Table Of Content

Immunology of Human Papillomav iruses Im.munology of Human Papillomav iruses Edited by Margaret A. Stanley Department of Pathology University of Cambridge Cambridge, United Kingdom Springer Science+Business Media, LLC Library of Congress Cataloglng-ln-Publlcatlon Data Immunology of human papillomaviruses I edited by Margaret A. Stanley. p. cm. Includes bibl iographical references and index. 1. Papillomavirus diseases--Immunological aspects--Congresses. 1. Stanley, Margaret A. II. International Workshop an HPV Immunology (2nd , 1993 , Cambridge, Englandl [DNLM, 1. Papillomavirus, Human--immunology--congresses. 2. Papovaviridae Infections--immunology--congressBs. 3. Tumor Virus Infections--immunology--congresses. ew 165.5.P2 133 1994] QR201.P26156 1994 616' . O1 94--dc20 DNLM/DLC for Library of Congress 94-10556 CIP Proceedings of the Second International Workshop on HPV Immunology, held July 5-7, 1993, in Cambridge, United Kingdom ISBN 978-1-4613-6041-4 ISBN 978-1-4615-2449-6 (eBook) DOI 10.1007/978-1-4615-2449-6 ©1994 Springer Science+Business Media New York Originally published by Plenum Press,New York in 1994 Softcover reprint of the hardcover 1s t edition 1994 AU rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher PREFACE This volume represents a series of papers presented at the Second International Workshop on HPV Immunology held at the University of Cambridge July 5-7 1993. This Workshop and its predecessor held in Amsterdam in May 1992 were two of the major activities of the European Concerted Action "Immunology of Human Papillomavirus and Vaccine Development". The Concerted Action (CA) was supported by grants from the Commission of the European Communities (EC), the French Association for Cancer Research (ARC) and the European Association for Medical Research (EAMR). Twenty two laboratories throughout Europe and Scandinavia were members of the CA, the objectives of which were to develop collaborations, implement scientific exchanges and co-operate in a collective effort to develop vaccination strategies for HPV. HPV's are ubiquitous pathogens and evidence which has been accumulated over the past decade leaves little doubt that infection with certain HPV types (the so called "oncogenic HPV's" 16, 18 and their relatives) is the major risk factor in the development of cancer of the uterine cervix in women. Since an infectious agent, a virus, is implicated as the main aetiologic factor in this disease, the possibility is raised that if one could prevent HPV infection or treat established infections this would be an effective anti-cancer strategy against what is the commonest cancer in women worldwide. The development and implementation of such strategies requires an understanding of the host immune response to HPV, -the mechanisms underlying virus clearance (or the failure of these) and the establishment of protective immunity. Meeting these objectives for papillomaviruses is more difficult than for most other viral pathogens. Papillomaviruses are strictly intraepithelial pathogens: they are slow growing and establish chronic persistent lesions of skin and internal mucosae. Viral gene expression is confined to keratinocytes and is linked inextricably to the differentiation programme of the epithelium. Vegetative viral growth and virus assembly occur only in terminally differentiating cells far removed from systemic immune defences. These facets of papillomavirus biology and the consequences for the host response were addressed in presentations at the Workshop. The meeting format was one of keynote v talks from internationally recognised authorities, oral presentations and posters. The sessions covered HPV gene expression, T cell responses, epitope recognition, MHC expression, serology and vaccine development. The chapters in this book are representative of the plenary and poster sessions although not all the