Review of DNA tumour viruses

Do we need another book on DNA tumour viruses?

A lot of water has flowed under the bridge since the initial epidemiological observation made by the physician Domenico Rigoni-Stern in 1842 who, analysing death certificates for women of Verona in the years from 1760 to 1839, noted that nuns and unmarried women had a lower risk of cervical cancer compared to married women, suggesting that the development of cervical cancer is related to sexual contact. Thus, the notion that a transmissible agent might play a role in some types of human cancer was dated back before the discovery of viruses. It was in 1911 that Peyton Rous isolated a filterable agent in a chicken sarcoma that became known as Rous sarcoma virus (RSV), discovering a virus that may cause cancer in animals. Fifty-five years later Rous obtained the Nobel Prize for his discovery and 42 years passed before the same award was assigned to Harald zur Hausen for the discovery that particular types of human papillomavirus (HPV) may cause cervical cancer. In between and after these pivotal achievements, researches on tumor viruses have produced fundamental discovery not only strictly on cancer development but also on molecular biology (i.e. discovery of RNA splicing in Adenoviruses). As a consequence, you can imagine that rivers of articles and books have been written about viruses and cancer. However, discoveries continuously flow as water in a river and new articles and books should catch those important and new one.

The book Edited by Sally Roberts and published by Caister Academic Press is depicting the landscape of DNA viruses associated with human tumours highlighting and catching the most important information.

The structure of the book

The book is structured as an up-to-date textbook-like piece and subdivision in chapters reflects a precise indication about what is really important in the current research of the burden of cancers attributable to DNA tumour viruses. As a consequence, we don’t have only chapters obviously related to the single DNA tumour virus, but also separate ones dealing with preventive intervention, global epidemiological data and specific interaction with the host DNA damage response. In addition, in the perspective of a careful evaluation of what is useful for understanding the interactions between DNA tumor viruses and the cell, there is also a chapter dedicated to adenoviruses. Indeed, much of what we know about viral carcinogenesis comes from studies on adenoviruses that are not cancer viruses for humans but are for experimental animals. The quality of authors guarantees to receive all timely and important information about molecular pathogenesis, vaccine development, and possible new therapies (i.e. adenovirus vectors as effective cancer therapeutics). This last aspect of new therapies emerge as a consequence of new discovery in DNA tumor virus interaction with several cellular pathways that are punctually evidenced by the authors within the chapters. Finally, a particular emphasis was given to the preventive aspects of DNA tumor viruses with dedicated chapters to HPV, HBV and EBV prophylactic and therapeutic vaccine, rendering this volume very interesting for “vaccinologists”.

Review by chapters

Since Rigoni-Stern’s studies, epidemiologists have played a key role in the definition of tumors that could be associated with infections (not just viral) and at the same time have helped to indicate the correct study methodologies to associate a virus with a particular type of cancer. In this light, the first chapter of the book is describing the epidemiological evidence of viral carcinogenesis built over time in relation to different tumors and is summarizing for each infectious agent and cancer site, the body of epidemiological evidence supporting our estimates of the attributable fractions. All the data are presented with well-defined figures and tables. In the second chapter, Sally Roberts and co-authors made a synthetic and exhaustive overview of key HPV life cycle events and the models used to interrogate virus-host interplay. In particular, very appreciable are paragraphs dealing with the use of animal PV and cell-based tissue culture models of the virus life cycle, combined with the generation of recombinant virions for infection studies, that revealed much about the complexities of the HPV life cycle. This complexity of HPV is further strengthened by Massimo Tommasino, in the following chapter by introducing difference among genera in relationship to transformation. This chapter gives us the most important information about the principal virus oncogenes, the E6 and E7 oncoproteins of HPV. Chapter 4 moves to a different virus, the Hepatitis B virus. A very comprehensive synopsis of mechanisms that are contributing to the progression and development of HBV-associated HCC, as well as established and emerging anti-HBV therapy strategies, are presented together with an efficacious and concise number of figures and tables. New therapeutic options like CRISPR/CAS targeting and HBV capsid-assembling inhibitors are discussed and a paragraph is dedicated to preventive vaccine. This last issue is more detailed described in the chapter 5 together with preventive vaccines for HPV. Both vaccines represent the major achievements reached in the fight of cancer. In the spirit of being critical I would have expected some mention of progress with therapeutic vaccines, particularly promising for HPV. However, being reflective, the title of this chapter clearly indicates that only preventive vaccines are described. In chapter 6, the reader is introduced to one of the first virus recognized to cause cancer in humans, the Epstein-Barr Virus. This chapter summarizes current knowledge of the role of EBV in lymphomagenesis, highlighting the importance of factors, including disorders of immunity, which render an an asymptomatic virus persistence in normal people a possible process of carcinogenesis. The paragraph on the discovery of this virus is particularly enjoyable, showing the importance to listen a seminar with an open mind. EBV was discovered in lymphomas, but this virus causes more cases of gastric carcinoma than lymphoma. The epithelial carcinogenesis by EBV virus is efficaciously described in the 7th chapter giving the major milestones in EBV and epithelial cancers together with some recent findings (with the advent of NGS) which improve knowledge of EBV in epithelial carcinogenesis. The part of the book dedicated to EBV is masterfully concluded in Chapter 8 where both preventive and therapeutic vaccines against this virus are presented. Despite the paucity of correlated figures and tables, the essential aspect of vaccines are described, including second generation prophylactic vaccines with a wider range of viral antigens and results from initial clinical trials with therapeutic vaccines. The 9th Chapter is somehow very (too much?) synthetic in describing molecular pathogenesis by KSHV. Nevertheless, not only the essential information is given to the reader, but also examples of how the study of KSHV molecular pathology could pave the way for new necessary therapeutic approaches. Although this book is not a romance, some chapter is more pleasant than another to the reading and in particular that on the biology of Merkel cell polyoma (Chapter 10) is particularly enjoyable. The right number of figures that help in understanding the script are the right corollaries to the rigorous overview on what we currently know about this particular polyomavirus. The following Chapter 11 is the right closure of the topics strictly related to human oncogenic viruses. Indeed, this chapter describes the evolutionary mechanisms of several DNA tumor viruses (EBV, KSHV, HPV and, even if not oncogenic for humans, adenovirus), which have led to the possibility of infecting cells without altering the host DNA damage response during lytic and latent infection. Finally, last chapter emphasizes the importance of adenoviruses in the field of viral carcinogenesis, not only as a fundamental tool for the study of cell transformation but also as a possible therapy of human cancers. In particular, this last aspect is well discussed and is giving information on promising results obtained in clinical trials with an adenovirus vector expressing wild-type p53.

Final remarks

In sum, going back to the first question, the response is “yes”. This book is an excellent, timely current summary of this field and provides further support for the potential clinical application of these studies. The only criticism on the structure of the book is the number of drawings, diagrams and tables that could be more making it easier to use as a textbook. Nonetheless, the book hits its mark and I would recommend it as a must have. For these reasons the book Edited by Sally Roberts will be of sure interest for anyone want to be informed about cancer related to viral infection.