Molecular Biology of Human Papillomavirus Infection

Lead Research Organisation: MRC National Inst for Medical Research

Abstract

There are many different types of human papillomavirus (HPV). They all infect epithelial tissue such as the skin, but some cause common warts while others cause genital warts. Certain HPV types are classified as high-risk, because they cause cervical lesions (flat warts) that can in some women progress to cervical cancer. These high-risk HPV types are responsible for virtually all cases of cervical cancer worldwide. Cervical cancer is the second most common cancer amongst women with about half a million cases occurring each year.||Our aim is to understand the molecular basis of disease, and to identify the events that deregulate the normal virus life cycle. This work follows a number of different paths. One aspect establishes the function of the viral proteins and aims to understand how they work together to produce disease. As part of this work we are using model systems of the skin to culture the virus in the laboratory. Another aspect of the work is looking at how the virus changes cellular gene expression, and what causes a wart like infection of the cervix to progress to neoplasia. This work has potential for improved cervical screening and better strategies for vaccination and therapy.

Technical Summary

Human papillomaviruses cause a range of epithelial lesions including benign genital warts and cervical intraepithelial neoplasia (CIN). Both are of significant medical importance, with certain HPV types (known as high-risk types) being responsible for the development of cervical cancer in women who cannot resolve their infection. Our focus is on the Alpha papillomaviruses that cause genital warts and cervical disease, but we are also interested in the four other evolutionary groups of papillomavirus including the Beta HPV types that may be involved in the development of skin cancers and which can be a problem in immunosuppressed individuals. The work of the lab falls into three broad areas, which are described below. 1. Molecular Analysis of Human Papillomavirus Protein Function. This has concentrated on the E4 protein, which we have shown previously to bind keratin and certain cyclin dependent kinases to induce G2 arrest. Our current studies centre around the finding that E4 can assemble into amyloid fibrils, and that its function is modulated by phosphorylation and proteolytic cleavage. The finding that high-risk E4 contributes to viral genome amplification in model systems has prompted us to study the importance of the association between the HPV16 E4 protein and the viral replication factor E2. 2. Role of Viral Gene Products During Infection using Model Systems. To understand how viral protein function is modulated during infection, we have used raft culture and gene knock-outs. This system is also allowing us to examine the mechanisms that regulate normal HPV gene expression and to establish what factors are involved in the progression to high-grade neoplasia and cancer. Raft culture provides an important system for the validation of the results generated from the molecular studies described above. Where involvement of the immune system needs to be considered, we are using the rabbit oral papillomavirus model. This is particularly valuable in understanding the basis of viral latency. 3. Natural History of Infection in Humans. The third part of the work examines gene expression patterns in clinical tissue, as this is the gold standard that the molecular studies and the use of model systems must explain. Our goal is to understand the intermediate states that connect productive infection to cervical cancer, and to establish what factors may contribute to life cycle de-regulation in infected cervix. An important off-shoot of this work is the development of biomarker approaches for the evaluation of cervical neoplasia. The biomarker work is of relevance to industry, and we have close contacts with a number of diagnostic and vaccine companies and are currently involved in collaborative studies aimed at improving cervical diagnosis. In addition to the above, we have recently used intrabodies to inhibit HPV protein function in cells. This has contributed to our knowledge of which viral proteins are important for maintenance of the disease state.

Publications

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Borgogna C (2014) Improved detection reveals active ß-papillomavirus infection in skin lesions from kidney transplant recipients. in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

 
Description Cancer Research France
Geographic Reach Europe 
Policy Influence Type Membership of a guidance committee
Impact Funding Review Board advisor
 
Description Institute Scientific Review Committee
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
Impact Influence on Virology Research at the Pasteur Institute, Paris; ICGEB, Trieste; Leibniz Institute for Age Research, Jenna
 
Description NCRI workshop
Geographic Reach National 
Policy Influence Type Participation in a national consultation
Impact direction of research program influenced
 
Description NIHR evaluation of HPV testing
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
Impact decision as to whether to use HPV testing more widely within the NIH
 
Description Roche, SPMSD, Merck, GSK consultancy
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact Advice to many companies on the best use of diagnostics, and on the HPV vaccine and its implementation
 
