History of Cervical Cancer and the Role of the Human Papillomavirus, 1960-2000

Annotated and edited transcript of a Witness Seminar held on 13 May 2008. Introduction by Professor Anne M Johnson, Division of Population Health and Institute for Global Health, UCL. First published by the Wellcome Trust Centre for the History of Medicine at UCL, 2009. ©The Trustee of the Wellcome Trust, London, 2009. All volumes are freely available online at: www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/Annotated and edited transcript of a Witness Seminar held on 13 May 2008. Introduction by Professor Anne M Johnson, Division of Population Health and Institute for Global Health, UCLAnnotated and edited transcript of a Witness Seminar held on 13 May 2008. Introduction by Professor Anne M Johnson, Division of Population Health and Institute for Global Health, UCLAnnotated and edited transcript of a Witness Seminar held on 13 May 2008. Introduction by Professor Anne M Johnson, Division of Population Health and Institute for Global Health, UCLAnnotated and edited transcript of a Witness Seminar held on 13 May 2008. Introduction by Professor Anne M Johnson, Division of Population Health and Institute for Global Health, UCLThe history, largely untold, of the development of cervical cytology, of effective screening and its ultimate success in reducing cervical cancer incidence and mortality, and the viral cause of cervical cancer, took place within a complex social background of changing attitudes to women’s health and sexual behaviour. Dr Georges Papanicolaou’s screening method (the Pap smear) started in the US in the 1940s. It was widely used in the UK a decade later and a national programme of cervical screening was established in 1988. The association of sexually transmitted human papillomavirus (HPV) with cervical cancer was less readily accepted. The detection of HPV16 in cervical cancers at the end of the 1970s was aided by the explosion of laboratory, clinical, and public health research on new screening tests and procedures. These made possible the successful development, licensing and use of preventive vaccines against the major oncogenic HPV types, HPV16 and -18. The Witness Seminar was attended by virologists, cytologists, gynaecologists, epidemiologists and others and addressed the development of cytology as a pathological discipline. They discussed who became cytologists and screeners; the evolution of screening in the UK and elsewhere; the impacts of colposcopy and of HPV; and the discovery of virus-like particles and the development of the HPV vaccine. The meeting was chaired by Professor Glenn McCluggage and the topic was suggested by Professor David Jenkins. Contributors include: Professor Valerie Beral, Professor Saveria Campo, Professor Jocelyn Chamberlain, Professor Dulcie Coleman, Dr Lionel Crawford, Professor Heather Cubie, Professor Jack Cuzick, Dr Ian Duncan, Dr Winifred Gray, Dr Amanda Herbert, Professor David Jenkins, Dr Elizabeth Mackenzie, Dr Joan Macnab, Professor Anthony Miller, Professor Julian Peto, Dr Catherine Pike, Professor Peter Sasieni, Professor Albert Singer, Dr John Smith, Professor Margaret Stanley, Mrs Marilyn Symonds, Dr Anne Szarewski, Professor Leslie Walker, Mr Patrick Walker, Dr Margaret Wolfendale and Professor Ciaran Woodman. Two appendices with reminiscences from Professor Leopold Koss, Dr Arthur Spriggs and Dr O A N (Nasseem) Husain complete the volume. Reynolds L A, Tansey E M. (eds) (2009) History of cervical cancer and the role of human papillomavirus, 1960–2000, Wellcome Witnesses to Twentieth Century Medicine, vol. 38. London: The Wellcome Trust Centre for the History of Medicine at UCL. ISBN 978 085484 1233The Wellcome Trust Centre for the History of MedicineMat UCL is funded by the Wellcome Trust, which is a registered charity, no. 210183

Fine-Needle Aspiration Biopsy of Hepatocellular Carcinoma and Related Hepatocellular Nodular Lesions in Cirrhosis: Controversies, Challenges, and Expectations

The role of hepatic fine-needle aspiration (FNA) biopsy has evolved. Advances in imaging modalities have obviated the need for tissue confirmation in most hepatocellular carcinomas (HCCs). There is risk of needle-tract seeding. Increasingly, small nodules are being detected on ultrasound surveillance of high-risk patients. Diagnostic challenges associated with cirrhosis include distinction of benign hepatocellular nodules, namely, large regenerative nodules and dysplastic nodules, from reactive hepatocytes; and distinction of well-differentiated HCCs from benign hepatocellular nodules. This paper will discuss (i) controversies regarding preoperative/pretransplantation FNA diagnosis of HCC, (ii) update of biological evolution, nomenclature, and histopathologic criteria for diagnosis of precancerous nodules and small HCCs, and (iii) algorithmic approach to FNA diagnosis of hepatocellular nodules. Optimal results depend on dedicated radiologist-cytopathologist team, on-site cytology service; combined cytohistologic approach, immunohistochemistry, and clinicopathologic correlation. Hepatic FNA is likely to be incorporated as a point of care as we move towards personalized medicine

An Optical Machine Vision System for Applications in Cytopathology

This paper discusses a new approach to the processes of object detection, recognition and classification in a digital image focusing on problem in Cytopathology. A unique self learning procedure is presented in order to incorporate expert knowledge. The classification method is based on the application of a set of features which includes fractal parameters such as the Lacunarity and Fourier dimension. Thus, the approach includes the characterisation of an object in terms of its fractal properties and texture characteristics. The principal issues associated with object recognition are presented which include the basic model and segmentation algorithms. The self-learning procedure for designing a decision making engine using fuzzy logic and membership function theory is also presented and a novel technique for the creation and extraction of information from a membership function considered. The methods discussed and the algorithms developed have a range of applications and in this work, we focus the engineering of a system for automating a Papanicolaou screening test

