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 [email protected] 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 de 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. Part 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 2University of Rio Grande do Norte State Brazil 1. Introduction The human papillomavirus (HPV) is one of the most common causes of sexually transmitted disease in both men and women around the world, especially in developing countries, where the prevalence of asymptomatic infection varies from 2 to 44%, depending on the population and studied region (Sanjosé et al., 2007). Most HPV infection is transient and some studies show that the majority of sexually active individuals are exposed to and acquire infection from this virus at some phase in their lives (Baseman and Koutsky, 2005; Trottier and Franco, 2006). HPV infection is more prevalent in young adults, at the beginning of their sexual activity, with a subsequent decline in the prevalence rate with increasing age, likely as a result of development of an immune response against the virus and reduction of sexual activity (Castle et al., 2005; Fernandes et al., 2009; Chan et al., 2010). HPV can infect basal epithelial cells of the skin or inner-lining tissues and are categorized as cutaneous types or mucosal types. Cutaneous types are epidermotropic and infect the keratinized surface of the skin, targeting the skin of the hands and feet. Mucosal types infect the lining of the mouth, throat, respiratory, or anogenital tract epithelium (Burd, 2003). Some HPVs are associated with warts while others have been well established as the main risk factor of invasive cervical cancers and their associated pre-cancerous lesions (Clifford et al., 2005; Zekri et al., 2006; Muñoz et al., 2006). However, only few HPV-infected individuals progress to invasive cervical cancer (Burd, 2003). Most infected individuals eliminate the virus without developing recognized clinical manifestation. (Bosch et al., 2008). Today, more than 150 different HPV types have been cataloged and about 40 can infect the epithelial lining of the anogenital tract and other mucosal areas of the human body. Based on their association with cervical cancer and precursor lesions, HPVs can also be classified as high-risk (HR-HPV) and low-risk (LR-HPV) oncogenic types. LR-HPV types, such as HPV 6 and 11, can cause common genital warts or benign hyperproliferative lesions with very limited tendency to malignant progression, while infection with HR-HPV types, highlighting HPV 16 and 18, is associated with the occurrence of pre-malignant and malignant cervical lesions (Muñoz et al., 2003; Bosch et al., 2002; Bosch et al., 2008). HR-HPV types are also associated with many penile, vulvar, anal, and head and neck