Description Scientific Presentations to Clinical Audiences
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Major seminars to key societies involved in implementing new policies on cervical diagnostics. e.g. 1. 10th October 2015 The Biology of HPV Infection at the Cervix. Advances in HPV Diagnostics, Tokyo, Japan (Invited Lecture) 2. 17th April 2015 Molecular Markers in Pre-Invasive Disease. How can they help the Colposcopist? British Society for Colposcopy and Cervical Pathology Annual Meeting, Nottingham, UK. 3. 6th February 2015 The Natural History of HPV Infections Current Thinking - Viral Gene Expression & Disease. Main Conference, EUROGIN 2015 Congress on HPV Cancer, Sevilla, February 4-7, 2015
 
Description University College London-Project
Amount £36,800 (GBP)
Organisation University College London 
Sector Academic/University
Country United Kingdom
Start 01/2011 
End 12/2013
 
Description Wellcome-Research Training Fellowship
Amount £204,354 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2007 
End 12/2010
 
Description gsk-Collaborative Research Grant-2007
Amount £236,718 (GBP)
Organisation GlaxoSmithKline (GSK) 
Sector Private
Country Global
Start 01/2007 
End 12/2010
 
Description gsk-Collaborative Research Grant-2008
Amount £217,209 (GBP)
Organisation GlaxoSmithKline (GSK) 
Sector Private
Country Global
Start 01/2008 
End 12/2010
 
Description sanofi pasteu MSD Research Project 2011
Amount £17,226 (GBP)
Organisation Sanofi Pasteur MSD 
Sector Private
Country United Kingdom
Start 01/2011 
End 12/2012
 
Description sanofi pasteu MSD Research Project-2011
Amount £22,000 (GBP)
Organisation Sanofi Pasteur MSD 
Sector Private
Country United Kingdom
Start 01/2011 
End 12/2013
 
Description sanofi pasteu MSD-Research Project-2009
Amount £93,783 (GBP)
Organisation Sanofi Pasteur MSD 
Sector Private
Country United Kingdom
Start 01/2009 
End 12/2010
 
Title Improvements in or relating to screening for Papilloma virus 
Description Method for using the E4 biomarker as an aid to cervical diagnosis. This patent underlies the approx 500000 of research funding previously provided by GSK to our lab. This work is now the subject of a licence agreement with DDL in the Netherlands. Collaborative manuscripts published 
Type Of Material Technology assay or reagent 
Year Produced 2011 
Provided To Others? Yes  
Impact Material transferred to Ventana Medical Systems Inc, May 2008 and CytoImmune Diagnostics GmbH, Aug 2009 for use in vaccine production/diagnostics. Currently being evaluated with a view to development as a commercial diagnostic. Is in final stage of being picked up as a diagnostic test by DDL, The Netherlands. 
 
Title PAVE Papillomavirus Database 
Description Cofounder of the Papillomavirus data base now in widespread use by researchers in the HPV field. Updated annually 
Type Of Material Database/Collection of data 
Year Produced 2014 
Provided To Others? Yes  
Impact Ease of analysis of all papillomavirus sequences and other data including reviews by members of the PV research community. 
URL http://pave.niaid.nih.gov
 
Description Beta HPV + Skin Disease 
Organisation Queen Mary University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution analysis of Beta HPV infections in the skin using specific reagent.
Collaborator Contribution collection of clinical material
Impact expected publication
Start Year 2013
 
Description Beta HPV Disease 
Organisation University of Eastern Piedmont
Department Dermatology Clinic
Country Italy 
Sector Hospitals 
PI Contribution Experimental Design, Development of methodologies, analysis of clinical material
Collaborator Contribution Intellectual Discussion
Impact Manuscript for Virology Published
Start Year 2009
 
Description GSK-Collaborative Research Grant 2007-2008 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution We head the Papillomavirus life-cycle side of the studies and are concerned with establishing new reagents that allow the HPV life-cycle to be better understood and to provide insight into HPV biology. We have done a considerable amount of analysis on GSK-collected clinical material that has provided valuable data for GSK and a significan new body of information that helps us to better understand how HPVs work. Two GSK-funded members of the lab are currently in place at NIMR and are supervised by myself.
Collaborator Contribution Regular (monthly) meetings with collaborators on this project at Glaxo Smith Kline, Rixensart, and at Delft Diagnostic Laboratories, Holland. These meetings comprise scientific strategy discussions. Insight from scientists with clinical and diagnostic backgrounds are passed to us which enhances our understanding and the general quality of our work.
Impact Two manuscripts is now in the final stage of preparation and are planned for publication in 2010. Copies can be provided if necessary.
Start Year 2006
 
