Infections Causing Human Cancer

Viral, bacterial, and parasitic diseases have accompanied humankind since the earliest times and have had more impact on history than any other single factor. Influenza and smallpox devastated cities and ruined empires, each claiming more lives worldwide than all wars combined. Plague killed approximately 200 million, and malaria still claims the life of a child every 30 seconds.

Other than the direct toll inflicted by infectious diseases, numerous studies have established a relationship between microorganisms and chronic conditions such as atherosclerosis, neurologic disorders, cancer, and obesity. The link between microorganisms and increasing numbers of diseases never before envisioned as having microbial etiology opens fascinating scientific, medical, and public health perspectives.

The causal relationship between infectious diseases and cancer is at the core of this engaging text authored by Harald zur Hausen. While 2 Danish pathologists presented evidence in 1908 that a “filterable agent” caused animal tumors, and Rous reported in 1911 that cell-free tumor extracts could induce malignancy in healthy animals, this newly discovered link between microorganisms and cancer fell into oblivion for several decades. It was not until 1966, when the Nobel Prize was conferred on Rous for his discovery of tumor-inducing viruses, that the concept reemerged. Today, microorganisms have come to occupy such a fundamental role in cancer biology that a recent review¹ noted that “Without the contributions of viral carcinogenesis, it is difficult to conceive that the molecular basis of cancer would stand revealed so clearly today.” According to recent global estimates, 20% of all cancers are linked to infectious agents.

The first 3 chapters provide an engaging introduction. This initial section opens with a historical perspective that underscores the difficulties, accomplishments, and disappointments that accompanied researchers for more than a century, until they conclusively demonstrated a link between infections and cancer. Koch's postulates for establishing causality between infections and cancer, an overview of the general aspects of tumors linked to infectious agents, and the global burden of cancers caused by infection are presented.

The goal of the text is not to delve into the molecular biology of the various microorganisms; rather, it proposes to examine groups of microorganisms linked to malignant transformation. Some of the most fascinating and instructive chapters revolve around herpesviruses, papillomaviruses, hepadnaviruses, retroviruses, and parasites. Each chapter highlights specific infectious agents, historical background, epidemiology of the infection, and a detailed history of observations and studies linking the respective microorganisms to cancer. Engaging discussions focus on mechanisms of viral transformation. Of note are the sections exploring the role of the Epstein-Barr virus in Burkitt lymphoma, nasopharyngeal carcinoma, and Hodgkin disease; of hepatitis B and C viruses in hepatocellular carcinoma; and of the relationship between papillomaviruses and cervical cancer.

Among the books' highlights, 2 chapters are noteworthy. One of them explores the link between Helicobacter and cancer, and the concluding chapter speculates about additional cancers with a possible or probable infectious etiology, such as childhood leukemias and lymphomas, breast cancer, prostate cancer, and cutaneous lymphomas.

Beyond the specific microorganisms that are the focus of individual chapters, memorable teachings emerge. For example, it is essential to appreciate the long and arduous road culminating with the recognition of microorganisms as a cause of cancer. The complex, multidirectional interaction between microbiology and cancer biology represents one of the most fascinating aspects of science. Throughout the book, one appreciates not only the time it took until this link was firmly established but also the challenges scientists faced at every step along this road. The journey will certainly continue, because the book concludes that “it would be very surprising if further links between specific infectious agents and human malignancies were not identified during the next few years.” Another fundamental teaching from this book does not pertain specifically to microbiology, cancer biology, or medicine, but to science as a discipline. A significant overlap often exists among what initially might appear as discrete spheres of science. One should not forget that the multidirectional interaction between disciplines is highly dynamic and in continuous expansion, as Blaise Pasxppcal's almost premonitory words predicted: “Nature is an infinite sphere of which the center is everywhere and the circumference nowhere.”