An Analysis Of Tumor Microbial Diversity And Composition Between Women With Cervical Cancer In Botswana And The United States

Objectives: We assessed geographic differences by characterizing the cervical 16S rDNA microbiome of women with locally advanced squamous cell carcinoma of the cervix being treated in Botswana and in the United States. Methods: We characterized the 16S rDNA cervical microbiome of 13 US women (0 HIV-infected, 13 HIV-uninfected) and 11 Botswana women (8 HIV-infected, 3 HIV-uninfected). Shannon diversity index was used to evaluate alpha (intra-sample) diversity, while the UniFrac (weighted and unweighted) and Bray-Curtis distances were employed to evaluate beta (inter-sample) diversity. The relative abundance of microbial taxa was compared among samples using Linear Discriminant Analysis Effect Size (LEfSe). Results: Neither α-diversity (p=0.36) nor β-diversity (p=0.70) varied significantly by geographic location in our patient group (Figure 2A and B). The top 15 most abundant genera in cervical samples was similar among all patients (Figure 2C), suggesting that bacterial taxa dominance does not vary by geographic location. Generally, all samples were most abundant in bacteria of the genera, Prevotella, Bacteroides, and Porphyromonas. LefSe identified the genus Chlamidya, of the family Chlamydiaceae, and the bacterial order Rhizobiales to be enriched in US patients, while several different bacteria were enriched in Botswanan patients. Most notably, bacteria belonging to the phylum Acidobacteria, specifically, the family of Blastocatellaceae (Figure 2D and E). With respect to Botswanan women and HIV status, LefSe showed an enrichment of the genus Intestinimonas, and the bacterial family Bifidobacteriaceae in the HIV positive patients (p<0.05, LDA score > 2) (Figure 1D and E). We observed no statistically significant differences in α-diversity as measured by SDI (p=0.28) (Figure 1A) nor β-diversity (unweighted Bray-Curtis Unifrac; p=0.15) (Figure 1B) with respect to HIV status. Conclusions: In this novel prospective international collaborative study, we characterized the cervical microbiome of women with cervical cancer living in Botswana and the US, with the hypothesis that the cervical microbiome would demonstrate distinct differences by region. We found similar cervical tumor diversity and composition between Botswana and US women. We found similar prevalence of most major bacterial genera andLactobacillus species in Botswana and US women. The cervical microbiome of Botswanan women with cervical cancer differed with respect to HIV status. Additional studies are warranted to establish whether observed differences have clinical significance and differentially impact women with cervical cancer residing in these two regions. We assessed geographic differences by characterizing the cervical 16S rDNA microbiome of women with locally advanced squamous cell carcinoma of the cervix being treated in Botswana and in the United States. We characterized the 16S rDNA cervical microbiome of 13 US women (0 HIV-infected, 13 HIV-uninfected) and 11 Botswana women (8 HIV-infected, 3 HIV-uninfected). Shannon diversity index was used to evaluate alpha (intra-sample) diversity, while the UniFrac (weighted and unweighted) and Bray-Curtis distances were employed to evaluate beta (inter-sample) diversity. The relative abundance of microbial taxa was compared among samples using Linear Discriminant Analysis Effect Size (LEfSe). Neither α-diversity (p=0.36) nor β-diversity (p=0.70) varied significantly by geographic location in our patient group (Figure 2A and B). The top 15 most abundant genera in cervical samples was similar among all patients (Figure 2C), suggesting that bacterial taxa dominance does not vary by geographic location. Generally, all samples were most abundant in bacteria of the genera, Prevotella, Bacteroides, and Porphyromonas. LefSe identified the genus Chlamidya, of the family Chlamydiaceae, and the bacterial order Rhizobiales to be enriched in US patients, while several different bacteria were enriched in Botswanan patients. Most notably, bacteria belonging to the phylum Acidobacteria, specifically, the family of Blastocatellaceae (Figure 2D and E). With respect to Botswanan women and HIV status, LefSe showed an enrichment of the genus Intestinimonas, and the bacterial family Bifidobacteriaceae in the HIV positive patients (p<0.05, LDA score > 2) (Figure 1D and E). We observed no statistically significant differences in α-diversity as measured by SDI (p=0.28) (Figure 1A) nor β-diversity (unweighted Bray-Curtis Unifrac; p=0.15) (Figure 1B) with respect to HIV status. In this novel prospective international collaborative study, we characterized the cervical microbiome of women with cervical cancer living in Botswana and the US, with the hypothesis that the cervical microbiome would demonstrate distinct differences by region. We found similar cervical tumor diversity and composition between Botswana and US women. We found similar prevalence of most major bacterial genera andLactobacillus species in Botswana and US women. The cervical microbiome of Botswanan women with cervical cancer differed with respect to HIV status. Additional studies are warranted to establish whether observed differences have clinical significance and differentially impact women with cervical cancer residing in these two regions.