Viruses in the etiology of human genital cancer.
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Animals↗
Biomedical subjects
L Gissmann
Publications and source records attributed to L Gissmann.
Identification of human papillomavirus in cervical swabs by deoxyribonucleic acid in situ hybridization.
A series of 47 lesions diagnosed cytologically as cervical intraepithelial neoplasia (CIN) III in 22 cases, CIN I/II in 13 cases, and 12 cases showing abnormal smears consistent with human papillomavirus infection were analyzed. Thirty-six cases with negative cytology were used as the control group. Sixty-eight percent of CIN III were positive for a mixture of human papillomavirus 16 and human papillomavirus 18, 18% reacted with human papillomavirus 6 or 11, and 14% were negative. Of the group with CIN I/II or with abnormal Papanicolaou smears, approximately one-third contained human papillomavirus 6 (11) and one-third human papillomavirus 16 and 18. Only 11% of the samples from the control group hybridized with human papillomavirus 6 (11), the others were negative with either probe. The data obtained by the rapid in situ hybridization of cervical cells are in agreement with the presence of human papillomavirus 16 and 18 in a high proportion of cervical carcinoma and carcinoma in situ lesions. Thus, the method can be applied to test the hypothesis that a lesion containing human papillomavirus 16/18 positive cells has a higher risk of progressing to cancer than a lesion harboring human papillomavirus 6 or 11.
Animals↗
Human papillomavirus DNA in genital tumours.
Human papillomaviruses (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 tumours by Southern blot analysis. HPV 16 or HPV 18 sequences 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 carcinoma in situ or invasive carcinomas. A similar distribution of the different papillomaviruses was observed when cell scrapings taken from the cervix were tested by in situ hybridization.
Animals↗
Human papillomavirus type-16-related DNA in genital Bowen's disease and in Bowenoid papulosis.
32P-labelled DNA of HPV 16 which has been isolated and molecularly cloned from a cervical carcinoma (Dürst et al., 1983) was used to screen the cellular DNAs obtained from 20 different biopsies of Morbus Bowen or Bowenoid papulosis, respectively, by Southern blot analysis. Under conditions of differing stringency for the hybridization, HPV 16 DNA or related sequences were identified in 6 out of 10 cases of Morbus Bowen (4 out of 5 from a genital localization) and in 8 out of 10 biopsies from Bowenoid papulosis. One additional case of the latter disease contained DNA sequences of an HPV type not yet classified. There is evidence for the presence of another HPV DNA in two of the HPV-16-positive tumors. A large number of normal genital tissue samples were negative for HPV DNA.
Adult↗
Herpes simplex virus-induced amplification of SV40 sequences in transformed Chinese hamster embryo cells.
Infection with Herpes simplex viruses (HSV) induces amplification of SV40 sequences in SV40-transformed Chinese hamster embryo cells (CO631). This is shown by in situ hybridization of the infected cells with cloned 32P-labelled SV40 DNA. The HSV-mediated synthesis of SV40 DNA is more pronounced than after treatment with chemical carcinogens. This initiator-like effect of HSV may, in concert with the previously reported mutagenic activity of this virus (Schlehofer and zur Hausen, 1982), point to a possible mechanism of HSV infection in human genital cancer.
Animals↗
Nucleic acid hybridization for the detection of viral genomes.
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Base Sequence↗
A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions.
DNA from one biopsy sample of invasive cancer of the cervix contained sequences hybridizing with human papillomavirus (HPV) type 11 DNA only under nonstringent conditions. This DNA was molecularly cloned in lambda phage. Under stringent conditions of hybridization it cross-hybridized to a minor extent (less than 0.1%) with HPV types 10, 14, and 15 and showed no homology with DNA of other human HPV types. We therefore propose to designate it tentatively as HPV 16. HPV 16 DNA was used as a probe to test additional cancer biopsy samples from cervical, vulval, and penile cancer, as well as benign genital warts (condylomata acuminata) and cervical dysplasias for the presence of homologous sequences. In 61.1% (11/18) of cervical cancer samples from German patients sequences were found hybridizing with HPV 16 DNA under conditions of high stringency. In contrast, only 34.8% (8/23) of cancer biopsy samples from Kenya and Brazil revealed this DNA. Vulval and penile cancer biopsy samples hybridized to 28.6% (2/7) or 25% (1/4), respectively. Only 2 out of 33 condylomata acuminata contained HPV 16 DNA. Both positive tumors harbored in addition HPV 6 or HPV 11 DNA. The data thus indicate that HPV 16 DNA prevails in malignant tumors, rendering an accidental contamination with papillomavirus DNA from adjacent papillomas rather unlikely. The rare presence in benign genital papillomas in addition to common genital papillomaviruses suggests a dependence of HPV 16 replication on helper virus.
