Odunsi K, Terry G, Ho L, Bell J, Cuzick J, Ganesan T S
ICRF Molecular Oncology Laboratories, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Int J Cancer. 1996 Sep 4;67(5):595-602. doi: 10.1002/(SICI)1097-0215(19960904)67:5<595::AID-IJC1>3.0.CO;2-P.
Human papillomaviruses (HPV) play a causative role in the aetiology of cervical intra-epithelial neoplasia (CIN) and cervical cancer. Human leukocyte antigens (HLA) are important in the regulation of immune response to foreign antigens. The role of genetic variation at the HLA class II loci (DR and DQ) in CIN (HPV 16, 18, 31 and 33 typed) was investigated by PCR DNA amplification and oligonucleotide probe typing of cervical smears from British Caucasian patients (n = 176) and controls (n = 416). The alleles of the DQB103, DRB104 and DRB111 loci were strongly associated with susceptibility to CIN. Specifically, the haplotypes DRB10401-DQB10301 and DRB11101-DQB10301 were significant and indicated susceptibility. The DQB103 locus was more contributory to this association than the DRB1 loci. A weak protective effect was shown for the haplotype DRB10101-DQB10501. Positive correlation was also observed for HPV-positive CIN, suggesting that specific HLA class II alleles may be important in determining the immune response to HPV antigens and the risk for CIN after HPV infection. Our results should help in the rational design of vaccines against HPV.
人乳头瘤病毒（HPV）在宫颈上皮内瘤变（CIN）和宫颈癌的病因学中起致病作用。人类白细胞抗原（HLA）在对外源抗原的免疫反应调节中起重要作用。通过对英国白种人患者（n = 176）和对照组（n = 416）的宫颈涂片进行PCR DNA扩增和寡核苷酸探针分型，研究了HLA II类基因座（DR和DQ）的基因变异在CIN（HPV 16、18、31和33分型）中的作用。DQB103、DRB104和DRB111基因座的等位基因与CIN易感性密切相关。具体而言，单倍型DRB10401-DQB10301和DRB11101-DQB10301具有显著性，表明存在易感性。DQB103基因座对这种关联的贡献大于DRB1基因座。单倍型DRB10101-DQB10501显示出微弱的保护作用。在HPV阳性的CIN中也观察到正相关，这表明特定的HLA II类等位基因在决定对HPV抗原的免疫反应以及HPV感染后发生CIN的风险方面可能很重要。我们的结果应有助于合理设计针对HPV的疫苗。
