Tolstov Yanis, Hadaschik Boris, Pahernik Sascha, Hohenfellner Markus, Duensing Stefan
Section of Molecular Urooncology, Department of Urology, University of Heidelberg School of Medicine, Heidelberg, Germany.
Department of Urology, University of Heidelberg School of Medicine, Heidelberg, Germany.
Urol Oncol. 2014 Jan;32(1):46.e19-27. doi: 10.1016/j.urolonc.2013.06.012. Epub 2013 Oct 17.
Infection with human papillomaviruses (HPVs) is intimately associated with anogenital tract malignancies including cervical and vulvar cancer, a subset of oropharyngeal cancers and certain types of skin cancer. A number of urological tumors have likewise been suggested to be associated with high-risk HPV infection; however, many studies are hampered by a limited number of detection methods. The goal of this review article is to define a set of key criteria when implicating a virus in a human cancer and to apply these criteria to HPV infection in urological cancers.
We performed a survey of the literature to corroborate the evidence to support a causal relationship between HPV infection and major urological malignancies.
A number of previous reports have implicated HPVs in urological malignancies including penile, prostate, and bladder cancer. Most reports, however, rely only on a limited number of detection methods and frequently use contamination-prone polymerase chain reaction based methods. To firmly establish a link between a viral infection and a human malignancy, it is paramount that an array of techniques is employed and that the virus is ultimately traced by either direct visualization or, in the case of viral genome that has integrated into the host genome, detection of viral genes and gene products as well as functional cellular perturbations. In any case, seroepidemiological studies are likewise crucial to support the evidence. Such evidence for a role of HPV in urological malignancies based on currently available techniques is only present for penile squamous cell carcinomas.
An increasing number of immunocompromised patients as well as novel developments in patient care may change the spectrum of HPV-associated neoplasms. This is examplified by results demonstrating a role of HPVs in rare urothelial carcinomas with squamous differentiation in patients with neurogenic bladder. Hence, it is important to keep HPV infection in mind when confronted with unusual disease manifestations of the urogenital tract.
人乳头瘤病毒（HPV）感染与包括宫颈癌和外阴癌、一部分口咽癌以及某些类型皮肤癌在内的肛门生殖道恶性肿瘤密切相关。同样有许多泌尿生殖系统肿瘤被认为与高危型HPV感染有关；然而，许多研究因检测方法有限而受到阻碍。这篇综述文章的目的是确定在将一种病毒与人类癌症联系起来时的一组关键标准，并将这些标准应用于泌尿生殖系统癌症中的HPV感染。
我们对文献进行了调查，以确证支持HPV感染与主要泌尿生殖系统恶性肿瘤之间因果关系的证据。
先前的一些报告已将HPV与包括阴茎癌、前列腺癌和膀胱癌在内的泌尿生殖系统恶性肿瘤联系起来。然而，大多数报告仅依赖有限的检测方法，并且经常使用容易污染的基于聚合酶链反应的方法。要牢固地建立病毒感染与人类恶性肿瘤之间的联系，至关重要的是采用一系列技术，并且最终通过直接可视化来追踪病毒，或者在病毒基因组已整合到宿主基因组的情况下，检测病毒基因和基因产物以及功能性细胞扰动。在任何情况下，血清流行病学研究同样对于确证证据至关重要。基于目前可用技术，HPV在泌尿生殖系统恶性肿瘤中发挥作用的此类证据仅见于阴茎鳞状细胞癌。
免疫功能低下患者数量的增加以及患者护理方面的新进展可能会改变HPV相关肿瘤的谱。这一点在结果中得到了体现，结果表明HPV在神经源性膀胱患者的罕见伴有鳞状分化的尿路上皮癌中发挥作用。因此，当面对泌尿生殖道不寻常的疾病表现时，牢记HPV感染很重要。
