HPV-16-related Bowenoid papulosis.
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Animals↗
Biomedical subjects
L Gissmann
Publications and source records attributed to L Gissmann.
Human papillomavirus type 16 related DNA in an anaplastic carcinoma of the lung.
Twenty-four biopsy specimens from various histologic types of human carcinomas in the lung were analyzed for the presence of human papillomavirus (HPV) DNA. DNA from the individual specimens was tested for the presence of homologous sequences to HPV genotypes 1, 2, 4, 8, 9, 10, 11, 13, 16 and 18. One anaplastic carcinoma in the lung contained multiple copies of DNA hybridizing under stringent conditions to HPV 16 DNA. The latter DNA has been found to be frequently associated with human genital cancer (cervical, penile, and vulval cancer) and genital Bowen's disease. The HPV 16 positive lung tumor originated from a 61-year-old female patient who underwent hysterectomy due to cervical cancer 9 years earlier.
Base Sequence↗
Papillomavirus infection of the lower genital tract: detection of viral DNA in gynecological swabs.
A total of 311 smears from the lower genital tract were examined by the filter in situ hybridization method to identify human papillomavirus (HPV) DNA. Of these 311 smears, 229 came from clinically and cytologically negative patients and served as a control group. In this group HPV-DNA was detected in 5 cases (2.2%). Of 82 cytologically positive cases (25 confirmed by histology) 56 (68%) contained HPV-DNA. A high prevalence of HPV 6/11 and absence of HPV 16/18 was found in cases with cytological signs of permissive HPV infection. In mild and moderate dysplasia all viruses occurred at almost the same frequency. In severe dysplasia/carcinoma in situ HPV 16/18 was found 5 times more frequently than HPV 6/11. HPV 16/18 was identified in all 4 invasive cancer cases. Cervical irrigation of colposcopically suspect areas was performed in 15 cytologically and HPV-DNA positive cases using the hydrodynamic filtration method. In 12 cases only the cells obtained from the colposcopically positive areas contained HPV-DNA. The sensitivity and reproducibility of the filter in situ hybridization was shown by: comparing the results obtained by HPV-DNA hybridization using Southern blot analysis of tumor biopsies; analysing the correlation of cytologic diagnosis and presence of HPV-DNA in follow-up examinations, and diagnosing presence or absence of HPV-DNA in parallel filters from the same patients.
Animals↗
Bowenoid papulosis. Presence of human papillomavirus (HPV) structural antigens and of HPV 16-related DNA sequences.
This study reviews 39 cases of anogenital bowenoid papulosis lesions in 22 individuals of both sexes that were analyzed clinically, histologically, immunocytochemically, and virologically. Macroscopically, three different types of lesions were demonstrated: erythematous macules; papules (lichenoid and/or pigmented papules); and leukoplakialike lesions. Microscopically, bowenoid papulosis fulfills the criteria of a squamous cell carcinoma in situ. Much like oral precancers, three distinct growth patterns (flat, endophytic, and exophytic) could be differentiated, which did not correlate with the clinical aspect of the lesions. In only two (5.12%) of the 39 cases of bowenoid papulosis could structural antigens of papillomaviruses be detected immunocytochemically (peroxidase-antiperoxidase technique). The DNA from 12 lesions that were analyzed for the presence of papillomavirus-specific sequences hybridized stringently in all cases with the human papillomavirus 16 specific DNA probe labeled with phosphorus 32.
Adolescent↗
Interferon therapy for bronchial papillomatosis controlled by papillomavirus-DNA hybridization.
In biopsy specimens from a patient with tracheal and bronchial papillomatosis, human papillomavirus (HPV) type 11 DNA was identified. Treatment with leukocyte interferon was initiated, and the results of therapy was monitored by molecular hybridization of biopsy specimens with phosphorus 32-labeled HPV type 11 DNA after interferon application. There was no improvement of the clinical course, although two of five biopsy specimens showed a considerable reduction in the amount of HPV type 11. We discuss the reasons for the insufficient effect of therapy and propose molecular hybridization as an additional method for therapy control in viral diseases.
