治疗性HPV疫苗的研发和临床应用展望

Development and Clinical Application of Therapeutic HPV Vaccine

宫颈癌是严重威胁女性健康的常见疾病。宫颈癌与高危型人乳头瘤病毒(HPV)持续性感染密切相关。预防性HPV疫苗可以有效预防HPV的感染,但其对已经感染或癌前病变患者无治疗效果。一项中国育龄女性高危型HPV(hrHPV)检测结果发现,hrHPV总阳性率为19.1%。从广泛的育龄样本、宫颈上皮内瘤变2/3级(CIN2/3)样本、宫颈癌样本调研结果发现,hrHPV型别排名前三的分别为HPV52/16/58、HPV16/52/58、HPV16/58/18,HPV16/18的比例逐渐升高。治疗性HPV疫苗通过细胞免疫来清除感染HPV的细胞,从而达到治疗目的。目前,治疗性HPV疫苗尚处在临床研究阶段,以HPV16/18 E6/E7抗原为主要靶点。2024年7月,世界卫生组织(WHO)发布《WHO首选治疗性HPV疫苗的产品特性》,建议其适应证扩大到广泛人群和HPV感染人群。因此,未来治疗性HPV疫苗的设计可以增加L2/E2/E4/E5等HPV抗原靶点或采用多价设计(如增加HPV52/58等)以惠及更多患者人群。治疗性HPV疫苗的开发是预防性HPV疫苗的重要补充。本研究通过对HPV的致病机制、治疗性HPV疫苗的研发现状和临床应用展望进行讨论,以期探索新型治疗方法,加快治疗性HPV疫苗研发步伐,使HPV感染、癌前病变以及HPV相关癌症患者及早受益。

Cervical cancer is a common disease that seriously threatens women's health.Cervical cancer is closely related to persis‐tent infection with high-risk human papilloma virus(HPV).The prophylactic HPV vaccine is effective in preventing HPV infection,but it is not effective in patients who are already infected or have precancerous lesions.A test for high-risk HPV(hrHPV)in Chinese women of childbearing age found that the overall positive rate of hrHPV was 19.1%.The top three hrHPV types in a wide range of childbearing age samples,CIN2/3 samples and cervical cancer samples were HPV52/16/58,HPV16/52/58,HPV16/58/18,respectively and the pro‐portion of HPV16/18 gradually increased.The therapeutic HPV vaccine uses cellular immunity to eliminate HPV-infected cells for thera‐peutic purposes.At present,the therapeutic HPV vaccine is still in the clinical research stage,with HPV16/18 E6/E7 antigen as the main target.In July 2024,the World Health Organization(WHO)released the"WHO preferred product characteristics for therapeutic HPV vaccines",suggesting that the indication be expanded to a wide range of people and HPV-infected people.Based on this,future therapeutic HPV vaccines can be designed to increase HPV antigen targets such as L2/E2/E4/E5 or adopt a multivalent design(such as adding HPV52/58,etc.)to benefit more people.The development of therapeutic HPV vaccines is an important complement to prophylac‐tic HPV vaccines.In this study,the pathogenic mechanism of HPV,the research and development status and the prospect of clinical application of therapeutic HPV vaccine were discussed,hoping that new treatment methods could be explored,and the development of therapeutic HPV vaccines could be accelerated,and to benefit patients with HPV infection,precancer and HPV-related cancer as soon as possible.