Abstract
High-risk human papillomaviruses (hrHPVs) are causally related to cervical intraepithelial neoplasia (CIN) and subsequent cervical cancer (CC). The vaginal microbiome has been suggested to play a role in the development of CC, but the effect of conservative surgical treatment on the microbiome and hrHPV elimination has not been elucidated. In this study, we aimed to characterize the vaginal microbiome and inflammatory chemokine profile in 85 women treated for CIN2-CIN3 lesions, before and after surgical CIN removal. The results showed, as expected, a high prevalence of dysbiotic microbiomes and vaginal pro-inflammatory cytokines in the CIN cohort, correlated with disease severity, at the basal level. By contrast, surgical CIN removal induced significant vaginal microbiome variations, and specific microbiome/cytokine profiles were associated with hrHPV clearance/persistence at 6-month follow-up. hrHPV-cleared patients, in fact, showed a specific increase of L. crispatus and decrease of dysbiosis and inflammatory cytokines compared to hrHPV-persistent patients. These data highlight the crosstalk between HPV and the local microbiome, and suggest that vaginal microbiome modulation might represent a novel approach to modifying the natural history of hrHPV-related CC.Study registration n. ISRCTN34437150 (https://www.isrctn.com/ISRCTN34437150).
Highlights
Cervical cancer (CC) is one of the most common cancer in women, with an estimated 570,000 new cases in 2018 representing 7.5% of all female cancer deaths, and approximately 85% of the estimated 311,000 deaths per year occurring in lowincome countries (Ferlay et al, 2018)
Given that the study aim was to assess the association between the vaginal microbiome and high-risk oncogenic HPV (hrHPV) persistence in cervical intraepithelial neoplasia (CIN) patients, the hrHPV-negative women were excluded from the subsequent analyses
The Community State Types (CSTs)-I increase was higher in CIN3 than in the CIN2 group, while the reverse was observed for CST-III, which was more prevalent in CIN3 compared to CIN2 patients (47 vs. 29%, p < 0.001)
Summary
Cervical cancer (CC) is one of the most common cancer in women, with an estimated 570,000 new cases in 2018 representing 7.5% of all female cancer deaths, and approximately 85% of the estimated 311,000 deaths per year occurring in lowincome countries (Ferlay et al, 2018). HrHPV infection is a necessary but not sufficient condition for CC development, as many factors including immunodeficiency, age, smoking, sexual promiscuity, and concomitant virus or bacterial infections have been associated with higher persistence rates and oncogenic risk (Wheeler, 2008; Vriend et al, 2015; Seraceni et al, 2016; Tamarelle et al, 2019). CST-IV is characterized by depletion of Lactobacillus spp and a significantly higher pH and bacterial diversity, with prevalence of anaerobic species, including Gardnerella, Prevotella, Peptostreptococcus genera, and/or aerobic bacteria of Enterobacteriacee (Pybus and Onderdonk, 1999; Turovskiy et al, 2011; Reid, 2016; Di Paola et al, 2017), frequently associated with bacterial vaginosis (BV), which is the most common vaginal infection in women of reproductive age (De Seta et al, 2019). BV is associated with increased risk of acquiring sexually transmitted infections including HPV-associated ones (Gillet et al, 2011; King et al, 2011; Gillet et al, 2012; Guo et al, 2012; Gosmann et al, 2017)
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