Bronchial Neoplasms↗
[Detection of various papilloma virus types in cytologic smears of precancerous conditions and cancers of the uterine cervix].
DNA-in situ hybridisation on epithelial cells taken from cervical swabs of 101 different patients cytologically diagnosed as III D to V (Munich classification 1975) were performed using 32P-labelled DNA of the human papilloma virus (HPV) types 6, 11, 16 and 18 as smears. The following correlations between the cytological classification and DNA hybridisation were obtained: 55 out of 58 women (94.8%) having a normal Pap smear (Pap II) were negative by hybridisation as well, three cases contained HPV 6 or 11.59.3% of patients revealing abnormalities characteristic of a papillomavirus infection reacted with the 32P-labelled DNA, while HPV 6/11 or 16/18, respectively, occurred at approximately the same rate of frequency. In cases with severe dysplasia, carcinoma in situ or invasive cervical carcinoma (IVa, IVb, V) HPV 16 or 18 were more frequently found (67%) than in materials with mild dysplasia (IIID; 32% positive). HPV 6 or 11, on the other hand, was present only once in nine IVb/V-cases (11%), in 17% of IVa-cases, but in 32% of patients with mild dysplasia. Infections with all different virus types were found in 9% of the IVa-und 16% of the IIID-cases. The high prevalence of HPV 16 or 18 in CIS as well as in invasive carcinomas is in line with the biological correlation between both types of lesions. HPV 6 or 11 is more frequently associated with the usually reversible mild dysplastic epithelial alterations. The DNA-in situ swab hybridisation should, therefore, be of diagnostic value and might help to optimise the therapy for the individual patient.
Animals↗
The physical state of human papillomavirus type 16 DNA in benign and malignant genital tumours.
Cloned DNA from human papillomavirus (HPV) type 16 was subjected to restriction enzyme analysis. A genome size of 7.8 +/- 0.1 kb was determined and restriction maps were prepared. Fragments of HPV 16 DNA were nick-translated and hybridized with fragments of HPV 6b DNA. The two genomes appeared to be colinear. The physical state of HPV 16 DNA in genital tumours was analysed. In each of six benign tumours the viral DNA was detected exclusively as 8 kb circles. In four malignant tumours the viral DNA appeared to be integrated within the host genome but one cervical carcinoma and one case of Bowen's disease also contained oligomeric episomal molecules of viral DNA. One cervical carcinoma (WV 2965), containing only integrated viral DNA, was examined in detail. HPV 16 DNA was integrated as head-to-tail tandem repeats at more than one site. Three virus/cell junction fragments from this tumour were cloned. Two contained lengths of repetitive cellular DNA and one a length of apparently single copy cellular DNA.
Animals↗
Analysis of oral papillomas, leukoplakias, and invasive carcinomas for human papillomavirus type related DNA.
Five papillomas, five leukoplakias, and six carcinomas were investigated for the presence of papillomavirus group-specific antigens and viral DNA. Viral proteins were identified with genus-specific papillomavirus antibodies. Cloned human papillomavirus (HPV) 11 and 16 DNA were used as probes in Southern blot hybridization at conditions of different stringency in order to determine viral DNA. Four of five papillomas, four of five leukoplakias, and three of six carcinomas reacted with HPV DNA probes and revealed some stained cells after exposure to HPV antibodies. HPV type 16 was found in one carcinoma and HPV type 11 was demonstrated in another case of carcinoma.
Adult↗
Papillomavirus infection of the anogenital region: correlation between histology, clinical picture, and virus type. Proposal of a new nomenclature.
