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J Clin Pathol. 1997 Nov; 50(11): 904–910.
PMCID: PMC500313

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


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.

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  • Jaworski RC. 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]
  • Shingleton HM, Gore H, Bradley DH, Soong SJ. Adenocarcinoma of the cervix. I. Clinical evaluation and pathologic features. Am J Obstet Gynecol. 1981 Apr 1;139(7):799–814. [PubMed]
  • Tamimi HK, Figge DC. Adenocarcinoma of the uterine cervix. Gynecol Oncol. 1982 Jun;13(3):335–344. [PubMed]
  • Silverberg SG, Hurt WG. Minimal deviation adenocarcinoma ("adenoma malignum") of the cervix: a reappraisal. Am J Obstet Gynecol. 1975 Apr 1;121(7):971–975. [PubMed]
  • Hasumi K, Ehrmann RL. Clear cell carcinoma of the uterine endocervix with an in situ component. Cancer. 1978 Nov;42(5):2435–2438. [PubMed]
  • Hart WR, Norris HJ. Mesonephric adenocarcinomas of the cervix. Cancer. 1972 Jan;29(1):106–113. [PubMed]
  • Fox H, Wells M, Harris M, McWilliam LJ, Anderson GS. Enteric tumours of the lower female genital tract: a report of three cases. Histopathology. 1988 Feb;12(2):167–176. [PubMed]
  • Wells M, Brown LJ. Glandular lesions of the uterine cervix: the present state of our knowledge. Histopathology. 1986 Aug;10(8):777–792. [PubMed]
  • Okagaki T, Tase T, Twiggs LB, Carson LF. Histogenesis of cervical adenocarcinoma with reference to human papillomavirus-18 as a carcinogen. J Reprod Med. 1989 Sep;34(9):639–644. [PubMed]
  • Tase T, Okagaki T, Clark BA, Twiggs LB, Ostrow RS, Faras AJ. 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. [PubMed]
  • Herrington CS. Human papillomaviruses and cervical neoplasia. I. Classification, virology, pathology, and epidemiology. J Clin Pathol. 1994 Dec;47(12):1066–1072. [PMC free article] [PubMed]
  • Arends MJ, Wyllie AH, Bird CC. Papillomaviruses and human cancer. Hum Pathol. 1990 Jul;21(7):686–698. [PubMed]
  • Landers RJ, O'Leary JJ, Crowley M, Healy I, Annis P, Burke L, O'Brien D, Hogan J, Kealy WF, Lewis FA, et al. Epstein-Barr virus in normal, pre-malignant, and malignant lesions of the uterine cervix. J Clin Pathol. 1993 Oct;46(10):931–935. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Nonoyama M, Huang CH, Pagano JS, 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. [PMC free article] [PubMed]
  • 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]
  • 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. [PubMed]
  • Saemundsen AK, Albeck H, Hansen JP, Nielsen NH, Anvret M, Henle W, Henle G, Thomsen KA, Kristensen HK, Klein G. Epstein-Barr virus in nasopharyngeal and salivary gland carcinomas of Greenland Eskimoes. Br J Cancer. 1982 Nov;46(5):721–728. [PMC free article] [PubMed]
  • Leyvraz S, Henle W, Chahinian AP, Perlmann C, Klein G, Gordon RE, Rosenblum M, Holland JF. Association of Epstein-Barr virus with thymic carcinoma. N Engl J Med. 1985 May 16;312(20):1296–1299. [PubMed]
  • Sixbey JW, Vesterinen EH, Nedrud JG, Raab-Traub N, Walton LA, Pagano JS. Replication of Epstein-Barr virus in human epithelial cells infected in vitro. Nature. 1983 Dec 1;306(5942):480–483. [PubMed]
  • Young LS, Clark D, Sixbey JW, Rickinson AB. Epstein-Barr virus receptors on human pharyngeal epithelia. Lancet. 1986 Feb 1;1(8475):240–242. [PubMed]
  • Kovacs JA, Gill V, Swan JC, Ognibene F, Shelhamer J, Parrillo JE, Masur H. Prospective evaluation of a monoclonal antibody in diagnosis of Pneumocystis carinii pneumonia. Lancet. 1986 Jul 5;2(8497):1–3. [PubMed]
  • Arends MJ, Donaldson YK, Duvall E, Wyllie AH, Bird CC. 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. [PubMed]
  • van den Brule AJ, Snijders PJ, Gordijn RL, Bleker OP, Meijer CJ, Walboomers JM. 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. [PubMed]
  • O'Leary JJ, Browne G, Johnson MI, Landers RJ, Crowley M, Healy I, Street JT, Pollock AM, Lewis FA, Andrew A, et al. 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. [PMC free article] [PubMed]
  • Boshoff C, Schulz TF, Kennedy MM, Graham AK, Fisher C, Thomas A, McGee JO, Weiss RA, O'Leary JJ. Kaposi's sarcoma-associated herpesvirus infects endothelial and spindle cells. Nat Med. 1995 Dec;1(12):1274–1278. [PubMed]
  • O'Leary JJ, Chetty R, Graham AK, McGee JO. In situ PCR: pathologist's dream or nightmare? J Pathol. 1996 Jan;178(1):11–20. [PubMed]
  • Cooper K, Herrington CS, Lo ES, Evans MF, McGee JO. Integration of human papillomavirus types 16 and 18 in cervical adenocarcinoma. J Clin Pathol. 1992 May;45(5):382–384. [PMC free article] [PubMed]
  • Nielsen AL. 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. [PubMed]
  • 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]
  • Effert PJ, Frye RA, Neubauer A, Liu ET, Walther PJ. 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. [PubMed]
  • Farnsworth A, Laverty C, Stoler MH. Human papillomavirus messenger RNA expression in adenocarcinoma in situ of the uterine cervix. Int J Gynecol Pathol. 1989;8(4):321–330. [PubMed]
  • Tsao SW, Mok SC, Fey EG, Fletcher JA, Wan TS, Chew EC, Muto MG, Knapp RC, Berkowitz RS. 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. [PubMed]
  • van den Brule AJ, Walboomers JM, Meijer CJ. Epstein-Barr virus infection as co-factor in cervical carcinogenesis? J Pathol. 1995 Jul;176(3):219–220. [PubMed]
  • Se Thoe SY, Wong KK, Pathmanathan R, Sam CK, Cheng HM, 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. [PubMed]
  • Wong KY, Collins RJ, Srivastava G, Pittaluga S, Cheung AN, Wong LC. Epstein Barr virus in carcinoma of the cervix. Int J Gynecol Pathol. 1993 Jul;12(3):224–227. [PubMed]

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