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Cervical Microbes Potentially Tied to Viral Infections, High-Grade Lesions

NEW YORK (GenomeWeb) – A team from the US and Tanzania has started characterizing the microbe community members found at pre-cancerous cervical lesions from women with or without accompanying infections by the known cervical cancer contributor human papillomavirus (HPV) and by human immunodeficiency virus (HIV), which is also suspected of influencing the cervical environment in a manner that might influence dysplasia and cancer risk.

"Understanding microbes that influence this environment will help identify cervical microbiota to be used as diagnostic markers for those at high risk of developing cervical cancer and for the development of preventative probiotic or antibiotic treatments that could control the cervical microbiome by promoting bacterial colonization with a microbiota associated with healthy cervical cytology," senior author Peter Angeletti, a virology researcher at the University of Nebraska at Lincoln, and his colleagues wrote.

Using deep RNA sequencing, the researchers analyzed 16S rRNA amplicons from cervical cytobrush samples from 144 Tanzanian women within the context of HPV infection status, HIV status, and cervical cytology. Compared to cytologically normal cervical samples, the high-grade squamous intraepithelial lesions appeared to be marked by an uptick in overall bacterial diversity, they reported yesterday in mBio, while samples from HIV-positive lesions tended to have increased bacterial richness.

"[H]IV was shown to have a significant effect on the cervical microbiome, increasing bacterial richness and decreasing beta diversity," they wrote, noting that those findings seem to line up with past cervical and vaginal microbiome analyses and "suggest that changes in the cervical epithelium microenvironment brought on by HIV exert some selective pressure on cervical bacterial communities."

For their study, the researchers focused on 144 women from Tanzania, who were 37 years old, on average. They noted that 41 of the women were HIV-positive, while 103 were negative for HIV. Just eight of the 134 women with available HPV test results were HPV-negative, and 126 were HPV-positive. All eight HPV-negative women were also negative for HIV.

Starting with 23 cervical cytobrush samples deemed free from intraepithelial lesions or malignancies, 72 samples from low-grade lesions and 50 samples from high-grade squamous lesions, the team amplified the 16S rRNA V4 hypervariable region and used deep Illumina sequencing to profile cervical microbe operational taxonomic units in relation to viral infection patterns and cervical cytology.

At least half a dozen microbial phyla, including Firmicutes, turned up in the samples regardless of individuals' HIV or HPV infection status or cervical cytology, the researchers reported. When they focused in on the microbes found in cervical communities from women with the risky, high-grade lesions, meanwhile, they saw a rise in Mycoplasmatales, Pseudomonadales, and Staphylococcus microbes in those cervical cancer-prone cases.

From these and other data, the team proposed that chronic infection by microbes from the Mycoplasma genus such as M. genitalium and M. hominis may contribute to cervical dysplasia found in women positive for HPV. A further rise in Mycoplasma levels was found in samples from women with concurrent HIV infections, hinting that these microbes may offer insights into the microbiome features associated with risky cervical lesions.

The investigators noted that larger, longitudinal studies are needed to explore such relationships in more detail and to determine whether Mycoplasma and other high-risk lesion-related microbes appear in the cervical microbiome before or after viral infections occur. 

"The data really speaks to the idea that these bacteria are present at the lesions," Angeletti said in a statement. "But what is the relationship, and are they there in advance of the HPV?"