Microbiota unbalance in relation to high-risk human papillomavirus cervical infection

Abstract

ObjectivesTo assess vaginal dysfunction using basic vaginal states and the presence of lactobacillary microbiota in patients with human papillomavirus (HPV) infection with no squamous intra-epithelial lesions (SIL), with low-grade squamous intra-epithelial lesions (L-SIL), and with high-grade squamous intra-epithelial lesions (H-SIL) or squamous cell carcinoma compared with a control group (HPV-negative); to establish the prevalence of bacterial vaginosis, candidiasis, and trichomoniasis in the different age groups; and to characterize the species of lactobacilli according to the type of lesion.MethodsA cross-sectional study was carried out of patients who underwent clinical examination and collection of vaginal fornixes to study basic vaginal states and culture. Species identification of lactobacilli was performed by mass spectrometry. The results were analyzed using the χ2and Fisher’s tests; p<0.05 was considered significant. High-risk viral types were determined using a multiplex real-time polymerase chain reaction test.ResultsA total of 741 patients were analyzed and divided into three age groups: Group 1 aged 18–24 years (n=138), Group 2 aged 25–50 years (n=456), and Group 3 aged >50 years (n=147). All groups were further divided into an HPV-negative (control) group and an HPV-positive group without lesions, with L-SIL, or with H-SIL/squamous cell carcinoma. The prevalence of unbalanced basic vaginal states in patients with H-SIL/squamous cell carcinoma was 72.7% (p=0.03) in Group 1, 53.1% (p=0.05) in Group 2, and no cases of unbalance were detected in Group 3. The prevalence of bacterial vaginosis in women with H-SIL/squamous cell carcinoma in Group 1 was 54.5% and in Group 2 was 43.7%. Patients with H-SIL/squamous cell carcinoma had a prevalence of 21.4% ofLactobacillus crispatus, 42.9% ofL. jensenii, and 14.3% ofL. iners.ConclusionsA greater unbalance of vaginal microbiota was observed in patients with SIL, especially in those with H-SIL/squamous cell carcinoma. In this group, an increase inL. jenseniiandL. inerscompared with control was found.L. crispatushad a similar prevalence to the control group. It is important to characterize the lactobacilli species since the unbalance alters the vaginal microenvironment and acts as a co-factor in the persistence of HPV infection.

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).…”

Methodological and analytical challenges in microbiome‐HPV association studies

“…10,11 The authors also attributed these associations to women's age, and therefore, it is unclear whether age or the occurrence of cervical abnormalities is the contributing factor in these correlations. 5,12 Even though the study referred to these contradictory results in the discussion, we believe that this inconsistency should be further clarified. An in-depth analysis of the potential contributing factors in this population, such as age, ethnicity, immunity, hrHPV genotyping, bacterial vaginosis (BV), microbiome continuity and dynamics, viral-induced dysbiosis, 6 and the results observed in the study is needed to fully understand these associations in the context of the natural history of HPV infections.…”

Human papillomavirus and cervical cancer in the microbial world: exploring the vaginal microecology

“…In Mexican women, HPV infection leading to cervical squamous intraepithelial lesions (SIL) is mainly associated with changes in VMB composition ( Nieves-Ramírez et al., 2021 ). SIL patients showed increased quantities of L. jensenii and L. iners ( Gomez Cherey et al., 2023 ). Additionally, L. crispatus (CST I) and L. gasseri (CST II) were most common in HPV-negative women, while CST III and IV were associated with HPV infection and the development of CC ( Audirac-Chalifour et al., 2016 ), closely related to VMB dysbiosis.…”