The cervical microbiota of Hispanics living in Puerto Rico is nonoptimal regardless of HPV status

Abstract

The cervicovaginal microbiota is influenced by host physiology, immunology, lifestyle, and ethnicity. We hypothesized that there would be differences in the cervicovaginal microbiota among pregnant, nonpregnant, and menopausal women living in Puerto Rico (PR) with and without human papillomavirus (HPV) infection and cervical cancer. We specifically wanted to determine if the microbiota is associated with variations in cervical cytology. A total of 294 women, including reproductive-age nonpregnant ( N = 196), pregnant ( N = 37), and menopausal ( N = 61) women, were enrolled. The cervicovaginal bacteria were characterized by 16S rRNA amplicon sequencing, the HPV was genotyped with SPF10-LiPA, and cervical cytology was quantified. High-risk HPV (HR-HPV, 67.3%) was prevalent, including genotypes not covered by the 9vt HPV vaccine. Cervical lesions (34%) were also common. The cervical microbiota was dominated by Lactobacillus iners . Pregnant women in the second and third trimesters exhibited a decrease in diversity and abundance of microbes associated with bacterial vaginosis. Women in menopause had greater alpha diversity, a greater proportion of facultative and strictly anaerobic bacteria, and higher cervicovaginal pH than premenopausal women. Cervical lesions were associated with greater alpha diversity. However, no significant associations between the microbiota and HPV infection (HR or LR-HPV types) were found. The cervicovaginal microbiota of women living in Puerto Rican were either dominated by L. iners or diverse microbial communities regardless of a woman’s physiological stage. We postulate that the microbiota and the high prevalence of HR-HPV increase the risk of cervical lesions among women living in PR. IMPORTANCE In the enclosed manuscript, we provide the first in-depth characterization of the cervicovaginal microbiota of Hispanic women living in Puerto Rico (PR), using a 16S rRNA approach, and include women of different physiological stages. Surprisingly we found that high-risk HPV was ubiquitous with a prevalence of 67.3%, including types not covered by the 9vt HPV vaccine. We also found highly diverse microbial communities across women groups—with a reduction in pregnant women, but dominated by nonoptimal Lactobacillus iners . Additionally, we found vaginosis-associated bacteria as Dialister spp., Gardnerella spp., Clostridium , or Prevotella among most women. We believe this is a relevant and timely article expanding knowledge on the cervicovaginal microbiome of PR women, where we postulate that these highly diverse communities are conducive to cervical disease.

Vaginal Microbiota and HPV in Latin America: A Narrative Review

“…Despite being in the Caribbean, women living in Puerto Rico vary from other Afro-Caribbean women from Barbados, where Prevotella predominates and non-Lactobacillus-dominated profiles (72%), likely due to a more significant African contribution than in Puerto Rico [ 14 ]. These findings are in line with earlier results from Hispanic women living in Puerto Rico [ 13 , 15 ], studies of U.S. Hispanics [ 6 ], and even in South America, such as Venezuelans [ 11 ].…”

“…HPV prevalence in other groups is in Costa Ricans (HR-HPV, 35%) [ 17 ], Europeans in the Netherlands (20%) [ 18 ], Japanese (20%) [ 19 ], and Nigerians (HR-HPV, 40%) [ 20 ]. Puerto Rican women without cervical lesions or HPV infections often have a diverse cervicovaginal microbial profile [ 13 , 15 ]. They also have a greater risk of HR-HPV infections [ 13 ], which renders them more susceptible to cervicovaginal dysregulation and inflammatory disorders.…”

“…Nevertheless, the reason why only a fraction of women acquires a long-lasting persistent HR-HPV infection that puts them at risk for developing Cervical Intraepithelial Neoplasia (CIN) remains unknown. One potential explanation for this variation could be the cervicovaginal microbiota and its related processes, as shown in a recent study that suggests an association between certain bacterial community types of the vaginal microbiota, HPV infection, and HPV-related disease, eventually leading up to carcinogenesis [ 11 , 15 , 36 ]. Also, previous studies showed that changes in processes like bacterial vaginosis, cervical inflammation, and increased vaginal pH affect susceptibility to cervical HPV [ 37 ].…”

“…Moreover, studies have demonstrated that changes in CSTs from Lactobacillus dominant states to polymicrobial states are one of the main risks for transitioning from persistent high-risk HPV infection to Cervical Intraepithelial Lesions (CIN) [ 52 ]. More cross-sectional and longitudinal studies, including high-risk populations in Puerto Rico and in many other Latin-American countries, are imperative so new microbiome-based therapeutic interventions can be developed [ 12 , 15 ].…”

“…The identified genotypes excluded from the 9vt HPV vaccine and Lactobacillus iners dominated the cervical microbiome. The diversity of microorganisms linked to bacterial vaginosis decreased in pregnant women in the second and third trimesters, and menopausal women had higher cervicovaginal pH, higher alpha diversity, and percentage of facultative and purely anaerobic bacteria [ 15 ]. Ortiz et al also pioneered the understanding of the prevalence of anogenital HPV infection in women living in the metropolitan area of Puerto Rico.…”