HUMAN PAPILLOMAVIRUS AND RELATED DISEASES – FROM BENCH TO BEDSIDE A CLINICAL PERSPECTIVE Edited by Davy Vanden Broeck Human Papillomavirus and Related Diseases – From Bench to Bedside – A Clinical Perspective Edited by Davy Vanden Broeck Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Ivona Lovric Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published January, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Human Papillomavirus and Related Diseases – From Bench to Bedside – A Clinical Perspective, Edited by Davy Vanden Broeck p. cm. ISBN 978-953-307-860-1 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Clinical Aspects of Human Papillomavirus Related Diseases 1 Chapter 1 Human Papillomavirus: Biology and Pathogenesis 3 José Veríssimo Fernandes and Thales Allyrio Araújo de Medeiros Fernandes Chapter 2 Immunohistochemistry in the Diagnosis of Squamous Intraepithelial Lesions of the Uterine Cervix 41 Evanthia A. Kostopoulou and George Koukoulis Chapter 3 Screening Methods in Prevention of Cervical Cancer 65 Robert Koiss Chapter 4 Clinical Manifestations of Genital HPV Infection 83 Edison Natal Fedrizzi Part 2 Human Papillomavirus Vaccines 99 Chapter 5 Development of New Human Papillomavirus Vaccines 101 Carmen Rodríguez-Cerdeira, Silvia Díez-Moreno, E. Sánchez and Alfonso Alba Chapter 6 Current Insight into Anti-HPV Immune Responses and Lessons for Prophylactic and Therapeutic Vaccines 125 Isabelle Bourgault-Villada and Simon Jacobelli Chapter 7 Plant Production of Vaccine Against HPV: A New Perspectives 147 Markéta Šmídková, Marcela Holá, Jitka Brouzdová and Karel J. Angelis Chapter 8 Development of Vaccines and Gene Therapy Against HPV Infection and Cervical Cancer 177 Zoraya De Guglielmo Cróquer and Armando Rodríguez Bermúdez VI Contents Part 3 Human Papillomavirus in Non-Uterine Disease 195 Chapter 9 Epidemiology of HPV in Head and Neck Cancer 197 Márcio Campos Oliveira, Maria da Conceição Andrade and Fabrício dos Santos Menezes Chapter 10 Implications of Human Papillomavirus Infections in the Biology of Head and Neck Cancers 221 Descamps Géraldine, Duray Anaëlle, Delvenne Philippe and Saussez Sven Chapter 11 The Role of Human Papillomavirus in Head and Neck Cancers 279 Lucinei Roberto Oliveira, Andrielle Castilho-Fernandes, Alícia Greyce Turatti Pessolato, Régia Caroline Peixoto Lira, João Paulo Oliveira-Costa, Luciana Souza Chavasco, Fabiana Alves Miranda, Ivan de Oliveira Pereira, Edson Garcia Soares and Alfredo Ribeiro-Silva Chapter 12 Human Papillomavirus in Donor Semen in Belgium 305 K.W.M. D’Hauwers, W.A.A. Tjalma, U. Punjabi and C.E. Depuydt Chapter 13 The Impact of Human Papillomavirus on Cancer Risk in Penile Cancer 319 Angela Adamski da Silva Reis and Aparecido Divino da Cruz Preface Cervical cancer is the second most prevalent cancer among women worldwide, mainly affecting young women. Infection with Human Papilloma Virus (HPV) has been identified as the causal agent for this condition. The natural history of cervical cancer is characterized by slow disease progression, generally taking over 10 years, from the initial infection with HPV, to the diagnosis of cancer. In essence, cervical cancer is a preventable disease, and treatable if diagnosed in early stage. Historically, the introduction of the Pap smear has markedly reduced the number of new cases in countries with an effective prevention program. The burden of disease is highest in developing countries, with peak incidence in Eastern Africa. Recently, prophylactic vaccines became available, equally contributing to a better disease prevention. Unfortunately, the global burden of disease is still very high. In the first section of this book, clinical aspects of HPV related disease are highlighted. Innovative clinical diagnostic tools are discussed and Dr Fedrizzi has provided a highly illustrative contribution on the clinical manifestation of HPV related disease. The introduction of the HPV prophylactic vaccine has been an important recent development in the fight against cervical cancer. The second section focuses on HPV vaccine related issues. Immune responses of the current vaccine are presented by Dr Bourgault-Villada, and options for the next generation vaccines, or more efficient production strategies, are discussed. Although HPV is most prominently known from its role in cervical carcinogenesis, the virus is also involved in other conditions. In the third section, HPV in non-uterine disease is discussed. Epidemiology and role of HPV in head-and-neck tumors are addressed. HPV also affects men, and this section covers the impact of HPV on penile cancers and its prevalence in semen. This book will be a useful tool for both researchers and clinicians dealing with cervical cancer, and it will provide them with the latest information in this field. Dr Davy Vanden Broeck, MSc, PhD Team Leader HPV/Cervical Cancer Research International Centre for Reproductive Health Ghent University Belgium X Preface Acknowledgements The editor of this book would like to express sincere thanks to all authors for their high quality contributions. The editor expresses the gratefulness to Ms. Bojana Zelenika and Ms. Ivona Lovric, process managers, for their continued cooperation. [...]