Shibo Lei,1,2,* Jing Wang,1,* Man Zhang,2 Jing Huang,3 Ying Liu,1 Ying Long,1 Yixuan Xing,4 Zheng Yu2 

1The Affiliated Cancer Hospital of Xiangya School of Medicine/Hunan Cancer Hospital, Central South University, Changsha, People’s Republic of China; 2Human Microbiome and Health Group, Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, People’s Republic of China; 3Department of Parasitology, School of Basic Medical Science, Central South University, Changsha, People’s Republic of China; 4The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yixuan Xing, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, People’s Republic of China, Email 234428043@qq.com Zheng Yu, Human Microbiome and Health Group, Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, People’s Republic of China, Email yuzheng@csu.edu.cn

Objective: To define stage-specific cervical canal microbiota signatures across the continuum of gynecologic malignancies from benign endometrial cancer (BE)/cervical cancer precancerous lesions (CIN) to endometrial cancer (EC)/cervical cancers (CC), and to evaluate their potential as diagnostic biomarkers and therapeutic targets.
Methods: In the observational study, metagenomic sequencing was employed to investigate the cervical canal microbiota of 45 patients, including BE, EC, CIN, and CC. Specimen collection was performed by an experienced physician. All samples were sequenced utilizing the shotgun approach. The microbial statistical analyses were conducted using R.
Results: Compared to the non-cancerous group (BE and CIN), the index related to microbial community stability decreases significantly and the incidence of cervical canal dysbiosis increases in the cancerous group (EC and CC). Microbial diversity exhibited significant differences between BE and EC, CIN and CC, as well as cancerous and non-cancerous groups. At the species level, some species were significantly decreased (eg, Lactobacillus iners) and increased (eg, Staphylococcus haemolyticus, Pasteurella multocida, Pseudomonas putida, and other opportunistic pathogen) in the cancerous group.
Conclusion: The cervical canal represents a distinct microbial niche, with its dysbiotic progression reflecting the trajectory of oncogenic transformation. The progression from non-cancerous to cancerous states is characterized by the replacement of the vaginal microbial community, which is dominated by Lactobacillus iners, with a gradual shift towards opportunistic pathogen. Disease diagnosis and complementary therapies focused on lactobacilli and hallmark opportunistic pathogen may offer new insights for precision oncology.

Keywords: community succession, cervical canal microbiota, microbial dysbiosis, endometrial cancer, cervical cancer