Department of Obstetrics & Gynecology , Medical University of Graz, Graz, Austria.
Diagnostic & Research Institute of Pathology, Medical University of Graz, Graz, Austria.
Virus Res. 2023 May;329:199068. doi: 10.1016/j.virusres.2023.199068. Epub 2023 Mar 16.
Human papilloma viruses (HPV), that are causative for most squamous cell cervical cancers (SCC), have a simple structure with only a few genes (six early and two late genes). Two of the early HPV genes (E6 and E7) are capable of transforming normal squamous epithelium into cancer. In the last 10 years, a controversial discussion arose as to which cells are primarily involved in cervical carcinogenesis. Virologists traditionally use a research model of stratified squamous epithelium, a permissive environment for completion of a full HPV-life cycle. Basic insights on HPV tropism, HPV life cycle, HPV-uptake, HPV-replication, HPV-gene expression were gained from this model. Stratified squamous epithelium, however, is a low-risk area for SCC. Most SCC develop in an area of endocervical columnar epithelium that undergoes squamous metaplasia. SCC arise after infection of immature squamous metaplasia, proliferating reserve cells/reserve cell hyperplasia and reserve cells of the endocervical columnar epithelium. Study models investigating this pathway of carcinogenesis do not exist and therapeutic consequences deduced from this knowledge are lacking. This review describes in detail cervical carcinogenesis after HPV infection of subcolumnar reserve cells and discusses new intervention strategies for patients. The WHO-launched global strategy to eliminate HPV-associated cervical cancer builds primarily on prophylactic vaccination, screening and treatment. New insights in cervical pathogenesis, may assist in reaching this ambitious WHO goal.
人乳头瘤病毒(HPV)是大多数鳞状细胞宫颈癌(SCC)的致病原因,其结构简单,只有少数几个基因(6 个早期基因和 2 个晚期基因)。早期 HPV 基因中的两个(E6 和 E7)能够将正常的鳞状上皮转化为癌症。在过去的 10 年中,人们对于哪些细胞是宫颈癌发生的主要参与者存在争议。病毒学家传统上使用分层鳞状上皮的研究模型,这是一个允许 HPV 生命周期完整完成的允许环境。从这个模型中获得了对 HPV 趋向性、HPV 生命周期、HPV 摄取、HPV 复制、HPV 基因表达的基本了解。然而,分层鳞状上皮是 SCC 的低风险区域。大多数 SCC 发生在经历鳞状化生的宫颈柱状上皮内,是由感染不成熟的鳞状化生、增殖储备细胞/储备细胞增生和宫颈柱状上皮的储备细胞引起的。不存在研究该致癌途径的研究模型,也缺乏从这些知识中推断出的治疗后果。本文详细描述了 HPV 感染柱状上皮下储备细胞后的宫颈癌变,并讨论了针对患者的新干预策略。世界卫生组织发起的消除 HPV 相关宫颈癌全球战略主要基于预防性疫苗接种、筛查和治疗。对宫颈发病机制的新见解可能有助于实现这一雄心勃勃的世卫组织目标。