... and neck carcinomas, and contribute to over 40% of oral cancers (Stanley, 2010) 4 Human Papillomavirus and Related Diseases – From Bench to Bedside – A Clinical Perspective Persistent infection with HR-HPV is unequivocally established as a necessary cause of cervival cancer (Trottier & Franco, 2006) The critical molecules for initiation and progression of this cancer are the oncoproteins E5, E6, and. .. proteins L1 and L2, which join to assemble the capsids and to form virions (Stanley et al., 2007) 2.2 Functions of viral proteins E1 Protein The E1 protein represents one of the the most conserved proteins among different HPV types It has DNA-binding functions and a binding site in the origin of replication localized 6 Human Papillomavirus and Related Diseases – From Bench to Bedside – A Clinical Perspective. .. replication 10 Human Papillomavirus and Related Diseases – From Bench to Bedside – A Clinical Perspective (McLaughlin-Drubin et al., 2008), and E7-HDAC binding facilitates HDAC removal at promoters to activate transcription (Longworth & Laimins, 2004) Another major apoptotic pathway targeted by HPV proteins is anoikis, a form of apoptosis that is triggered when normal cells attempt to divide in the... cells, and this contributes to immune avasion and persistence (Bodily & Laimins, 2011) 14 Human Papillomavirus and Related Diseases – From Bench to Bedside – A Clinical Perspective The maintenance of the viral episome in basal cells is the basic function of the early or maintenance phase of the viral cycle The expression of E6, E7, E1, and E2 are necessary for continued episomal maintenance E1 and E2... (TZ), located in the boundary 12 Human Papillomavirus and Related Diseases – From Bench to Bedside – A Clinical Perspective between the squamous epithelium of ectocervix and the columnar epithelium of endocervix Basal cells in the TZ retain the ability to differentiate, a property required for virion production (Crum & McKeon, 2010) The basal cells in TZ are more susceptible to HPV infection in that there... 1 Clinical Aspects of Human Papillomavirus Related Diseases 1 Human Papillomavirus: Biology and Pathogenesis José Veríssimo Fernandes1 and Thales Allyrio Araújo de Medeiros Fernandes2 1Federal University of Rio Grande do Norte of Rio Grande do Norte State Brazil 2University 1 Introduction The human papillomavirus (HPV) is one of the most common causes of sexually transmitted disease in both men and. .. HR-HPV is capable of binding to the core 22 Human Papillomavirus and Related Diseases – From Bench to Bedside – A Clinical Perspective region of p53 and this binding of the core region is required for p53 degradation mediated by E6 Three other mechanisms have been proposed to explain the interaction of the viral E6 protein with p53 The first is by inhibiting the binding of p53 to its site-specific DNA... that regulates growth factor receptors, is also a PDZ protein that binds and is disrupted by E6 (Jing et al., 2007; Spanos et al., 2008) 24 Human Papillomavirus and Related Diseases – From Bench to Bedside – A Clinical Perspective 5.4.3 The role of the E7 protein HR-HPVE7 proteins destabilize pRb through its proteosomal degradation via a mechanism that involves association with and reprogramming of the... fusion HR-HPV E5-induced and cell cycle deregulation seems to have an important role in 8 Human Papillomavirus and Related Diseases – From Bench to Bedside – A Clinical Perspective the early stages of the transformation process This suggests that HR-HPV E5-induced cell fusion can be a critical event in the early stage of the development of HPV-associated cervical cancer (Gao and Zheng et al., 2010)... cellmediated immune response and is accompanied by interaction of CD8+ and CD4+ limphocytic Langerhans cells (LCs) are the major dendritic cells (DCs) found in squamous epithelia, and these are probably responsible for triggering an anti-HPV immune response 18 Human Papillomavirus and Related Diseases – From Bench to Bedside – A Clinical Perspective The function of LCs is disrupted by HPV at several levels . HUMAN PAPILLOMAVIRUS AND RELATED DISEASES – FROM BENCH TO BEDSIDE A CLINICAL PERSPECTIVE Edited by Davy Vanden Broeck Human Papillomavirus and Related Diseases –. vulvar, anal, and head and neck carcinomas, and contribute to over 40% of oral cancers (Stanley, 2010). Human Papillomavirus and Related Diseases – From Bench to Bedside – A Clinical Perspective. hard copies can be obtained from orders@intechweb.org Human Papillomavirus and Related Diseases – From Bench to Bedside – A Clinical Perspective, Edited by Davy Vanden Broeck p. cm. ISBN