The Search for Infectious Causes of Human Cancers: Where and Why (Nobel Lecture)

Abstract

Slightly more than 20% of the global cancer burden can currently be linked to infectious agents, including viruses, bacteria, and parasites. In this Review the reasons for their relatively late discovery are analyzed, and epidemiological observations that may point to an involvement of additional infectious agents in specific human cancers are highlighted. Emphasis is placed on hematopoietic malignancies, breast and colorectal cancers, as well as basal cell carcinomas of the skin and lung cancers in nonsmokers.

The role of human papillomavirus infection in breast cancer

“…With respect to their possible role in breast cancer, HPV meets virtually all of the above criteria, with the important exceptions of evidence of a positive effect of an intervention and consistent immunologic evidence. However, the evidence presented to date seems inconclusive for a definitive role of HPV in breast cancer because the strength of any study has been too low [22,[65][66][67][68]. We can image this scene: HPV transmission occurs between a woman and her spouse around the age of 20 or even younger through their mother's milk, body fluid, blood or even the air.…”

In Vivo and In Vitro Studies Suggest a Possible Involvement of HPV Infection in the Early Stage of Breast Carcinogenesis via APOBEC3B Induction

“…However, it is well known that some infectious agents (e.g. Helicobacter pylori for gastric cancer and hepatitis viruses for hepatocellular carcinoma) act as indirect carcinogens, without persistence of their genes within the respective cancer cells [1]. Even in HPV, some cutaneous types are attributed as indirect carcinogens [1].…”

“…Helicobacter pylori for gastric cancer and hepatitis viruses for hepatocellular carcinoma) act as indirect carcinogens, without persistence of their genes within the respective cancer cells [1]. Even in HPV, some cutaneous types are attributed as indirect carcinogens [1]. Another important fact to support HPV as possible cause of BC is high-risk HPV E6 and E7 are used as the most efficient and reproducible model for human mammary epithelial carcinogenesis in vitro.…”

“…Epidemiology gave the first hints for an involvement of viral agents in specific human cancers [1]. Since the mid-20 th century when mouse mammary tumor virus (MMTV) was discovered to cause mammary cancers in mice, some viruses, especially lately HPV, have been suspected to play an etiological role in BC.…”

The Antiviral Effects of Na,K-ATPase Inhibition: A Minireview

“…Once the viral components are in the intracellular environment and the genome is transcribed, the viral proteins are synthesized using the host cell translational machinery, and the new viral particles are transported to the surface to be released and infect other cells [9]. Viruses are very frequent causative agents of human infectious diseases and cancer, and their treatment is often challenging, as resistance to antiviral drugs has been reported for many important pathogens such as influenza, hepatitis B, and herpes simplex virus [10,11,12,13]. Targeting host cell components such as Na,K-ATPase is a very promising antiviral strategy in order to minimize the resistance to antiviral drugs, and has been shown to be effective in a broad spectrum of viral species.…”