Article Data

  • Views 654
  • Dowloads 120

Original Research

Open Access

HLA DRB allele polymorphisms and risk of cervical cancer associated with human papillomavirus infection: a population study in China

  • M. Zhao1
  • L. Qiu1
  • N. Tao1,2
  • L. Zhang1
  • X. Wu3,*,
  • Q. She1
  • F. Zeng1
  • Y. Wang1
  • S. Wei4
  • X. Wu1

1Institute of Virology, School of Medicine,Wuhan University, Wuhan

2Institute of Biophysics, Chinese Academy of Sciences, Beijing

3Hospital for women and Children of Hubei, Wuhan, Hubei (China)

4Department of Pediatrics and Human Development, Michigan State University, Life Sciences Building East Lansing, Michigan (USA)

DOI: 10.12892/ejgo340110 Vol.34,Issue 1,January 2013 pp.54-59

Published: 10 January 2013

*Corresponding Author(s): X. Wu E-mail:


Objective: Persistent infection with high-risk human papillomavirus (HPV) is the main cause of cervical cancer. Environmental, behavioral, and ill-defined genetic factors have also been implicated in the pathogenesis of this disease. To determine whether human leukocyte antigen (HLA) DRB alleles are associated with cervical cancer and HPV infections in the Chinese population, HLA genotypes were examined in 69 cervical cancer patients and 201 controls. Materials and Methods: Polymorphisms in HLA-DRB genes were genotyped using oligoneucleotide arrays, and the magnitude of associations was determined by logistic regression analysis. Results: HLA-DRB1*13 (OR = 4.01 95% CI, 1.703 - 9.442) and HLA-DRB1*3(17) (OR = 2.661 95% CI, 1.267 - 5.558) were associated with an increased risk of cervical cancer, and DRB1*09012 (OR = 0.182, 95% CI, 0.079 - 0.418 and DRB1*1201 (OR = 0.35 95% CI, 0.142 - 0.863 were associated with a decreased risk. The risk associations of HPV infection were increased in women carrying the HLA-DRB1*09012 (OR = 1.924; 95% CI, 1.08 - 3.427) and DRB3(52)*0101 (OR = 7.527 95% CI, 0.909 - 62.347) alleles. Among cervical cancer patients, the risk associations differed between HPV positive and negative cases for several alleles; increased risk of cervical cancer was associated with DRB3 (52)*02/03 (OR, 12.794; 95% CI, 5.007 - 32.691) and DRB1*3(17) (OR = 3.48; 95% CI, 1.261 - 9.604), and decreased risk was associated with DRB1*09012 and DRB5(51)*01/02. Furthermore, HPV16-containing cervical cancer cases differed from non-HPV16 subjects in their positive association with DRB1*1501 (OR = 4.173; 95% CI, 1.065 - 16.356) and DRB5(51)*0101/0201, and their negative association with DRB4(53)*0101 (OR = 0.329; 95% CI,0.122 - 0.888). Conclusions: The present results provide further evidence that certain HLA class II allele polymorphisms are involved in the genetic susceptibility to cervical cancer and HPV infection in the Chinese population from an area with a high incidence of this neoplasia.


Cervical cancer; Human leukocyte antigens; Human papillomavirus.

Cite and Share

M. Zhao,L. Qiu,N. Tao,L. Zhang,X. Wu,Q. She,F. Zeng, Y. Wang,S. Wei,X. Wu. HLA DRB allele polymorphisms and risk of cervical cancer associated with human papillomavirus infection: a population study in China. European Journal of Gynaecological Oncology. 2013. 34(1);54-59.


[1] Parkin D.M., Bray F., Ferlay J., Pisani P.: “Global cancer statistics, 2002”. CA Cancer J. Clin., 2005, 55, 74.

[2] Schlecht N.F., Kulaga S., Robitaille J., Ferreira S., Santos M., Miyamura R.A. et al.: “Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia”. JAMA, 2001, 286, 3106.

[3] Hilders C.G., Houbiers J.G., Krul E.J.: “The expression of histocompatibility-related leukocyte antigens in the pathway to cervical carcinoma”. Am. J. Clin. Pathol., 1994, 101, 5.

[4] Madeleine M.M., Brumback B., Cushing-Haugen K.L., Schwartz S.M., Daling J.R., Smith A.G. et al.: “Human leukocyte antigen class II and cervical cancer risk: a population-based study”. J. Infect. Dis., 2002, 186, 1565.

[5] Sastre G.X., Loste M.N., Salomon A.V., Favre M., Mouret E., de la Rochefordiere A. et al.: “Decreased frequency of HLADRB1*13 alleles in French women with HPV positive carcinoma of the cervix”. Int. J. Cancer, 1996, 69, 159.

