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Volume 14
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Review

The Relationship Between the Vaginal Microbiota and the Ovarian Cancer Microenvironment: A Journey from Ideas to Insights

by
Stefano Restaino
1,2,
Giulia Pellecchia
1,3,
Martina Arcieri
1,*,
Eva Pericolini
4,
Giorgio Bogani
5,
Alice Poli
1,3,
Federico Paparcura
1,3,
Sara Pregnolato
1,3,
Doriana Armenise
1,3,
Barbara Frossi
6,
Gianluca Tell
7,
Carlo Tascini
8,
Lorenza Driul
1,3,
Anna Biasioli
1,
Vito Andrea Capozzi
9,
Carlo Ronsini
10,
Luigi Della Corte
11,
Canio Martinelli
12,13,
Alfredo Ercoli
12,
Francesco De Seta
14 and
Giuseppe Vizzielli
1,3add Show full author list remove Hide full author list
1
Department of Maternal and Child Health, Obstetrics and Gynecology Clinic, University Hospital of Udine, 33100 Udine, Italy
2
PhD School in Biomedical Sciences, Gender Medicine, Child and Women Health, University of Sassari, 07100 Sassari, Italy
3
Department of Medicine, University of Udine, 33100 Udine, Italy
4
Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, 41125 Modena, Italy
5
Gynaecological Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy
6
Department of Medicine (DMED), University of Udine, 33100 Udine, Italy
7
Molecular Biology Section, Department of Medicine, University of Udine, 33100 Udine, Italy
8
Infectious Diseases Clinic, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy
9
Department of Obstetrics and Gynecology, University of Parma, 43125 Parma, Italy
10
Unit of Gynecologic Oncology, National Cancer Institute, IRCCS, Fondazione “G. Pascale”, 80131 Naples, Italy
11
Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples “Federico II”, 80131 Naples, Italy
12
Unit of Gynecology and Obstetrics, Department of Human Pathology of Adults and Developmental Age, G, Martino University Hospital, 98124 Messina, Italy
13
Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
14
Department of Medical Sciences, University of Trieste, 34127 Trieste, Italy
 
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*
Author to whom correspondence should be addressed.
Cells 2025, 14(20), 1590; https://doi.org/10.3390/cells14201590 (registering DOI)
Submission received: 26 August 2025 / Revised: 23 September 2025 / Accepted: 3 October 2025 / Published: 13 October 2025
(This article belongs to the Section Cellular Pathology)
Versions Notes

Abstract

Background: The tumor microenvironment offers a new perspective in gynecologic oncology. In ovarian cancer, numerous preclinical studies, especially organoid models, have highlighted cellular, immune, and biochemical mechanisms. Beyond these sophisticated findings, more practical aspects require attention, such as the role of vaginal microbiota, which represents an interplay between external agents and internal genitalia, and its potential profiling role in early detection beyond the promise of microbiota-targeted therapies. Objectives: This review aims to assess whether such a correlation is speculative or scientifically grounded. Methods: A focused literature search was conducted on vaginal microbiota and its correlation with ovarian cancer to define the current state of knowledge. Results: Mixed outcomes have been reported, yet there is a rational and scientific basis supporting further investigation. Clinical approaches increasingly consider vaginal microbiota as relevant. However, we have to say that most available evidence is still preliminary and largely preclinical to set realistic expectations for readers. Although additional studies are needed, emerging insights highlight its importance and practical implications. We present a diagnostic–therapeutic management flowchart summarizing current evidence). Discussion: Most links between the vaginal microbiota and ovarian cancer are correlational rather than causal. The idea that microbes ascend from the vagina to the ovaries is proposed but still definitely not demonstrated. Confounding factors like age, hormones, and BRCA status complicate interpretation, and ovarian cancer itself could secondarily alter the microbiota. Mechanistic studies and longitudinal data are still needed to clarify whether dysbiosis contributes to carcinogenesis or is merely a consequence. As gynecologists, we summarize key aspects and emphasize to colleagues the importance of incorporating these findings into daily clinical practice. Vaginal dysbiosis should be considered not only a local imbalance but also a potential strategy for primary cancer prevention. Conclusions: Future research on the tumor microenvironment and vaginal microbiota will expand scientific knowledge and guide innovative preventive and therapeutic strategies.
Keywords: microenvironment; tumor; genital neoplasms; female/prevention & control; microbiota microenvironment; tumor; genital neoplasms; female/prevention & control; microbiota

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MDPI and ACS Style

Restaino, S.; Pellecchia, G.; Arcieri, M.; Pericolini, E.; Bogani, G.; Poli, A.; Paparcura, F.; Pregnolato, S.; Armenise, D.; Frossi, B.; et al. The Relationship Between the Vaginal Microbiota and the Ovarian Cancer Microenvironment: A Journey from Ideas to Insights. Cells 2025, 14, 1590. https://doi.org/10.3390/cells14201590

AMA Style

Restaino S, Pellecchia G, Arcieri M, Pericolini E, Bogani G, Poli A, Paparcura F, Pregnolato S, Armenise D, Frossi B, et al. The Relationship Between the Vaginal Microbiota and the Ovarian Cancer Microenvironment: A Journey from Ideas to Insights. Cells. 2025; 14(20):1590. https://doi.org/10.3390/cells14201590

Chicago/Turabian Style

Restaino, Stefano, Giulia Pellecchia, Martina Arcieri, Eva Pericolini, Giorgio Bogani, Alice Poli, Federico Paparcura, Sara Pregnolato, Doriana Armenise, Barbara Frossi, and et al. 2025. "The Relationship Between the Vaginal Microbiota and the Ovarian Cancer Microenvironment: A Journey from Ideas to Insights" Cells 14, no. 20: 1590. https://doi.org/10.3390/cells14201590

APA Style

Restaino, S., Pellecchia, G., Arcieri, M., Pericolini, E., Bogani, G., Poli, A., Paparcura, F., Pregnolato, S., Armenise, D., Frossi, B., Tell, G., Tascini, C., Driul, L., Biasioli, A., Capozzi, V. A., Ronsini, C., Della Corte, L., Martinelli, C., Ercoli, A., ... Vizzielli, G. (2025). The Relationship Between the Vaginal Microbiota and the Ovarian Cancer Microenvironment: A Journey from Ideas to Insights. Cells, 14(20), 1590. https://doi.org/10.3390/cells14201590

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