presentations are included. Contributions to the volume were made voluntarily in order to encourage presentation of unpublished data and to implement widespread participation. The meeting was highly successful due to the participation of those who attended and their truly international backgrounds. More than 150 people from Europe, USA, South America, South Mrica, China, India, South East Asia and Australasia attended. Particularly important were the keynote speakers David Lane, Peter Parham, Klas Klirre, Herman Waldmann, Lutz Gissmann, Kes Melief and Alan Rickinson who reviewed viral and cellular immunological topics of related importance thus broadening and informing the discussions for HPV. Particular thanks and acknowledgement must be given to: the Scientific Committee of Peter Beverley, Arsene Burny, Lutz Gissmann, Mark Krul, Kes Melief, Gim Meneguzzi, Bodil Norrild and Peter Stern for the content and balance of the programme: to Hans Stauss, Peter Beverley and Peter Stern of the local organising committee for their hard work: to Philip Stanley of CRTT Ltd for the smooth conference organisation and administration and to Ann Aves for indefatigable secretarial support. The Workshop and the pUblication of these Proceedings were generously supported by the EC, ARC and EAMR. I am grateful also to Cantab Pharmaceuticals Research pIc; British Biotechnology Ltd; The Wellcome Foundation; Roche Produpts Ltd and Murex Diagnostics Ltd for their sponsorship of the Workshop. Margaret Stanley Department of Pathology University of Cambridge vi CONTENTS HPV GENE EXPRESSION The Antibody Response Against p53 in Cancer Patients . . . . . . . . . . . . . . . . . . .. 1 G. Matlashewski Enhanced Production of Wild-Type p53 Inhibits Growth and Differentiation of Normal Foreskin Epithelial Cells but Not Cell Lines Containing Human Papillomavirus DNA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 9 C.D. Woodworth, H. Wang, L.M. Alvarez-Salas and J.A. DiPaolo Detection of Human Papillomavirus, Epstein Barr Virus and Elevated or Mutant p53 Expression in Squamous Cell Carcinoma of the Head and Neck. . . . 15 I. Lewensohn-Fuchs, E. Munck-Wikland, Z. Berke, G. Pallesen, A. Linde, K.G. Wiman and T. Dalianis Elevated Levels of the p53 Tumour Suppressor Gene in the Basal Layer of Recurrent Laryngeal Papillomas .............................. 21 L.J. Clark, K. MacKenzie and E.K. Parkinson Expression of the E6 and E7 Genes of Human Papillomaviruses in Tumours of Different Dignity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 25 T. Iftner, S. Bohm, M. Oft, S.P. Wilczynski and H. Pfister Detection of HPV- 16 E2 Protein in Cervical Keratinocytes . . . . . . . . . . . . . . . .. 33 V. Bouvard, A. Storey, D. Pim, E. Baraggino, U. Wisenfeld and L. Banks Evaluation of the Hybrid Capture Assay for Determination of Human Papilloma Virus ................................................. 39 K.F. Czerwenka, Y. Lu, F. Heuss, M. Manavi, J.W. Hosmann, D. Jelencic and E. Kubista Utilization of a PCR-based, Multiple Restriction Endonuclease Digest Technique for Enhanced Detection and Typing of HPV from Clinical Samples ..... 45 E. Epsaro, J. Burton, S. Mathieson, J. Merola and J.A. Sands A Gene Cassette for High Level Expression of the LI Capsid Protein of HPV -16 in Heterologous Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 51 S.R. Kelsall and.J.K. Kulski Genotyping of Human Papillomavirus (HPV) by Single-Strand Conformational Polymorphism (SSCP) ..................................... 55 I. Zehbe, E. Rylander, J. SiillstrOm and E. Wilander vii Human Papillomavirus Infection in Women with Cervical Cancer but without Cytological Abnormalities in the Preceding Years .. . . . . . . . . . . . . . . .. 59 M. Chabaud, N. Munoz, M.e. Cottu, P. Coursaget, P. Anthonioz, N. Day and E. MacGregor HPV Infection and Carcinomas of the Larynx . . . . . . . . . . . . . . . . . . . . . . . . .. 