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

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 (rs66554220) and + 3142 (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, (38.5% vs 29.2%, OR = 1.52,  < 0.05) and + 3142 (72.7% vs 57.0%, OR = 2.01,  < 0.05), were significantly increased in the HPV18-infected group compared with the control group. The polymorphisms (alleles and + 3142) 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 and + 3142 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.