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当前和未来治疗 HPV 相关宫颈疾病的方向。

Current and future direction in treatment of HPV-related cervical disease.

机构信息

Department of Molecular Medicine, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.

出版信息

J Mol Med (Berl). 2022 Jun;100(6):829-845. doi: 10.1007/s00109-022-02199-y. Epub 2022 Apr 27.

Abstract

Human papillomavirus (HPV) is the most common sexually transmitted virus in the world. About 70% of cervical cancers are caused by the most oncogenic HPV genotypes of 16 and 18. Since available prophylactic vaccines do not induce immunity in those with established HPV infections, the development of therapeutic HPV vaccines using E6 and E7 oncogenes, or both as the target antigens remains essential. Also, knocking out the E6 and E7 oncogenes in host genome by genome-editing CRISPR/Cas system can result in tumor growth suppression. These methods have shown promising results in both preclinical and clinical trials and can be used for controlling the progression of HPV-related cervical diseases. This comprehensive review will detail the current treatment of HPV-related cervical precancerous and cancerous diseases. We also reviewed the future direction of treatment including different kinds of therapeutic methods and vaccines, genome-editing CRISPR/Cas system being studied in clinical trials. Although the progress in the development of therapeutic HPV vaccine has been slow, encouraging results from recent trials showed vaccine-induced regression in high-grade CIN lesions. CRISPR/Cas genome-editing system is also a promising strategy for HPV cancer therapy. However, its safety and specificity need to be optimized before it is used in clinical setting.

摘要

人乳头瘤病毒(HPV)是世界上最常见的性传播病毒。大约 70%的宫颈癌是由最致癌的 HPV 基因型 16 和 18 引起的。由于现有的预防性疫苗不能在已感染 HPV 的人群中诱导免疫,因此使用 E6 和 E7 致癌基因或两者作为靶抗原开发治疗性 HPV 疫苗仍然至关重要。此外,通过基因组编辑 CRISPR/Cas 系统敲除宿主基因组中的 E6 和 E7 致癌基因可导致肿瘤生长抑制。这些方法在临床前和临床试验中均显示出有希望的结果,可用于控制 HPV 相关宫颈疾病的进展。本综述详细介绍了 HPV 相关宫颈癌前病变和癌症的当前治疗方法。我们还回顾了未来的治疗方向,包括不同类型的治疗方法和疫苗,以及正在临床试验中研究的基因组编辑 CRISPR/Cas 系统。尽管治疗性 HPV 疫苗的开发进展缓慢,但最近试验的令人鼓舞结果表明,疫苗可诱导高级别 CIN 病变消退。CRISPR/Cas 基因组编辑系统也是 HPV 癌症治疗的有前途的策略。然而,在将其用于临床环境之前,需要优化其安全性和特异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1dd/9045016/f42d939f2dd2/109_2022_2199_Fig1_HTML.jpg

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