The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next?

Abstract

The vaginal microbiota plays a significant role in health and disease of the female reproductive tract. Next-generation sequencing techniques based upon the analysis of bacterial 16S rRNA genes permit in-depth study of vaginal microbial community structure to a level of detail not possible with standard culture-based microbiological techniques. The human papillomavirus (HPV) causes both cervical intraepithelial neoplasia (CIN) and cervical cancer. Although the virus is highly prevalent, only a small number of women have a persistent HPV infection and subsequently develop clinically significant disease. There is emerging evidence which leads us to conclude that increased diversity of vaginal microbiota combined with reduced relative abundance of Lactobacillus spp. is involved in HPV acquisition and persistence and the development of cervical precancer and cancer. In this review, we summarise the current literature and discuss potential mechanisms for the involvement of vaginal microbiota in the evolution of CIN and cervical cancer. The concept of manipulation of vaginal bacterial communities using pre- and probiotics is also discussed as an exciting prospect for the field of cervical pathology.

Keywords: CIN; Cervical cancer; Cervical intraepithelial neoplasia; HPV; Human papillomavirus; Lactobacillus species; Prebiotics; Probiotics; Vaginal microbiota.

Fig. 1

Summary of potential mechanisms associating the VMB with cervical disease. a VMB structure appears to be associated with acquisition and persistence of HPV infection, and CST II in particular is associated with most rapid clearance of an acute HPV infection. b Dysbiosis can result in a proinflammatory environment, which can facilitate several of the necessary steps in viral transformation including E6 and E7 expression, genomic instability, viral integration and telomerase activation, which are necessary for carcinogenesis. c Higher diversity with lower Lactobacillus spp. content has been associated with increasing severity of CIN. Particular species associated with high diversity VMBs may produce sialidases which cause mucus breakdown, predisposing the cervical epithelium to tissue damage, as well as producing biological amines which are responsible for oxidative stress; a key mechanism in carcinogenesis. Certain species Lactobacillus spp. have been shown to mop up these amines, and therefore their presence may reduce the risk of oxidative damage. L. iners does not appear to share many of the protective mechanisms of other Lactobacillus species and therefore appears intermediate in its ability to prevent cervical disease