Skip to main content
NCBI home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1994 Dec;47(12):1077–1081. doi: 10.1136/jcp.47.12.1077

Role of human papillomavirus in determining the HLA associated risk of cervical carcinogenesis.

W Z Mehal 1, Y M Lo 1, C S Herrington 1, M F Evans 1, M C Papadopoulos 1, K Odunis 1, T S Ganesan 1, J O McGee 1, J I Bell 1, K A Fleming 1
PMCID: PMC502196  PMID: 7876378

Abstract

AIMS--To investigate the role of human papillomavirus (HPV) in the association between HLA DQw3 and squamous cell cancer of the cervix (SCCC). METHODS--Tissue from 194 cervical samples, ranging from normal, through cervical intraepithelial neoplasia, to SCCC, were typed for HPV by amplification of the L1 gene using degenerate consensus primers, followed by oligonucleotide probing. HLA DQw3 typing was undertaken in the same samples using a new PCR amplification system using primers common to all DQ loci, followed by restriction digestion with Mlu 1 to differentiate HLA DQw3 types--null, heterozygous, and homozygous. The data were analysed using chi 2 analysis and by calculating relative risks with the 95% confidence interval. RESULTS--Samples (n = 188) were successfully typed for HPV and 177 were typed for HLA DQw3. There was a nonsignificant rise in the prevalence of HLA DQw3 in SCCC (64.3%) compared with the group with normal histology (53.2%). Analysis of the prevalence of HLA DQw3 on the basis of HPV infection rather than histology showed that 63 of 95 (66.3%) of the HPV positive samples contained HLA DQw3 alleles, compared with 39 of 78 (50.0%) of the HPV negative samples (chi 2 4.06; p < 0.05). CONCLUSIONS--There was a significant association between HLA DQw3 and cervical HPV infection. This may be because people with HLA DQw3 are less able to mount an effective immune response to HPV, which predisposes them to the development of SCCC.

