The cervicovaginal microbiome: an emerging determinant of HPV infection and disease

Human papillomaviruses (HPVs) are epitheliotropic viruses that cause diseases ranging from cutaneous warts to invasive cancers. HPVs exhibit tropism for the epithelial lining of the skin, oral cavity, and anogenital tract. A subset of HPVs, known as high-risk HPVs, have oncogenic potential and cause nearly one-third of all virus-associated cancers worldwide, including essentially all cervical cancers, most other anogenital cancers, and a growing percentage of head and neck cancers. A large and growing body of clinical and epidemiological research has established the host microbiome, or the collection of microorganisms on and within the body, as a key determinant of HPV infection, persistence, and disease development. In this review, an overview of the current understanding of associations between bacterial components of the host cervicovaginal microbiome (CVM) and aspects of HPV pathogenesis is discussed. Potential mechanisms through which the CVM influences HPV infection and neoplastic disease development are also presented. The inherent challenges of studying HPVs and the microbiome have impeded progress to define not only the underlying mechanisms involved in HPV-CVM interactions, but also the ability to address remaining questions such as causality, temporal dynamics, and the directionality of this relationship. Emerging in vitro and in vivo models provide powerful opportunities to address these outstanding questions and increase our understanding of trans-kingdom interactions that contribute to HPV infection and subsequent disease.