Dataset Information

The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis.

ABSTRACT:

Objective

Characterise the vaginal metabolome of cervical HPV-infected and uninfected women.

Design

Cross-sectional.

Setting

The Center for Health Behavior Research at the University of Maryland School of Public Health.

Sample

Thirty-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).

Method

Self-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 measures

Metabolite abundances.

Results

Vaginal 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).

Conclusions

The 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 abstract

Metabolomics study: Vaginal microenvironment of HPV⁺ women may be informative for non-surgical interventions.

SUBMITTER: Borgogna JC

PROVIDER: S-EPMC6982399 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis.

Borgogna J C JC Shardell M D MD Santori E K EK Nelson T M TM Rath J M JM Glover E D ED Ravel J J Gravitt P E PE Yeoman C J CJ Brotman R M RM

BJOG : an international journal of obstetrics and gynaecology 20191120 2

<h4>Objective</h4>Characterise the vaginal metabolome of cervical HPV-infected and uninfected women.<h4>Design</h4>Cross-sectional.<h4>Setting</h4>The Center for Health Behavior Research at the University of Maryland School of Public Health.<h4>Sample</h4>Thirty-nine participants, 13 categorised as HPV-negative and 26 as HPV-positive (any genotype; HPV<sup>+</sup> ), 14 of whom were positive with at least one high-risk HPV strain (hrHPV).<h4>Method</h4>Self-collected mid-vaginal swabs were profi ...[more]

PMID: 31749298

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Project description:BackgroundHigh-risk human papillomavirus HPV (HR-HPV) modifies cervical cancer risk in people living with HIV, yet African populations are under-represented. We aimed to compare the frequency, multiplicity and consanguinity of HR-HPVs in HIV-negative and HIV-positive Zimbabwean women.MethodsThis was a cross-sectional study consisting of women with histologically confirmed cervical cancer attending Parirenyatwa Group of Hospitals in Harare, Zimbabwe. Information on HIV status was also collected for comparative analysis. Genomic DNA was extracted from 258 formalin fixed paraffin embedded tumour tissue samples, and analysed for 14 HR-HPV genotypes. Data was analysed using Graphpad Prism and STATA.ResultsForty-five percent of the cohort was HIV-positive, with a median age of 51 (IQR = 42-62) years. HR-HPV positivity was detected in 96% of biospecimens analysed. HPV16 (48%), was the most prevalent genotype, followed by HPV35 (26%), HPV18 (25%), HPV58 (11%) and HPV33 (10%), irrespective of HIV status. One third of the cohort harboured a single HPV infection, and HPV16 (41%), HPV18 (21%) and HPV35 (21%) were the most prevalent. HIV status did not influence the prevalence and rate of multiple HPV infections (p>0.05). We reported significant (p<0.05) consanguinity of HPV16/18 (OR = 0.3; 95% CI = 0.1-0.9), HPV16/33 (OR = 0.3; 95% CI = 0.1-1.0), HPV16/35 (OR = 3.3; 95% CI = 2.0-6.0), HPV35/51 (OR = 6.0; 95%CI = 1.8-15.0); HPV39/51 (OR = 6.4; 95% CI = 1.8-15), HPV31/52 (OR = 6.2; 95% CI = 1.8-15), HPV39/56 (OR = 11 95% CI = 8-12), HPV59/68 (OR = 8.2; 95% CI = 5.3-12.4), HPV66/68 (OR = 7; 95% CI = 2.4-13.5), independent of age and HIV status.ConclusionWe found that HIV does not influence the frequency, multiplicity and consanguinity of HR-HPV in cervical cancer. For the first time, we report high prevalence of HPV35 among women with confirmed cervical cancer in Zimbabwe, providing additional evidence of HPV diversity in sub-Saharan Africa. The data obtained here probes the need for larger prospective studies to further elucidate HPV diversity and possibility of selective pressure on genotypes.

Project description:ObjectivesHuman papillomavirus (HPV) testing in cervical screening offers the potential for self-sampling to improve uptake among non-attenders. High-risk (HR) HPV detection in urine shows promise, but few studies have examined its sensitivity for cervical intraepithelial neoplasia (CIN2+) detection compared with standard cervical samples. The aims of this cross-sectional study were to optimise conditions for urine testing for HPV detection; to determine concordance for HR-HPV detection in matched urine, vaginal and cervical samples; to compare the sensitivity of HR-HPV testing for the detection of CIN2+ in matched samples; and to determine the acceptability of urine testing for cervical screening.DesignCross-sectional study.SettingSecondary care colposcopy clinic in North West England.ParticipantsWomen aged 25 years of age or older, attending colposcopy clinic for management of abnormal cervical screening results or a suspicious-looking cervix. In total, 104 women took part in the study. Triple matched samples were available for 79 and 66 women using Abbott RealTime (ART) and Roche Cobas 4800 (RC), respectively.InterventionSelf-collected urine and vaginal samples and practitioner-obtained cervical samples were tested for HR-HPV by ART and RC assays, including comparison of neat and preservative-fixed urine. Colposcopic opinion was recorded and directed cervical biopsies taken if clinically indicated. The acceptability of self-testing was evaluated by questionnaire.Primary outcome measureThe sensitivity of urine to detect underlying CIN2+.Secondary outcome measuresThe comparative sensitivity of vaginal and cervical samples to detect CIN2+; the acceptability of urine sampling.ResultsPreservative-fixed, but not neat urine, showed good concordance with vaginal samples for the detection of HR-HPV. The sensitivity for detecting CIN2+ was 15/18 (83%) for urine and 16/18 (89%) for cervical and vaginal samples by ART, and 15/17 (88%) for all samples by RC. Urine-based testing was broadly acceptable to women.ConclusionsUrinary HR-HPV detection offers an alternative strategy of cervical screening. Larger studies to determine its clinical utility are warranted.

Dataset Information

The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis.

Objective

Design

Setting

Sample

Method

Main outcome measures

Results

Conclusions

Tweetable abstract

Publications

The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis.

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