Therapy of human papillomavirus-related disease.
Therapy of human papillomavirus-related disease.
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DOI：
10.1016/j.vaccine.2012.05.091
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发表时间：
2012-11-20
期刊：
影响因子：
5.5
通讯作者：
Einstein MH
中科院分区：
文献类型：
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作者：
Stern PL;van der Burg SH;Hampson IN;Broker TR;Fiander A;Lacey CJ;Kitchener HC;Einstein MH
本章回顾了目前的治疗慢性和肿瘤HPV相关的条件和新的治疗方法的发展。手术切除HPV相关的下生殖道肿瘤是非常成功的，但在很大程度上取决于二级预防计划，以确定疾病。只有高危HPV驱动的慢性、癌前病变和一些非常早期的癌症不能单独通过外科手术成功治疗。宫颈癌的放化疗治疗有助于66-79%的宫颈癌5年生存率。治疗后持续或复发的宫颈癌患者的前景非常差。局部药物如咪喹莫特（免疫反应调节剂）、西多福韦（抑制病毒复制;诱导细胞凋亡）或光动力疗法（直接损伤肿瘤和增强抗肿瘤免疫力）在治疗高级别外阴上皮内瘤变方面都显示出一些有用的疗效（约50-60%）。生殖器疣的提供者管理的治疗包括冷冻疗法，三氯乙酸，或手术切除具有最高的原发性清除率。患者应用的疗法包括鬼臼毒素和咪喹莫特。“成功”治疗后的复发率为30- 40%。进一步的改善可能来自于当前治疗与靶向癌症中HPV介导的分子途径的新药的合理组合。靶向HPV E1/E2的DNA结合活性或E6/E7癌基因的抗凋亡结果的小分子抑制剂处于临床前开发中。蛋白酶体和组蛋白去乙酰化酶抑制剂可以增强HPV阳性肿瘤细胞的凋亡，正在早期临床试验中进行测试。慢性高危型HPV感染/瘤形成的特征是全身和/或局部免疫抑制调节或逃逸因子。最近，两种E6/E7疫苗在高级别VIN患者中显示出一定的临床疗效，这与强而广泛的全身HPV特异性T细胞应答和关键局部免疫因子的调节相关。目前正在测试与疫苗接种相结合的局部免疫效应平衡的治疗方法。这篇文章是题为“全面控制HPV感染和相关疾病的机会”的特别增刊的一部分，疫苗第30卷，增刊X，2012年。
This chapter reviews the current treatment of chronic and neoplastic HPV-associated conditions and the development of novel therapeutic approaches. Surgical excision of HPV-associated lower genital tract neoplasia is very successful but largely depends on secondary prevention programmes for identification of disease. Only high-risk HPV-driven chronic, preneoplastic lesions and some very early cancers cannot be successfully treated by surgical procedures alone. Chemoradiation therapy of cervical cancer contributes to the 66–79% cervical cancer survival at 5 years. Outlook for those patients with persistent or recurrent cervical cancer following treatment is very poor. Topical agents such as imiquimod (immune response modifier), cidofovir (inhibition of viral replication; induction apoptosis) or photodynamic therapy (direct damage of tumour and augmentation of anti-tumour immunity) have all shown some useful efficacy (~50–60%) in treatment of high grade vulvar intraepithelial neoplasia. Provider administered treatments of genital warts include cryotherapy, trichloracetic acid, or surgical removal which has the highest primary clearance rate. Patient applied therapies include podophyllotoxin and imiquimod. Recurrence after “successful” treatment is 30–40%. Further improvements could derive from a rational combination of current therapy with new drugs targeting molecular pathways mediated by HPV in cancer. Small molecule inhibitors targeting the DNA binding activities of HPV E1/E2 or the anti-apoptotic consequences of E6/E7 oncogenes are in preclinical development. Proteasome and histone deacetylase inhibitors, which can enhance apoptosis in HPV positive tumour cells, are being tested in early clinical trials. Chronic high-risk HPV infection/neoplasia is characterised by systemic and/or local immune suppressive regulatory or escape factors. Recently two E6/E7 vaccines have shown some clinical efficacy in high grade VIN patients and this correlated with strong and broad systemic HPV-specific T cell response and modulation of key local immune factors. Treatments that can shift the balance of immune effectors locally in combination with vaccination are now being tested. This article forms part of a special supplement entitled “Opportunities for comprehensive control of HPV infections and related diseases” Vaccine Volume 30, Supplement X, 2012.
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影响因子：
1.2
作者：
Batman, Gavin;Oliver, Anthony W.;Hampson, Ian N.
通讯作者：
Hampson, Ian N.
影响因子：
3.7
作者：
Amine A;Rivera S;Opolon P;Dekkal M;Biard DS;Bouamar H;Louache F;McKay MJ;Bourhis J;Deutsch E;Vozenin-Brotons MC
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4.8
作者：
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通讯作者：
Dueñas-González A
影响因子：
1.2
作者：
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通讯作者：
Hampson, Ian N.
影响因子：
8.8
作者：
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