Interplay between the temporal dynamics of the vaginal microbiota and human papillomavirus detection

Abstract

Background: We sought to describe the temporal relationship between vaginal microbiota and human papillomavirus (HPV) detection.

Methods: Thirty-two reproductive-age women self-collected midvaginal swabs twice weekly for 16 weeks (937 samples). Vaginal bacterial communities were characterized by pyrosequencing of barcoded 16S rRNA genes and clustered into 6 community state types (CSTs). Each swab was tested for 37 HPV types. The effects of CSTs on the rate of transition between HPV-negative and HPV-positive states were assessed using continuous-time Markov models.

Results: Participants had an average of 29 samples, with HPV point prevalence between 58%-77%. CST was associated with changes in HPV status (P<.001). Lactobacillus gasseri-dominated CSTs had the fastest HPV remission rate, and a low Lactobacillus community with high proportions of the genera Atopobium (CST IV-B) had the slowest rate compared to L. crispatus-dominated CSTs (adjusted transition rate ratio [aTRR], 4.43, 95% confidence interval [CI], 1.11-17.7; aTRR, 0.33, 95% CI, .12-1.19, respectively). The rate ratio of incident HPV for low Lactobacillus CST IV-A was 1.86 (95% CI, .52-6.74).

Conclusions: Vaginal microbiota dominated by L. gasseri was associated with increased clearance of detectable HPV. Frequent longitudinal sampling is necessary for evaluation of the association between HPV detection and dynamic microbiota.

Keywords: 16S rRNA gene analysis; human papillomavirus (HPV); transition model; vaginal microbiota.

Figure 1.

Heatmap of relative percent abundance of bacterial taxa found in the vaginal samples of 32 reproductive-age women who contributed 930 samples in a longitudinal study. Each vertical line represents 1 sample. Bacterial community state type (CST) was described by Gajer and Brotman et al [19], and relative abundance is indicated by the key. HPV positivity is also shown across the top of the figure. Abbreviations: CST, community state type; HPV, human papillomavirus.

Figure 2.

Number of hrHPV-positive samples per participant and stratified by CST. During the longitudinal study, each participant collected up to 33 samples and could have samples in numerous CSTs [19]. This figure displays the number of hrHPV-positive and -negative samples by each CST. ID#s were double blinded, and reassignment was based on the dominant CST observed in each woman's series of samples. Abbreviations: CST, community state type; hrHPV, high-risk human papillomavirus; ID#s, identification numbers.

Figure 3.

Dynamics of vaginal CSTs and HPV detection in 32 women over 16 weeks. Double-blinded participant ID#s are indicated on the right. Each symbol represents 1 sample in the time series. The absence of a symbol indicates a missing HPV sample. The CST in the time series for each woman are color coded and the HPV status by symbol according to the key above. Participants are clustered by bacterial community class, which groups together women of similar bacterial community patterns over time [19]. Abbreviations: CSTs, community state types; HPV, human papillomavirus; ID#s, identification numbers.