1887

Abstract

Summary

The DNA of distinct human papillomaviruses (HPVs) is regularly detected in the majority of human cervical carcinomas. In contrast to benign HPV-induced genital lesions, where the viral genomes are exclusively present as episomes, in cervical carcinomas HPV type 16 (HPV16) DNA was found to be integrated into the host DNA. In order to determine the physical state and expression of HPV DNA sequences at different stages of tumour development, we analysed a series of cervical lesions (mild, moderate and severe dysplasia and carcinoma ) that are considered precursors of carcinomas of the cervix. In 66.6% (18 of 27) of the tumours, HPV16 DNA was present. While in mild dysplasias only episomal HPV genomes were found, in all higher grade lesions integration of the viral DNA was detected. There was a close correlation between the episomal state and the expression of the HPV16 genomes:in 15 cases harbouring episomal HPV16 DNA (seven of which also contained integrated genomes) viral transcripts were present. We conclude that integration of HPV genomes takes place very early in cervical cancer development. In addition, the episomal state of the viral DNA depends on viral gene expression. The same conclusion, however, is not applicable in those lesions (three severe dysplasias) containing exclusively integrated HPV16 DNA. Thus, HPV16 DNA can persist in an integrated state without recognizable transcriptional activity. These results point to HPV16 as one potential prerequisite for the first steps in the multistage development of human cervical cancer.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-69-1-187
1988-01-01
2021-10-27
Loading full text...

Full text loading...

/deliver/fulltext/jgv/69/1/JV0690010187.html?itemId=/content/journal/jgv/10.1099/0022-1317-69-1-187&mimeType=html&fmt=ahah

