BV associated bacteria specifically BVAB 1 and BVAB 3 as biomarkers for HPV risk and progression of cervical neoplasia

Abstract

Background. Bacterial vaginosis (BV) is associated with high-risk HPV (hrHPV) genotypes. There is a proposed bidirectional relationship between hrHPV and vaginal microbial diversity. This study investigated the association between BV associated bacteria in women co-infected with Human immunodeficiency virus (HIV) and hrHPV. Methods. Stored cervical cytobrush samples were used for real time PCR detection of eight BV associated bacteria. Analysis of BV bacteria detected against HPV infection, socio-demographics and HIV data were conducted in R Statistical computing software of the R Core Team, 2020, version 3.6.3. Results. A total of 190 samples were analysed. A. vaginae (p <0.001) BVAB 1 (p <0.001), BVAB 2 (p =0.428), BVAB 3 (p <0.001), Lactobacillus species (p =0.016) and S. sanguinegens (p =0.007) were associated with prevalent hrHPV. Increasing CIN severity was independently associated with detection of BVAB 1 OR 1.51(95% CI: 0.42-5.55), BVAB 3 OR 2.72(95% CI:0.90-8.55) and S. sanguinegens OR 1.02(95% CI:0.37-2.80). All HPV genotypes/groups, gravida <2, A. vaginae (p =0.002) and BVAB 1 (p =0.026) were significantly associated with HPV persistence. BVAB 3, p =0.010 and HPV 16 were significantly associated with HPV reinfection. Conclusion. There is a significant association of A. vaginae, BVAB 1, BVAB 3, S. sanguinegens and Lactobacillus spp to prevalent hrHPV. BVAB 1, BVAB 3 and S. sanguinegens had an increased odds for increasing CIN severity. A vaginae, BVAB 1, gravida and all the HPV genotypes/groups were significantly associated with HPV persistence. Only BVAB 3 and HPV 16 were significantly associated with hrHPV reinfection at 1 year review. BVAB 1 and BVAB 3 are possible biomarkers for HPV infection and CIN progression.

Molecular Characterization of Vaginal Microbiota Using a New 22-Species qRT-PCR Test to Achieve a Relative-abundance and Species-based Diagnosis of Bacterial Vaginosis

“…A Brazilian study using 223 BV-positive samples also reported the same findings regarding the relative abundance of BVAB-1, BVAB-2, and BVAB-3, affirming our observations [32]. A positive association between BV and high-risk Human Papilloma Virus (HPV) genotypes has been reported, owing to the occurrence of BVAB 1 and 3, and other BV-associated-bacteria in women co-infected with HIV and HPV [39]. The same study also showed that the presence of BVAB 1 and 3 had an elevated likelihood of increasing the severity of cervical neoplasia in this population [39].…”

“…A positive association between BV and high-risk Human Papilloma Virus (HPV) genotypes has been reported, owing to the occurrence of BVAB 1 and 3, and other BV-associated-bacteria in women co-infected with HIV and HPV [39]. The same study also showed that the presence of BVAB 1 and 3 had an elevated likelihood of increasing the severity of cervical neoplasia in this population [39]. Nevertheless, these species are not as closely related as initially thought as a recent phylogenetic analysis identified BVAB 1, 2, and 3 to be Clostridiales genomosp., Oscillospiraceae bacterium strain CHIC02, and Mageeibacillus indolicus, respectively [37].…”

DataSheet_1.pdf

“…A Brazilian study using 223 BV-positive samples also reported the same findings regarding the relative abundance of BVAB-1, BVAB-2, and BVAB-3, affirming our observations (Malaguti et al, 2015). A positive association between BV and high-risk Human Papilloma Virus (HPV) genotypes has been reported, owing to the occurrence of BVAB 1 and 3, and other BV-associated-bacteria in women coinfected with HIV and HPV (Naidoo et al, 2022). The same study also showed that the presence of BVAB 1 and 3 had an elevated likelihood of increasing the severity of cervical neoplasia in this population (Naidoo et al, 2022).…”

“…A positive association between BV and high-risk Human Papilloma Virus (HPV) genotypes has been reported, owing to the occurrence of BVAB 1 and 3, and other BV-associated-bacteria in women coinfected with HIV and HPV (Naidoo et al, 2022). The same study also showed that the presence of BVAB 1 and 3 had an elevated likelihood of increasing the severity of cervical neoplasia in this population (Naidoo et al, 2022). Nevertheless, these species are not as closely related as initially thought as a recent phylogenetic analysis identified BVAB 1, 2, and 3 to be "Clostridiales genomosp.…”

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

“…Some authors consider microbial diversity as well as changes in the qualitative and quantitative composition of the cervicovaginal microbiota to be crucial for triggering the proliferation of the stratified squamous epithelial cells and to accompany HPV persistence. Conversely, the viral infection can alter bacterial composition irrespective of the SIL severity looping a ‘vicious circle’ in the development and progression of the disease ( Kang et al, 2021 ; Naidoo et al, 2022 ; Ntuli et al, 2022 ). Recently, special attention has been paid to the influence of individual microorganisms on SIL development ( Norenhag et al, 2020 ; Gardella et al, 2022 ; Lin et al, 2022 ).…”