Dataset Information

Cervical-Vaginal Microbiome and Associated Cytokine Profiles in a Prospective Study of HPV 16 Acquisition, Persistence, and Clearance.

ABSTRACT: Persistent human papillomavirus (HPV) infections is necessary for the development of cervical cancers. Consequently, understanding the biologic mechanisms resulting in clearance is key in cancer prevention. Similar to other mucosal sites, it is expected that the local microbiome plays a significant role in shaping the immune response responsible for HPV clearance. Using cervical wash repository samples from a prospective study of HPV in women, this study investigates the microbiome and its associated inflammatory milieu during HPV 16 pre-acquisition, persistence and clearance states. For comparison, samples from women with no history of HPV ever during the study period were selected. We showed that 9 of 13 inflammatory cytokines were found to be significantly increased in the immediate post-clearance visit compared to the pre-acquisition or infection visits. Gardnerella vaginalis was associated with higher levels of inflammatory cytokines. Women with no history of HPV infection had similar cytokine profiles as those with HPV 16 post-clearance. This in vivo study documented an immune response shortly after HPV 16 clearance. G. vaginalis appeared to be involved in shaping this immune response. The appearance of G. vaginalis may have resulted from a shift from anti-microbial to anti-viral immune response with loss of bacterial control. The similar high levels of cytokines seen in women with no history of HPV suggest that a certain level of inflammatory surveillance is required to maintain an HPV negative state. This data may inform therapies such as probiotics or pro-inflammatory agents for treatment of persistent HPV.

SUBMITTER: Moscicki AB

PROVIDER: S-EPMC7546785 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Cervical-Vaginal Microbiome and Associated Cytokine Profiles in a Prospective Study of HPV 16 Acquisition, Persistence, and Clearance.

Moscicki Anna-Barbara AB Shi Baochen B Huang Hazel H Barnard Emma E Li Huiying H

Frontiers in cellular and infection microbiology 20200925

Persistent human papillomavirus (HPV) infections is necessary for the development of cervical cancers. Consequently, understanding the biologic mechanisms resulting in clearance is key in cancer prevention. Similar to other mucosal sites, it is expected that the local microbiome plays a significant role in shaping the immune response responsible for HPV clearance. Using cervical wash repository samples from a prospective study of HPV in women, this study investigates the microbiome and its assoc ...[more]

PMID: 33102255

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Project description:Vaginal flora plays a vital role in human papillomavirus (HPV) infection and progression to cancer. To reveal a role of the vaginal flora in HPV persistence and clearance, 90 patients with HPV infection and 45 healthy individuals were enrolled in this study and their vaginal flora were analyzed. Women with HPV infection were treated with Lactobacillus in the vaginal environment as a supplement to interferon therapy. Our results indicated that patients with high risk HPV (Hr-HPV) 16/18 infection had a significantly higher alpha diversity compared with the healthy control (p < 0.01), while there was no significant difference between the non-Hr-HPV16/18 group and the controls (p > 0.05). Patients with multiple HPV infection had insignificantly higher alpha diversity compared with single HPV infection (p > 0.05). The vaginal flora of patients with HPV infection exhibited different compositions when compared to the healthy controls. The dominant bacteria with the highest prevalence in HPV-positive group were Lactobacillus iners (n = 49, 54.44%), and the top 3 dominant bacteria in the HPV-persistent group were Lactobacillus iners (n = 34, 53.13%), Sneathia amnii (n = 9, 14.06%), and Lactobacillus delbrueckii (n = 3, 4.69%). Patients with HPV clearance had significantly lower alpha diversity, and the flora pattern was also different between groups displaying HPV clearance vs. persistence. The patients with persistent HPV infection had significantly higher levels of Bacteroidaceae, Erysipelotrichaceae, Helicobacteraceae, Neisseriaceae, Streptococcaceae (family level), and Fusobacterium, Bacteroides, Neisseria, and Helicobacter (genus level) than patients who had cleared HPV (p < 0.05).ImportanceOur study revealed differences in vaginal flora patterns are associated with HPV persistence and its clearance. Interferon plus probiotics can greatly improve virus clearance in some patients. Distinguishing bacterial features associated with HPV clearance in patients would be helpful for early intervention and reverse persistent infection.

Project description:ObjectiveCharacterise the vaginal metabolome of cervical HPV-infected and uninfected women.DesignCross-sectional.SettingThe Center for Health Behavior Research at the University of Maryland School of Public Health.SampleThirty-nine participants, 13 categorised as HPV-negative and 26 as HPV-positive (any genotype; HPV+ ), 14 of whom were positive with at least one high-risk HPV strain (hrHPV).MethodSelf-collected mid-vaginal swabs were profiled for bacterial composition by 16S rRNA gene amplicon sequencing, metabolites by both gas and liquid chromatography mass spectrometry, and 37 types of HPV DNA.Main outcome measuresMetabolite abundances.ResultsVaginal microbiota clustered into Community State Type (CST) I (Lactobacillus crispatus-dominated), CST III (Lactobacillus iners-dominated), and CST IV (low-Lactobacillus, 'molecular-BV'). HPV+ women had higher biogenic amine and phospholipid concentrations compared with HPV- women after adjustment for CST and cigarette smoking. Metabolomic profiles of HPV+ and HPV- women differed in strata of CST. In CST III, there were higher concentrations of biogenic amines and glycogen-related metabolites in HPV+ women than in HPV- women. In CST IV, there were lower concentrations of glutathione, glycogen, and phospholipid-related metabolites in HPV+ participants than in HPV- participants. Across all CSTs, women with hrHPV strains had lower concentrations of amino acids, lipids, and peptides compared with women who had only low-risk HPV (lrHPV).ConclusionsThe vaginal metabolome of HPV+ women differed from HPV- women in terms of several metabolites, including biogenic amines, glutathione, and lipid-related metabolites. If the temporal relation between increased levels of reduced glutathione and oxidised glutathione and HPV incidence/persistence is confirmed in future studies, anti-oxidant therapies may be considered as a non-surgical HPV control intervention.Tweetable abstractMetabolomics study: Vaginal microenvironment of HPV+ women may be informative for non-surgical interventions.

Dataset Information

Cervical-Vaginal Microbiome and Associated Cytokine Profiles in a Prospective Study of HPV 16 Acquisition, Persistence, and Clearance.

Publications

Cervical-Vaginal Microbiome and Associated Cytokine Profiles in a Prospective Study of HPV 16 Acquisition, Persistence, and Clearance.

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