Intratumoral microbiota composition in women's cancers: a systematic review and meta-analysis

Qin Wen^1,2Shubin Wang^1,2Shunlian Fu³Xinxiang Zhou^1,2Yalan Min^1,2Jinyi Lang^1,2*Meihua Chen^2*

• ¹School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
• ²Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, Affiliated cancer hospital of University of Electronic Science and Technology of China, Chengdu, China
• ³School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China

The intratumoral microbiota has attracted considerable interest in carcinogenesis, progression, and treatment owing to advancements in sequencing technology. This systematic review provides a comprehensive overview of the current literature regarding the diversity and compositional characteristics of the intratumoral microbiota in women's cancers. Additionally, it also explores potential associations among intratumoral microbiota, estrogen, and anti-tumor therapies.A comprehensive literature search was conducted using PubMed, Embase, Web of Science, and the Cochrane Library from their inception to May 1, 2024. The review protocol was pre-registered in PROSPERO (CRD 42024601213). Articles were assessed utilizing the Newcastle-Ottawa Scale (NOS). To estimate the effect size and variability in microbial diversity changes, the standardized mean difference (SMD) and 95% confidence intervals (CIs) were employed. This systematic review included 29 of 8,291 studies after a thorough screening process. Of the 22 studies investigating α-diversity in women's cancers, disease-free controls, and those with benign conditions, notable changes in diversity indices were observed. Compared to adjacent normal tissues, the Simpson index significantly decreased in breast cancer (SMD = -0.75, 95% CI: [-0.94, -0.55]) and endometrial cancer (SMD = -0.83, 95% CI: [-1.37, -0.28]). The Chao1 index was reduced in endometrial cancer tumor tissues relative to normal tissues (SMD = -2.25, 95% CI: [-3.13, -1.36]), while the Shannon index decreased in ovarian cancer tumor tissues (SMD = -0.61, 95% CI: [-1.18, -0.04]). In comparisons between tumor and benign tissues, the Chao1 index was decreased (SMD = -0.64, 95% CI: [-1.20, -0.08], I² = 0%), while the Simpson index was increased (SMD = 0.36, 95% CI: [0.01, 0.71], I² = 0%) in patients with ovarian cancer.Other microbial diversity indices showed no significant differences between tumor and non-tumor tissues. This study highlights significant differences in microbiota composition between tumor and nontumor tissues in women's cancers, emphasizing changes in intratumoral microbiota influenced by estrogen and antineoplastic treatments. Further research is needed to explore the potential for developing targeted therapies based on estrogen-driven microbiota alterations. Investigations may yield insights into the enhancement of female reproductive health and the improvement of treatment efficacy for female cancers.