Human papillomavirus (HPV) infection is a necessary cause for cervical cancer (CC), but it also depends on genetic factors, such as HLA polymorphism. However, few reports addressed the role of amino acids residues at the HLA peptide-binding cleft in HPV-related cervical disease. Therefore, we aimed to investigate the association between HLA-B, HLA-C, and HLA-DRB1 polymorphism and amino acid residues composing the pockets of the peptide-binding cleft of the respective polypeptide chains with cervical intraepithelial neoplasia (CIN II/III). HLA typing was performed by PCR-SSOP in 184 women with CIN II/III and 174 controls from South Brazil. Associations were estimated by multivariate logistic regression. FDR test was performed to correct the p-value for multiple comparisons. HLA-DRB1*13:01 was associated with protection against CIN II/III, while HLA-C*03:04 was associated with susceptibility. The amino acid residues isoleucine, tyrosine, and leucine at positions 95, 116, and 163 of HLA-C, respectively, were associated with CIN II/III susceptibility. In contrast, serine at positions 11 and 13 of HLA-DRB1 was associated with protection against the disease. Our results confirm previously reported associations between HLA and cervical diseases caused by HPV and suggest a role for amino acid residues at different positions of HLA-C and HLA-DRB1 in CIN II/III. This finding may be further explored to better understand the genetic risk and the influence of immune response to CC development.

中文翻译：

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口袋里：HLA 介导的宫颈癌前病变易感性的关键因素

人乳头瘤病毒 (HPV) 感染是宫颈癌 (CC) 的必要原因，但它也取决于遗传因素，例如 HLA 多态性。然而，很少有报道涉及 HLA 肽结合裂缝处的氨基酸残基在 HPV 相关宫颈疾病中的作用。因此，我们旨在研究HLA-B、HLA-C和HLA-DRB1多态性与构成相应多肽链肽结合裂缝口袋的氨基酸残基与宫颈上皮内瘤变 (CIN II/III)之间的关联. HLA 分型是通过 PCR-SSOP 对来自巴西南部的 184 名 CIN II/III 女性和 174 名对照者进行的。通过多变量逻辑回归估计关联。执行 FDR 测试以校正p- 多重比较的值。HLA-DRB1*13:01与针对 CIN II/III 的保护相关，而HLA-C*03:04与易感性相关。HLA-C 的第 95、116 和 163 位的氨基酸残基异亮氨酸、酪氨酸和亮氨酸分别与 CIN II/III 易感性相关。相比之下，HLA-DRB1 11 和 13 位的丝氨酸与对疾病的保护有关。我们的结果证实了先前报道的 HLA 与由 HPV 引起的宫颈疾病之间的关联，并表明 HLA-C 和 HLA-DRB1 不同位置的氨基酸残基在 CIN II/III 中的作用。可以进一步探索这一发现，以更好地了解遗传风险和免疫反应对 CC 发展的影响。