The clinical and histologic picture of 84 anogenital condylomatous and condyloma-like lesions of both sexes were analyzed in an effort to establish a correlation to the different papillomavirus (PV) types. The presence of human papillomavirus (HPV)-specific DNA sequences was confirmed through molecular hybridization and the presence of PV structure antigens was verified in thin sections by means of a group-specific anti-PV-antiserum using the peroxidase-antiperoxidase (PAP) technique. Three distinct clinical forms harboring distinct HPV types were distinguished: (1) Condylomata acuminata in which HPV-6 DNA was present in 37 of 59 samples and HPV-11 DNA in only 13 of 59 samples. HPV-16 DNA was not detected at all and 9 condylomatous lesions remained unclassified. (2) Flat condyloma-like lesions, where HPV-6 and HPV-11 were associated with lesions of low epidermal atypia in 8 and in 2 of 18 cases, respectively, and where HPV-16 was associated exclusively with 6 of 18 such lesions with severe atypia, called bowenoid papulosis. (3) Pigmented papules where HPV-16 was detected twice in lesions of bowenoid papulosis and HPV-11 in 2 of the benign pigmented lesions. The fourth clinical manifestation of genital papillomavirus infections--the so-called condylomata plana--was not available for virologic analysis. Histologically 5 different koilocytotic features were determined which could not be correlated either with one of the clinical pictures or with a specific PV type. HPV-16, however, was found frequently in non-koilocytotic lesions exhibiting the features of severe epithelial atypia known in bowenoid papulosis. The existence of PV structure antigens in these lesions could not be verified using the indirect immunoperoxidase--PAP-technique--in contrast to the koilocytotic lesions where clear evidence of the presence of HPV was proved in 36 of 56 (64.3%) of the cases.
Animals↗
Demonstration of HPV-16 genomes in the nuclei of cervix carcinoma cells.
Specimens of 4 different cervical cancers, 1 flat condyloma of the cervix, 1 condyloma acuminatum, 1 morbus Bowen of the skin and 1 skin wart were subjected to in situ hybridization using human papilloma virus type 16 (HPV-16) DNA nick translated with 3H-TTP as a probe. Within each cervical cancer biopsy we found a certain number of tumor cell clusters with clearly labelled nuclei, while sections of the other skin lesions did not reveal any accumulation of grains within their nuclei. Southern blot hybridization of the DNA extracted from the 4 cervical carcinomas with 32p-labelled HPV-16 DNA gave a positive reaction in 3 tumors. Non-reactivity in the 4th biopsy might be due to a low concentration of HPV-genomes within the total extracted DNA of this tissue part.
Biopsy↗
[Bowenoid papulosis and carcinoma in situ of the cervix uteri in sex partners. An example of the transmissibility of HPV-16 infection].
The development of bowenoid papules in a 20-year-old man and a carcinoma in situ of the portio uteri of the 22-year-old female sexual partner is reported. In both lesions HPV-16 DNA could be detected by molecular biological means. This observation led us to the conclusion that HPV 16 had been transmitted sexually. The same seems to be true for HPV-11-induced condylomata acuminata, which appeared on the external genitalia of both patients after recuperation from the HPV-16-induced lesions and conisation treatment. The clinical significance of this observation and its consequences for dermatologists and gynecologists are discussed.
Adult↗
[Condylomas--evidence for the involvement of papillomaviruses in the development of cervical cancer].
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Carcinoma, Squamous Cell↗
[Detection of papillomavirus capsid antigens and human papillomavirus 16-related DNA in Bowenoid papulosis and Bowen disease].
In one out of 22 cases of histologically diagnosed bowenoid papulosis, we could detect human papilloma virus (HPV) capsid antigen in paraffin sections fixed with formalin by means of the peroxidase-antiperoxidase (PAP) test; there were no positive findings regarding biopsies taken from Bowen's disease. Southern blot hybridization technique revealed HPV 16 DNA in 8 out of 10 cases of bowenoid papulosis; there was one positive identification out of 5 cases of Bowen's disease.
Adult↗
A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer.
