The vaginal microbiota, human papillomavirus and cervical dysplasia: a systematic review and network meta‐analysis

Abstract

Background Persistent infection with high-risk human papillomavirus can lead to cervical dysplasia and cancer. Recent studies have suggested associations between the composition of the vaginal microbiota, infection with human papillomavirus (HPV) and progression to cervical dysplasia and cancer.Objective To assess how specific cervico-vaginal microbiota compositions are associated with HPV infection, cervical dysplasia and cancer, we conducted a systematic review and network metaanalysis (registered in PROSPERO: CRD42018112862).Search strategy PubMed, Web of science, Embase and Cochrane database.Selection criteria All original studies describing at least two community state types of bacteria (CST), based on molecular techniques enabling identification of bacteria, and reporting the association with HPV infection, cervical dysplasia and/or cervical cancer.Data collection and analysis For the meta-analysis, a network map was constructed to provide an overview of the network relationships and to assess how many studies provided direct evidence for the different vaginal microbiota compositions and HPV, cervical dysplasia or cancer. Thereafter, the consistency of the model was assessed, and forest plots were constructed to pool and summarise the available evidence, presenting odds ratios and 95% confidence intervals.Main results Vaginal microbiota dominated by non-Lactobacilli species or Lactobacillus iners were associated with three to five times higher odds of any prevalent HPV and two to three times higher for high-risk HPV and dysplasia/cervical cancer compared with Lactobacillus crispatus.Conclusions These findings suggest an association between certain bacterial community types of the vaginal microbiota and HPV infection and HPV-related disease. This may be useful for guiding treatment options or serve as biomarkers for HPV-related disease.Tweetable abstract This network meta-analysis suggests an association between different vaginal bacterial community types and the risk of HPV.

Human papillomavirus infection and cervical intraepithelial neoplasia progression are associated with increased vaginal microbiome diversity in a Chinese cohort

“…Similarly to the previous studies [2,4,17,18,23,24,40,42,47], we found increased abundances of several anaerobic bacteria such as Prevotella, Bacillus, Anaerococcus, Sneathia, Megasphaera, Streptococcus and Anaerococcus in HPV-infected women. We recognized Megasphaera of Firmicutes phylum as the most signi cant genus related with HPV infection, while Lee et al identi ed Sneathia spp.…”

“…However, L. iners has many properties different from other Lactobacillus spp., for example unable to produce H 2 O 2, and it often predominates in the presence of HPV infection [4,17,18] and CIN [18,19].…”

“…Caucasian and Asian women display a signi cantly greater prevalence of Lactobacillus in the vagina compared to Hispanic and Black women [8,10,31]. To our knowledge, data with regard to the vaginal bacterial composition of Chinese populations are inadequate [8,18,32]. The analysis, which is performed in a large cohort of women living in a different country and with supposed different hygiene habits [10], is helpful to reinforce the underlying associations.…”

HIV and Development of Epithelial Cell Abnormalities in women with prior normal cervical cytology in Nigeria

“…This nding contradicts the well-known evidence that Bacterial vaginosis and sexually transmissible infections are associated with persistent high-risk human Papillomavirus and precancer. [30,31] It is possible that reporting bias may have affected the analysis for vaginal infection given that over 80% of the women in the sample reported having vaginal infection. This is possible since, anecdotally, women in our population often perceive vaginal discharge as "toilet" infection.…”

Response letter to comments related to “The clinical role of LASER for vulvar and vaginal treatments in gynecology and female urology: An ICS/ISSVD best practice consensus document”

“…26,27 Do these changes affect the vaginal microbiome and its relationship with HPV infection? [28][29][30] Is HPV entry at the vaginal epithelium basal layer following LASER easier? 31,32 These are important questions that research needs to address.…”