Cervical Microbiome in Women Infected with HPV16 and High-Risk HPVs

Abstract

Human papillomavirus type 16 (HPV16) and/or high-risk (Hr-) HPV are the main causes of cervical cancer. Another element that may contribute to the development of cervical cancer is the microbiota. To date, no study has investigated the entire cervical microbiome, which consists of bacteria, fungi, and viruses. In this study, cervical samples with different histopathology (CIN1, CIN2, and CIN3), with or without HPV16 and Hr-HPVs infection, were enrolled. From bacterial community analysis, 115 bacterial species were found and separated into 2 distinct categories based on Lactobacillus abundance: Lactobacilli-dominated (LD) and non-Lactobacilli-dominated (NLD) groups. The LD group had significantly less bacterial diversity than the NLD group. In addition, the variety of bacteria was contingent on the prevalence of HPV infection. Among distinct histological groups, an abundance of L. iners (>60% of total Lactobacillus spp.) was discovered in both groups. A few fungi, e.g., C. albicans, were identified in the fungal community. The viral community analysis revealed that the presence of HPV considerably reduced the diversity of human viruses. Taken together, when we analyzed all our results collectively, we discovered that HPV infection was a significant determinant in the diversity of bacteria and human viruses in the cervix.

Microbiome markers in HPV-positive and HPV-negative women of reproductive age with ASCUS and SIL determined by V4 region of 16S rRNA gene sequencing

“…For example, L. crispatus turned out to be the predominant Lactobacillus species in women with normocenosis for the ASCUS and LSIL groups, while L. iners prevailed in the HSIL group. There are contradictions in the works of other authors concerning L. iners: some studies show that it accompanies HPV infection and SIL (Wang et al, 2019;Sasivimolrattana et al, 2022;Xu et al, 2022), whereas other studies demonstrate no association of the kind (McKee et al, 2020;Gomez Cherey et al, 2023;Ivanov et al, 2023). L. crispatus is considered to protect from SIL progressing in HPV (Cheng et al, 2020), since it produces a lot of the D-isomer of lactic acid which increases the viscosity of the vaginal secrete and elevates its ability to sequester virions, in contrast to L. iners which produces only the L-isomer (Kalia et al, 2020;Nicolò et al, 2023).…”

Human Papillomavirus Infections and the Role Played by Cervical and Cervico-Vaginal Microbiota—Evidence from Next-Generation Sequencing Studies

“…Based on the analyzed literature (Table 1), significant differences were observed in the cervicovaginal microbiome between the HPV-positive and HPV-negative women. Generally, a wider variety of bacterial species was observed in the HPV-positive women, primarily due to the abundance of species other than Lactobacillus and a shift towards anaerobic bacteria [31,36,41,111,117,130,133,[135][136][137]139,143]. The majority of the studies indicated that HPV-negative women had a normal cervical microbiota characterized by the abundance of Lactobacillus.…”

Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

“… 16 , 248 , 249 The VMB has been found correlated with the severity of cervical lesions. As cervical lesions advance, VMB diversity escalates, 250 , 251 accompanied by increased abundance of Lactobacillus iners and dysbiosis‐related bacteria such as Porphyromonas , Prevotella , Bacteroides , and Anaerococcus species predominating. 252 , 253 , 254 , 255 HPV infection can also adversely affect the VMB, 96 , 256 and these two factors synergistically drive cervical lesions progression.…”