Description GSK-Collaborative Research Grant 2008-2009 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution We head the Papillomavirus life-cycle side of the studies and are concerned with establishing new reagents that allow the HPV life-cycle to be better understood and to provide insight into HPV biology. We have done a considerable amount of analysis on GSK-collected clinical material that has provided valuable data for GSK and a significan new body of information that helps us to better understand how HPVs work. Two GSK-funded members of the lab are currently in place at NIMR and are supervised by myself.
Collaborator Contribution Regular (monthly) meetings with collaborators on this project at Glaxo Smith Kline, Rixensart, and at Delft Diagnostic Laboratories, Holland. These meetings comprise scientific strategy discussions. Insight from scientists with clinical and diagnostic backgrounds are passed to us which enhances our understanding and the general quality of our work.
Impact Two manuscripts is now in the final stage of preparation and are planned for publication in 2010. Copies can be provided if necessary.
Start Year 2006
 
Description HPV Infection and Pathology 
Organisation DDL Diagnostic Laboratory
Country Netherlands 
Sector Private 
PI Contribution Initiation and development of laser capture methods as part of external project
Collaborator Contribution Intellectual discussion. Access to clinical community
Impact J Pathol. 2011 Nov 30. doi: 10.1002/path.3970. [Epub ahead of print]
Start Year 2010
 
Description ICGEB Trieste/Oncogene expression 
Organisation International Centre for Genetic Engineering and Biotechnology
Country Italy 
Sector Charity/Non Profit 
PI Contribution Hosting visitors from ICGEB. Providing advice and training in specific methods. Development of ideas through discussion.
Collaborator Contribution Discussion of scientific data and ideas. Acquisition of specific research skills.
Impact 19421149; 10. Gammoh, N., Isaacson, E., Doorbar, J and Banks, L. Inhibition of HPV16 E7 Oncogene Expression by E2. Oncogene (2009) 28, 2299-2304
 
Description Protein Engineering/Intrabodies 
Organisation Medical Research Council (MRC)
Department MRC Centre for Protein Engineering
Country United Kingdom 
Sector Public 
PI Contribution Driven research into the use of intrabodies in HPV therapy. This has now been followed up by other groups.
Collaborator Contribution Joint research publication. Scientific discussion and advice.
Impact 16324714; 19. Griffin, H., R. Elston, D. Jackson, K. Ansell, M. Coleman, G. Winter, and J. Doorbar. 2006. Inhibition of papillomavirus protein function in cervical cancer cells by intrabody targeting. J Mol Biol 355:360-78.
 
Description SPMSD Denmark 
Organisation Sanofi Pasteur MSD
Department Department of Gynaecology
Country United Kingdom 
Sector Private 
PI Contribution technology input and knowledge
Collaborator Contribution Intellectual input. Cross discipline research
Impact presentations at meetings. Eventually a manuscript.
Start Year 2014
 
Description SPMSD Lyon 
Organisation Sanofi Pasteur MSD
Country United Kingdom 
Sector Private 
PI Contribution project design and implementation
Collaborator Contribution Intellectual input. Access to new research area
Impact manuscript in viral latency published. Review in press
Start Year 2009
 
Description University of Otago/Immunology of Papillomaviruses 
Organisation University of Otago
Department Department of Microbiology & Immunology
Country New Zealand 
Sector Academic/University 
PI Contribution Hosted scientists from University of Otago (Leong,C-M and Hibma,M.) who have worked in our lab. Through discussion, we have developed the project with them and provided specific training in the use of approaches. We have provided archived clinical material and helped with HPV typing and immunostaining.
Collaborator Contribution This is a research collaboration in which researchers at the University of Otago (lead by Dr. Merilyn Hibma)contributed to a joint research project. This lead to a publication in 2009.
Impact 19759549 ; 7. Leong, C-M, Doorbar, J., Yoon, H-S, Hibma, M.H. Analysis of Langerhans cells in epidermis infected with human papillomavirus types from four genera. J. Invest. Dermatol. (2009) Sept 17 (Epub ahead of print)
 
Description University of Philadelphia/HPV11 life cycle 
Organisation Drexel University
Country United States 
Sector Academic/University 
PI Contribution Carrying out specific scientific experiments.
Collaborator Contribution Research discussions.
Impact 16687161; 17. Fang, L., L.R. Budgeon, J Doorbar, E.R. Briggs and MK Howett. 2006. The human papillomavirus type 11 E1^E4 protein is not essential for viral genome amplification. Virology 351:271-279
 
