Does the vaginal microbiota play a role in the development of cervical cancer?

Abstract

Persistent infection with oncogenic human papillomavirus (HPV) is necessary but not sufficient for the development of cervical cancer. The factors promoting persistence as well those triggering carcinogenetic pathways are incompletely understood. Rapidly evolving evidence indicates that the vaginal microbiome (VM) may play a functional role (both protective and harmful) in the acquisition and persistence of HPV, and subsequent development of cervical cancer. The first studies examining the VM and the presence of an HPV infection using next-generation sequencing techniques identified higher microbial diversity in HPV-positive as opposed to HPV-negative women. Furthermore, there appears to be a temporal relationship between the VM and HPV infection in that specific community state types may be correlated with a higher chance of progression or regression of the infection. Studies describing the VM in women with preinvasive disease (squamous intraepithelial neoplasia [SIL]) consistently demonstrate a dysbiosis in women with the more severe disease. Although it is plausible that the composition of the VM may influence the host's innate immune response, susceptibility to infection, and the development of cervical disease, the studies to date do not prove causality. Future studies should explore the causal link between the VM and the clinical outcome in longitudinal samples from existing biobanks.

Figure 1. Interactions between the HPV, the vaginal microbiome and the host

CST I and a high relative abundance of L.crispatus may be protective against HPV acquisition. Longitudinal studies have shown that transition states such as CST III and a BV-like state, CST IV-B, likely lead to pro-inflammatory states which cause tissue damage and promote E6/E7 expression, genomic instability and viral integration which ultimately promotes development of HSIL. Increasing lack of L.crispatus has also been associated with increasing SIL severity, and various other species have been associated with both presence of HPV infection and SIL disease states.