Abstract

Many studies investigating the human microbiome-cancer interface have focused on the gut microbiome and gastrointestinal cancers. Outside of human papillomavirus driving cervical cancer, little is known about the relationship between the vaginal microbiome and other gynecological cancers, such as ovarian cancer. In this retrospective study, we investigated the relationship between ovarian cancer, platinum-free interval (PFI) length, and vaginal and gut microbiomes. We observed that Lactobacillus-dominated vaginal communities were less common in women with ovarian cancer, as compared to existing datasets of similarly aged women without cancer. Primary platinum-resistance (PPR) disease is strongly associated with survivability under one year, and we found over one-third of patients with PPR (PFI < 6 months, n = 17) to have a vaginal microbiome dominated by Escherichia (>20% relative abundance), while only one platinum super-sensitive (PFI > 24 months, n = 23) patient had an Escherichia-dominated microbiome. Additionally, L. iners was associated with little, or no, gross residual disease, while other Lactobacillus species were dominant in women with >1 cm gross residual disease. In the gut microbiome, we found patients with PPR disease to have lower phylogenetic diversity than platinum-sensitive patients. The trends we observe in women with ovarian cancer and PPR disease, such as the absence of Lactobacillus and presence of Escherichia in the vaginal microbiome as well as low gut microbiome phylogenetic diversity have all been linked to other diseases and/or pro-inflammatory states, including bacterial vaginosis and autoimmune disorders. Future prospective studies are necessary to explore the translational potential and underlying mechanisms driving these associations.

Highlights

  • Ovarian cancer is the most deadly gynecological cancer (Siegel, Miller & Jemal, 2019); it kills approximately 14,000 women in the United States annually, accounting for 4.9% of all cancer-related deaths in females in the United States

  • Even though iterative cytoreductive surgery and Escherichia are more common in platinum-free interval (PFI) < 6 months individuals, we found no significant relationship between iterative Cytoreductive Surgery (iCRS) and Escherichia abundance (Table S3, Fig. 2A, p-value = 0.292)

  • Our results demonstrate an association between the vaginal and gut microbiomes and platinum-sensitivity in women with ovarian cancer

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Summary

Introduction

Ovarian cancer is the most deadly gynecological cancer (Siegel, Miller & Jemal, 2019); it kills approximately 14,000 women in the United States annually, accounting for 4.9% of all cancer-related deaths in females in the United States. Other patients may remain free of cancerous growth for more than two years, but the risk of recurrence and eventual development of treatment-resistant cancer is still unacceptably high (Bookman, 1999; Gore et al, 1990; Markman et al, 1991; Pfisterer & Ledermann, 2006). This merits a focus on discovering biomarkers of ovarian cancer and drivers of platinum-resistance to facilitate early cancer detection as well as better understand variation in treatment outcomes

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