DNA of a new papillomavirus type was cloned from a cervical carcinoma biopsy. Two EcoRI clones of 7.8 and 6.9 kb in length were obtained, the latter contained a 900-bp deletion. The BamHI fragments of both clones were used to characterize the DNA. It represents a distinct type of papillomavirus as determined by its size, its cross-hybridization with DNA of other papillomavirus types under conditions of low stringency only, the co-linear alignment of its genome with HPV 6 and HPV 16 prototypes and its occasional occurrence as oligomeric episomes. We tentatively propose to designate it as HPV 18. DNA hybridizing with HPV 18 under stringent conditions was detected in 9/36 cervical carcinomas from Africa and Brazil, in 2/13 cervical tumors from Germany and 1/10 penile carcinomas. Benign tumors (17 cervical dysplasias, 29 genital warts), eight carcinomata in situ and 15 biopsies of normal cervical tissue were devoid of detectable HPV 18 DNA. HPV 18-related DNA was found, however, in cells of the HeLa, KB and C4-1 lines all derived from cervical cancer. The state of the viral DNA was investigated in four cervical cancer biopsies. The data reveal that the DNA might be integrated into the host cell genome. One tumor provided evidence for head to tail tandem repeats some of which persisted as circular episomes.
Base Sequence↗
A human papillomavirus closely related to HPV 13 found in a focal epithelial hyperplasia lesion (Heck disease).
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Adult↗
Epstein-Barr virus (P3HR-1) defective DNA codes for components of both the early antigen and viral capsid antigen complexes.
A set of lambda phages containing overlapping fragments of Epstein-Barr virus (EBV) defective DNA has been cloned from P3HR-1-superinfected Raji cells. Mapping data obtained using these cloned DNA fragments confirmed the structure of P3HR-1 defective DNA previously deduced directly from virion DNA (M.-S. Cho, G. W. Bornkamm, and H. zur Hausen, 1984, J. Virol., in press). The ability of the cloned defective DNA fragments to induce EBV antigens in transfected baby hamster kidney (BHK) cells was tested using indirect immunofluorescence assays. Up to 5% of those cells receiving a defective DNA fragment BamHI-W'C' transiently expressed a de novo nuclear antigen which was identified as being a component of the EAD complex by its reactivity with characterized EBV-positive human sera. A 20-kb clone of P3HR-1 defective DNA (EcoRI-C1) was found to induce the synthesis of a component of the VCA complex. One percent of cells transfected with this clone showed cytoplasmic fluorescence when tested with either VCA+ human sera or EBV anti-VCA monoclonal antibody. Subcloning of the EcoRI-C1 fragment localized the VCA gene to a 4.1-kb segment which maps within the BamHI-A fragment of the standard genome. This segment contains a single large open reading frame of 2.6 kb (B. Barrell, A. Bankier, R. Baer, P. Biggin, P. Deininger, P. Farrell, T. Gibson, G. Hatfull, G. Hudson, S. Stachwell, and C. Sequin, 1984, Nature (London), in press). None of the defective DNA clones were capable of inducing EBV-specific nuclear antigens (EBNAs) which is consistent with the absence of the known EBNA coding regions from the defective genome.
Animals↗
A complete set of overlapping cosmid clones of M-ABA virus derived from nasopharyngeal carcinoma and its similarity to other Epstein-Barr virus isolates.
DNA of the transforming, nondefective Epstein-Barr virus (EBV) strain M-ABA, which is derived from nasopharyngeal carcinoma cells, was cloned as large overlapping pieces into the cosmid pHC79 . The termini were cloned from closed circular virus DNA molecules out of M-ABA cell DNA in phage lambda L47 . The large overlapping clones were used to prepare a library of subclones with inserts of 1-15 kb. A detailed restriction enzyme map of M-ABA virus DNA reveals the close similarity to isolates from other sources. The high number of tandem repeats in EBV DNA stresses the importance of using cloning vectors that can be propagated in recA- Escherichia coli hosts.
Carcinoma↗
Presence of human papillomavirus in genital tumors.
Human papillomavirus (HPV) types 16 and 18 have been identified in two different human cervical carcinomas. The viral DNAs were molecularly cloned and used as probes to screen a large number of genital tumors by Southern blot analysis. HPV-16 or HPV-18 sequences, respectively, were found in a high percentage of cervical carcinomas, but only in a small number of condylomata acuminata or flat condylomas. The majority of the latter lesions, however, contained HPV-6 or HPV-11 sequences, respectively, which in contrast were detected only rarely in carcinomas in situ or invasively growing carcinomas. A similar distribution of the different papillomaviruses was observed when cell swabs taken from the cervix were tested by in situ hybridization.
Animals↗