Quality Assurance of Cervical Smear Slide Inspection Using a Novel Eye-Tracking Technique

A novel objective quality assurance system for smear slide screening is investigated in this thesis. A method of data validation was developed that compares data from an eye tracked image display, machine image colour texture analysis and expert judgements in a statistical manner to identify salient areas of cervical cytological images. These data are used to construct screener performance profiles, which have been compared to screener experience. The experimental methodology is described and how the screener performance profile is constructed. Results from a study of 10 screeners, checkers and pathologists are presented showing predicted trends of human performance. Relations to experience and strategy are also shown, though these relationships are not statistically significant. A standardised quality assurance test is developed that profiles screeners across many performance measures. Highly significant correlations were found between fixation saliency and machine colour texture (maxima density), though fixation saliency suffers from a lack of a significant statistical basis. Further fixation data is needed, however if it conforms to the existing trends then the results would support the new data validation method as a framework from which image analysis techniques applied to cytology may be objectively tested. Furthermore, this new approach to cervical cytology quality assurance would have the potential to further reduce human errors in the cervical smear inspection process by lowering levels of observer variation found in all aspects of the cervical screening process

Acinic cell carcinoma of the salivary gland: A Continuing Medical Education Case

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58660/1/20852_ftp.pd

Chromosome in situ hybridisation, Ki-67, and telomerase immunocytochemistry in liquid based cervical cytology

Aims: To assess the potential value of chromosome in situ hybridisation (CISH), Ki-67, and telomerase immunocytochemistry in liquid based cervical cytology to help detect carcinoma cells and precursors. Method: Sixty ThinPrep processed cervical cytology samples were studied: 23 cases within the normal limit, 13 low grade squamous intraepithelial lesions (LSILs), 10 high grade squamous intraepithelial lesions (HSILs), six squamous cell carcinomas, three endocervical adenocarcinomas, two cervical adenosquamous cell carcinomas, and three endometrial adenocarcinomas. CISH was performed with DNA probes specific for the pericentromeric regions of chromosome 11 and 16. Hybridisation signals were visualised with the streptavidin-biotin peroxidase technique. The monoclonal MIB1 and polyclonal TRT-H231 antibodies were used to detect Ki-67 and telomerase immunoreactivity, respectively. Results: Non-specific background staining was almost absent in CISH slides. Normal squamous and glandular cells showed a diploid chromosomal pattern. A relative gain in chromosomes 11 and 16 (aneusomy) was seen in HSIL and the carcinomas (p<0.0001 ). In MIB1 stained smears, normal cells and koilocytes showed inconspicuous immunoreactivity, whereas strongly immunoreactive nuclei were found in cancer cells and HSIL (p<0.0001). Not only carcinoma and HSIL cells, but also some normal cells, showed cytoplasmic staining for telomerase. Conclusions: These preliminary results indicate that ThinPrep processed cervical smears are suitable for CISH and immunocytochemical studies. The neoplastic squamous and glandular cells were easily identified based on nuclear aneusomy and strong Ki-67 immuoreactivity in the context of abnormal nuclear morphology. This is the first study to apply CISH in cervical cytology using an immunoenzymatic approach.published_or_final_versio

History of cervical cancer and the role of the human papillomavirus, 1960–2000

The history, largely untold, of the development of cervical cytology, of effective screening and its ultimate success in reducing cervical cancer incidence and mortality, and the viral cause of cervical cancer, took place within a complex social background of changing attitudes to women’s health and sexual behaviour. Dr Georges Papanicolaou’s screening method (the Pap smear) started in the US in the 1940s. It was widely used in the UK a decade later and a national programme of cervical screening was established in 1988. The association of sexually transmitted human papillomavirus (HPV) with cervical cancer was less readily accepted. The detection of HPV16 in cervical cancers at the end of the 1970s was aided by the explosion of laboratory, clinical, and public health research on new screening tests and procedures. These made possible the successful development, licensing and use of preventive vaccines against the major oncogenic HPV types, HPV16 and -18. The Witness Seminar was attended by virologists, cytologists, gynaecologists, epidemiologists and others and addressed the development of cytology as a pathological discipline. They discussed who became cytologists and screeners; the evolution of screening in the UK and elsewhere; the impacts of colposcopy and of HPV; and the discovery of virus-like particles and the development of the HPV vaccine. The meeting was chaired by Professor Glenn McCluggage and the topic was suggested by Professor David Jenkins. Contributors include: Professor Valerie Beral, Professor Saveria Campo, Professor Jocelyn Chamberlain, Professor Dulcie Coleman, Dr Lionel Crawford, Professor Heather Cubie, Professor Jack Cuzick, Dr Ian Duncan, Dr Winifred Gray, Dr Amanda Herbert, Professor David Jenkins, Dr Elizabeth Mackenzie, Dr Joan Macnab, Professor Anthony Miller, Professor Julian Peto, Dr Catherine Pike, Professor Peter Sasieni, Professor Albert Singer, Dr John Smith, Professor Margaret Stanley, Mrs Marilyn Symonds, Dr Anne Szarewski, Professor Leslie Walker, Mr Patrick Walker, Dr Margaret Wolfendale and Professor Ciaran Woodman. Two appendices with reminiscences from Professor Leopold Koss, Dr Arthur Spriggs and Dr O A N (Nasseem) Husain complete the volume