Bacteriophage lambda↗
Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers.
Human genital tumors as well as recurrent laryngeal papillomas were analyzed for the presence of human papillomavirus (HPV) 6 and HPV 11 sequences. HPV 11 DNA was found in 7 of 14 laryngeal papillomas; in the 7 other tumors no HPV DNA was demonstrated. HPV 11 DNA was also found in all five atypical condylomata of the cervix included in this study. Condylomata acuminata mainly contained HPV 6 DNA. From 63 biopsy specimens, 41 clearly harbored HPV 6 DNA and 13 harbored HPV 11 DNA. In three tumors accurate typing was impossible, and in six additional ones neither HPV 6 nor HPV 11 DNA could be demonstrated. The data support a genital origin of laryngeal papillomavirus infections. In 4 of 24 malignant tumors, HPV 11 DNA or related sequences were demonstrated; 2 of the 4 were biopsy specimens from invasive cancer, and the other 2 originated from carcinomata in situ. A possible role of this or related papillomavirus types in the induction of malignant genital tumors remains to be elucidated.
Carcinoma, Squamous Cell↗
Correlation between content of viral DNA and evidence of mature virus particles in HPV-1, HPV-4, and HPV-6 induced virus acanthomata.
In HPV-1 and HPV-4 induced warts as well as in HPV-6 positive condylomata acuminata the quantity of viral DNA encapsulated into virus particles was determined and compared to the total amount of viral DNA present in the papillomas. As shown by filter hybridization using 3H-labeled viral DNA molecularly cloned in Escherichia coli, the amount of total viral DNA found in HPV-1 or HPV-4 induced skin warts is similar. HPV-4 DNA, however, is encapsulated into virus particles with less efficiency. HPV-6 DNA can be detected only at minute amounts in condylomata acuminata and the percentage of DNA recovered from virions is extremely low.
Condylomata Acuminata↗
Characterization of human papillomavirus type 13 from focal epithelial hyperplasia Heck lesions.
Focal epithelial hyperplasia Heck lesions of a Turkish patient were shown to contain papillomavirus-specific DNA, which was molecularly cloned into bacteriophage lambda. It proved to be related to human papillomavirus (HPV) type 6 DNA and HPV type 11 DNA. Reassociation kinetics revealed a cross-hybridization of 4 and 3%, respectively. There was no cross-reactivity with HPV type 1, 2, 3, 4, 5, 8, or 10. This papillomavirus type will be referred to as HPV type 13. The DNA was characterized by cleavage with several restriction enzymes, and the cleavage sites were physically mapped. Papules from two additional cases of Morbus Heck contained HPV type 13 DNA as shown by Southern blot hybridization and by the characteristic cleavage patterns. This may indicate that HPV type 13 is more frequently associated with focal epithelial hyperplasia Heck than are other HPV types.
Adolescent↗
Molecular cloning and partial nucleotide sequence of human papillomavirus type 1a DNA.
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Base Sequence↗
Analysis of human genital warts (condylomata acuminata) and other genital tumors for human papillomavirus type 6 DNA.
32P-labelled cloned HPV 6 DNA was used as probe to analyze human genital tumors for DNA sequences homologous to HPV 6 DNA. Ninety three percent of all condylomata acuminata (41 out of 44) were found to harbor HPV 6 DNA. Of the remaining three, one contained HPV 1 DNA. No papillomavirus DNA was identified in the two other tumors. All three invasively growing giant condylomata acuminata (Buschke-Löwenstein tumors) investigated also contained HPV 6 DNA. Two out of six atypical condylomata of the cervix hybridized with HPV 6 DNA under stringent conditions, one only under conditions of low stringency. All DNA preparations from malignant tumors studies (54 cervical carcinomas, 10 penile carcinomas, two vulvar carcinomas) failed to anneal with HPV 6 DNA, even under conditions of low stringency. Although all HPV 6-positive condylomata acuminata analyzed in this study revealed HPV 6 DNA of regular molecular weight (5.1 x 10(6)), two of the Buschke-Löwenstein tumors, as well as one of the two positive atypical condylomata of the cervix, contained HPV 6 DNA with a remarkable size classes occurred in a supercoiled form without evidence for integration into host cell DNA.
Animals↗
Correlation between human papillomavirus (HPV) type and histology of warts.