Full text

PDF
1077

Images in this article

1079Image
on p.1079

Selected References

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

  1. An S. F., Fleming K. A. Removal of inhibitor(s) of the polymerase chain reaction from formalin fixed, paraffin wax embedded tissues. J Clin Pathol. 1991 Nov;44(11):924–927. doi: 10.1136/jcp.44.11.924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Braciale T. J., Braciale V. L. Viral antigen presentation and MHC assembly. Semin Immunol. 1992 Apr;4(2):81–84. [PubMed] [Google Scholar]
  3. Brinton L. A., Hamman R. F., Huggins G. R., Lehman H. F., Levine R. S., Mallin K., Fraumeni J. F., Jr Sexual and reproductive risk factors for invasive squamous cell cervical cancer. J Natl Cancer Inst. 1987 Jul;79(1):23–30. [PubMed] [Google Scholar]
  4. Bugawan T. L., Erlich H. A. Rapid typing of HLA-DQB1 DNA polymorphism using nonradioactive oligonucleotide probes and amplified DNA. Immunogenetics. 1991;33(3):163–170. doi: 10.1007/BF01719235. [DOI] [PubMed] [Google Scholar]
  5. Burk R. D., Kadish A. S., Calderin S., Romney S. L. Human papillomavirus infection of the cervix detected by cervicovaginal lavage and molecular hybridization: correlation with biopsy results and Papanicolaou smear. Am J Obstet Gynecol. 1986 May;154(5):982–989. doi: 10.1016/0002-9378(86)90733-7. [DOI] [PubMed] [Google Scholar]
  6. Cooper K., Herrington C. S., Graham A. K., Evans M. F., McGee J. O. In situ evidence for HPV 16, 18, 33 integration in cervical squamous cell cancer in Britain and South Africa. J Clin Pathol. 1991 May;44(5):406–409. doi: 10.1136/jcp.44.5.406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. David A. L., Taylor G. M., Gokhale D., Aplin J. D., Seif M. W., Tindall V. R. HLA-DQB1*03 and cervical intraepithelial neoplasia type III. Lancet. 1992 Jul 4;340(8810):52–52. doi: 10.1016/0140-6736(92)92464-q. [DOI] [PubMed] [Google Scholar]
  8. Franceschi S., Doll R., Gallwey J., La Vecchia C., Peto R., Spriggs A. I. Genital warts and cervical neoplasia: an epidemiological study. Br J Cancer. 1983 Nov;48(5):621–628. doi: 10.1038/bjc.1983.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Glew S. S., Stern P. L., Davidson J. A., Dyer P. A. HLA antigens and cervical carcinoma. Nature. 1992 Mar 5;356(6364):22–22. doi: 10.1038/356022a0. [DOI] [PubMed] [Google Scholar]
  10. Han R., Breitburd F., Marche P. N., Orth G. Linkage of regression and malignant conversion of rabbit viral papillomas to MHC class II genes. Nature. 1992 Mar 5;356(6364):66–68. doi: 10.1038/356066a0. [DOI] [PubMed] [Google Scholar]
  11. Helland A., Børresen A. L., Kaern J., Rønningen K. S., Thorsby E. HLA antigens and cervical carcinoma. Nature. 1992 Mar 5;356(6364):23–23. doi: 10.1038/356023a0. [DOI] [PubMed] [Google Scholar]
  12. Hill A. V., Elvin J., Willis A. C., Aidoo M., Allsopp C. E., Gotch F. M., Gao X. M., Takiguchi M., Greenwood B. M., Townsend A. R. Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature. 1992 Dec 3;360(6403):434–439. doi: 10.1038/360434a0. [DOI] [PubMed] [Google Scholar]
  13. Li J. Y., Li F. P., Blot W. J., Miller R. W., Fraumeni J. F., Jr Correlation between cancers of the uterine cervix and penis in China. J Natl Cancer Inst. 1982 Nov;69(5):1063–1065. [PubMed] [Google Scholar]
  14. Lo D. T-cell tolerance. Curr Opin Immunol. 1992 Dec;4(6):711–715. doi: 10.1016/0952-7915(92)90050-o. [DOI] [PubMed] [Google Scholar]
  15. Lu S. J., Day N. E., Degos L., Lepage V., Wang P. C., Chan S. H., Simons M., McKnight B., Easton D., Zeng Y. Linkage of a nasopharyngeal carcinoma susceptibility locus to the HLA region. Nature. 1990 Aug 2;346(6283):470–471. doi: 10.1038/346470a0. [DOI] [PubMed] [Google Scholar]
  16. Nahmias A. J., Naib Z. M., Josey W. E., Franklin E., Jenkins R. Prospective studies of the association of genital herpes simplex infection and cervical anaplasia. Cancer Res. 1973 Jun;33(6):1491–1497. [PubMed] [Google Scholar]
  17. Palefsky J. Human papillomavirus infection among HIV-infected individuals. Implications for development of malignant tumors. Hematol Oncol Clin North Am. 1991 Apr;5(2):357–370. [PubMed] [Google Scholar]
  18. Panza N., Del Vecchio L., Maio M., De Felice M., Lombardi G., Minozzi M., Zappacosta S. Strong association between an HLA-DR antigen and thyroid carcinoma. Tissue Antigens. 1982 Aug;20(2):155–158. doi: 10.1111/j.1399-0039.1982.tb00340.x. [DOI] [PubMed] [Google Scholar]
  19. Reeves W. C., Rawls W. E., Brinton L. A. Epidemiology of genital papillomaviruses and cervical cancer. Rev Infect Dis. 1989 May-Jun;11(3):426–439. doi: 10.1093/clinids/11.3.426. [DOI] [PubMed] [Google Scholar]
  20. Reid R., Greenberg M., Jenson A. B., Husain M., Willett J., Daoud Y., Temple G., Stanhope C. R., Sherman A. I., Phibbs G. D. 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. doi: 10.1016/0002-9378(87)90241-9. [DOI] [PubMed] [Google Scholar]
  21. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  22. Shirasawa H., Tomita Y., Kubota K., Kasai T., Sekiya S., Takamizawa H., Simizu B. Detection of human papillomavirus type 16 DNA and evidence for integration into the cell DNA in cervical dysplasia. J Gen Virol. 1986 Sep;67(Pt 9):2011–2015. doi: 10.1099/0022-1317-67-9-2011. [DOI] [PubMed] [Google Scholar]
  23. Syrjänen K., Syrjänen S. Epidemiology of human papilloma virus infections and genital neoplasia. Scand J Infect Dis Suppl. 1990;69:7–17. [PubMed] [Google Scholar]
  24. Tagami H., Aiba S., Rokugo M. Regression of flat warts and common warts. Clin Dermatol. 1985 Oct-Dec;3(4):170–178. doi: 10.1016/0738-081x(85)90062-8. [DOI] [PubMed] [Google Scholar]
  25. Terris M., Wilson F., Smith H., Nelson J. H., Jr Epidemiology of cancer of the cervix. V. The relationship of coitus to carcinoma of the cervix. Am J Public Health Nations Health. 1967 May;57(5):840–847. doi: 10.2105/ajph.57.5.840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Toon P. G., Arrand J. R., Wilson L. P., Sharp D. S. Human papillomavirus infection of the uterine cervix of women without cytological signs of neoplasia. Br Med J (Clin Res Ed) 1986 Nov 15;293(6557):1261–1264. doi: 10.1136/bmj.293.6557.1261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Vandenvelde C., De Foor M., van Beers D. HLA-DOB1*03 and cervical intraepithelial neoplasia grades I-III. Lancet. 1993 Feb 13;341(8842):442–442. doi: 10.1016/0140-6736(93)93044-2. [DOI] [PubMed] [Google Scholar]
  28. Vonka V., Kanka J., Hirsch I., Závadová H., Krcmár M., Suchánková A., Rezácová D., Broucek J., Press M., Domorázková E. Prospective study on the relationship between cervical neoplasia and herpes simplex type-2 virus. II. Herpes simplex type-2 antibody presence in sera taken at enrollment. Int J Cancer. 1984 Jan 15;33(1):61–66. doi: 10.1002/ijc.2910330111. [DOI] [PubMed] [Google Scholar]
  29. Wank R., Thomssen C. High risk of squamous cell carcinoma of the cervix for women with HLA-DQw3. Nature. 1991 Aug 22;352(6337):723–725. doi: 10.1038/352723a0. [DOI] [PubMed] [Google Scholar]
  30. Zunzunegui M. V., King M. C., Coria C. F., Charlet J. Male influences on cervical cancer risk. Am J Epidemiol. 1986 Feb;123(2):302–307. doi: 10.1093/oxfordjournals.aje.a114238. [DOI] [PubMed] [Google Scholar]

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

RESOURCES