Book Review

Human Cancer Viruses: Principles of Transformation and Pathogenesis

N Engl J Med 2009; 360:312-313January 15, 2009

Article

Human Cancer Viruses: Principles of Transformation and Pathogenesis
(Translational Research in Biomedicine. Vol. 1.) Edited by John Nicholas, Kuan-Teh Jeang, and T.-C. Wu. 244 pp., illustrated. Basel, Switzerland, Karger, 2008. $212. ISBN: 978-3-8055-8576-7 (cloth); 978-3-8055-8577-4 (e-book).

Viruses are responsible for 20% of malignant conditions in humans, including some of the most common cancers worldwide, and are especially common in immunosuppressed patients. The identification of viruses associated with cancers may provide prognostic information or alternative treatments. Moreover, vaccines are now available for two classes of viruses that are associated with cancer: hepatitis B virus and human papilloma viruses (HPV). With exciting new molecular approaches for virus discovery, the number of cancers that can be linked to viruses with certainty will grow in the next few years.

In light of these facts, the publication of this book — the first volume of a new series in translational biomedicine from Karger — is timely and important. The authors delve into the molecular mechanisms that underlie virus-associated malignant conditions, including those that are the result of induction of preneoplastic dysplastic conditions, infection of cancer stem cells, or paracrine inflammatory effects. The preface is essential reading; thereafter, the order in which the chapters are read is unimportant. The central theme of the book is the analysis of putative intracellular signaling pathways that are involved in viral oncogenesis, and many clear figures and tables are included. In contrast, there is less discussion of animal models, a vexing limitation in studies of human cancer viruses, which generally do not infect mice or most other experimental animals. There is also limited information from translational science studies that emanate from clinical trials conducted with patients who have virus-associated malignant conditions.

The book includes one to three chapters on each human oncogenic virus. There is some redundancy in the chapters on hepatitis B virus and human T-cell leukemia virus because the contributions come from different groups of authors. Most of the chapters are terse but comprehensive overviews of the molecular biology of oncogenic viruses. In addition, there are chapters on HPV vaccines and the molecular epidemiology of HPV and on diseases associated with Epstein–Barr virus and Kaposi's sarcoma–associated herpesvirus. The author of the chapter on the epidemiology of HPV describes the worldwide prevalence of oncogenic HPV strains that are associated with cervical dysplasia and cancer, anal carcinoma, and a large proportion of oropharyngeal carcinomas. The activity of current vaccines and the advantages of different approaches in the development of preventive and therapeutic vaccines are described in another chapter. The chapters on Epstein–Barr virus and Kaposi's sarcoma–associated herpesvirus are concise, clear, comprehensive, and well written, and their authors contrast the oncogenic mechanisms of these two different, but related, viruses.

The chapter on hepatitis C virus is longer than other chapters, with less emphasis on molecular biology, but the author includes detailed information on amino acid residues that vary between strains and those that are implicated in resistance to inhibitors of viral polymerase and protease. Although this information will be valuable to those who are involved in drug development, it is excessive for most readers. The chapters on human T-cell leukemia virus are outstanding reviews of the function of individual gene products and of the genetic instability that is induced by the viral oncoprotein Tax, but the authors could have discussed new approaches to prevention and treatment further.

I would recommend that the editors of the next edition of this book include an introductory chapter covering the highlights of the 44-year history of human tumor viruses, including technical advances, descriptions of studies on viruses that led to new insights into the biology of neoplasia in general, and pitfalls. I would also suggest an additional chapter focused on a relative of xenotropic murine leukemia virus that is associated with human prostate cancer, and another chapter on a polyoma virus that is associated with Merkel's neuroendocrine carcinoma. The discoveries of these two viruses highlight new approaches with virus gene chips, high-throughput sequences, and techniques for virus isolation and polymerase chain reaction.

This book is a valuable and unique resource for students, postdoctoral fellows, and physicians who work with oncogenic viruses in the laboratory or in the clinic. It is unique and current, published on the heels of the approval of the HPV vaccine and the awarding of the 2008 Nobel Prize in Physiology or Medicine for the discoveries of the global viral pathogens HPV and HIV.

Lee Ratner, M.D., Ph.D.
Washington University School of Medicine, St. Louis, MO 63110
lratner@dom.wustl.edu