPV 2 in 17.4% of patients. The clinical features were similar in warts induced by genital and cutaneous HPVs. Even the HPV 2-associated warts in the vulva of two girls were typical of condyloma acuminatum. In all children with HPV 2-induced condylomata, cutaneous common warts coexisted, also induced by HPV 2. However, three mothers had cutaneous warts, and the children's condylomata were associated with HPV 6. Thus, the mere presence of skin warts in family members does not rule out other sources of infection. Sexual abuse was suspected in four girls and two boys, but was not confirmed in any. Nonsexual transmission could occur by persons with the lesions taking care of children. Perinatal transmission also appears to be an important route of infection in small babies. Infection in utero was probable in one girl in whom anal warts appeared in the first week of life and whose mother had cervical condylomata during pregnancy. This study provides further confirmation of possible nonsexual transmission of genital HPVs and the not infrequent association of childhood condylomata with HPV 2.

Human papillomavirus (HPV) types specific of epidermodysplasia verruciformis detected in warts induced by HPV3 or HPV3-related types in immunosuppressed patients.

Epidermodysplasia verruciformis (EV) is characterized by an abnormal genetic predisposition to infection with specific types of human papillomavirus (HPV). Specific defects of the cell-mediated immunity and/or of the control of HPV infection in keratinocytes are assumed to be involved in the development of the disease. As a model to test this hypothesis, we have studied the prevalence of EV-specific HPV in skin warts of 56 immunosuppressed patients. All main types of cutaneous HPV (HPV1, 2, 3, 4, 10, and 28) responsible for skin warts in the general population were detected by blot hybridization. EV-specific HPV (HPV5, 20, and 23) were detected in three patients. Four additional patients were found infected with HPV49, first characterized in the course of this study, and found to be related to EV HPV. A most important finding was that HPV5, 20, 23, and 49 were always codetected with HPV3 or the related types HPV10 and 28. None of the specimens showed the typical clinical morphology of EV lesions. In none of these specimens was the specific cytopathic effect of EV recognized; instead that of HPV3 and related types was seen. No evidence for productive EV HPV DNA replication was obtained for the three specimens that could be further analyzed by in situ hybridization. Our data suggest that HPV3 infection favors infection with EV HPV in immunosuppressed patients but that the full expression of EV HPV is usually restricted as in the general population.

Premalignant lesions and cancers of the skin in the general population: evaluation of the role of human papillomaviruses.

To evaluate the role of human papillomaviruses (HPV) in the development of premalignant lesions and cancers of the skin in the general population, 314 biopsies obtained from 227 patients with benign neoplasms, premalignant lesions, and cancers of the skin and from 25 patients with squamous cell carcinoma of the lip were analyzed by Southern blot hybridization. DNA probes specific for various cutaneous and genital HPV types were used in hybridizations conducted under nonstringent or stringent conditions. HPV DNA sequences were only detected in eight specimens obtained from six patients: HPV 34 in one case of periungual Bowen's disease, HPV 36 and an as yet uncharacterized HPV in two cases of actinic keratosis, HPV 20 in one case of basal cell carcinoma, an as yet unrecognized HPV in one case of squamous cell carcinoma, and HPV 16 in one case of squamous cell carcinoma of the lip. None of the specimens of cutaneous horn and keratoacanthoma contained detectable HPV DNA. In contrast, HPV DNA sequences, mostly HPV 16, were detected in 13 of 23 cases of anogenital Bowen's disease and invasive Bowen's carcinoma. HPV DNA sequences were not detected in 90 cutaneous samples further analyzed by the polymerase chain-reaction technique, using amplification primers that contain conserved sequences among the genomes of HPV. These results strongly suggest that the known HPV types play only a minor role, if any, in skin carcinogenesis in the general population.

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 children's condylomata with papillomaviruses responsible for skin warts, possibly transmitted by heteroinoculation or autoinoculation.

Natural cell-mediated cytotoxicity against various target cells in patients with epidermodysplasia verruciformis.

Natural cell-mediated cytotoxicity of peripheral blood mononuclear cells was studied in eight patients with epidermodysplasia verruciformis induced by human papillomaviruses specific for epidermodysplasia verruciformis and in five patients with epidermodysplasia verruciformis-induced exclusively by human papillomavirus type 3. Nine patients with various cutaneous warts and 25 age- and sex-matched healthy persons were control subjects. Natural cell-mediated cytotoxicity against both K-562 erythroleukemic and Sk-v cells was in the normal range in patients with epidermodysplasia verruciformis induced by epidermodysplasia verruciformis-specific human papillomaviruses and in patients with cutaneous warts. The lysis of both targets, however, was significantly decreased in patients with the form of epidermodysplasia verruciformis associated with human papillomavirus type 3. Experiments with normal keratinocytes and with keratinocytes isolated from a malignant lesion bearing human papillomavirus type 5 genomes showed that the latter were susceptible to lysis by the peripheral blood mononuclear cells of healthy persons and of patients with cutaneous warts. Lysis of keratinocytes in epidermodysplasia verruciformis, however, was strongly reduced in patients with epidermodysplasia verruciformis induced by specific human papillomaviruses. This reduction was not associated with a decrease in anti-K-562 natural cell-mediated cytotoxicity. Our results suggest that in patients with epidermodysplasia verruciformis induced by disease-specific human papillomaviruses, there is reduced natural cell-mediated cytotoxicity against epidermodysplasia verruciformis keratinocytes.

