"The forgotten organ", the human microbiome, comprises a community of microorganisms that colonizes various sites of the human body. Through coevolution of bacteria, archaea and fungi with the human host over thousands of years, a complex host-microbiome relationship emerged in which many functions, including metabolism and immune responses, became codependent. This coupling becomes evident when disruption in the microbiome composition, termed dysbiosis, is mirrored by the development of pathologies in the host. Among the most serious consequences of dysbiosis, is the development of cancer. As many as 20% of total cancers worldwide are caused by a microbial agent. To date, a vast majority of microbiome-cancer studies focus solely on the microbiome of the large intestine and the development of gastrointestinal cancers. Here, we will review the available evidence implicating microbiome involvement in the development and progression of non-gastrointestinal cancers, while distinguishing between viral and bacterial drivers of cancer, as well as "local" and "systemic", "cancer-stimulating" and "cancer-suppressing" effects of the microbiome. Developing a system-wide approach to cancer-microbiome studies will be crucial in understanding how microbiome influences carcinogenesis, and may enable to employ microbiome-targeting approaches as part of cancer treatment.
Keywords: Carcinogenesis; Dysbiosis; Microbial agent; Microbiome; Non-gastrointestinal cancers.