Abstract
ABSTRACTCervical cancer is an important health concern worldwide and is one of the leading causes of death in Mexican women. Previous studies have shown changes in the female genital tract microbe community related to human papillomavirus (HPV) infection and cervical cancer; yet, this link remains unexplored in many human populations. This study evaluated the vaginal bacterial community among Mexican women with precancerous squamous intraepithelial lesions (SIL). We sequenced the V3 region of the 16S rRNA gene in cervical samples from 228 Mexican women, including 121 participants with SIL, most of which were HPV positive, and 107 healthy women without HPV infection or SIL. The presence of SIL was associated with changes in composition (beta diversity) and with a higher species richness (Chao1). A comparison of HPV-positive women with and without SIL showed that microbiota changes occurred even in the absence of SIL. Multivariate association with linear models (MaAsLin) analysis yielded independent associations between HPV infection and an increase in the relative abundance of Brachybacterium conglomeratum and Brevibacterium aureum as well as a decrease in two Lactobacillus iners operational taxonomic units (OTUs). We also identified a positive independent association between HPV-16, the most common HPV subtype linked to SIL, and Brachybacterium conglomeratum. Our work indicates that HPV infection leading to SIL is primarily associated with shifts in vaginal microbiota composition, some of which may be specific to this human population.IMPORTANCE Human papillomavirus (HPV) plays a critical role in cervical carcinogenesis but is not sufficient for cervical cancer development, indicating the involvement of other factors. The vaginal microbiota is an important factor in controlling infections caused by HPV, and, depending on its composition, it can modulate the microenvironment in vaginal mucosa against viral infections. Ethnic and sociodemographic factors influence differences in vaginal microbiome composition, which underlies the dysbiotic patterns linked to HPV infection and cervical cancer across different populations of women. Here, we provide evidence for associations between vaginal microbiota patterns and HPV infection linked to ethnic and sociodemographic factors. To our knowledge, this is the first report of the species Brevibacterium aureum and Brachybacterium conglomeratum linked to HPV infection or squamous intraepithelial lesions (SIL).
Highlights
Cervical cancer is an important health concern worldwide and is one of the leading causes of death in Mexican women
Of the 121 cases, 90 were diagnosed with low squamous intraepithelial lesion (LSIL), and 31 were diagnosed
Several factors are known to play a role in cervical carcinogenesis, with human papillomavirus (HPV) infection being one of the most important in the development of the disease [1]
Summary
Cervical cancer is an important health concern worldwide and is one of the leading causes of death in Mexican women. We provide evidence for associations between vaginal microbiota patterns and HPV infection linked to ethnic and sociodemographic factors To our knowledge, this is the first report of the species Brevibacterium aureum and Brachybacterium conglomeratum linked to HPV infection or squamous intraepithelial lesions (SIL). Many factors have been associated with the appearance of SIL, such as intermenstrual bleeding, multiparity, use of contraceptives, multiple sexual partners, and smoking [8] In addition to these variables, it has been proposed that the vaginal microbiota plays an important role in the development of HPV infection leading to cervical neoplasm [9]. Following imbalance of this defense system, physicochemical changes arise, inducing histological alterations of the vaginal mucosa and the cervical epithelium, all of which put a selective pressure on the microbiota [13,14,15]
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