The Vaginal Microbiota, Human Papillomavirus Infection, and Cervical Carcinogenesis: A Systematic Review in the Latina Population

Abstract

Background: Latina women experience disproportionately higher rates of HPV infection, persistence, and progression to cervical dysplasia and cancer compared to other racial-ethnic groups. This systematic review explores the relationship between the cervicovaginal microbiome and human papillomavirus infection, cervical dysplasia, and cervical cancer in Latinas.

Methods: The review abides by the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, EMBASE, and Scopus databases were searched from January 2000 through November 11, 2022. The review included observational studies reporting on the cervicovaginal microbiota in premenopausal Latina women with human papillomavirus infection, cervical dysplasia, and cervical cancer.

Results: Twenty-five articles were eligible for final inclusion (N = 131,183). Forty-two unique bacteria were reported in the cervicovaginal microbiome of Latinas. Seven bacteria: Lactobacillus crispatus, Lactobacillus iners, Chlamydia trachomatis, Prevotella spp., Prevotella amnii, Fusobacterium spp. and Sneathia spp. were enriched across multiple stages of cervical carcinogenesis in Latinas. Therefore, the total number of reported bacteria includes four bacteria associated with the healthy state, 16 bacteria enriched in human papillomavirus outcomes, 24 unique bacteria associated with abnormal cytology/dysplasia, and five bacteria associated with cervical cancer. Furthermore, three studies reported significantly higher alpha and beta diversity in Latinas with cervical dysplasia and cancer compared to controls. Lactobacillus depletion and an increased abundance of L. iners in Latinas compared to non-Latinas, regardless of human papillomavirus status or lesions, were observed.

Conclusions: The identification of 42 unique bacteria and their enrichment in cervical carcinogenesis can guide future cervicovaginal microbiome research to better inform cervical cancer prevention strategies in Latinas.

Keywords: Cervical cancer; Health disparities; Human papillomavirus; Latin America and the Caribbean; Latinas; Microbiome.

Fig. 1

PRISMA Methodological Flowchart. The flowchart depicts the identification, selection, and final inclusion of articles. Records of excluded articles and reasons for exclusion are also included. ^aThe total number of full-text articles excluded was n = 79. However, articles could be excluded for more than one reason. Two articles were excluded for multiple reasons, therefore the total sum for each reason is 81

Fig. 2

Cervicovaginal Bacteria Associated With Cervical Carcinogenesis in Latinas. Differences and similarities in the cervicovaginal microbiome composition from (1) healthy state to (2) HPV infection, (3) abnormal cytology/dysplasia, and (4) cervical cancer are depicted. Panel 1 is a light green color indicating an association with vaginal health. The following disease conditions proceed in a pink-to-red gradient according to severity: Panel 2 is light pink for HPV infection, Panel 3 is dark pink for abnormal cytology/dysplasia, and Panel 4 is bright red for cervical cancer. Enrichment or depletion of bacterial taxa associated with each stage is indicated with an up or down arrow, respectively. A question mark denotes differences in reports with regard to bacterial enrichment or depletion within the same panel. Bolded bacteria were reported in more than one study

Fig. 3

Cervicovaginal Bacteria Enriched Across Stages of Cervical Carcinogenesis in Latinas. The quadruple Venn diagram highlights seven bacteria enriched across outcome groups, including healthy controls. Sneathia spp. and L. iners were associated with multiple outcome groups across cervical carcinogenesis. The numbers listed after each bacterial species correspond to the article reporting on the enrichment of the bacteria (reference Table 2)