Description University of Queensland/L1 expression in G2 
Organisation University of Queensland
Department University of Queensland Diamantina Institute
Country Australia 
Sector Academic/University 
PI Contribution We have provided scientific input and carried out experiments at NIMR to complete aspects of the study.
Collaborator Contribution Research collaboration involving the interchange of ideas and the hosting of visitors from the Diamantina Institute at NIMR.
Impact Research manuscript just accepted for publication in Virology. 5. Ding, J., Doorbar, J., Li,B., Zhou, F., Gu, W., Zhao, L., Saunders, N.A., Frazer, I.H. and Zhao, K-N. Expression of papillomavirus L1 proteins is favoured in G2/M-like cells in differentiating keratinocytes. Virology (2010) in press
 
Title HPV identification 
Description Use of the E4 Human Papilloma Virus (HPV) marker to screen for precancerous lesions of the cervix and E4-specific antibody that could be used in screening. Patent granted in Europe, Canada, US, Japan and Australia. 
IP Reference US2003219726  
Protection Patent granted
Year Protection Granted
Licensed Yes
Impact collaborative research in place as a result and ongoing interest from diagnostic companies Roche, Becton Dickinson and DDL.
 
Title Scientific animations for public awareness 
Description Advanced version with descriptive menu. Animations of all aspects of HPV biology produced in conjunction with Joe Brock at MRC-NIMR and distributed widely to research, education and health care workers to enhance understanding of disease mechanisms and vaccine utility. 
Type Of Technology Software 
Year Produced 2014 
Impact Adding the animation to presentations has generally increased the status of the research group and its prominence worldwide. 
 
Description Colposcopy course - UCL 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Education into papillomavirus biology

Collaboration with clinical scientists
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description HPV training sessions for Clinical Scientists 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Seminar presentation followed by workshop discussions and often clinical collaborative work to answer research questions.

Many requests for slides and information and possible follow-up work to answer research questions.
Year(s) Of Engagement Activity Pre-2006,2006,2007,2008,
 
Description Health Professional Education 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Dissemination of knowledge to individuals who are interested in learning more about HPV in light of the new HPV vaccine

Valuable collaboration with clinical scientists set up.
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description Invited Presentations to Health Care Professionals, Medical Professionals and Researchers 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 1. January 31st 2007 HPV Infection and Human Disease. National Institute for Medical Research, London, UK. (Institute Seminar Series (Research Seminar))

2. February 20th 2007 E4 Function During HPV Infection. University of Sussex, Falmer, Brighton, UK. (Invited Research Seminar)

3. March 23rd 2007 The Papillomavirus Life Cycle. GlaxoSmithKline Biologicals, Rixensart, Belgium. (Invited Research Seminar)

4. March 28th 2007 Papillomavirus Replication: From Entry through to Exit. 160th meeting of the Society for General Microbiology, University of Manchester (Plenary Lecture)

5. April 26th 2007 The Biology of HPV Infection and Cervical Disease. The VI Conference of The Israeli Society of Gynecologic Oncology, Herzeliya, Israel. (Plenary Lecture)

6. May 9th 2007, September 24th 2007, October 17th 2007, November 26th 2007 HPV : the missing link. Preventing cervical cancer: a realistic goal?
One-day conference for Clinical Scientists and Health Care professionals organised by The Royal Society of Medicine to coincide with the introduction of the HPV vaccine in the UK. St Anne's College, Oxford, UK., University of Sussex, Brighton, UK., John Innes Centre, Norwich, UK., University of Birmingham, UK. (Invited Lectures)

7. May 25th 2007 Advances in the Molecular Biology of HPV Infection and its Application in Cervical Cancer Early Detection. International HPV Clinical Training and Scientific Workshop, University of Antioquia, Medellin, Columbia. (Plenary Lecture, Session Chair)

8. June 5th 2007 Papillomavirus Gene Expression and Protein Function. International Centre for Genetic Engineering and Biotechnology, Trieste, Italy. (Invited Research Seminar)

9. July 6th 2007 Molecular Basis of HPV-associated Disease. 31st British International Congress of Obstetrics & Gynaecology, ExCel Docklands, London (Invited Lecture)

10. July 10th 2007 HPV-Associated Disease and Intrabody Therapy. GlaxoSmithKline Medicines Research Centre, Stevenage, United Kingdom, (Invited Research Seminar)

