Significant personal factors and bacteria
The baseline personal significant factors and metagenomic data are shown as eleven items in Table 1. Among the HPV-negative cohort, negative conversion and HPV-positive subjects, both age and history of reproductive tract infection had a consistent pattern. Another two significant demographic and behavioral factors were the salary range and the total number of sex partners with an inconsistent pattern. The negative HPV test results tended to be associated with higher salaries. HPV-negative subjects had the lowest number of total sex partners.
After adjusting for age, salary, history of reproductive tract infection and the total number of sexual partners, the metagenomics data showed that both Lactobacillus jensenii and Streptococcus agalactiae were a relatively abundant part of the VMB, and another 5 types were pseudosignificant due to the limited sample size in this pilot study. Lactobacillus jensenii, for example, had a relatively higher proportion in the HPV-positive group and a reduced proportion in the seroconversion group. The presence of Streptococcus agalactiae seemed to have a correlation between HPV-negative and HPV-positive seroconversion.
Correlation between personal factors and microbiome
To determine the stable potential candidate biomarkers, a correlation analysis was conducted between four significant personal factors and seven microorganism species, as shown in Fig 5. Age has a significant association with atopobium vaginae and mycoplasma hominis in HPV-negative samples; atopobium vaginae and prevotella bivia are present in the seroconversion cases; mycoplasma hominis and prevotella bivia are abundant in the HPV-positive group. Mycoplasma hominis was not found in the seroconverted cohort. Other associations between personal factors and vaginal bacteria were not significant.
Legend: Correlation coefficients between four potential biomarkers and personal indicators in HPV-negative vs negative-conversion, negative-conversion men seeking women best site vs HPV-positive, and HPV-negative vs HPV-positive cohorts. Red and blue represent positive and negative associations. Crosses represent no significant correlation (p-value > 0.05). The size of the circle represents the R-value of the personal factors and the microorganisms calculated from the linear regression.
To identify robust biomarkers of correlation with gynecological health, finding a stable bioental. To increase the potential of using microbiome analysis as a useful tool in the community setting, the overlap was theoretically defined of the microorganism present within all three cohorts. Lactobacillus gasseri, Streptococcus agalactiae, and Timona prevotella were identified as candidate biomarkers of cervicovaginal health and differentiate HPV status.
This study explores the effect of the presence of different microorganisms in the vaginal microbiome of HPV-negative, HPV-positive to HPV-negative individuals and persistent HPV-positive individuals. In regard to the microorganisms that were found in vaginal mucus samples, the presence of species from the Lactobacillus genus dominated the microbiome, with notable representation of the Lactobacillus iners species. Notably, the three bacteria Lactobacillus gasseri, Streptococcus agalactiae, and Timona prevotella were differentially correlated to the three cohorts analyzed in this study. Overall, five microorganisms are beneficial to humans, including Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii; 12 are pathogenic, including Gardnerella vaginalis, Atopobium vaginae, Trachoma chlamydia, Neisseria gonorrheae, Microureaplasma, Mycoplasma hominis, Candida albicans, Prevotella bivia, Diallisteria, Streptococcus agalactiae and Timona prevotella, among these 17 microorganisms. Overall, we did not find that an increased level of pathogenic bacteria was correlated with HPV status, but changes in the balance of the normal vaginal microbiome were associated with HPV infection.
Our study agrees with previous studies showing that Lactobacillus spp. are highly abundant in the vaginal microbiome [33–35]. However, the proportion of anerobic bacteria was quite discrepant with the lower abundance. For example, Ureaplasma urealyticum was low at 0.55% in the HPV-negative cohort, 1.95% in the negative conversion cohort and 0.67% in the HPV-positive cohort.