Cervical lesions have a high clinical incidence. When the lesion progresses, it is likely to lead to cervical cancer, which poses a great threat to the health and life safety of patients. Therefore, early diagnosis of cervical lesions is of great significance for the determination of clinical diagnosis and treatment plan and the smooth development of treatment. Although infection with HR-HPV can lead to HSIL and even cervical cancer, this condition does not occur in all individuals(Castle et al. 2011). An increasing body of data suggests that both HPV and vaginal flora disorders play an important role in cervical lesion development and even deterioration(Li et al. 2020). Therefore, exploring the relationship between HPV infection, different degrees of CIN and patients’ vaginal flora is of great significance to the diagnosis and treatment of cervical lesions.
In this study, 16S rDNA sequencing technology was used to detect the vaginal flora of patients, and patients were divided into four groups according to cervical lesions and subjected to biodiversity analysis by using bioinformatics method. Overall, in terms of taxonomy and diversity, the α diversity of vaginal flora in the HPVN group was mostly lower than that in the three HPV-positive groups. The results of the analysis on the abundance of vaginal flora in patients were similar to the results of α diversity. The biodiversity of HPVN group was significantly lower than that of HPV-positive group, and the Lactobacillus content was relatively high. This result was similar to the results of previous studies. It has been proved in a number of studies that HPV infection can increase the richness and diversity of vaginal flora while reducing the proportion of Lactobacillus in vaginal flora(Curty, de Carvalho, and Soares 2019; Anita Mitra et al. 2016; Norenhag et al. 2020). Meanwhile, the abundance analysis of vaginal flora in different groups showed that the abundance of vaginal flora in HPVN group, HPN group and HPL group were generally similar, but that in HPH group was evidently different. Studies have suggested that there is no difference between HPV positive and negative groups of vaginal flora(Tuominen et al. 2018; X.-P. Chao et al. 2019), which explains the similarity in the abundance of individuals in the HPV-negative and HPV-positive groups in this study.
Increasing studies have proved that the occurrence and progression of tumor are closely related to the microecology of tumor environment, and the change of bacteria species plays an important role in the change of microecology(Sepich-Poore et al. 2021). Most studies believe that Lactobacillus plays a certain protective role in the vagina microecology(Fan et al. 2021). The conclusion of the current study was similar to that of previous studies. Interestingly, in our results, although Lactobacillus was dominant in HPVN and HPN groups, the β diversity in the two groups was always higher than that in HPL group. This also indicated that considering only the abundance of Lactobacillus in vaginal flora had some deviation in predicting cervical lesions.
We should also admit that there is indeed a large difference in the abundance of vaginal flora between the HPH group and the other groups, and this was also demonstrated by the β diversity comparison between different groups. Therefore, we analyzed the different species of vaginal flora between HPL group and HPH group. The analysis showed that Lactobacillus was the dominant group in HPL group, while Bifidobacteriaceae and Enterobacteriaceae were relatively abundant in HPH group. Studies have shown that HPV infection changes the physical and chemical environment of the vagina, raise PH value, and possibly lead to bacterial outbreaks(Lee et al. 2013). HPV infection is also seen to induce the host vaginal mucosal immune response and changes in the reproductive interior, thus inducing changes in the vaginal flora(Shannon et al. 2017; Woodworth 2002). Combined with the relationship between HPV infection, cervical lesions and vaginal flora changes, we analyzed the differences of metabolic pathways between HPH group and HPL group. The results showed that there were 24 major differential expression pathways in the HPL group, which were mainly related to PH regulation and mucosal formation. This result was similar to the results of vaginal flora metabolic pathways in uninfected women reported by Pramanick et al.(Pramanick et al. 2021), which also indicated that the metabolic status of vaginal flora in the HPL group was similar to that in normal patients. Thus, it was also verified from the side that although tissue lesions appeared in the HPL group, the condition was relatively mild and could be cured by active treatment. The energy metabolism of HPH group is mainly glucose metabolism. Studies have proved that there is a close relationship between glycolysis and vaginal flora imbalance(Liu et al. 2021; Borgdorff et al. 2016). Meanwhile, it has been proved that HPV infection is associated with human glycogen metabolism(Sitarz et al. 2022). Metabolic reprogramming is one of the markers of tumors, and it has been proved that HPV can interact with cell metabolic molecules to promote cell glycolysis and lead to disease deterioration(Arizmendi-Izazaga et al. 2021). Combined with the above evidence, we can see that HPV can affect cervical epithelial cells by changing the balance of vaginal flora and affecting the metabolism of microbiota. Therefore, the possibility of cervical epithelial lesions can be predicted by detecting the changes of vaginal flora and metabolic changes of the flora.