a Laboratório de Estudos Moleculares e Terapia Experimental - LEMTE , Brazil Universidade Federal de Pernambuco - UFPE , Brazil.
b HPV-Unit UOSD Immunology and Tumor Immunotherapy , IRCCS Regina Elena National Cancer Institute , Rome , Italy.
Expert Rev Anticancer Ther. 2018 Apr;18(4):365-376. doi: 10.1080/14737140.2018.1445527. Epub 2018 Mar 13.
Cervical cancer and cervical intraepithelial neoplasia (CIN) are well-known outcomes of a human papillomavirus (HPV) infection. Viral oncogenes expressions like E6, E7, and, recently recognized E5, lead to HPV-related malignant progression. Although HPV prevention by powerful vaccines against most frequent and oncogenic genotypes is feasible, current treatment against cervical neoplasia is distant from an ideal one. In addition, late diagnosis is commonly associated with a poor prognosis. On top of that, radiotherapy, chemotherapy, or surgery are less effective in high-grade lesions. Areas covered: Due to their peculiarities, HPV oncogenes represent an excellent target for cancer immunotherapy. Safety, efficacy, and potential immunogenicity are features achieved by DNA vaccines targeting HPV. The literature search has indicated that genetic immunotherapy is becoming a pharmacological tool and therapeutic option against cervical disease, as more and more DNA vaccines are reaching clinical trial phases. Expert commentary: Among some of the promising results, a phase II randomized trial showed a clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN patients. The concept of a synergic combination of anti-HPV DNA vaccines with radiotherapy, chemotherapy, sophisticated delivery methods, immunomodulators or immune adjuvants opens a new and interesting perspective in cervical malignancy treatment.
宫颈癌和宫颈上皮内瘤变(CIN)是众所周知的人乳头瘤病毒(HPV)感染的结果。病毒癌基因如 E6、E7 和最近被识别的 E5 的表达导致 HPV 相关的恶性进展。尽管针对最常见和致癌基因型的强大疫苗可以预防 HPV,但目前针对宫颈癌的治疗方法还远非理想。此外,晚期诊断通常与预后不良相关。更重要的是,放疗、化疗或手术对高级别病变的效果较差。
由于其特殊性,HPV 癌基因是癌症免疫治疗的一个极好的靶点。针对 HPV 的 DNA 疫苗具有安全性、疗效和潜在免疫原性等特点。文献检索表明,基因免疫疗法正成为一种针对宫颈疾病的药理学工具和治疗选择,因为越来越多的 DNA 疫苗正在进入临床试验阶段。
在一些有前途的结果中,一项 II 期随机试验显示了一种基于核酸的疫苗在 HPV16 或 HPV18 阳性 CIN 患者中的临床活性。抗 HPV DNA 疫苗与放疗、化疗、复杂的给药方法、免疫调节剂或免疫佐剂的协同组合的概念为宫颈癌治疗开辟了一个新的、有趣的视角。