[6] Maciag P.C., Schlecht N.F., Souza P.S., Franco E.L., Villa L.L., Petzl-Erler M.L.: “Major histocompatibility complex class II polymorphisms and risk of cervical cancer and human papillomavirus infection in Brazilian women”. Cancer Epidemiol. Biomarkers Prev., 2000, 9, 1183.

[7] Wang S.S., Wheeler C.M., Hildesheim A., Schiffman M., Herrero R., Bratti M.C. et al.: “Human leukocyte antigen class I and II alleles and risk of cervical neoplasia: results from a populationbased study in Costa Rica”. J. Infect. Dis., 2001, 184, 1310.

[8] Sastre-Garau X., Cartier I., Jourdan-Da Silva N., De Crémoux P., Lepage V., Charron D.: “Regression of low-grade cervical intraepithelial neoplasia in patients with HLA-DRB1*13 genotype”. Obstet. Gynecol., 2004, 104, 751.

[9] Schiffman M., Wentzensen N., Wacholder S., Kinney W., Gage J.C., Castle P.E.: “Human papillomavirus testing in the prevention of cervical cancer”. J. Natl. Cancer Inst., 2011, 103, 368.

[10] Bodily J., Laimins L.A.: “Persistence of human papillomavirus infection: keys to malignant progression”. Trends Microbiol., 2011, 19, 33.

[11] Doeberitz M.K., Vinokurova S.: “Host factors in HPV-related carcinogenesis: cellular mechanisms controlling HPV infections”. Arch. Med. Res., 2009, 40, 435.

[12] Baussano I., Garnett G., Segnan N., Ronco G., Vineis P.: “Modelling patterns of clearance of HPV-16 infection and vaccination efficacy”. Vaccine, 2011, 29, 1270.

[13] Albers A.E., Kaufmann A.M.: “Therapeutic human papillomavirus vaccination”. Public Health Genomics, 2009, 12, 331.

[14] Einstein M.H.: “Acquired immune response to oncogenic human papillomavirus associated with prophylactic cervical cancer vaccines”. Cancer Immunol. Immunother., 2008, 57, 443

[15] Hernández-Hernández D.M., Cerda-Flores R.M., Juárez-Cedillo T., Granados-Arriola J., Vargas-Alarcón G., Apresa-García T. et al.: “Human leukocyte antigens I and II haplotypes associated with human papillomavirus 16-positive invasive cervical cancer in Mexican women”. Int. J. Gynecol. Cancer, 2009, 19, 1099.

[16] de Araujo Souza P.S., Maciag P.C., Ribeiro K.B., Petzl-Erler M.L., Franco E.L., Villa L.L.: “Interaction between polymorphisms of the human leukocyte antigen and HPV-16 variants on the risk of invasive cervical cancer”. BMC Cancer, 2008, 8, 246.

[17] Saito M., Okubo M., Hirata R., Takeda S., Maeda H.: “Association of human leukocyte antigen and T cell message with human papillomavirus 16-positive cervical neoplasia in Japanese women”. Int. J. Gynecol. Cancer, 2007, 17, 1314.

[18] Madeleine M.M., Johnson L.G., Smith A.G., Hansen J.A., Nisperos B.B., Li S. et al.: “Comprehensive Analysis of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 Loci and Squamous Cell Cervical Cancer Risk”. Cancer Res., 2008, 68, 3532.

[19] Odunsi K., Ganesan T.: “Motif analysis of HLA class II molecules that determine the HPV associated risk of cervical carcinogenesis”. Int. J. Mol. Med., 2001, 8, 405.

[20] Hildesheim A., Schiffman M., Scott D.R., Marti D., Kissner T., Sherman M.E. et al.: “Human leukocyte antigen class I/II alleles and development of human papillomavirus-related cervical neoplasia: results from a case-control study conducted in the United States”. Cancer Epidemiol. Biomarkers Prev., 1998, 7, 1035.

[21] Cuzick J., Terry G., Ho L., Monaghan J., Lopes A., Clarkson P. et al.: “Association between high-risk HPV types, HLA DRB1* and DQB1* alleles and cervical cancer in British women”. Br. J. Cancer, 2000, 82, 1348.

[22] Engelmark M., Beskow A., Magnusson J., Erlich H., Gyllensten U.: “Affected sib-pair analysis of the contribution of HLA class I and class II loci to development of cervical cancer”. Hum. Mol. Genet., 2004, 13, 1951.

[23] Zoodsma M., Nolte I.M., Schipper M., Oosterom E., van der Steege G., de Vries E.G. et al.: “Analysis of the entire HLA region in susceptibility for cervical cancer: a comprehensive study”. J. Med. Genet., 2005, 42, e49.

[24] Carreon J.D., Martin M.P., Hildesheim A., Gao X., Schiffman M., Herrero R. et al.: “Human leukocyte antigen class I and II haplotypes and risk of cervical cancer”. Tissue Antigens, 2005, 66, 321.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time