Ma Yingying, Li Yanpeng, Liu Yanmei, Cao Le, Han Xiao, Gao Shujun, Zhang Chiyu
Shanghai Public Health Clinical Center, Fudan University, Shanghai, 200437, People's Republic of China.
Center of Diagnosis and Treatment for Cervical and Uterine Cavity Disease, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People's Republic of China.
J Microbiol. 2023 Apr;61(4):423-432. doi: 10.1007/s12275-023-00039-3. Epub 2023 Apr 3.
Vaginal microbiome composition was demonstrated to be associated with cervical disease. The colonization characteristics of vaginal microbes and their association with the different cervical disease status, especially cervical cancer (CC), are rarely investigated. In this cross-sectional study, we characterized the vaginal microbiome of women with different status of cervical diseases, including 22 NV + (normal tissue with HPV infection), low-grade squamous intraepithelial lesion (LSIL, n = 45), high-grade squamous intraepithelial lesion (HSIL, n = 36) and CC (n = 27) using bacterial 16S DNA sequencing. Thirty HPV-negative women with normal tissue were used as the control group. We found that higher diversity of microbiome with gradual depletion of Lactobacillus, especially L. crispatus, was associated with the severity of cervical disease. High-risk HPV16 infection was associated with higher microbiome diversity and depletion of Lactobacillus in high-grade cervical diseases (i.e. HSIL and CC). The CC group was characterized by higher levels of Fannyhessea vaginae, Prevotella, Bacteroides, Finegoldia, Vibrio, Veillonella, Peptostreptococcus, and Dialister. Co-occurrence network analyses showed that negative correlations were exclusively observed between Lactobacillus and other bacteria, and almost all non-Lactobacillus bacteria were positively correlated with each other. In particular, the most diverse and complex co-occurrence network of vaginal bacteria, as well as a complete loss of L. crispatus, was observed in women with CC. Logistic regression model identified HPV16 and Lactobacillus as significant risk and protective factors for CC, respectively. These results suggest that specific Lactobacillus species (e.g. L. crispatus and L. iners) can be used as important markers to target prevention measures prioritizing HPV16-infected women and other hrHPV-infected women for test, vaccination and treat initiatives.
阴道微生物群组成被证明与宫颈疾病有关。阴道微生物的定植特征及其与不同宫颈疾病状态，尤其是宫颈癌（CC）的关联很少被研究。在这项横断面研究中，我们使用细菌16S DNA测序对不同宫颈疾病状态的女性阴道微生物群进行了特征分析，包括22例NV +（HPV感染的正常组织）、低级别鳞状上皮内病变（LSIL，n = 45）、高级别鳞状上皮内病变（HSIL，n = 36）和CC（n = 27）。30名HPV阴性的正常组织女性作为对照组。我们发现微生物群多样性增加以及乳酸杆菌尤其是卷曲乳酸杆菌逐渐减少与宫颈疾病的严重程度相关。高危型HPV16感染与高级别宫颈疾病（即HSIL和CC）中较高的微生物群多样性和乳酸杆菌减少有关。CC组的特征是阴道芬尼酵母、普雷沃菌属、拟杆菌属、纤细杆菌属、弧菌属、韦荣球菌属、消化链球菌属和戴阿李斯特菌属水平较高。共现网络分析表明，仅在乳酸杆菌和其他细菌之间观察到负相关，几乎所有非乳酸杆菌细菌之间呈正相关。特别是，在CC女性中观察到阴道细菌最具多样性和复杂性的共现网络，以及卷曲乳酸杆菌的完全缺失。逻辑回归模型确定HPV16和乳酸杆菌分别是CC的显著风险和保护因素。这些结果表明，特定的乳酸杆菌种类（如卷曲乳酸杆菌和惰性乳酸杆菌）可作为重要标志物，用于针对HPV16感染女性和其他高危型人乳头瘤病毒（hrHPV）感染女性进行检测、疫苗接种和治疗的预防措施。