63 o. Arndt, J. Brock, I. Bauer and G. Kundt Perinatal Transmission and Persistence of the Cancer Associated Human PapiUomaviruses ......................................... 71 F. Pakarian, J. Kaye, J. Cason, B. KeU, R. Jewers, K.S. Raju and J.M. Best HPV -DNA on Colpocytological Smears from HIV Positive Females 75 R. Zarcone HUMORAL RESPONSES TO HPV Humoral Immune Response to Genital Human Papillomavirus Infections 81 L. Gissmann HPV 16 Antibodies in Cervical Cancer Patients and Healthy Control Women . . .. 85 V. Vonka, E. Hamsikovli, J. Novak, V. Hofinannovli, N. Munoz, S. de Sanjose, K. Shah and Z. Roth Prevalence of Antibodies Against Defmed HPV Epitopes Among Incident Cases of Cervical Neoplasia: Current Status and Concepts. . . . . . . . . . . . . . . .. 91 L. DiUner and J. Dillner Serological Response to HPV 16 Infection ........................... 103 A Di Lonardo, M.S. Campo and M.L. Marcante Detection of Antibodies to Ll, L2, and E4 Gene Products of Human Papillomavirus Types 6, 11, and 16 among HPV Infected Patients and Controls . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 109 P. Le Cann, D. LebouUeux, C. Bernard, C. Calvet, M.C. Legrand, G. Lesage, E. Postec, e. Mougin, J. Moutou and P. Coursaget IgG Antibodies to Human Papillomavirus Type 16 and Serum Retinol May Jointly Protect against Cervical Neoplasia. . . . . . . . . . . . . . . . . . . . . .. 113 M. Lehinten, J. Dillner, A Aromaa, R-K. Aaran, T. Hakulinen, P. Knekt, P. Leinikki, T. Luostarinen, J. Maatela, J. Paavonen and M. Hakama Prognostic Significance of Antibodies to HPV -16 E71E4 Proteins and Fragments of Cytokeratin 19 in Invasive Cervical Carcinoma. . . . . . . . . . . . . . . .. 119 K.N. Gaarenstroom, J.M.G. Bonfrer, G.G. Kenter, e.M. Korse, Th.J.M. Helmerhorst and J.B. Trimbos Development of Serological Assays for Detection of Anti-HPV-16 E6 and E7 Antibodies ................... ,........................ 125 AK. Ghosh, S.N. Stacey, L.R. Zavaleta, N.K. Smith, J.R. Arrand and P.L. Stern Detection by ELISA Test of Antibodies to Human Papillomavirus (HPV) Type 16 E7 in Patients with Benign or Malignant Papillomas from Skin or Mucosa .............................................. 133 Y. Chardonnet, A Janiaud, J.J. Chomel, J. Viac, S. Euvrard, D. Schmitt and M. Aymard viii Seroreactivity to a L2-derived Synthetic Peptide Correlates with the Number of Surgery-Necessitating Recurrences in Patients with Laryngeal papillomatosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 139 R. Tachezy, E. Hamsikova, J. Valvoda, J. Betka, R.D. Burk, V. Vonka and M.A. Van Ranst Comparison of p V Conformational Epitopes Expressed by L1 Proteins in Mammalian (COS) and Insect (Sf9)Cells . . . . . . . . . . . . . . . . . . . . . .. 147 S-J. Ghim, R. Schlegel, J.F. Hines, N.D. Christensen, J. Kreider and A. Bennett Jenson Detection of Class-Specific Antibodies to Baculovirus-Derived Human Papillomarvirus Type 16 (HPV-16) Capsid Proteins. . . . . . . . . . . . . . . . 155 J. Cason, P.K. Kambo, B. Shergill, J. Bible, B. Kell, R.J. Jewers and 1M. Best CELL MEDIAT ED IMMUNITY TO HPV Evolution of Class I HLA antigen Presenting Molecules. . . . . . . . . . . . . . . . .. 161 P.Parham Major Histocompatibility Complex (MHC) Expression and Antigen Presentation in Cervical Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 173 J.S. Bartholomew, S.N. Stacey, B. Coles, M. Duggan-Keen, P.A. Dyer, S.S. Glew, P.J. Keating, J.R. Arrand and P.L. Stern Analysis of MHC Class I Expression in HPV 16 Positive Cervical Carcinomas, in Relation to c-myc Overexpression .......................... 181 F.V. Cromme, P.J.F Snijders, A.J.C. van den Brule, M.J. Stukart, P. Kenemans, C.J.L.M. Meijer and J.M.M. Walboomers Immunogenetic Study of Women with HPV Related Cancer of the Uterine Cervix ............................................... 