[Papillomavirus and cancer of the uterine cervix. The virologist's point of view].
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Female↗
Biomedical subjects
G Orth
Publications and source records attributed to G Orth.
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.
Adult↗
Presence of papilloma virus type 11 in condyloma acuminatum of bladder in female renal transplant recipient.
A case is reported of a female renal transplant recipient in whom, after two years of immunosuppression, condylomata acuminata of the genital tract with urethral and bladder extension developed. The condyloma of the bladder was resected endoscopically with no relapse. Virologic examination revealed a human papilloma virus type 11.
Adult↗
Correlative study of human papillomavirus DNA, histopathology and morphometry in cervical condyloma and intraepithelial neoplasia.
This study includes 28 intraepithelial squamous lesions of the cervix associated with human papillomavirus (HPV) DNA sequences detected by the Southern blot technique. Objective analyses of the histologic features by morphometric parameters and mitotic index have demonstrated that lesions of HPV types 6 and 11 can be distinguished from types 16, 18, and 33 by stepwise discriminant functions. The latter lesions have higher mitotic and cellularity indexes and greater nuclear atypia than the former, supporting a greater degree of epithelial proliferation and abnormality seen in association with HPV types 16/18/33.
Biopsy↗
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.
Abattoirs↗
[Giant HPV 6 Buschke-Lowenstein tumor with metastases in the abdominal wall].
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Abdominal Muscles↗
High prevalence of papillomavirus-associated penile intraepithelial neoplasia in sexual partners of women with cervical intraepithelial neoplasia.
To determine whether neoplastic cervical lesions in women are associated with papillomavirus infections in their sexual partners, we used a colposcope to examine male sexual partners of women with cervical flat condyloma (294 cases) or cervical intraepithelial neoplasia (186 cases), before and after 5 percent acetic acid was applied to the penis and the anogenital area. Condylomata acuminata, papules, and macules were observed in 309 of the 480 men (64.4 percent). In 204 of them (42.5 percent), macules or slightly elevated papules were detected only after application of acetic acid. Condylomata acuminata or lesions showing histologic features of condyloma were found in 121 partners (41.2 percent) of women with condyloma, but in only 10 partners (5.4 percent) of women with cervical intraepithelial neoplasia. Penile lesions showing histologic features of intraepithelial neoplasia were found in 61 partners (32.8 percent) of women with cervical intraepithelial neoplasia, but in only 4 partners (1.4 percent) of women with flat condyloma. Thirty-six (60 percent) of the 60 macules or papules tested contained papillomavirus DNA sequences. Human papillomavirus types 16 and 33 were almost exclusively found in penile intraepithelial neoplasia. Type 6, type 11, and the recently recognized type 42 were found in lesions showing features of condyloma or minimal histologic changes. As yet uncharacterized papillomaviruses were found in 15 percent of the specimens. These data support the concept that cervical carcinomas and precancerous lesions in women may be associated with genital papillomavirus infection in their male sexual partners.
Adolescent↗
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.
DNA↗
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.
Cloning, Molecular↗
A new type of human papillomavirus associated with oral focal epithelial hyperplasia.
Lesions from 10 patients suffering from focal epithelial hyperplasia (FEH) of the oral mucosa, including those of 4 Greenlandic Eskimos, were investigated for the presence of human papillomavirus (HPV) DNA sequences by blot hybridization experiments. Two distinct HPVs were detected in the DNA extracted from these lesions, and their genomes were molecularly cloned and characterized. One of these HPVs, detected in 4 patients, was found to be identical with HPV13, whose association with FEH was already known. The other one, detected in 6 patients, was only weakly related to HPV13 and to the other HPVs associated with lesions of the mucous membranes, and constituted a new HPV type, tentatively named HPV32. Lesions from other types of oral papillomas, obtained from 14 additional patients, were also analyzed. Human papillomavirus DNA sequences were detected in the DNA preparations extracted from 5 specimens: HPV6 DNA in a condyloma and in a papilloma, 2 as yet uncharacterized HPV DNAs in 2 papillomas, and HPV32 DNA in a papilloma which showed histologic similarities to FEH. Thus, it seems likely that FEH of the oral mucosa is a disease associated with 2 specific HPVs--HPV13 and HPV32.
