Microbiome, Human Papillomavirus and Cervical Carcinogenesis

The microbiome describes the collection of genes derived from microorganisms that live in body systems. After the discovery of Lactobacilli as important for vaginal health, the vaginal microbiome was initially binarily classified into healthy or bacterial vaginosis (BV), before being further explored using 16S sequencing and the development of community state types (CST) by Ravel et al. There are a plethora of studies describing the vaginal microbiome composition in relation to cervical disease outcomes, more specifically human papillomavirus infection and persistence, cervical preinvasive and invasive disease. While there is some conflicting evidence, the general consensus is that Lactobacillus spp., in particular Lactobacillus crispatus or CST I, is associated with healthy status, and BV, CST IV and Lactobacillus depletion are associated with cervical intraepithelial neoplasia. What constitutes a 'normal' vaginal microbiome is not clear; in Ravel's study, around a quarter of women had CST I, and a quarter had CST IV. Although directionality is not established, mechanistic studies suggest immunomodulation and support biological plausibility. More recently, prebiotics and probiotics have been studied and there is some emerging evidence that this may be associated with increased clearance of cytological abnormalities. Important future work includes larger longitudinal studies, patient-derived organoids to examine causality and mechanistic insights, and development and trial of novel therapeutic treatments.