11. October 9th 2007 Understanding the Biology of HPV Infection. NIBSC, Potters Bar, United Kingdom. (Invited Research Seminar)

12. October 20th 2007 Biology of HPV Infection and Persistence. Symposium on HPV infection and Associated Disease. Limassol, Cyprus. (Invited Lecture)

13. November 3rd 2007 The Human Papillomavirus Life Cycle. Clinical Workshop, 24th IPV Meeting, Beijing, China. (Invited Lecture, Session Chair)

14. December 7th 2007 Molecular Basis of HPV-Associated Disease. European Vaccine Symposium, Brussels, Belgium. (Invited Lecture)

15. February 21-22nd 2008 The Papillomavirus Life Cycle and Vaccine Effects. SPMSD European Expert Panel Meeting, Paris, France. (Invited Lecture)

16. March 5-8, 2008 Papillomavirus Infection and Disease. German Society of Virology Annual Meeting, Heidelberg, Germany. (Plenary Lecture)

17. May 2nd 2008 Understanding the molecular biology of human papillomavirus infection and cervical neoplasia. Griffith University, Gold Coast, Australia. (Invited Research Seminar)

18. May 5th 2008 Understanding the Papillomavirus Life Cycle in Infected Epithelium. University of Otago, Dunedin, New Zealand. (Invited Research Seminar)

19. May 6th 2008 Current Problems in Papillomavirus Research. Diamantina Institute, University of Queensland, Queensland, Australia. (Invited Research Seminar)

20. May 13th 2008 The Biology of Papillomavirus Infection. European Society of Pediatric Infectious Diseases Annual Meeting, Graz, Austria. (Invited Lecture)

21. May 15th 2008, June 5th 2008 Understanding HPV Infection and Vaccination. HPV Immunization Workshop. Royal Horticultural Halls, London, Vermont Hotel, Newcastle-on-Tyne (Invited Lectures)

22. May 19th 2008 The HPV Life Cycle; From Infection to Cervical Cancer. SPMSD European Expert Meeting, Sheraton Hotel, Frankfurt, Germany (Invited Lecture)

23. June 13th 2008 Molecular Understanding of Papillomaviruses and Neoplasia. Irish Colposcopy Training Course, Coombe Womens Hospital, Dublin, Ireland. (Invited Lecture)

24. September 18th 2008 Human Papillomavirus Infection and Vaccination, European Association of Dermatology and Venerology, Palais de Congress, Paris (Invited Lecture)

25. October 23rd 2008 Papillomavirus Life Cycle Events During Productive and Abortive Infection and During Viral Latency. 5th International HPV and Skin Cancer Conference, Heidelberg, Germany. (Invited Lecture)

26. November 27th 2008 The Papilomavirus Life Cycle and Human Disease. Institut Catala d'Oncologica, Barcelona, Spain. (Invited Lecture)

27. January 28th 2009 Papillomavirus Regulation and Deregulation. National Cancer Institute, Bethesda, Maryland, USA (Invited Research Seminar)

28. March 16th 2009 Papillomaviruses and Neoplastic Progression, ICGEB, Trieste, Italy (Invited Research Seminar)

29. May 7th 2009 The Biology of HPV and Disease, British Society for Colposcopy and Cervical Pathology (Annual Scientific Meeting), Dublin, Ireland. (Plenary Lecture)

30. May 1st 2009 Latent HPV Infection - Reactivation vs Reinfection. HPV Specialist Symposium, Copenhagen, Denmark (Invited Lecture)

31. May 11th 2009 The Future of Papillomavirus Research (the viral life cycle), 25th International Papillomavirus Meeting, Malmo, Sweden (Plenary Lecture, Session Chair)

32. June 24th 2009 The Biology of Human Papillomavirus Infection an Disease, University of York (Invited Research Seminar)

33. October 2nd 2009 How Papillomaviruses cause Warts, Neoplasia and Cancers, British Association of Sexual Health and HIV, Royal Society of Medicine, London, UK (Invited Lecture)

34. October 8th 2009 Papillomaviruses - How they cause warts and why some types cause cancers, UCL Virology Research Day, Royal Free Campus, London (Invited Research Seminar)

35. October 13th 2009 Understanding HPV and HPV Vaccines, 16th International Meeting of the European Society of Gynaecological Oncology, Belgrade, Serbia (Invited Lecture)