Adolescent↗
Integration of human papillomavirus type 16 DNA sequences: a possible early event in the progression of genital tumors.
The keratinocyte line SK-v harbors only integrated human papillomavirus type 16 (HPV 16) DNA sequences, although it originated from vulvar Bowenoid papules predominantly containing multiple copies of free HPV 16 genomes. We have cloned a fragment of cell DNA that contains the integrated HPV 16 DNA sequences and have shown that integration interrupts the HPV 16 genome in open reading frames E2 and L2 and creates a deletion of 813 base pairs. This allows the expression of open reading frames E6 and E7, as actually substantiated by Northern (RNA) blot analysis of SK-v RNAs with subgenomic HPV 16 RNA probes. Using a unique flanking cellular DNA sequence as the probe, we have shown that the integration of HPV 16 sequences had already occurred in the premalignant lesions from which the SK-v cell line was derived.
Base Sequence↗
[Histological aspects of lesions of the cervix uteri correlated with different types of human papillomavirus].
Cervical biopsies from 66 women presenting an abnormal smear, with HPV related features were studied and histologic features were correlated to the HPV type, as determined by molecular hybridisation studies. HPV DNA sequences were evidenced in 13 of 19 lesions corresponding to exophytic or flat condyloma (HPV type 16 in seven cases, HPV type 11 in four cases, as yet uncharacterized HPV types, HPV X, in two cases). Fourty biopsies were histologically interpreted as CIN, on the basis of atypical mitotic figures (AMF) and/or basal-parabasal cell atypia. HPV type 16 was evidenced in 20 cases (3 cases of double infection: HPV types 16 and 18, HPV types 16 and 33, HPV types 16 and X). In 10 other cases, HPV DNA sequences corresponding to HPV type 11 (one case), HPV 18 (one case) and HPV X (8 cases) were evidenced. In this study, potentially oncogenic HPV types (HPV 16, HPV 18, HPV 33) have been found only in CIN lesions defined on the presence of AMFs and/or basal-parabasal cells atypia. These histologic criteria seem to allow a distinction between low and high risk cervical lesions.
Adult↗
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.
Aged↗
[Bowenoid papulosis and its relation to Bowen's disease and atypical condyloma].
All the 5 sexual partners of male patients suffering from bowenoid papulosis and bearing the HPV 16 genome showed cervical lesions induced by HPV. 2 of them proved to be noncondylomatous infections, 3 cases were cervical condylomas, and 2 patients revealed severe dysplasia or carcinoma in situ (CIS). 3 out of 4 women suffering from multicentrical pigmented Bowen's disease of the vulva showed plain condylomas of the cervix, with severe dysplasia or CIS in 2 cases and slight dysplasia in one case. Thus bowenoid papulosis as well as multicentrical pigmented Bowen's disease of the vulva are high risk factors for cervical HPV infection and carcinoma, both for the patients themselves and their sexual partners. Atypical pigmented genital condylomas induced by HPV 6 also bear a risk for cervical HPV infection of the sexual partners. Malignant transformation, however, seems to depend on the type of the infecting virus (mainly HPV 16).
Bowen's Disease↗
Epidermodysplasia verruciformis: a model for understanding the oncogenicity of human papillomaviruses.
