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Tumor microbial diversity and compositional differences among women in Botswana with high-grade cervical dysplasia and cervical cancer
  1. Travis T Sims1,
  2. Greyson W G Biegert2,
  3. Doreen Ramogola-Masire3,
  4. Kebatshabile Ngoni4,
  5. Travis Solley2,
  6. Matthew S Ning2,
  7. Molly B El Alam2,
  8. Melissa Mezzari5,
  9. Joseph Petrosino5,
  10. Nicola M Zetola6,
  11. Kathleen M Schmeler1,
  12. Lauren E Colbert2,
  13. Ann H Klopp2 and
  14. Surbhi Grover6
  1. 1 Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  2. 2 Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  3. 3 Obstetrics and Gynecology, Faculty of Medicine, University of Botswana, Gaborone, Botswana
  4. 4 Department of Biological Sciences, University of Botswana, Gaborone, Botswana
  5. 5 Molecular Virology and Microbiology, Baylor College of Medicine Alkek Center for Molecular Discovery, Houston, Texas, USA
  6. 6 Radiation Oncology, Botswana-University of Pennsylvania Partnership, Philadelphia, Pennsylvania, USA
  1. Correspondence to Dr Travis T Sims, Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; ttsims{at}mdanderson.org

Abstract

Introduction We characterized the cervical 16S rDNA microbiome of patients in Botswana with high-grade cervical dysplasia and locally advanced cervical cancer.

Methods This prospective study included 31 patients: 21 with dysplasia and 10 with cancer. The Shannon diversity index was used to evaluate alpha (intra-sample) diversity, while the UniFrac (weighted and unweighted) and Bray–Curtis distances were employed to evaluate beta (inter-sample) diversity. The relative abundance of microbial taxa was compared among samples using linear discriminant analysis effect size.

Results Alpha diversity was significantly higher in patients with cervical cancer than in patients with cervical dysplasia (P<0.05). Beta diversity also differed significantly (weighted UniFrac Bray–Curtis, P<0.01). Neither alpha diversity (P=0.8) nor beta diversity (P=0.19) varied by HIV status. The results of linear discriminant analysis effect size demonstrated that multiple taxa differed significantly between patients with cervical dysplasia vs cancer. Lachnospira bacteria (in the Clostridia class) were particularly enriched among cervical dysplasia patients, while Proteobacteria (members of the Firmicutes phyla and the Comamonadaceae family) were enriched in patients with cervical cancer.

Discussion The results of our study suggest that differences exist in the diversity and composition of the cervical microbiota between patients with cervical dysplasia and patients with cervical cancer in Botswana. Additional studies are warranted to validate these findings and elucidate their clinical significance among women living in sub-Saharan Africa, as well as other regions of the world.

  • cervical cancer
  • uterine cervical neoplasms
  • gynecology
  • cervix uteri

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Footnotes

  • TTS and GWGB are joint senior authors.

  • Twitter @MollyAlam, @mpmezzari, @colbertle

  • Collaborators Stephen Hahn, Tatiana V. Karpinets, Kyoko Yoshida-Court, Xiaogang Wu, Andrea Y. Delgado Medrano, Nadim J. Ajami, Mustljapha Ahmed-Kaddar.

  • Contributors All authors were involved with subject identification and data collection, interpretation of the statistical analysis, and review and approval of the final manuscript. The study concept was developed by LEC, AK, SG, GWGB, and TTS. GWGB and TTS drafted the manuscript.

  • Funding This research was supported in part by the National Institutes of Health (NIH) through MD Anderson’s Cancer Center Support Grant P30 CA016672 (TTS), the National Institutes of Health T32 grant 5T32 CA101642-14 (TTS), and the Mentored Patient Oriented Career Research Development Award 1-K08CA230170-01A1 (SG). This study was partially funded by the MD Anderson HPV-Related Cancers Moonshot (AK).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. The data that support the findings of this study are available from the corresponding author, [TTS], upon reasonable request. Contact: Travis T. Sims, MD, MPH Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center 1155 Herman Pressler, CPB 6.3258, Unit 1362 Houston, TX 77030 Phone: 713-563-4578 Fax: 713-745-2398 Email: ttsims@mdanderson.org.