Abstract
HPV infection is an established risk factor for cervical cancer. However, more broadly, the role of the cervicovaginal virome in cervical cancer progression is not well understood.
ABSTRACT
While the link between the cervicovaginal bacterial microbiome, human papillomavirus (HPV) infection, and cervical cancer is recognized (P. Łaniewski, D. Barnes, A. Goulder, H. Cui, et al., Sci. Rep. 8:7593, 2018,
http://dx.doi.org/10.1038/s41598-018-25879-7
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; A. Mitra, D. A. MacIntyre, J. R. Marchesi, Y. S. Lee, et al., Microbiome 4:58, 2016,
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; J. Norenhag, J. Du, M. Olovsson, H. Verstraelen, et al., BJOG, 127:171–180, 2020,
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; E. O. Dareng, B. Ma, A. O. Famooto, S. N. Adebamowo, et al., Epidemiol. Infect. 144:123–137, 2016,
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), the role of the cervicovaginal virome remains poorly understood. In this pilot study, we conducted metagenomic next-generation sequencing of cervicovaginal lavage specimens to investigate the relationship between the cervicovaginal DNA virome, bacterial microbiome, genital inflammation, and HPV infection. Specific virome alterations were associated with features of the local microenvironment related to HPV persistence and progression to cervical cancer. Cervicovaginal viromes clustered distinctly by genital inflammation state. Genital inflammation was associated with decreased virome richness and alpha diversity and an increased abundance of
Anelloviridae
species from the genus
Alphatorquevirus
.
Lactobacillus
bacteriophages were closely associated with increased
Lactobacillus
abundance, consistent with phage-host relationships. Interestingly, bacteria-bacteriophage transkingdom interactions were linked to genital inflammation and showed specific interactions with bacterial vaginosis-associated bacteria, including
Gardnerella, Prevotella,
and
Sneathia
. Taken together, our results reveal prominent virome interactions with features of the cervicovaginal microenvironment that are associated with HPV and cervical cancer. These findings expand our understanding of the cervicovaginal host-microbiome interactions in women’s health.
IMPORTANCE
HPV infection is an established risk factor for cervical cancer. However, more broadly, the role of the cervicovaginal virome in cervical cancer progression is not well understood. Here, we identified cervicovaginal DNA virome alterations associated with local microenvironment factors (vaginal microbiota and genital inflammation) that influence HPV persistence and progression to cervical cancer. These findings indicate that the cervicovaginal virome plays an important role in women’s health.