What I presented here at the conference was actually results that we haven’t published yet in which we systematically searched for all the available literature that links the vaginal microbiome to the acquisition of HPV infection but also the progression from HPV infection to epithelial premalignant lesions and eventually also to neoplasia.
What are the main aims for your systematic review?
Firstly we reviewed all the more recent sequencing-based microbiome data but the vaginal microbiome is quite unique if you compare it to other body niches in as much that the vaginal microbiome has been studied by non-PCR based methods for, let’s say, the past 25 years. It’s quite different from the gut or the oral microbiome. The older literature, the methods to assess dysbiosis is somewhat less refined than we hope to achieve with 16S based sequencing. But still there’s a body of evidence out there that is now so much sounding older and therefore often overlooked. So that is why we specifically aimed to look at the more recent sequencing based data as well as to the older body of evidence.
What are the characteristics of a healthy vaginal microbiome?
The vaginal microbiome is quite unique in as much that in ecology in general outside the human body, but especially for most human microbiome sites, that health is closely related to the diversity of the microbiome. It’s quite the opposite in the vaginal microbiome where what we consider a healthy microbiome with regard to all health outcomes that we have studied thus far, like preterm birth, acquisition of HIV and so on, it is the low diversity, lactobacillus dominated microbiome that is the most protective one. If it gets more diverse it’s more what we call dysbiosis. So it’s quite the opposite of what we know, for instance, for the gut microbiome, the oral microbiome and so on.
How can this dysbiosis lead to the onset of disease and potentially cancer?
What we found in our systematic review that there are a number of studies, especially now among the more recent sequencing basis, most studies are cross-sectional which means that the dysbiosis was assessed at the same time, or the vaginal microbiome status was assessed at the same time, as the outcome which we know is an association but doesn’t learn us anything about the direction of the association. So what we did in a second step was to specifically look for what we call longitudinal studies where we have first or repeatedly vaginal microbiome status assessed to whatever method and then look for various endpoints, being HPV acquisition, but also because most women will get HPV sooner or later, at least once in their lives. The thing is most of these women will not get cervical cancer, they will clear it through ways that we don’t quite understand but we presume that it is the immune system that clears the virus. Part of these women will progress to what we call premalignant stages and that is where we come in with screening strategies. Especially in low resource countries part of these women with premalignant lesions will even further progress to cervical cancer which is actually still the fourth most common cancer in women worldwide. So we specifically looked for studies that addressed dysbiosis of the vaginal microbiome in relation to all of these different health outcomes.
What approaches can be taken for treatment or prevention following this review?
Cervical cancer is quite unique within oncology in as much that it is about the only very common cancer that has proven to be largely preventable due to population-based screening which is now for decades in use and has been improving even more so as we’re moving from cytology based screening to HPV based screening that’s even more sensitive, more accurate.
The second that will eventually will prevent cervical cancer and premalignant lesions leading to it will largely lie in vaccination strategies and new vaccines with more types being targeted by new vaccines. This is already translated in a sharply decreased incidence in the happy few countries like the United States, Scandinavia, Western Europe, Australia and some parts of Southeast Asia. In most other countries this has not been achieved and this will not be achieved for another couple of decades. What we were hoping that for all the time that we can’t get vaccines and well-established screening programmes to those low resource settings that we might do it as simply as working with probiotics. I know of one trial that’s connected with a colleague that I collaborate a lot with, Janneke Van De Wijgert, she’s from the University of Liverpool, and now she’s finishing up, actually, such a trial in Rwanda.
Are there other infections agents that people should be more aware of to prevent and manage neoplasia?
There’s not much that we know apart from vaginal microbiome dysbiosis when I’m talking about the regular bacteria, so to speak. We know for some sexually transmitted infections, chlamydia being one of these, that they might increase the risk on the part way from HPV to cervical cancer but, if I’m honest, the literature base is very limited.
Is there anything else important that you have found from your systematic review?
I try to emphasise study design considerations. As important as we want to standardise in the laboratory protocols to go to the sequencing, that designing a good study is equally important to make all this research clinically relevant. That’s something I see, there is so much missing at present.