人乳头瘤病毒 (HPV) 是双链 DNA (dsDNA) 肿瘤病毒，与 5% 的人类癌症有因果关系，包括肛门生殖器癌和上呼吸消化道癌。尽管有预防性疫苗可供使用，但 HPV 仍然对全球健康构成重大挑战，这主要是由于疫苗获取和覆盖范围不足。这些病毒可以通过逃避受感染组织的内在防御和专业先天免疫细胞提供的外在防御来建立持续感染。它们逃避策略的关键是它们独特的上皮内生命周期，这有效地保护它们免受宿主检测。因此，旨在重新激活受感染或转化的上皮细胞内先天免疫反应的策略，特别是通过产生 I 型干扰素 (IFN) 和淋巴细胞募集趋化因子，被认为是抵消这些致癌病毒持续感染的不利影响的可行解决方案。 。本综述重点关注高危 HPV 癌蛋白 E6 和 E7 与上皮细胞和 HPV 相关癌症中的先天免疫反应之间的复杂相互作用。特别是，它详细介绍了 E6 和 E7 调节先天免疫反应的分子机制，强调了我们在理解这些过程方面取得的重大进展。它还研究了利用先天免疫系统改善现有抗癌疗法的前瞻性策略，从而为未来的治疗发展提供了重要的见解。© 2024 作者。 《医学病毒学杂志》由 Wiley periodicals LLC 出版。

Human papillomaviruses (HPVs) are double-stranded DNA (dsDNA) tumor viruses causally associated with 5% of human cancers, comprising both anogenital and upper aerodigestive tract carcinomas. Despite the availability of prophylactic vaccines, HPVs continue to pose a significant global health challenge, primarily due to inadequate vaccine access and coverage. These viruses can establish persistent infections by evading both the intrinsic defenses of infected tissues and the extrinsic defenses provided by professional innate immune cells. Crucial for their evasion strategies is their unique intraepithelial life cycle, which effectively shields them from host detection. Thus, strategies aimed at reactivating the innate immune response within infected or transformed epithelial cells, particularly through the production of type I interferons (IFNs) and lymphocyte-recruiting chemokines, are considered viable solutions to counteract the adverse effects of persistent infections by these oncogenic viruses. This review focuses on the complex interplay between the high-risk HPV oncoproteins E6 and E7 and the innate immune response in epithelial cells and HPV-associated cancers. In particular, it details the molecular mechanisms by which E6 and E7 modulate the innate immune response, highlighting significant progress in our comprehension of these processes. It also examines forward-looking strategies that exploit the innate immune system to ameliorate existing anticancer therapies, thereby providing crucial insights into future therapeutic developments.© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.