College of Medicine, The Ohio State University, OH, USA.
Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus, OH.
Clin Exp Immunol. 2020 Feb;199(2):131-142. doi: 10.1111/cei.13387. Epub 2019 Oct 31.
Recurrent respiratory papillomatosis (RRP) is characterized by benign exophytic lesions of the respiratory tract caused by the human papillomavirus (HPV), in particular low-risk HPV6 and HPV11. Aggressiveness varies greatly among patients. Surgical excision is the current standard of care for RRP, with adjuvant therapy used when surgery cannot control disease recurrence. Numerous adjuvant therapies have been used to control RRP with some success, but none are curative. Current literature supports a polarization of the adaptive immune response to a T helper type 2 (Th2)-like or T regulatory phenotype, driven by a complex interplay between innate immunity, adaptive immunity and HPV6/11 proteins. Additionally, certain immunogenetic polymorphisms can predispose individuals to an HPV6/11-tolerant microenvironment. As a result, immunomodulatory efforts are being made to restore the host immune system to a more balanced T cell phenotype and clear viral infection. Literature has shown exciting evidence for the role of HPV vaccination with Gardasil or Gardasil-9 as both primary prevention, by decreasing incidence through childhood vaccinations, and secondary prevention, by treating active RRP disease. Multi-institution randomized clinical trials are needed to better assess their efficacy as treatment for active disease. Interestingly, a DNA vaccine has recently shown in-vitro success in generating a more robust CD8 T cell response. Furthermore, clinical trials for programmed death 1 (PD-1) inhibitors are under investigation for RRP management. Molecular insights into RRP, in particular the interplay between RRP and the immune system, are needed to advance our understanding of this disease and may lead to the identification of immunomodulatory agents to better manage RRP.
复发性呼吸道乳头瘤病（RRP）的特征是由人乳头瘤病毒（HPV）引起的呼吸道良性外生性病变，特别是低危型 HPV6 和 HPV11。患者的侵袭性差异很大。手术切除是 RRP 的当前标准治疗方法，当手术无法控制疾病复发时，会使用辅助治疗。已经使用了许多辅助治疗来控制 RRP，取得了一定的成功，但没有一种是治愈性的。目前的文献支持适应性免疫反应向 T 辅助型 2（Th2）样或 T 调节表型极化，这是由固有免疫、适应性免疫和 HPV6/11 蛋白之间的复杂相互作用驱动的。此外，某些免疫遗传多态性可能使个体易患 HPV6/11 耐受的微环境。因此，正在进行免疫调节努力，以使宿主免疫系统恢复到更平衡的 T 细胞表型并清除病毒感染。文献表明，Gardasil 或 Gardasil-9 疫苗接种在作为一级预防（通过儿童期疫苗接种降低发病率）和二级预防（通过治疗活跃的 RRP 疾病）方面发挥作用的令人兴奋的证据。需要多机构随机临床试验来更好地评估它们作为治疗活跃疾病的疗效。有趣的是，最近一种 DNA 疫苗在体外成功地产生了更强大的 CD8 T 细胞反应。此外，正在研究程序性死亡 1（PD-1）抑制剂的临床试验，以用于 RRP 管理。RRP 的分子见解，特别是 RRP 与免疫系统之间的相互作用，有助于我们深入了解这种疾病，并可能导致鉴定出免疫调节剂来更好地管理 RRP。