Forty warts from different patients and of different clinical type were examined histologically and virologically. Eight lesions were found to be associated with human papillomavirus type 1 (HPV 1), 15 tumors were induced by HPV 2, HPV 3 was detected 4 times, HPV 4 twice, and HPV 6 eleven times. HPV 3, HPV 4, and HPV 6 induced warts revealed a correlation between histology and virus type. They are characterized by the so called "edematous type clear cells". In HPV 3 associated flat warts pycnotic nuclei were mainly localized in the center of large vacuoles. In genital warts sickle shaped nuclei were pushed to the margin of the vacuolized cells. The histology of HPV 1 and HPV 2 induced warts was more heterogenous. With one exception HPV 1-induced lesions represented typical myrmecia warts, varying in the number and shape of inclusion bodies. HPV 2 associated common warts, however, revealed 3 very distinct histologic features: (1) Inclusion wart typical for HPV 1, (2) Classical common wart with marked condensation of keratohyalin granules, (3) Warts with extreme vacuolization of squamous and granular cells leading to a honeycomb-like picture.
Animals↗
Molecular cloning and characterization of human papilloma virus DNA derived from a laryngeal papilloma.
Papilloma virus DNA from a laryngeal papilloma was cloned in phage lambda L 47 and characterized after cleavage with different restriction enzymes. Hybridization with the DNAs of human papilloma virus types 1, 2, 3, 4, 5, and 8 showed no homology under stringent hybridization conditions. Human papilloma virus type 6 DNA, however, was partially identical to laryngeal papilloma virus DNA; different restriction enzyme fragments hybridizing with the other DNA were identified on each genome. The degree of homology was determined by reassociation kinetics to be 25%. According to the present nomenclature, laryngeal papilloma virus therefore represents a different type of human papilloma virus and is tentatively designated as human papilloma virus type 11. Sequences homologous to laryngeal papilloma virus DNA were also found in four of nine additional laryngeal papillomas. Attempt to detect homologous DNA in 12 carcinomas of the larynx were negative.
Adolescent↗
Characterization of a human papillomavirus from epidermodysplasia verruciformis lesions of a patient from Upper-volta.
A case of epidermodysplasia verruciformis in a patient from Upper-Volta is described. Slightly elevated, flat warts were observed on hands, feet, arms and legs, and pityriasis versicolor-like lesions were found mainly on the trunk. The patient showed no malignant tumors. Histological examination revealed hyperkeratosis, granulosis and moderate acanthosis with large, foamy, basophilic keratinocytes in stratum granulosum and stratum spinosum. Papillomavirus particles could be prepared from these lesions and were differentiated from known papillomavirus types by immune electron microscopy with monospecific antisera and by DNA-DNA hybridization. The viral DNA was characterized by cleavage with several restriction endonucleases and a physical map of the resulting fragments was established. The virus is designated as HPV 8. Preliminary seroepidemiologic studies with human sera indicate a rather wide distribution of HPV 8. Blot hybridization of DNA from human carcinomas with 32P-labelled virus DNA detected no HPV 8-specific sequences.
Adult↗
Papillomavirus infections and human genital cancer.
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Animals↗
Molecular cloning of viral DNA from human genital warts.
The DNA of human papilloma virus type 6 (HPV 6) has been cloned in Escherichia coli K-12 by using pBR322 as vector. The DNA was cloned at the BamHI and EcoRI cleavage sites. This DNA was mapped by employing further restriction endonucleases and by terminal labeling. No major differences were noted as compared to HPV 6 DNA originating directly from a genital wart. The existence of at least two DNA subtypes (HPV 6a and 6b) became apparent.
Animals↗
Partial characterization of viral DNA from human genital warts (Condylomata acuminata).
By centrifuging total cellular DNA derived from human genital warts (condylomata acuminata) in CsCl-ethidium bromide gradients, supercoiled DNA was isolated. The molecular weight of this DNA was determined by agarose gel electrophoresis and amounted to 5.1 X 10(4). This DNA isolated from an individual genital wart was annealed to fractions of aqueous supernatants of the same wart after prior centrifugation of this material in CsCl density gradients. Annealing was observed at a density of approximately 1.32 g/ml corresponding to the expected density of papilloma virus particles. Since such particles were also observed in the same preparation by electron microscopy, it was concluded that the supercoiled DNA molecules were derived from papilloma virus nucleocapsids. Positive hybridization was found with six additional preparations from individual genital warts. Therefore, it seems that the isolated DNA prevails in condylomata acuminata. The DNA is different from the other five types of human papilloma viruses described thus far in regard to its restriction endonuclease cleavage patterns. The virus analyzed is tentatively designated as human papilloma virus type 6 (HPV 6).
Autoradiography↗