Histopathology and Cytopathology of Cervical Cancer

Histopathology and cytopathology form the scientific and clinical basis for current prevention and treatment of cervical cancer. Histopathology determines treatment of cancer and precancer through classifying into a diagnosis the patterns of microscopic organization of cells in tissue sections from biopsy or surgical specimens. Although morphological concepts of cervical cancer and precancer evolution are giving way to viral and molecular knowledge, histopathology also remains important as the most widely used clinical endpoints by which the performance of new techniques for cervical cancer prevention are currently evaluated. Cervical cytopathology studies exfoliated cells taken from the surface of the cervix and is the main method of cervical screening in successful cervical cancer prevention programmes. These techniques have contributed hugely to reducing the burden of cervical cancer. Countries with successful implementation of cytological screening have shown a reduction in incidence and mortality by 70% or more [1,2]. These figures are historical comparisons and may underestimate the impact as they do not take account of observed increased rates in young women for whom screening provides little protection, and the impact of increasing exposure to oncogenic HPV and other risk factors in some countries as a consequence of major behavioural changes. On this basis, in the UK, the national programme started in 1988 has been estimated to prevent 4,500–6,000 deaths per year, with a very marked decline in [3] rates in women aged 30–34 y. Despite this, because of the difficulties and costs of this approach, globally, there are almost half a million cases of cervical cancer each year. Concurrently with the enormous success of cytological screening, there has been increasing knowledge of the challenges of the limited reproducibility of the diagnoses, of the complex relationships between cytological and histological diagnosis and the natural history of cervical precancer, particularly the driving role of infection with genital human papillomavirus (HPV). This review focuses on the concepts and terminology used in classifying morphological changes of cervical precancer and HPV infection, how this links to natural history through information from cervical screening and more recent cohort studies of HPV infection. It addresses the issues around the performance characteristics (reproducibility and accuracy) of cytopathology and histopathology as diagnostic tests, and the implications for cervical screening practice. Finally it discusses the use of cytopathology and histopathology as reference standards and endpoints in clinical research and biomarker development.