Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR-1163, Necker Hospital for Sick Children, Paris, EU, France.
University of Paris, Imagine Institute, Paris, EU, France.
Hum Genet. 2020 Jun;139(6-7):919-939. doi: 10.1007/s00439-020-02183-x. Epub 2020 May 20.
Human papillomaviruses (HPVs) infect mucosal or cutaneous stratified epithelia. There are 5 genera and more than 200 types of HPV, each with a specific tropism and virulence. HPV infections are typically asymptomatic or result in benign tumors, which may be disseminated or persistent in rare cases, but a few oncogenic HPVs can cause cancers. This review deals with the human genetic and immunological basis of interindividual clinical variability in the course of HPV infections of the skin and mucosae. Typical epidermodysplasia verruciformis (EV) is characterized by β-HPV-driven flat wart-like and pityriasis-like cutaneous lesions and non-melanoma skin cancers in patients with inborn errors of EVER1-EVER2-CIB1-dependent skin-intrinsic immunity. Atypical EV is associated with other infectious diseases in patients with inborn errors of T cells. Severe cutaneous or anogenital warts, including anogenital cancers, are also driven by certain α-, γ-, μ or ν-HPVs in patients with inborn errors of T lymphocytes and antigen-presenting cells. The genetic basis of HPV diseases at other mucosal sites, such as oral multifocal epithelial hyperplasia or juvenile recurrent respiratory papillomatosis (JRRP), remains poorly understood. The human genetic dissection of HPV-driven lesions will clarify the molecular and cellular basis of protective immunity to HPVs, and should lead to novel diagnostic, preventive, and curative approaches in patients.
人乳头瘤病毒（HPV）感染黏膜或皮肤的分层上皮。有 5 个属和 200 多种 HPV，每种 HPV 都有特定的嗜性和毒力。HPV 感染通常无症状或导致良性肿瘤，在极少数情况下可能会扩散或持续存在，但少数致癌 HPV 可导致癌症。这篇综述涉及皮肤和黏膜 HPV 感染过程中个体间临床变异性的人类遗传和免疫基础。典型的疣状表皮发育不良（EV）的特征是β-HPV 驱动的扁平疣状和糠疹样皮肤病变和非黑色素瘤皮肤癌，发生于 EVER1-EVER2-CIB1 依赖性皮肤固有免疫的先天性缺陷患者中。非典型 EV 与先天性缺陷 T 细胞患者的其他传染病有关。严重的皮肤或肛门生殖器疣，包括肛门生殖器癌症，也与先天性缺陷 T 淋巴细胞和抗原呈递细胞的某些α、γ、μ或ν-HPV 有关。其他黏膜部位如口腔多灶性上皮增生或青少年复发性呼吸道乳头状瘤病（JRRP）的 HPV 疾病的遗传基础仍知之甚少。HPV 驱动病变的人类遗传分析将阐明对 HPV 的保护性免疫的分子和细胞基础，并应导致患者的新型诊断、预防和治疗方法。