The first evidence for the oncogenic potential of human papillomaviruses (HPVs) was obtained through the study of epidermodysplasia verruciformis (EV). This rare skin disease is characterized by disseminated, refractor, pityriasis versicolor-like lesions as well as flat wart-like lesions, and by the development of skin carcinomas in about 30% of the patients. EV is a multifactorial disease involving genetic, immunological and extrinsic (actinic) factors, in addition to infection with specific HPV types. A number of HPVs (at least 15 types) have been characterized in benign EV lesions. HPV DNA sequences are regularly detected in EV carcinomas but, in contrast to benign lesions, the types associated with cancers are usually restricted to HPV-5 and, less frequently, HPV-8, an HPV-5-related type. HPV-5 genomes are usually found as free monomeric or oligomeric DNA molecules in EV carcinomas, and frequently contain deletions. This is in contrast with HPV DNA sequences in genital cancers, which are often integrated into the host DNA. Evidence for the transcription of HPV-5 genomes in primary and metastatic EV carcinomas has recently been obtained. The available data indicate that HPV-5 and some HPV-5-related types have an oncogenic potential and play a role in the malignant transformation of EV lesions. Infection by these HPVs must be considered a major risk factor for the development of cancers in EV patients. EV HPV DNA sequences have only rarely been detected in premalignant or malignant lesions of the skin in the general population. This further stresses the role of genetic, immunological and extrinsic factors in the abnormal susceptibility of EV patients to a set of specific HPV types.
Carcinoma in Situ↗
Bowenoid papulosis of the male and female genitalia: risk of cervical neoplasia.
Sixteen patients with bowenoid papulosis (eleven male patients with bowenoid papulosis of the penis and five female patients with bowenoid papulosis of the vulva) were studied clinically, histologically, and virologically and followed up from 12 months to 5 years. In eleven of sixteen cases of bowenoid papulosis, molecular hybridization disclosed the presence of human papillomavirus type 16. In four cases we found new, not fully characterized human papillomavirus, and in two cases, we found both human papillomavirus 16 and new human papillomavirus (double infection). The mean age of male patients was 33 years and of female patients, 31 years. The mean duration of the disease was 2.4 and 3.6 years, respectively. The lesions cleared or did not recur in eight of eleven male patients after repeated partial excisions and in two of five female patients after conservative surgery. Cervical intraepithelial neoplasia (severe dysplasia) was present in three of five female patients, and human papillomavirus infection of the cervix was present in five of six sexual partners of male patients available for examination. Thus bowenoid papulosis presents a high risk for cervical neoplasia both for female patients and for sexual partners of male patients.
Adult↗
Partial defects of cell-mediated immunity in patients with epidermodysplasia verruciformis.
Different parameters of cell-mediated immunity, including natural cytotoxic reactions, were studied in nine patients with epidermodysplasia verruciformis with or without cutaneous malignancy. We found decreased total number of T lymphocytes and T-helper cells in peripheral blood of the patients, and normal T-suppressor cell number, as detected by monoclonal antibody typing and functional E-rosette test with the use of theophylline. This decrease was found both in active and in late rosette-forming cell subpopulations. Natural killer cell activity of peripheral blood mononuclear cells was found to be increased in four of nine patients with epidermodysplasia verruciformis, whereas antibody-dependent cellular cytotoxicity was within the normal range in all patients studied. Lymphocyte-induced angiogenesis assay, which is a sensitive test for the estimation of the immunocompetence of lymphoid cells, revealed increased angiogenic capability of peripheral blood mononuclear cells in the majority of the patients. Our results suggest that cellular defects in patients with epidermodysplasia verruciformis did not relate to all functions of the immune system.
Adult↗
Characterization of a new type of human papillomavirus found in a lesion of Bowen's disease of the skin.
The genome of a human papillomavirus (HPV) found in a patient with Bowen's disease of the skin was molecularly cloned. Blot hybridization experiments, performed under stringent conditions, revealed no cross-hybridization between this HPV DNA and the other known HPV DNAs, showing that this HPV represents a new type, tentatively named HPV34. In relaxed hybridization conditions, the highest cross-hybridization was observed with HPV16 DNA. The physical map of HPV34 DNA was aligned with the genetic map of HPV16 DNA by heteroduplex mapping. HPV34 was not detected in 12 additional patients with Bowen's disease of the skin, but a closely related HPV DNA was found in one patient with penile Bowenoid papulosis.
Bowen's Disease↗