Skip to main content
NCBI home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1997 Nov;50(11):904–910. doi: 10.1136/jcp.50.11.904

Genotypic mapping of HPV and assessment of EBV prevalence in endocervical lesions.

J J O'Leary 1, R J Landers 1, M Crowley 1, I Healy 1, W F Kealy 1, J Hogan 1, C Cullinane 1, P Kelehan 1, C T Doyle 1
PMCID: PMC500313  PMID: 9462238

Abstract

AIMS: To examine the prevalence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) in low grade glandular intraepithelial lesions of the cervix, adenocarcinoma with high grade glandular intraepithelial lesions combined, and adenocarcinomas; and to perform a genotyping mapping analysis of endocervical carcinomas to determine the extent of HPV infections in such lesions. MATERIAL: Archival paraffin wax embeded material from the files of the departments of pathology, National Maternity Hospital, Dublin, and University College Cork, Ireland. METHODS: HPV prevalence was examined using type specific HPV PCR, general primer HPV PCR (pan HPV screen), nonisotopic in situ hybridisation (NISH), and PCR in situ hybridisation (PCR-ISH). In situ hybridisation was performed using fluorescein labelled oligonucleotide cocktail for eber transcripts of EBV. Genotypic analysis was performed, in all cases where possible, using a grid system. RESULTS: HPV 16 and 18 were predominantly identified in low grade glandular intraepithelial lesions, high grade glandular intraepithelial lesions, and adenocarcinomas, with HPV prevalence increasing with grade of dysplasia. EBV was only identified in subepithelial lymphocytes in a minority of cases. No link could be shown between HPV and EBV in endocervical lesions. HPV infection was not clonal in endocervical cancer and coexistent adjacent cervical intraepithelial neoplasia, where present, tended to show a similar HPV type. CONCLUSIONS: The restriction of HPV types 16 and 18 to endocervical lesions suggests that their effect is restricted and specific to endocervical mucosa, but the mechanism of interaction is currently unknown.