36. November 6th 2009 Human Papillomaviruses; Past, Present and Future, North London Colposcopy Society, Royal Free Hospital, London (Invited Research Seminar)

37. November 10th 2009 Human Papillomavirus Infection an Disease, Sanofi Pateur MSD, Lyon, France (Invited Research Seminar)

38. November 17th 2009 Understanding the Biology of HPV-Associated Disease, Fritz Lipmann Institute, Jena, Germany (Invited Research Seminar)

39. December 3rd 2009 Papillomavirus Regulation and De-regulation during Neoplastic Progression, Division of Virology, University of Tubingen, Germany (Invited Research Seminar)

40. February 3rd 2010 The Molecular Basis of Papillomavirus Infection and Disease, University of Leeds. (Invited Research Seminar)

41. February 15th 2010 Regulation and De-Regulation of The Human Papillomavirus Life Cycle, Infection and Cancer Symposium, DKFZ, Heidelberg, Germany. (Plenary Lecture)

42. February 17th 2010 Updating Papillomavirus Molecular Biology and Pathogenesis, Eurogin training course, Monaco (Invited Lecture, Session Chair)

43. March 6th & 7th 2010 1) Current thinking on Papillomavirus Infection, Lesion Formation, Regression and Latency. 2) Regulation of the normal Papillomavirus Life Cycle and Why Things Sometimes go Wrong. Second Advanced Summer School in Africa on Molecular Mechanisms of Virus Infection and Propogation. Hermanus, South Africa, March 6 -14th 2010 (Invited Lectures, Session Chair)

44. May 6th 2010 The Molecular Basis of Papillomavirus Infection and Disease, University of Piemonte Orientale, Novara, Italy. (Invited Research Seminar)

45. March 12th 2010 The Link between Viruses and Cancer. 1st Nordic Gynecologic Meeting on HPV Vaccination, Copenhagen, Denmark. (Invited Lecture)

46. May 27th 2010 Understanding the Biology of Human Papillomavirus Infection and Disease. University College Hospital, Cardiff, UK. (Invited Research Seminar)

47. April 9th 2010 The Biology and Role of HPV in Genital Infection. Irish Colposcopy Training Course, Coombe Womens Hospital, Dublin, Ireland. (Invited Lecture)

48. May 19th 2010 Viral Epithelial Interactions in Cervical HPV Infection. Oslo University Hospital, Norway (Invited Lecture)

49. June 2nd 2010 Biomarker Combinations for the Diagnosis of Cervical Disease, Becton Dickinson, Raleigh, USA. (Invited Lecture)

50. June 9th 2010 The Papillomavirus Life Cycle; gaps in knowledge and the use of model systems. Roche, Palo Alto, USA. (Invited Lecture)

51. June 10th 2010 Biomarker Combinations for the Diagnosis of Cervical Disease, Ventana Diagnostics, Tucson, USA. (Invited Lecture)

52. July 3rd 2010 Natural History of HPV Infection from the Biological Perspective. IPV Clinical Training Course, Montreal, Canada. (Invited Lecture)

53. July 7th 2010 The Natural History of Papilomavirus Disease. IPV Conference, Montreal, Canada. (Plenary Lecture, Session Chair)

54. July 26th 2010 HPV Pathogenesis. (two lectures). Principles of Sexually Transmitted Disease Course, Seattle, USA. (Invited Lecture)

55. July 27th 2010 Understanding the Biology of Human Papillomavirus Infection and Disease. Fred Hutchinson Cancer Research Centre, Seattle, USA. (Invited Research Seminar)

56. November 25/26th 2010 Molecular biology of human papillomavirus infection and cervical cancer; The papillomavirus life cycle; Papillomavirus life cycle organization and biomaker selection Regional Meeting on HPV, Izmir, Turkey. (Invited Lecture, Session Chair)

57. January 13th 2011 Papillomavirus Life Cycle Regulation in Infected Epithelium. ICGEB, Trieste, Italy. (Invited Research Seminar)

58. March 15th 2011 Regulation of the Papillomavirus Life Cycle in the Skin. Institute Pasteur, Paris, France. (Invited Research Seminar)

59. April 18th 2011 The Rational Selection of Biomarkers for HPV Diagnosis. Scottish HPV Investigators Meeting, Edinburgh, Scotland. (Invited Research Seminar)

60. June 28th 2011 Papillomavirus and Disease. Fortismere School Medical Society, East Finchley, London. (Invited Lecture)

