J Cancer 2019; 10(10):2145-2152. doi:10.7150/jca.25600

Research Paper

Human Leukocyte Antigen (HLA) Class II -DRB1 and -DQB1 Alleles and the Association with Cervical Cancer in HIV/HPV Co-Infected Women in South Africa

Ramadhani Chambuso1,2✉, Raj Ramesar1,3, Evelyn Kaambo4,5, Lynette Denny6,7, Jo-Ann Passmore3,4,7, Anna-Lise Williamson3,4,7, Clive M Gray3,8

1. MRC Unit for Genomic and Precision Medicine, Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, South Africa,
2. Department of Gynaecology, Morogoro Regional Referral Hospital, Morogoro, Tanzania,
3. Institute of Infectious Disease and Molecular Medicine, Department of Pathology, Faculty of Health Sciences, University of Cape Town, South Africa,
4. Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, South Africa,
5. Department of Biochemistry and Medical Microbiology, University of Namibia School of Medicine, Windhoek, Namibia,
6. Department of Obstetrics and Gynaecology, Groote Schuur Hospital, University of Cape Town, South Africa
7. MRC/UCT Clinical Gynaecological Cancer Research Centre, Groote Schuur Hospital/University of Cape Town, South Africa,
8. Division of Immunology, Laboratory for Tissue Immunology, Department of Pathology and National Health Laboratory Service, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.

Abstract

Background: A subset of women who are co-infected with Human Immunodeficiency Virus type 1 (HIV) and Human papillomavirus (HPV), progress rapidly to invasive cervical cancer regardless of antiretroviral therapy (ART) or immune status. We posit that HIV/HPV co-infection along with specific host HLA II -DRB1 and -DQB1 alleles play a major role in cervical cancer development.

Methodology: We conducted a hospital-based genetic susceptibility case-control study in Cape Town, South Africa. We recruited 256 women of the same race, from which a total of 624 HLA-DRB1 and -DQB1 class II genotypes were studied. We characterized HLA II candidate genes using PCR based, Luminex intermediate resolution genotyping and confirmed significant associated genotypes at four-digit resolution by high resolution gel typing. We analyzed 160 alleles from cancer, 64 alleles from pre-cancer and 400 alleles from healthy control women. Whole blood was used for HIV antibody test and HLA II typing. Cervical tumor tissue biopsies were used for HPV genotyping. Tests were statistically significant if p<0.05.

Results: Women who were co-infected with HIV/HPV had advanced cervical disease compared to women who were HIV negative. HLA class II -DQB1*03:01 and -DQB1*06:02 alleles were associated with cervical cancer in HIV/HPV co-infected women (p=0.001 and p<0.0001, respectively) while HLA class II -DRB1*13:01 and -DQB1*03:19 were rare or absent in women with cervical disease when compared to the control population (p=0.012 and 0.011, respectively).

Conclusion: We describe associations between HLA class II genotypes with cervical cancer, or likely protection from cervical cancer disease in HIV/HPV co-infected South African women. Identifying mechanisms that give rise to this likely protective HLA association will provide insight into development of immune-based prevention measures.

Keywords: HIV/HPV co-infection, HLA II allele association, cervical cancer susceptibility

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Chambuso R, Ramesar R, Kaambo E, Denny L, Passmore JA, Williamson AL, Gray CM. Human Leukocyte Antigen (HLA) Class II -DRB1 and -DQB1 Alleles and the Association with Cervical Cancer in HIV/HPV Co-Infected Women in South Africa. J Cancer 2019; 10(10):2145-2152. doi:10.7150/jca.25600. Available from http://www.jcancer.org/v10p2145.htm