References

  1. AMTMANN E., RANDERIA J., WAYSS K. 1987 The interaction of papillomaviruses with carcinogens and tumor promoters. Cancer Cells 5 Papillomaviruses Edited by Steinberg B. M., Brandsma J. L., Taichman L. B. New York: Cold Spring Harbor Laboratory; in press
    [Google Scholar]
  2. BAIRD P. J. 1985; The role of human papilloma and other viruses. Clinics in Obstetrics and Gynecology 12:19–32
    [Google Scholar]
  3. BOSHART M., GISSMANN L., IKENBERG H., KLEINHEINZ A., SCHEURLEN W., ZUR HAUSEN H. 1984; A new type of papillomavirus DNA: its presence in genital cancer biopsies and in cell lines derived from cervical cancer. EMBO Journal 3:1151–1157
    [Google Scholar]
  4. CAMPO M. S., MOAR M. H., SARTIRANA M. L., KENNEDY L. M., JARRETT W. F. H. 1985; The presence of bovine papillomavirus type 4 DNA is not required for the progression to, or the maintenance of the malignant state in cancers of the alimentary canal in cattle. EMBO Journal 4:1819–1825
    [Google Scholar]
  5. CRUM C. P., MITAO M., LEVINE R. V., SILVERSTEIN S. 1985; Cervical papillomaviruses segregate within morphologically distinct precancerous lesions. Journal of Virology 54:675–681
    [Google Scholar]
  6. DENHARDT D. 1966; A membrane-filter technique for the detection of complementary DNA. Biochemical and Biophysical Research Communications 23:641–646
    [Google Scholar]
  7. DURST M., GISSMANN L., IKENBERG H., ZUR HAUSEN H. 1983; A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proceedings of the National Academy of Sciences, U.S.A 80:3812–3815
    [Google Scholar]
  8. DURST M., KLEINHEINZ A., HOTZ M., GISSMANN L. 1985; The physical state of human papillomavirus type 16 DNA in benign and malignant genital tumours. Journal of General Virology 66:1515–1522
    [Google Scholar]
  9. FRANCHINI G., WONG-STAAL F., GALLO R. C. 1984; Human T-cell leukemia virus (HTLV-I) transcripts in fresh and cultured cells of patients with adult T-cell leukemia. Proceedings of the National Academy of Sciences, U.S.A 81:6207–6211
    [Google Scholar]
  10. GISSMANN L., DE VILLIERS E.-M., ZUR HAUSEN H. 1982; Analysis of human genital warts (condylomata acuminata) and other genital tumors for human papillomavirus type 6 DNA. International Journal of Cancer 29:143–146
    [Google Scholar]
  11. KADISH A. S., BURK R. D., KRESS Y., CALDERIN S., ROMNEY S. L. 1986; Human papillomaviruses of different types in precancerous lesions of the uterine cervix: histologic, immunocytochemical and ultrastructural studies. Human Pathology 17:384–392
    [Google Scholar]
  12. KRIEG P., AMTMANN E., SAUER G. 1983; The simultaneous extraction of high molecular weight DNA and of RNA from solid tumors. Analytical Biochemistry 134:288–294
    [Google Scholar]
  13. LEHN H. 1986; Human papillomavirus DNA replication mediated by simian virus 40 T antigen in trans. Journal of General Virology 67:1581–1589
    [Google Scholar]
  14. LEHN H., SAUER G. 1985 Organization and expression of human papillomavirus type 16 genomes in human cervical carcinomas. Papillomaviruses: Molecular and Clinical Aspects 3257–65 Edited by Howley P. M., Broker T. R. New York: Alan R. Liss;
    [Google Scholar]
  15. LEHN H., ERNST T.-M., SAUER G. 1984; Transcription of episomal papillomavirus DNA in human condylomata acuminata and Buschke-Löwenstein tumours. Journal of General Virology 65:2003–2010
    [Google Scholar]
  16. LEHN H., KRIEG P., SAUER G. 1985; Papillomavirus genomes in human cervical tumors: analysis of their transcriptional activity. Proceedings of the National Academy of Sciences, U.S.A 82:5540–5544
    [Google Scholar]
  17. LUSKY M., BOTCHAN M. R. 1984; Characterization of the bovine papillomavirus plasmid maintenance sequences. Cell 36:391–401
    [Google Scholar]
  18. LUSKY M., BOTCHAN M. R. 1985; Genetic analysis of bovine papillomavirus type 1 trans-acting replication factors. Journal of Virology 53:955–965
    [Google Scholar]
  19. McCANCE D. J. 1986; Human papillomaviruses and cancer. Biochimica et biophysica acta 823:195–205
    [Google Scholar]
  20. NELSON J. H. JR, AVERETTE H. E., RICHART R. M. 1984; Dysplasia, carcinoma in situ, and early invasive cervical carcinoma. CA- A Cancer Journal for Clinicians 34:306–327
    [Google Scholar]
  21. ORTH G., FAVRE M., BREITBURD F., CROISSANT O., JABLONSKA S., OBALEK S., JARZABEK-CHORZELSKA M., RZESA G. 1980 Epidermodysplasia verruciformis: a model for the role of papillomaviruses in human cancer. Viruses in Naturally Occurring Cancers. Cold Spring Harbor Conferences on Cell Proliferation 7259–282 Edited by Essex M., Todaro G., zur Hausen H. New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  22. PFISTER H. 1984; Biology and biochemistry of papillomaviruses. Review of Physiology and Biochemical Pharmacology 99:111–181
    [Google Scholar]
  23. RIGBY P. W. J., DIECKMANN M., RHODES C., BERG P. 1977; Labelling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. Journal of Molecular Biology 113:237–251
    [Google Scholar]
  24. SARVER N., RABSON M. S., YANG Y. C, BYRNE J. C., HOWLEY P. M. 1984; Localization and analysis of bovine papilloma virus type 1 transforming functions. Journal of Virology 52:377–388
    [Google Scholar]
  25. SCHNEIDER A., KRAUS H., SCHUHMANN R., GISSMANN L. 1985; Papillomavirus infection of the lower genital tract: detection of viral DNA in gynaecological swabs. International Journal of Cancer 35:443–448
    [Google Scholar]
  26. SCHNEIDER-GäDICKE A., SCHWARZ E. 1986; Different human cervical carcinoma cell lines show similar transcription patterns of human papillomavirus type 18 early genes. EMBO Journal 5:2285–2292
    [Google Scholar]
  27. SCHOLL S. M., KINGSLEY PILLERS E. M., ROBINSON R. E., FARRELL P. J. 1985; Prevalence of human papillomavirus type 16 DNA in cervical carcinoma samples in East Anglia. International Journal of Cancer 35:215–218
    [Google Scholar]
  28. SCHWARZ E., FREESE U. K., GISSMANN L., MAYER W., ROGGENBUCK B., STREMLAU A., ZUR HAUSEN H. 1985; Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature, London 314:111–114
    [Google Scholar]
  29. SHIRASAWA H., TOMITA Y., KUBOTA K., KASAI T., SEKIYA S., TAKAMIZAWA H., SIMIZU B. 1986; Detection of human papillomavirus type 16 DNA and evidence for integration into the cell DNA in cervical dysplasia. Journal of General Virology 67:2011–2015
    [Google Scholar]
  30. SMOTKIN D., WETTSTEIN F. O. 1986; Transcription of human papillomavirus type 16 early genes in a cervical cancer and a cancer-derived cell line and identification of the E7 protein. Proceedings of the National Academy of Sciences, U.S.A 83:4680–4684
    [Google Scholar]
  31. VILLA L. L., LOPES A. 1986; Human papillomavirus DNA sequences in penile carcinomas in Brazil. International Journal of Cancer 37:853–855
    [Google Scholar]
  32. WICKENDEN C, STEELE A., MALCOLM A. D. B., COLEMAN D. V. 1985; Screening for wart virus infection in normal and abnormal cervices by DNA hybridization of cervical scrapes. Lancet i:65–67
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-69-1-187
Loading
/content/journal/jgv/10.1099/0022-1317-69-1-187
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error