61. July 4th, 5th, 6th 2011 Papillomaviruses, Therapy and Diagnostics. (four lectures) 14th World Congress of Cervical Pathology and Colposcopy, Rio be Janeiro, Brazil. (Invited Lectures, Session Chair)

62. September 13th 2011 How Papillomaviruses Cause Serious Human Disease. British Association of Sexual Health and HIV, Keele, UK. (Plenary Lecture)

63. November 9th 2011 HPV life-cycle regulation during productive infection, neoplasia and latency. Cancer Colloquia on HPV Therapeutics. St Andrews, Scotland. (Invited Research Seminar)

64. November 25th 2011 The Biology of HPV-Associated Disease. 2nd Colposcopy and Cervical Pathology Congress, Antalya, Turkey. (Invited Lecture, Session Chair)

65. February 7th 2012 The Life-Cycle of Mucosal and Cutaneous Papillomaviruses. Centre for Virus Research, Glasgow, UK. (Invited Research Seminar)

66. March 20th 2012 The Basis for Papillomavirus Latency. SPMSD Lyon, France. (Invited Lecture)

67. March 21th 2012 Alpha and Beta HPV types in latency, disease and cancers. CLARA Cancer Meeting, Lyon, France. (Invited Lecture)

68. April 20th 2012 HPV Disease Aetiology. 40th Annual Scientific Meeting. British Society for Colposcopy and Cervical Pathology, Newcastle, UK. (Invited Lecture)

69. July 7th 2012 The Biology of HPV Disease. Eurogin Conference on HPV-Associated Cancers. Prague, Czechoslovakia. (Invited Lecture)

70. September 24th 2012 HPV life-cycle regulation in the epithelium. Department of Medicine, Imperial College, London, UK. (Invited Research Seminar)

71. 19th October 2012 Beta and Alpha Papillomaviruses. 6th International Conference of HPV, Polyomavirus and UV Radiation in Skin Cancer. Berlin, Germany (Invited Lecture, Session Chair)

72. 26th October 2012 Understanding the Biology of Human Papillomavirus Infection and Disease. Viruses, Genes and Cancer Meeting. Venice, Italy (Plenary Lecture)

73. 15th November 2012 The HPV Life Cycle. NCRI Clinical Trials Meeting, Academy of Medical Sciences, London, UK. (Invited Lecture)

74. 30th November 2012 The Molecular Biology of HPV Infection. 28th International Papillomavirus Meeting, Clinical Workshop, San Juan, Puerto Rico, USA (Invited Lecture, Session Chair)

75. 25th January 2013 Papillomaviruses, Epithelial Differentiation and the Regulation of Productive Infection. ICGEB, Trieste, Italy. (Invited Research Seminar) Available on Itunes U.

76. 22nd June 2013 Development of an LSIL Biomarker for use in Conjunction with HSIL Biomarkers for Diagnosis of Cervical Disease Severity. 10th Congress of Colposcopy and Cervical Pathophysiology, Krakow, Poland (Invited Lecture)

77. 20th September 2013 The Human Papillomavirus Life Cycle; Regulation and Deregulation. Danish Cancer Research Centre, Copenhagen, Denmark. (Invited Research Seminar)

78. 3rd November 2013 Current Understanding of HPV Disease. Eurogin Conference on HPV-Disease. Florence, Italy. (Invited Lecture)

79. 10th April 2014 Life Cycle Strategies, Epithelial Tropisms and Disease Outcome. 7th International Conference of HPV, Polyomavirus and UV Radiation in Skin Cancer. Novarello Village, Novara, Italy. (Invited Lecture, Session Chair)

80. 28th May 2014 Use of Viral and Cellular Biomarker Combinations to Assess Disease Severity. 15th World Congress for Cervical Pathology and Colposcopy (IFCPC 2014). Queen Elizabeth 2nd Centre, London (Plenary Lecture)

81. 30th May 2014 1) The Papillomavirus Life Cycle, 2) The Role of Viral Biomarkers in the Detection of Premalignancies of Cervical Cancer, 3) HPV Latency, Molecular Mechanisms and Patterns of Gene Expression. IFCPC Molecular Markers Workshop, NIMR, London (Invited Lecture Series, Session Chair)

82. 2nd June 2014 HPV Diversity, Capsid Structure & Immune Recognition. SPMSD Advisory Board. Royal College of Physicians, St Andrews Place, Regent's Park, London NW1 4LE (Invited Lecture)

