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.

中文翻译：

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乳头瘤病毒驱动疾病的人类遗传解剖：对其发病机理的新见解。

人乳头瘤病毒（HPV）感染粘膜或皮肤分层上皮。HPV有5个属和200多种类型，每种都有特定的向性和毒力。HPV感染通常是无症状的或导致良性肿瘤，在极少数情况下可能会散播或持续存在，但少数致癌性HPV可能导致癌症。这篇综述涉及皮肤和粘膜HPV感染过程中个体间临床变异性的人类遗传学和免疫学基础。对于患有先天性EVER1-EVER2-CIB1依赖性皮肤内源性免疫缺陷的患者，典型的疣状表皮发育不良（EV）的特征在于β-HPV驱动的扁平疣样和糠疹样皮肤样病变以及非黑素瘤皮肤癌。具有先天性T细胞错误的患者中，非典型性EV与其他传染病相关。对于患有T淋巴细胞和抗原呈递细胞先天性错误的患者，某些α-，γ-，μ或ν-HPV也会导致严重的皮肤或肛门生殖器疣，包括肛门生殖器癌。在其他粘膜部位，如口腔多灶上皮增生或青少年反复呼吸道乳头状瘤病（JRRP），HPV疾病的遗传基础仍然知之甚少。HPV驱动病变的人类遗传解剖将阐明对HPV的保护性免疫的分子和细胞基础，并应为患者带来新颖的诊断，预防和治疗方法。诸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）之类的知识仍知之甚少。HPV驱动病变的人类遗传解剖将阐明对HPV的保护性免疫的分子和细胞基础，并应为患者带来新颖的诊断，预防和治疗方法。诸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）的了解仍然很少。HPV驱动病变的人类遗传解剖将阐明对HPV的保护性免疫的分子和细胞基础，并应为患者带来新颖的诊断，预防和治疗方法。