It is a sad fact that despite being almost completely preventable through human papillomavirus (HPV) vaccination and screening, cervical cancer remains the fourth most common cancer to affect women worldwide. Persistent high-risk HPV (hrHPV) infection is the primary etiologic factor for cervical cancer. Upward of 70% of cases are driven by HPV types 16 and 18, with a dozen other hrHPVs associated with the remainder of cases. Current standard-of-care treatments include radiotherapy, chemotherapy, and/or surgical resection. However, they have significant side effects and limited efficacy against advanced disease. There are a few treatment options for recurrent or metastatic cases. Immunotherapy offers new hope, as demonstrated by the recent approval of programmed cell death protein 1–blocking antibody for recurrent or metastatic disease. This might be augmented by combination with antigen-specific immunotherapy approaches, such as vaccines or adoptive cell transfer, to enhance the host cellular immune response targeting HPV-positive cancer cells. As cervical cancer progresses, it can foster an immunosuppressive microenvironment and counteract host anticancer immunity. Thus, approaches to reverse suppressive immune environments and bolster effector T-cell functioning are likely to enhance the success of such cervical cancer immunotherapy. The success of nonspecific immunostimulants like imiquimod against genital warts also suggest the possibility of utilizing these immunotherapeutic strategies in cervical cancer prevention to treat precursor lesions (cervical intraepithelial neoplasia) and persistent hrHPV infections against which the licensed prophylactic HPV vaccines have no efficacy. Here, we review the progress and challenges in the development of immunotherapeutic approaches for the prevention and treatment of cervical cancer.

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宫颈癌免疫疗法：事实与希望

令人遗憾的是，尽管通过人乳头瘤病毒 (HPV) 疫苗接种和筛查几乎可以完全预防宫颈癌，但宫颈癌仍然是影响全球女性的第四大常见癌症。持续性高危 HPV (hrHPV) 感染是宫颈癌的主要病因。超过 70% 的病例是由 16 型和 18 型 HPV 驱动的，其余的病例与十几种其他 hrHPV 相关。目前的标准护理治疗包括放疗、化疗和/或手术切除。然而，它们对晚期疾病具有显着的副作用和有限的功效。复发或转移病例有几种治疗选择。免疫疗法提供了新的希望，正如最近批准的用于复发或转移性疾病的程序性细胞死亡蛋白 1 阻断抗体所证明的那样。这可以通过与抗原特异性免疫治疗方法（例如疫苗或过继细胞转移）相结合来增强，以增强针对 HPV 阳性癌细胞的宿主细胞免疫反应。随着宫颈癌的进展，它可以促进免疫抑制微环境并抵消宿主的抗癌免疫。因此，逆转抑制性免疫环境和增强效应 T 细胞功能的方法可能会提高这种宫颈癌免疫疗法的成功率。非特异性免疫刺激剂（如咪喹莫特）对尖锐湿疣的成功也表明，在宫颈癌预防中利用这些免疫治疗策略来治疗前体病变（宫颈上皮内瘤变）和经许可的预防性 HPV 疫苗无效的持续性 hrHPV 感染的可能性。在这里，我们回顾了开发用于预防和治疗宫颈癌的免疫治疗方法的进展和挑战。