Full text

PDF
904

Images in this article

906Image
on p.906
908Image
on p.908

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anwar K., Nakakuki K., Shiraishi T., Naiki H., Yatani R., Inuzuka M. Presence of ras oncogene mutations and human papillomavirus DNA in human prostate carcinomas. Cancer Res. 1992 Nov 1;52(21):5991–5996. [PubMed] [Google Scholar]
  2. Arends M. J., Donaldson Y. K., Duvall E., Wyllie A. H., Bird C. C. HPV in full thickness cervical biopsies: high prevalence in CIN 2 and CIN 3 detected by a sensitive PCR method. J Pathol. 1991 Dec;165(4):301–309. doi: 10.1002/path.1711650405. [DOI] [PubMed] [Google Scholar]
  3. Arends M. J., Wyllie A. H., Bird C. C. Papillomaviruses and human cancer. Hum Pathol. 1990 Jul;21(7):686–698. doi: 10.1016/0046-8177(90)90027-3. [DOI] [PubMed] [Google Scholar]
  4. Boshoff C., Schulz T. F., Kennedy M. M., Graham A. K., Fisher C., Thomas A., McGee J. O., Weiss R. A., O'Leary J. J. Kaposi's sarcoma-associated herpesvirus infects endothelial and spindle cells. Nat Med. 1995 Dec;1(12):1274–1278. doi: 10.1038/nm1295-1274. [DOI] [PubMed] [Google Scholar]
  5. Brichácek B., Hirsch I., Síbl O., Vilikusová E., Vonka V. Association of some supraglottic laryngeal carcinomas with EB virus. Int J Cancer. 1983 Aug 15;32(2):193–197. doi: 10.1002/ijc.2910320209. [DOI] [PubMed] [Google Scholar]
  6. Brichácek B., Hirsch I., Síbl O., Vilikusová E., Vonka V. Presence of Epstein-Barr virus DNA in carcinomas of the palatine tonsil. J Natl Cancer Inst. 1984 Apr;72(4):809–815. [PubMed] [Google Scholar]
  7. Cooper K., Herrington C. S., Lo E. S., Evans M. F., McGee J. O. Integration of human papillomavirus types 16 and 18 in cervical adenocarcinoma. J Clin Pathol. 1992 May;45(5):382–384. doi: 10.1136/jcp.45.5.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Effert P. J., Frye R. A., Neubauer A., Liu E. T., Walther P. J. Human papillomavirus types 16 and 18 are not involved in human prostate carcinogenesis: analysis of archival human prostate cancer specimens by differential polymerase chain reaction. J Urol. 1992 Jan;147(1):192–196. doi: 10.1016/s0022-5347(17)37195-1. [DOI] [PubMed] [Google Scholar]
  9. Farnsworth A., Laverty C., Stoler M. H. Human papillomavirus messenger RNA expression in adenocarcinoma in situ of the uterine cervix. Int J Gynecol Pathol. 1989;8(4):321–330. doi: 10.1097/00004347-198912000-00003. [DOI] [PubMed] [Google Scholar]
  10. Fox H., Wells M., Harris M., McWilliam L. J., Anderson G. S. Enteric tumours of the lower female genital tract: a report of three cases. Histopathology. 1988 Feb;12(2):167–176. doi: 10.1111/j.1365-2559.1988.tb01927.x. [DOI] [PubMed] [Google Scholar]
  11. Hart W. R., Norris H. J. Mesonephric adenocarcinomas of the cervix. Cancer. 1972 Jan;29(1):106–113. doi: 10.1002/1097-0142(197201)29:1<106::aid-cncr2820290117>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  12. Hasumi K., Ehrmann R. L. Clear cell carcinoma of the uterine endocervix with an in situ component. Cancer. 1978 Nov;42(5):2435–2438. doi: 10.1002/1097-0142(197811)42:5<2435::aid-cncr2820420545>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  13. Herrington C. S. Human papillomaviruses and cervical neoplasia. I. Classification, virology, pathology, and epidemiology. J Clin Pathol. 1994 Dec;47(12):1066–1072. doi: 10.1136/jcp.47.12.1066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jaworski R. C. Endocervical glandular dysplasia, adenocarcinoma in situ, and early invasive (microinvasive) adenocarcinoma of the uterine cervix. Semin Diagn Pathol. 1990 Aug;7(3):190–204. [PubMed] [Google Scholar]
  15. Kovacs J. A., Gill V., Swan J. C., Ognibene F., Shelhamer J., Parrillo J. E., Masur H. Prospective evaluation of a monoclonal antibody in diagnosis of Pneumocystis carinii pneumonia. Lancet. 1986 Jul 5;2(8497):1–3. doi: 10.1016/s0140-6736(86)92555-9. [DOI] [PubMed] [Google Scholar]
  16. Landers R. J., O'Leary J. J., Crowley M., Healy I., Annis P., Burke L., O'Brien D., Hogan J., Kealy W. F., Lewis F. A. Epstein-Barr virus in normal, pre-malignant, and malignant lesions of the uterine cervix. J Clin Pathol. 1993 Oct;46(10):931–935. doi: 10.1136/jcp.46.10.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Leyvraz S., Henle W., Chahinian A. P., Perlmann C., Klein G., Gordon R. E., Rosenblum M., Holland J. F. Association of Epstein-Barr virus with thymic carcinoma. N Engl J Med. 1985 May 16;312(20):1296–1299. doi: 10.1056/NEJM198505163122006. [DOI] [PubMed] [Google Scholar]
