J Cancer 2017; 8(12):2401-2409. doi:10.7150/jca.19809

Research Paper

Association of HLA-DRB1, HLA-DQB1 Polymorphisms with HPV 16 E6 Variants among Young Cervical Cancer Patients in China

Yan Hu1✉, Jin-Ze Wu2*, Hua Zhu1, Sheng-Hui Zhang3, Yan-Ying Zhu4, Yi-Yao Wu5, Ci-Xia Shuai1

1. Department of Gynecology, 1 st Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R.China;
2. Department of Anesthesiology, 1 st Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R.China;
3. Department of Hematology, 1 st Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R.China;
4. Laboratory Diagnosis Center, 1 st Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R.China;
5. College of Medicine, Jiaxing University, Jiaxing, Zhejiang, P.R.China.
*Equal contributors and co-first authors.

Abstract

Potential correlation of human papillomavirus (HPV) 16 E6 variants and human leukocyte antigen (HLA) class II polymorphisms has been suggested in patients with cervical cancer, so far little information is available about the possible interaction between E6 variants and HLA class II variability during the obviously accelerated progression to cervical cancer in young women. In this study, we aimed to explore the association between the HPV16 E6 variants and HLA-DRB1, DQB1 alleles in a Chinese young cervical cancer population. The HLA-DRB1, HLA-DQB1 polymophisms were genotyped by low-resolution polymerase chain reaction (PCR) with sequence-specific primer. HPV16 E6 DNA was tested by Sanger fluorescent dye dideoxy-termination technique. The difference of DRB1, DQB1 polymorphisms between young cervical cancer patients (≤35ys, n=61) and older ones (>35ys, n=85) and the association with E6 variants were analyzed. Results showed that the distribution pattern of HLA-DRB1, DQB1 alleles was different between young cervical cancer patients and older ones. The allele frequency of DQB1*0501 in young patients was significantly lower than older ones (6.6% vs. 23.5%, p<0.05). The HPV16 E6 A4 lineage was the exclusive type observed in young patients, and its prevalence was significantly higher than that of older cases (82.86% vs.41.94%, p<0.05). DRB1*03 was not found in young patients positive for the HPV16 E6 A4 lineage, whereas it was observed in 19.2 % older patients with A4 positive(Pc<0.05). In conclusion, specific association between certain HPV16 E6 variant and genetic polymorphisms of HLA may play a role during the progression of early onset cervical cancer in young patients. Certain HLA-DRB1 and HLA-DQB1 alleles may be related to the A4 lineage among young cervical cancer patients, which was the unique HPV16 E6 variant found in Chinese young patients. Our finding may provide an insight into the pathogenic factors that associated with cervical cancer in young women.

Keywords: human papillomavirus, human leukocyte antigen, polymorphism, variant, age

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How to cite this article:
Hu Y, Wu JZ, Zhu H, Zhang SH, Zhu YY, Wu YY, Shuai CX. Association of HLA-DRB1, HLA-DQB1 Polymorphisms with HPV 16 E6 Variants among Young Cervical Cancer Patients in China. J Cancer 2017; 8(12):2401-2409. doi:10.7150/jca.19809. Available from http://www.jcancer.org/v08p2401.htm