189 P. Tenti, M. Martinetti, S. Romagnoli, E. Silini, C. Pizzochero, R. Zappatore, L. Babilonti, L. Carnevali and M. Cuccia Recurrent Respiratory Papillomatosis (RRP): Enriched HLA DQw3 Phenotype and Decreased Class I MHC Expression ....................... 195 V.R. Bonagura, M.E. O'Reilly, A.L. Abramson and B.M. Steinberg HPV 16-Derived Synthetic Peptides with Ability to Upregulate MHC Class I Expression on RMA-S or T2 Cells as Detected by Enzyme Immunoassay . .. 201 J. Dillner Regulation of MHC Class I, Class IT and ICAM-1 Expression by Cytokines and Retinoids in HPV -Harboring Keratinocyte Lines .. . . . . . . . . . . . . . . .. 207 S. Majewski, F. Breitburd, G. Orth and S. Jablonska Murine Cytotoxic T Cell Responses to Human Papillomavirus E7 Protein ..... 213 E. Sadovnikova, X. Xhu, S.M. Collins, P. Beverley and H.J. Stauss Immune Response to Human Papillomavirus Type 16 E6 Oncoprotein ....... , 219 L. Gao, B. Chain, C. Sinclair, L. Crawford, J. Zhou, J. Morris, X. Xhu, H. Stauss and P.C.L. Beverley ix Human Cytotoxic T Cell Epitopes in HPV 11: Relationships Between Allele- Specific Motifs, HLA Binding and Stimulation In Vitro ........... " 227 H. Davies, 1. Tarpey, S. Stacey, J. Hickling, J. Bartholomew, H. Birley, A Renton and A. McIndoe An Imunodominant Region in HPV16.L1 Identified by T Cell Responses in Patients with Cervical Dysplasias ............................ 233 P.S. Shepherd, AJ. Rowe, J.e. Cridland, M.G. Chapman, J.e. Luxton and L.S. Rayfield Immunological Aspects of Cervical Carcinoma ...................... .. 243 C.G.J.M. Rilders, J.D.H. van Eendenburg, Y. Nooyen and G.J. Fleuren Analysis of Tumour-Infiltrating Lymphocytes in Cervical Carcinoma. . . . . . . .. 249 AK. Ghosh, S. Glenville, J. Bartholomew and P.L. Stem Lymphocyte-Mediated Natural Cytotoxicity to HPV16 Infected Cervical Keratinocytes .......................................... 255 R. Wu, N. Coleman, G. Higgins, E. Choolun and M.A Stanley ANIMAL MODELS AND THERAPEUTIC STRATEGIES Skin Test Reactivity to Papilloma Cells is Long Lasting in Domestic Rabbits after Regression of Cottontail Rabbit Papillomavirus Induced Papillomas 259 R.M. Hopfl, N.D. Christensen, K. Heim and J.W. Kreider Modulation of the DTH Response to HPV 16 E7 ...................... 267 M. Chambers, Z. Wei, N. Coleman, A Nash and M. Stanley Fine Characterization of the HPVl6 E7 49-57 Tumor Protective Cytotoxic T Cell Epitope "RAHYNIVTF" . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 275 M.C.W. Feltkamp, M.P.M. Vierboom, J. ter Schegget, e.J.M. Melief and W.MKast Vaccination of Cattle With L2 Protein Prevents BPV- 4 Infection . . . . . . . . . . .. 283 G.M. McGarvie, L.M. Chandrachud, J.M. Gaukroger, G.J. Grindlay, B.W. O'Neil, J.W. Baird, E.R. Wagner, W.F.H. Jarrett and M.S. Campo Immune Responses to HPV 16 E7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 291 M.H. Hibma, M. Tommasino, G. Van Nest, S.J. Ely, M. Contomi, R.P. Rappuoli and L.V. Crawford Use of Double aro Salmonella Mutants to Stably Express HPV16 E7 Protein Epitopes Carried by HBV Core Antigen. . . . . . . . . . . . . . . . . . . . . . .. 299 P. Londono, R. Tindle, 1. Frazer, S. Chatfield and G. Dougan An Experimental Tetracycline and Vitamin A Therapy of HPV Infections of the Lower Female Genital Tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 305 J. Madej, A Basta, G. Madej Jnr. and M Strama Retinoids and IFN-a. Synergistically Decrease Tumor Cell-Induced Angiogenesis and Stimulate Lymphocyte Induced Angiogenesis ............... .. 309 S. Majewski, A Szmurlo, M. Marczak, M. Malejczyk, M. Noszczyk, W. Bollag and S. Jablonska x Release of Soluble Tumor Necrosis Factor-a (TNF-a) Receptor by HPV- Associated Neoplastic Cells ................................ 315 J. Malejczyk, M. Malejczyk, S. Majewski, A. Hyc, F. Breitburd, G. Orth and S. Jablonska Contributors Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 321 Subject Index ................................................ 323 xi