Association of HLA-G 3′ UTR polymorphism and expression with the progression of cervical lesions in human papillomavirus 18 infections

• Main Authors: Hui-Hui Xu, Xia Zhang, Hai-Hong Zheng, Qiu-Yue Han, Ai-Fen Lin, Wei-Hua Yan
• Format: Article
• Language: English
• Published: BMC 2018-12-01
• Series: Infectious Agents and Cancer
• Subjects: Human leukocyte antigen-G; Polymorphism; Expression; Human papillomavirus 18; Precancerous cervical lesions; Cervical cancer
• Online Access: http://link.springer.com/article/10.1186/s13027-018-0217-2

Abstract Background Human leukocyte antigen (HLA)-G is an immune checkpoint molecule, which expression in cervical cancer cells enables them to escape immunosurveillance. To date, limited information has been published on the association of HLA-G genetic background in malignant cells with levels of HLA-G expression and the clinical outcome of patients. Methods We investigated the influence of the HLA-G 14 bp In/Del (rs66554220) and + 3142C/G (rs1063320) polymorphisms in 130 cases of HPV16 infection, 130 cases of HPV18 infection and 185 age-matched, unrelated, HPV-negative, and cytologically normal Chinese Han women. Case-matched cervical biopsy tissues were evaluated by immunohistochemistry. Results Our findings show that the frequency of alleles, 14 bp In (38.5% vs 29.2%, OR = 1.52, P < 0.05) and + 3142G (72.7% vs 57.0%, OR = 2.01, P < 0.05), were significantly increased in the HPV18-infected group compared with the control group. The HLA-G polymorphisms (alleles 14 bp In and + 3142G) are also associated with the progression of HPV18-related cervical lesions. Moreover, HLA-G expression increased from CIN1 to CIN2/3 lesions and was highest in patients with adenocarcinoma; however, a significant association between these characteristics and the HLA-G polymorphisms was not observed. Conclusion Our results support that the HLA-G 14 bp In and + 3142G alleles are risk factors for HPV18 infections and influence the progression of HPV18-related cervical lesions. This suggests that HLA-G-driven immune mechanisms play an important role in cervical carcinogenesis.