  18. Nielsen A. L. Human papillomavirus type 16/18 in uterine cervical adenocarcinoma in situ and adenocarcinoma. A study by in situ hybridization with biotinylated DNA probes. Cancer. 1990 Jun 1;65(11):2588–2593. doi: 10.1002/1097-0142(19900601)65:11<2588::aid-cncr2820651132>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  19. Nonoyama M., Huang C. H., Pagano J. S., Klein G., Singh S. DNA of Epstein-Barr virus detected in tissue of Burkitt's lymphoma and nasopharyngeal carcinoma. Proc Natl Acad Sci U S A. 1973 Nov;70(11):3265–3268. doi: 10.1073/pnas.70.11.3265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. O'Leary J. J., Browne G., Johnson M. I., Landers R. J., Crowley M., Healy I., Street J. T., Pollock A. M., Lewis F. A., Andrew A. PCR in situ hybridisation detection of HPV 16 in fixed CaSki and fixed SiHa cell lines. J Clin Pathol. 1994 Oct;47(10):933–938. doi: 10.1136/jcp.47.10.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. O'Leary J. J., Chetty R., Graham A. K., McGee J. O. In situ PCR: pathologist's dream or nightmare? J Pathol. 1996 Jan;178(1):11–20. doi: 10.1002/(SICI)1096-9896(199601)178:1<11::AID-PATH459>3.0.CO;2-R. [DOI] [PubMed] [Google Scholar]
  22. Okagaki T., Tase T., Twiggs L. B., Carson L. F. Histogenesis of cervical adenocarcinoma with reference to human papillomavirus-18 as a carcinogen. J Reprod Med. 1989 Sep;34(9):639–644. [PubMed] [Google Scholar]
  23. Saemundsen A. K., Albeck H., Hansen J. P., Nielsen N. H., Anvret M., Henle W., Henle G., Thomsen K. A., Kristensen H. K., Klein G. Epstein-Barr virus in nasopharyngeal and salivary gland carcinomas of Greenland Eskimoes. Br J Cancer. 1982 Nov;46(5):721–728. doi: 10.1038/bjc.1982.264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Se Thoe S. Y., Wong K. K., Pathmanathan R., Sam C. K., Cheng H. M., Prasad U. Elevated secretory IgA antibodies to Epstein-Barr virus (EBV) and presence of EBV DNA and EBV receptors in patients with cervical carcinoma. Gynecol Oncol. 1993 Aug;50(2):168–172. doi: 10.1006/gyno.1993.1187. [DOI] [PubMed] [Google Scholar]
  25. Shingleton H. M., Gore H., Bradley D. H., Soong S. J. Adenocarcinoma of the cervix. I. Clinical evaluation and pathologic features. Am J Obstet Gynecol. 1981 Apr 1;139(7):799–814. doi: 10.1016/0002-9378(81)90547-0. [DOI] [PubMed] [Google Scholar]
  26. Silverberg S. G., Hurt W. G. Minimal deviation adenocarcinoma ("adenoma malignum") of the cervix: a reappraisal. Am J Obstet Gynecol. 1975 Apr 1;121(7):971–975. doi: 10.1016/0002-9378(75)90920-5. [DOI] [PubMed] [Google Scholar]
  27. Sixbey J. W., Vesterinen E. H., Nedrud J. G., Raab-Traub N., Walton L. A., Pagano J. S. Replication of Epstein-Barr virus in human epithelial cells infected in vitro. Nature. 1983 Dec 1;306(5942):480–483. doi: 10.1038/306480a0. [DOI] [PubMed] [Google Scholar]
  28. Tamimi H. K., Figge D. C. Adenocarcinoma of the uterine cervix. Gynecol Oncol. 1982 Jun;13(3):335–344. doi: 10.1016/0090-8258(82)90072-5. [DOI] [PubMed] [Google Scholar]
  29. Tase T., Okagaki T., Clark B. A., Twiggs L. B., Ostrow R. S., Faras A. J. Human papillomavirus DNA in adenocarcinoma in situ, microinvasive adenocarcinoma of the uterine cervix, and coexisting cervical squamous intraepithelial neoplasia. Int J Gynecol Pathol. 1989;8(1):8–17. doi: 10.1097/00004347-198903000-00002. [DOI] [PubMed] [Google Scholar]
  30. Tsao S. W., Mok S. C., Fey E. G., Fletcher J. A., Wan T. S., Chew E. C., Muto M. G., Knapp R. C., Berkowitz R. S. Characterization of human ovarian surface epithelial cells immortalized by human papilloma viral oncogenes (HPV-E6E7 ORFs). Exp Cell Res. 1995 Jun;218(2):499–507. doi: 10.1006/excr.1995.1184. [DOI] [PubMed] [Google Scholar]
  31. Wells M., Brown L. J. Glandular lesions of the uterine cervix: the present state of our knowledge. Histopathology. 1986 Aug;10(8):777–792. doi: 10.1111/j.1365-2559.1986.tb02578.x. [DOI] [PubMed] [Google Scholar]
  32. Wong K. Y., Collins R. J., Srivastava G., Pittaluga S., Cheung A. N., Wong L. C. Epstein Barr virus in carcinoma of the cervix. Int J Gynecol Pathol. 1993 Jul;12(3):224–227. doi: 10.1097/00004347-199307000-00004. [DOI] [PubMed] [Google Scholar]
  33. Young L. S., Clark D., Sixbey J. W., Rickinson A. B. Epstein-Barr virus receptors on human pharyngeal epithelia. Lancet. 1986 Feb 1;1(8475):240–242. doi: 10.1016/s0140-6736(86)90776-2. [DOI] [PubMed] [Google Scholar]
  34. van den Brule A. J., Snijders P. J., Gordijn R. L., Bleker O. P., Meijer C. J., Walboomers J. M. General primer-mediated polymerase chain reaction permits the detection of sequenced and still unsequenced human papillomavirus genotypes in cervical scrapes and carcinomas. Int J Cancer. 1990 Apr 15;45(4):644–649. doi: 10.1002/ijc.2910450412. [DOI] [PubMed] [Google Scholar]
  35. van den Brule A. J., Walboomers J. M., Meijer C. J. Epstein-Barr virus infection as co-factor in cervical carcinogenesis? J Pathol. 1995 Jul;176(3):219–220. doi: 10.1002/path.1711760302. [DOI] [PubMed] [Google Scholar]
  36. zur Hausen H. Human genital cancer: synergism between two virus infections or synergism between a virus infection and initiating events? Lancet. 1982 Dec 18;2(8312):1370–1372. doi: 10.1016/s0140-6736(82)91273-9. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES