The collection of bacteria in our gut, known as the gut microbiome, is influenced by various factors including diet and geography. Our gut microbiome affects our metabolism and immune system, and has been associated with both positive and negative health effects. In particular, having lots of different bacteria is associated with gut health, while low diversity is linked to conditions like inflammatory bowel disease and obesity.
Unlike the gut, where more bacterial diversity is best, multiple studies to date have demonstrated an association between greater diversity of the microbiome of the female reproductive tract and infection with human papillomavirus, or HPV, the major cause of cervical cancer. It is unclear whether a more diverse microbiome in the female reproductive tract is associated with the persistence and progression of HPV-related cervical cancer.
This question was examined in a study published in PLOS Pathogens in March of this year. HPV infections are typically cleared by the immune system; however, some persist into precancer of the cervix, which can then progress to cervical cancer. Using data and patient samples from an HPV vaccine trial that included 273 women with a high-risk HPV infection, the authors evaluated how the microbiome in the female reproductive tract affected HPV clearance, HPV infection persistence, and progression of HPV infection to precancer.
The authors compared cervical microbial diversity during two visits, which were on average 1.5 years apart. They defined three HPV infection outcome categories: clearance, persistence, and progression. At Visit 1, there were no microbial diversity differences between outcomes; however, by Visit 2, they found that microbial diversity increased with severity of the outcomes, with the lowest diversity found for clearance and highest diversity for progression.
To determine whether the prevalence of particular bacterial species at either visit was promoting HPV clearance or promoting progression to precancer, the authors used a multivariate model that accounted for age, community state type, smoking, and infection with HPV16 (a high-risk HPV strain). They found that among other factors, an abundance of bacteria belonging to the Lactobacillus genus (found in yoghurt!) at Visit 1 protected against progression, while microbial diversity at Visit 2 was a risk factor for progression.
Additionally, using a second mathematical model, the authors found that higher levels of bacteria of the Gardnerella genus at Visit 1 were associated with greater microbial diversity at Visit 2, which in turn, is associated with HPV infection progression.
Together, although the results of this study did not provide a direct explanation for how greater microbial diversity leads to persistent and progressive HPV infections, the results do identify potential biomarkers for HPV clearance and infection progression. Further research is needed to understand how interactions between the host and the cervicovaginal microbiome affect the natural history of HPV.
Although cervical cancer screening and the HPV vaccine are available and have drastically reduced the number of deaths from cervical cancer in the United States, there is a global disparity in access to these resources. In many regions of the world, cervical cancer is still a significant health concern. A more thorough understanding of how geography and socioeconomic status affect the diversity of the female tract microbiome, and how therapeutic approaches might promote a “healthier” collection of bacteria may help improve health outcomes for women in these areas of the world
