Department of Pathology, University of Cambridge, Cambridge, UK.
Department of Gynae-Oncology, Addenbrookes Hospital, Cambridge, UK.
Cytopathology. 2020 Jul;31(4):258-270. doi: 10.1111/cyt.12835.
Cervical cancer prevention has undergone dramatic changes over the past decade. With the introduction of human papillomavirus (HPV) vaccination, some countries have seen a dramatic decline in HPV-mediated cervical disease. However, widespread implementation has been limited by economic considerations and the varying healthcare priorities of different countries, as well as by vaccine availability and, in some instances, vaccine hesitancy amongst the population/government. In this environment, it is clear that cervical screening will retain a critical role in the prevention of cervical cancer and will in due course need to adapt to the changing incidence of HPV-associated neoplasia. Cervical screening has, for many years, been performed using Papanicolaou staining of cytology samples. As our understanding of the role of HPV in cervical cancer progression has advanced, and with the availability of sensitive detection systems, cervical screening now incorporates HPV testing. Although such tests improve disease detection, they are not specific, and cannot discriminate high-grade from low-grade disease. This has necessitated the development of effective triage approaches to stratify HPV-positive women according to their risk of cancer progression. Although cytology triage remains the mainstay of screening, novel strategies under evaluation include DNA methylation, biomarker detection and the incorporation of artificial intelligence systems to detect cervical abnormalities. These tests, which can be partially anchored in a molecular understanding of HPV pathogenesis, will enhance the sensitivity of disease detection and improve patient outcomes. This review will provide insight on these innovative methodologies while explaining their scientific basis drawing from our understanding of HPV tumour biology.
在过去的十年中，宫颈癌预防发生了重大变化。随着人乳头瘤病毒（HPV）疫苗的引入，一些国家的 HPV 介导的宫颈癌发病率出现了大幅下降。然而，由于经济考虑因素以及不同国家的医疗保健重点的不同，以及疫苗的供应情况，在某些情况下，包括民众和政府在内的对疫苗的犹豫态度，疫苗的广泛实施受到了限制。在这种情况下，很明显，宫颈筛查将在宫颈癌的预防中继续发挥重要作用，并将需要适应 HPV 相关肿瘤发病率的变化。多年来，宫颈筛查一直通过巴氏染色细胞学样本进行。随着我们对 HPV 在宫颈癌进展中的作用的理解的提高，以及敏感检测系统的可用性，宫颈筛查现在纳入了 HPV 检测。尽管这些测试提高了疾病的检出率，但它们并不具有特异性，也无法区分高级别和低级别疾病。这就需要开发有效的分诊方法，根据癌症进展的风险对 HPV 阳性女性进行分层。虽然细胞学分诊仍然是筛查的主要方法，但正在评估的新策略包括 DNA 甲基化、生物标志物检测以及人工智能系统的引入，以检测宫颈异常。这些测试部分基于对 HPV 发病机制的分子理解，将提高疾病检测的敏感性并改善患者的预后。本综述将提供对这些创新方法的深入了解，并从我们对 HPV 肿瘤生物学的理解中解释其科学依据。
