PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
 
J Virol. 1991 February; 65(2): 606–612.
PMCID: PMC239798

Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm.

Abstract

The integration of human papillomavirus (HPV) DNA into the human genome has been generally accepted as a characteristic of malignant lesions. To gain a better understanding of this phenomenon, genomic DNA from 181 cervical biopsy specimens was isolated and analyzed for HPV type and physical state of the HPV genome. These specimens represented the full spectrum of cervical disease, from condyloma to invasive carcinoma. Discrimination between integrated and episomal HPV DNA was accomplished by the detection of HPV-human DNA junction fragments on Southern blots. In most cases in which ambiguous Southern blot results were obtained, the specimens were reanalyzed by two-dimensional gel electrophoresis. Of the 100 biopsy specimens of cervical intraepithelial neoplasia analyzed, only 3 showed integrated HPV DNA, in contrast to 56 (81%) of 69 cervical carcinomas (P less than 0.001) showing integrated HPV DNA. Of the 40 carcinomas containing HPV 16 DNA, 29 (72%) had integrated HPV DNA, of which 8 (20%) also had episomal HPV DNA. In 11 (27%) cancers, only episomal HPV 16 DNA was detected. All 23 HPV 18-containing carcinomas had integrated HPV DNA, and 1 also had episomal HPV 18 DNA. The difference between HPV types 16 and 18 with respect to frequency of integration was statistically significant (P less than 0.01). The results of this study indicate that detectable integration of HPV DNA, regardless of type, occurs infrequently in cervical intraepithelial neoplasia. The absence of HPV 16 DNA integration in some carcinomas implies that integration is not always required for malignant progression. In contrast, the consistent integration of HPV 18 DNA in all cervical cancers examined may be related to its greater transforming efficiency in vitro and its reported clinical association with more aggressive cervical cancers.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • el Awady MK, Kaplan JB, O'Brien SJ, Burk RD. Molecular analysis of integrated human papillomavirus 16 sequences in the cervical cancer cell line SiHa. Virology. 1987 Aug;159(2):389–398. [PubMed]
  • Barbosa MS, Schlegel R. The E6 and E7 genes of HPV-18 are sufficient for inducing two-stage in vitro transformation of human keratinocytes. Oncogene. 1989 Dec;4(12):1529–1532. [PubMed]
  • Barnes W, Delgado G, Kurman RJ, Petrilli ES, Smith DM, Ahmed S, Lorincz AT, Temple GF, Jenson AB, Lancaster WD. Possible prognostic significance of human papillomavirus type in cervical cancer. Gynecol Oncol. 1988 Mar;29(3):267–273. [PubMed]
  • Beaudenon S, Kremsdorf D, Croissant O, Jablonska S, Wain-Hobson S, Orth G. A novel type of human papillomavirus associated with genital neoplasias. Nature. 1986 May 15;321(6067):246–249. [PubMed]
  • Beaudenon S, Kremsdorf D, Obalek S, Jablonska S, Pehau-Arnaudet G, Croissant O, Orth G. Plurality of genital human papillomaviruses: characterization of two new types with distinct biological properties. Virology. 1987 Dec;161(2):374–384. [PubMed]
  • Choo KB, Cheung WF, Liew LN, Lee HH, Han SH. Presence of catenated human papillomavirus type 16 episomes in a cervical carcinoma cell line. J Virol. 1989 Feb;63(2):782–789. [PMC free article] [PubMed]
  • Choo KB, Lee HH, Pan CC, Wu SM, Liew LN, Cheung WF, Han SH. Sequence duplication and internal deletion in the integrated human papillomavirus type 16 genome cloned from a cervical carcinoma. J Virol. 1988 May;62(5):1659–1666. [PMC free article] [PubMed]
  • Choo KB, Pan CC, Han SH. Integration of human papillomavirus type 16 into cellular DNA of cervical carcinoma: preferential deletion of the E2 gene and invariable retention of the long control region and the E6/E7 open reading frames. Virology. 1987 Nov;161(1):259–261. [PubMed]
  • Di Luca D, Caselli E, Monini P, Rotola A, Savioli A, Cassai E. Episomal HPV 16 DNA isolated from a cervical carcinoma presents a partial duplication of the early region. Virus Res. 1989 Sep;14(1):49–55. [PubMed]