83. 3rd June 2014 HPV Life Cycle - An Overview. Abbott Molecular Symposium on Cervical Cancer Prevention and HPV - are we there yet? Midland Hotel, Peter St, Manchester (Invited Lecture)

84. 13th June 2014 Understanding the papillomavirus Life Cycle and Disease. Cancer and Development Graduate Research Symposium, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL Canada (Invited Research Seminar, Session Chair)

85. 23rd June Pathology Symposium Human Papillomavirus Protein Regulation & Function in the Epithelium. Annual Research Symposium, Li Ka Shing Centre, Cambridge Cancer Research UK. (Invited Research Seminar)

86. 24th June Reading Human Papillomavirus Life Cycle Regulation & Association with Cancer. School of Biological Sciences University of Reading. (Invited Research Seminar)

87. August 20, 2014. Viral Tropisms & the Site-Specific Development of HPV-Associated Neoplasias. 29th International Papillomavirus Conference & Clinical Workshop, Pre-Conference Clinical & Public Health Workshop, Washington State Convention Center (Invited Lecture)

88. August 24, 2014. The Natural History of HPV Infections Current Thinking. 29th International Papillomavirus Conference & Clinical Workshop, Main Conference, Washington State Convention Center (Invited Lecture, session chair)

89. 1st October 2014 The Role of Viral Biomarkers in the Detection of Premalignancies of Cervical Cancer. Erasmus Medical School, University of Rotterdam, The Netherlands. (Invited Research Seminar)

90. 6th November 2014 Pathogenesis of HPV-Related Neoplasia. European Anioscopy Meeting, Homerton Hospital, UK (Invited Lecture)

91. 20th & 21st November 2014 1) Biology and Life-Cycle of High and Low-Risk Human Papillomaviruses. 2) Biomarker Patterns in the Diagnosis of Cervical Neoplasia. ICGEB South American Workshop on HPV, University of Rosario, Rosario, Argentina. (Invited Research Seminar)

92. 4th February 2015 The Biology of HPV Infection at Different Epithelial Sites. Training Session, EUROGIN 2015 Congress on HPV Cancer, Sevilla, February 4-7, 2015 (Invited Lecture)

93. 6th February 2015 The Natural History of HPV Infections Current Thinking - Viral Gene Expression & Disease. Main Conference, EUROGIN 2015 Congress on HPV Cancer, Sevilla, February 4-7, 2015 (Invited Lecture, session chair)

94. 20th March 2015 The Natural History of HPV Infections. Current Thinking - Viral Gene Expression & Disease. German Society of Virology Meeting, Dusseldorf, Germany (Invited Lecture)

95. 17th April 2015 Molecular Markers in Pre-Invasive Disease. How can they help the Colposcopist? British Society for Colposcopy and Cervical Pathology Annual Meeting, Nottingham, UK. (Invited Research Seminar)

96. 9th Sept 2015 Papillomavirus Life Cycle Biology and Models of Disease. Huntingdon Life Sciences, Huntingdon, Cambridgeshire, UK. (Invited Research Seminar)

97. 17th September 2015 HPV Carcinogenesis: Step by Step. Clinical Workshop, 30th International Papillomavirus Conference & Clinical and Public Health Workshops, Lisbon, Portugal. (Invited Lecture)

98. 18th September 2015 Human Papillomavirus Molecular Biology & Pathogenesis. Main Conference 30th International Papillomavirus Conference & Clinical and Public Health Workshops (HPV 2015) (Invited Lecture)

99. 10th October 2015 The Biology of HPV Infection at the Cervix. Advances in HPV Diagnostics, Tokyo, Japan (Invited Lecture)

100. 15th October 2015 HPV Pathogenesis and the Basis of Disease. 2nd European Anioscopy Meeting, Homerton Hospital, London. (Invited Lecture)
Year(s) Of Engagement Activity Pre-2006,2006,2007,2008,
 
Description School visits/Events During National Science week 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Talks to school children at their schools. Workshop during science week at NIMR.

Generation of good links with the local community
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description Students - LSHTM, Imperial, UCL, Cambridge 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Lecture

Recruitment of students wishing to do PhD-level research
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description UCL and Imperial College Lecture Course 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact student learnt about papillomaviruses

recruitment of PhD student
Year(s) Of Engagement Activity Pre-2006,2006,2007,2008,