Bontkes H J, van Duin M, de Gruijl T D, Duggan-Keen M F, Walboomers J M, Stukart M J, Verheijen R H, Helmerhorst T J, Meijer C J, Scheper R J, Stevens F R, Dyer P A, Sinnott P, Stern P L
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
Int J Cancer. 1998 Oct 5;78(2):166-71. doi: 10.1002/(sici)1097-0215(19981005)78:2<166::aid-ijc8>3.0.co;2-x.
High-risk human papillomavirus (HPV) infection plays an important role in cervical intra-epithelial neoplasia (CIN), but HPV infection alone is not sufficient for progression to cervical cancer. Several lines of evidence suggest that cellular immune surveillance is important in the control of HPV infection and the development of CIN. The presentation to T cells of target viral peptides in the context of HLA molecules is influenced by the genetic polymorphisms of both HPV and HLA and thereby influences the host immune response and clinical outcome of HPV infection. HLA class I and II polymorphism in susceptibility for HPV 16 infection, development and progression of CIN was analyzed in a group of 118 patients participating in a prospective study of women with initial abnormal cytology. Patients were stratified according to HPV status and course of the disease. HLA-B44 frequency was increased in the small group of patients with a lesion that showed clinical progression during follow-up [OR = 9.0 (4.6-17.5), p = 0.007]. HLA-DRB107 frequency was increased among HPV 16-positive patients compared with patients who were negative for all HPV types [OR = 5.9 (3.0-11.3), p = 0.02]. Our results are consistent with the immunogenetic factors associated with disease progression being different from those associated with susceptibility to HPV 16 infection. Sequencing of the HPV 16 E6 and E7 open reading frames of a subset of these patients (n = 40) showed the frequency of HPV 16 variants to be similar to other studies. However, there was no significant correlation between variant incidence and disease progression or viral persistence and no significant correlation with any HLA allele. It appears that multiple HLA types can influence HPV 16-associated cervical dysplasia but the role of HPV 16 variants in disease progression and susceptibility in relation to HLA polymorphism remains unclear.
高危型人乳头瘤病毒（HPV）感染在宫颈上皮内瘤变（CIN）中起重要作用，但单纯HPV感染并不足以进展为宫颈癌。多项证据表明，细胞免疫监视在控制HPV感染及CIN发生发展中起重要作用。HPV和HLA的基因多态性会影响靶病毒肽在HLA分子背景下呈递给T细胞的过程，进而影响宿主免疫反应及HPV感染的临床结局。对118例参与初诊细胞学异常女性前瞻性研究的患者分析了HLAⅠ类和Ⅱ类多态性在HPV 16感染易感性、CIN发生发展中的作用。患者根据HPV状态和病程进行分层。在随访期间出现临床进展的一小部分患者中，HLA-B44频率升高[比值比（OR）=9.0（4.6 - 17.5），p = 0.007]。与所有HPV类型均为阴性的患者相比，HPV 16阳性患者中HLA-DRB107频率升高[OR = 5.9（3.0 - 11.3），p = 0.02]。我们的结果与以下观点一致，即与疾病进展相关的免疫遗传因素不同于与HPV 16感染易感性相关的因素。对这些患者中的一部分（n = 40）的HPV 16 E6和E7开放阅读框进行测序，结果显示HPV 16变异体的频率与其他研究相似。然而，变异体发生率与疾病进展或病毒持续存在之间无显著相关性，与任何HLA等位基因也无显著相关性。似乎多种HLA类型可影响HPV 16相关的宫颈发育异常，但HPV 16变异体在疾病进展及与HLA多态性相关的易感性中的作用仍不清楚。