  • Di Luca D, Pilotti S, Stefanon B, Rotola A, Monini P, Tognon M, De Palo G, Rilke F, Cassai E. Human papillomavirus type 16 DNA in genital tumours: a pathological and molecular analysis. J Gen Virol. 1986 Mar;67(Pt 3):583–589. [PubMed]
  • Dürst M, Gissmann L, Ikenberg H, zur Hausen H. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3812–3815. [PubMed]
  • Dürst M, Kleinheinz A, Hotz M, Gissmann L. The physical state of human papillomavirus type 16 DNA in benign and malignant genital tumours. J Gen Virol. 1985 Jul;66(Pt 7):1515–1522. [PubMed]
  • Fuchs PG, Girardi F, Pfister H. Human papillomavirus 16 DNA in cervical cancers and in lymph nodes of cervical cancer patients: a diagnostic marker for early metastases? Int J Cancer. 1989 Jan 15;43(1):41–44. [PubMed]
  • Johnson PH, Grossman LI. Electrophoresis of DNA in agarose gels. Optimizing separations of conformational isomers of double- and single-stranded DNAs. Biochemistry. 1977 Sep 20;16(19):4217–4225. [PubMed]
  • Kurman RJ, Schiffman MH, Lancaster WD, Reid R, Jenson AB, Temple GF, Lorincz AT. Analysis of individual human papillomavirus types in cervical neoplasia: a possible role for type 18 in rapid progression. Am J Obstet Gynecol. 1988 Aug;159(2):293–296. [PubMed]
  • Lehn H, Krieg P, Sauer G. Papillomavirus genomes in human cervical tumors: analysis of their transcriptional activity. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5540–5544. [PubMed]
  • Lehn H, Villa LL, Marziona F, Hilgarth M, Hillemans HG, Sauer G. Physical state and biological activity of human papillomavirus genomes in precancerous lesions of the female genital tract. J Gen Virol. 1988 Jan;69(Pt 1):187–196. [PubMed]
  • Lörincz AT, Quinn AP, Goldsborough MD, McAllister P, Temple GF. Human papillomavirus type 56: a new virus detected in cervical cancers. J Gen Virol. 1989 Nov;70(Pt 11):3099–3104. [PubMed]
  • Lörincz AT, Quinn AP, Goldsborough MD, Schmidt BJ, Temple GF. Cloning and partial DNA sequencing of two new human papillomavirus types associated with condylomas and low-grade cervical neoplasia. J Virol. 1989 Jun;63(6):2829–2834. [PMC free article] [PubMed]
  • Lorincz AT, Quinn AP, Lancaster WD, Temple GF. A new type of papillomavirus associated with cancer of the uterine cervix. Virology. 1987 Jul;159(1):187–190. [PubMed]
  • Lorincz AT, Temple GF, Kurman RJ, Jenson AB, Lancaster WD. Oncogenic association of specific human papillomavirus types with cervical neoplasia. J Natl Cancer Inst. 1987 Oct;79(4):671–677. [PubMed]
  • Matsukura T, Koi S, Sugase M. Both episomal and integrated forms of human papillomavirus type 16 are involved in invasive cervical cancers. Virology. 1989 Sep;172(1):63–72. [PubMed]
  • Naghashfar ZS, Rosenshein NB, Lorincz AT, Buscema J, Shah KV. Characterization of human papillomavirus type 45, a new type 18-related virus of the genital tract. J Gen Virol. 1987 Dec;68(Pt 12):3073–3079. [PubMed]
  • Nuovo GJ, Crum CP, De Villiers EM, Levine RU, Silverstein SJ. Isolation of a novel human papillomavirus (type 51) from a cervical condyloma. J Virol. 1988 Apr;62(4):1452–1455. [PMC free article] [PubMed]
  • Reid R, Greenberg M, Jenson AB, Husain M, Willett J, Daoud Y, Temple G, Stanhope CR, Sherman AI, Phibbs GD, et al. Sexually transmitted papillomaviral infections. I. The anatomic distribution and pathologic grade of neoplastic lesions associated with different viral types. Am J Obstet Gynecol. 1987 Jan;156(1):212–222. [PubMed]
  • Shimoda K, Lorincz AT, Temple GF, Lancaster WD. Human papillomavirus type 52: a new virus associated with cervical neoplasia. J Gen Virol. 1988 Nov;69(Pt 11):2925–2928. [PubMed]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed]
  • Walker J, Bloss JD, Liao SY, Berman M, Bergen S, Wilczynski SP. Human papillomavirus genotype as a prognostic indicator in carcinoma of the uterine cervix. Obstet Gynecol. 1989 Nov;74(5):781–785. [PubMed]
  • Yee C, Krishnan-Hewlett I, Baker CC, Schlegel R, Howley PM. Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. Am J Pathol. 1985 Jun;119(3):361–366. [PubMed]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)