Alani R M, Münger K
Department of Pathology, Harvard Medical School, Massachusetts General Hospital, Boston 02115, USA.
J Clin Oncol. 1998 Jan;16(1):330-7. doi: 10.1200/JCO.1998.16.1.330.
The human papillomaviruses (HPVS) are small DNA tumor viruses that infect epithelial cells and induce proliferative lesions. Substantial epidemiologic data along with in vitro and in vivo studies have led to the implication of particular HPVs with the development of epithelial malignancies. Greater than 90% of all cervical carcinomas are positive for HPV infection. Most of these lesions are caused by infection with mucosal-associated high-risk HPV subtypes. Much work has been undertaken in basic science laboratories to determine the molecular basis for HPV-associated malignancies. Although many significant advances have been made in understanding the biologic properties of these viruses using in vitro analyses, the field has been greatly hindered until recently by the inability to propagate the virus in culture. In this review, we discuss the basic biologic properties of HPVs and the current understanding of the mechanisms of cellular transformation by malignancy-associated viral subtypes. We place particular emphasis on discussion of the HPV oncogenes, E6 and E7. We also discuss premalignant and malignant disorders of squamous and mucosal epithelia, which have been associated with HPV infections, and the current understanding of the mechanism of HPV-associated carcinogenesis in these settings. We focus these discussions on cervical carcinogenesis and briefly review the particulars regarding HPV-associated malignancies in normal and immunocompromised hosts. We end with a discussion of potential targeted molecular therapies for HPV-associated malignancies that may result from the current knowledge of HPV-related cellular growth dysregulation and carcinogenesis.
人乳头瘤病毒（HPVs）是一类感染上皮细胞并诱导增殖性病变的小型DNA肿瘤病毒。大量的流行病学数据以及体外和体内研究表明，特定的HPV与上皮恶性肿瘤的发生有关。超过90%的宫颈癌HPV感染呈阳性。这些病变大多是由黏膜相关高危HPV亚型感染引起的。基础科学实验室已经开展了大量工作来确定HPV相关恶性肿瘤的分子基础。尽管利用体外分析在了解这些病毒的生物学特性方面取得了许多重大进展，但直到最近，该领域一直因无法在培养中繁殖病毒而受到极大阻碍。在这篇综述中，我们讨论了HPVs的基本生物学特性以及目前对与恶性肿瘤相关的病毒亚型诱导细胞转化机制的理解。我们特别强调对HPV癌基因E6和E7的讨论。我们还讨论了与HPV感染相关的鳞状上皮和黏膜上皮的癌前和恶性疾病，以及目前对这些情况下HPV相关致癌机制的理解。我们将这些讨论聚焦于宫颈癌发生，并简要回顾正常和免疫受损宿主中HPV相关恶性肿瘤的具体情况。最后，我们讨论了基于目前对HPV相关细胞生长失调和致癌作用的认识，针对HPV相关恶性肿瘤可能的靶向分子疗法。
