Department of Gynecology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Expert Rev Vaccines. 2012 Jul;11(7):821-40. doi: 10.1586/erv.12.56.
Failure of the immune system to launch a strong and effective immune response to high-risk HPV is related to viral persistence and the development of anogenital (pre)malignant lesions such as vulvar intraepithelial neoplasia (VIN). Different forms of immunotherapy, aimed at overcoming the inertia of the immune system, have been developed and met with clinical success. Unfortunately these, in principal successful, therapeutic approaches also fail to induce clinical responses in a substantial number of cases. In this review, the authors summarize the traits of the immune response to HPV in healthy individuals and in patients with HPV-induced neoplasia. The potential mechanisms involved in the escape of HPV-induced lesions from the immune system indicate gaps in our knowledge. Finally, the interaction between the immune system and VIN is discussed with a special focus on the different forms of immunotherapy applied to treat VIN and the potential causes of therapy failure. The authors conclude that there are a number of pre-existing conditions that determine the patients' responsiveness to immunotherapy. An immunotherapeutic strategy in which different aspects of immune failure are attacked by complementary approaches, will improve the clinical response rate.
免疫系统未能对高危型 HPV 产生强烈有效的免疫反应，与病毒持续存在以及外阴上皮内瘤变（VIN）等肛门生殖器（前）恶性病变的发展有关。已经开发了不同形式的免疫疗法，旨在克服免疫系统的惰性，并取得了临床成功。不幸的是，这些在原则上成功的治疗方法也未能在大量病例中诱导临床反应。在这篇综述中，作者总结了 HPV 在健康个体和 HPV 诱导性肿瘤患者中引起的免疫反应的特征。HPV 诱导的病变逃避免疫系统的潜在机制表明我们的知识存在空白。最后，讨论了免疫系统与 VIN 之间的相互作用，特别关注应用于治疗 VIN 的不同形式的免疫疗法以及治疗失败的潜在原因。作者得出结论，存在许多决定患者对免疫疗法反应性的既定条件。通过互补方法攻击免疫失败不同方面的免疫治疗策略将提高临床反应率。