Two new human papillomavirus types (HPV54 and 55) characterized from genital tumours illustrate the plurality of genital HPVs.

The genomes of two new human papillomavirus (HPV) types, named HPV54 and HPV55, were cloned from penile lesions of 2 patients. HPV54 was isolated from a verrucous carcinoma (Buschke-Löwenstein tumour) together with full-length HPV6 genomes and HPV6 DNA molecules with a deletion of about 0.3 kb located in the non-coding region. HPV55 was isolated from a condyloma acuminatum. No cross-hybridization was observed between HPV54 DNA and the DNAs of the known cutaneous and genital HPVs by blot hybridization experiments performed under stringent conditions. In contrast, significant cross-hybridization was detected between HPV55 DNA and the DNA of HPV13, associated with benign oral lesions, and, to a lesser extent, with the DNAs of HPV6, 11, and 44, associated with benign genital proliferative lesions. The DNA sequence homology between HPV55 and HPV6, 11, and 13 was estimated at 12%, 12%, and 20%, respectively, by hybridization in liquid phase at saturation, followed by nuclease S1 analysis. The physical maps of HPV54 and 55 were aligned with the genetic maps of HPV16 and 11, respectively, by heteroduplex mapping and partial DNA sequencing. HPV54 is thus only weakly related to the known HPVs, while HPV55 represents an additional HPV6-related HPV type. HPV54 and HPV55 are uncommon genital HPV types since, in a survey of a large series of specimens of benign, pre-malignant or malignant anogenital and orolaryngeal tumours, HPV54 was not detected, and HPV55 was found in another case of condyloma acuminatum.

Human papillomavirus type 28 (HPV-28), an HPV-3-related type associated with skin warts.

The cloning and partial characterization of the genome of human papillomavirus type 28 (HPV-28) is presented. The virus is a distinct type and by hybridization analyses is most closely related to HPV-3 and HPV-10.

Human papillomavirus type 49, a type isolated from flat warts of renal transplant patients.

The cloning and characterization of the genome of human papillomavirus type 49 (HPV-49) is described. The viral DNA, which is most closely related to the DNAs of HPVs seen in patients with epidermodysplasia verruciformis, was aligned to the HPV-5 genome by electron microscopic analysis of heteroduplexes between the cloned viral DNAs.

Human papillomavirus (HPV) type 50, a type associated with epidermodysplasia verruciformis (EV) and only weakly related to other EV-specific HPVs.

The cloning and partial characterization of the genome of human papillomavirus type 50 is presented. Alignment of the genomic map with that of human papillomavirus type 5, with which it is only weakly related, was permitted by partial DNA sequence analysis.

[Coexistence of multifocal bowen disease of the vulva and cervix carcinoma]. / Wspólistnienie wieloogniskowej choroby Bowena sromu i raka szyjki macicy.

The authors described a case of a young woman with vulva carcinoma with features of multifocal pigmentary Bowen disease coexisting with atypical flat condylomas in the uterine cervix with focuses of carcinoma in situ. Both within the vulva and the uterine cervix there were histological features of carcinoma in situ, virological examination revealed the presence of virus HPV 16 genome. Sparing vulvectomy, the removal of pigmentary changes and electrocoagulation were performed. The authors discussed this rare case and presented therapeutic procedures.

Human papillomavirus type 2-associated basal cell carcinoma in two immunosuppressed patients.

Human papillomavirus-2 genomes were detected by molecular hybridization in two cases of basal cell carcinomas that developed in immunosuppressed individuals. This form of human papillomavirus is usually responsible for common warts in the general population. Although it does not appear to have oncogenic potential, it may be, in some cases, associated with cutaneous malignancy.

Epidemiology of butchers' warts.

Studies were carried out in two slaughter-houses in different cities differing in the degree of work automation and, for comparison, in workers of nearby factories of the same two cities. There was a high incidence of warts (49.2%) in a slaughterhouse where the workers had direct contact with animals and meat, while a significantly lower incidence (9%) was observed in a modern slaughterhouse where the work was almost completely automated. The types of human papillomaviruses (HPVs) were similar in warts of butchers from these slaughterhouses and of 63 butchers from various slaughterhouses all over the country. All cutaneous HPVs were present in butchers' warts. The so-called butchers' wart virus HPV-7 was found in about 30% of the butchers from all slaughterhouses. Cell-mediated immunity of the butchers was found to be unimpaired. There was no correlation between the incidence of infection and the frequency of antibodies against HPV-1, HPV-2, or HPV-3.

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.

The morphology of butchers' warts as related to papillomavirus types.

Hand warts were studied in 160 butchers. Clinical and histological studies were performed in 190 warts and virological studies in 165 warts from 104 butchers. Since we found almost perfect correlation between the histological pattern and the type of infecting virus, it was possible to evaluate the virus types in a further 39 of 56 butchers without virological studies, on the basis of the histology of the warts. The most common infection was with HPV-2 (human papilloma virus) and HPV-7. Thirty-three butchers were infected with two types of viruses and three butchers with three HPVs. The morphology of warts varied considerably. The majority were similar to verrucae vulgares or verrucae planae. Some deep warts resembled myrmecia-type verrucae plantares. Often, several types of warts coexisted. Some clinical patterns were shown to be preferentially associated with distinct types of papillomaviruses: common warts with HPV-2, HPV-4, or HPV-7, plane and intermediate warts with HPV-3, HPV-10, HPV-28. HPV-7, previously identified for the first time in these butchers, was found to be associated with common warts or common wart-like, papillomatous lesions.