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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. 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.

Cervical cancer (CC) is women’s fourth most common cancer worldwide. A worrying increase in CC rates in Hispanics suggests that besides Human papillomavirus infections, there may be other cofactors included in the epithelial microenvironment that could play a role in promoting the disease. We hypothesized that the cervical microbiome and the epithelial microenvironment favoring inflammation is conducive to disease progression in a group of Hispanics attending gynecology clinics in Puerto Rico. Few studies have focused on the joint microbiota and cytokine profile response in Hispanics outside the US, especially regarding the development of precancerous lesions. We aimed to investigate the relationship between the cervicovaginal microbiome and inflammation in Hispanic women living in PR while considering cervical dysplasia and HPV genotype risk. Cervical samples collected from 91 participants coming to gynecology clinics in San Juan, underwent 16S rRNA genes (V4 region) profiling, and cytokines were measured using Luminex MAGPIX technology. Cytokines were grouped as inflammatory (IL-1β, TNFα, IFNγ, IL-6), anti-inflammatory (IL- 4, IL-10, TGFβ1), and traffic-associated (IL-8, MIP1a, MCP1, IP10). They were related to microbes via an inflammation scoring index based on the quartile and tercile distribution of the cytokine’s concentration. We found significant differences in the diversity and composition of the microbiota according to HPV type according to carcinogenic risk, cervical disease, and cytokine abundance. Community State Types (CSTs) represents a profile of microbial communities observed within the vaginal microbiome ecological niche, and Lactobacillus- depleted CST IV had ~ 90% dominance in participants with high-grade squamous intraepithelial lesions and high-risk HPV. The increasing concentration of pro-inflammatory cytokines was associated with a decrease in L . crispatus . In contrast, dysbiosis-associated bacteria such as Gardnerella , Prevotella , Atopobium concomitantly increased with pro-inflammatory cytokines. Our study highlights that the cervical microbiota of Hispanics living in Puerto Rico is composed mostly of diverse CST profiles with decreased Lactobacillus and is associated with a higher pro-inflammatory environment. The joint host-microbe interaction analyses via cytokine and microbiota profiling have very good translational potential.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has posed major risks for healthcare workers (HCWs) worldwide. This study assessed the prevalence of infection and its relationship with demographic and clinical characteristics among HCWs at the University of Puerto Rico Adult Hospital. A total of 132 individuals were enrolled, of whom six tested positive (4.55%). The study population was predominantly female (78.8%) with a mean age of 41 years, and although men showed higher odds of infection (OR = 3.98), the difference was not significant. Symptom presence was strongly associated with infection: 7.4% of symptomatic participants tested positive compared to none of the asymptomatic (p < 0.001). Symptom count was also predictive, with those reporting three to four symptoms showing the highest positivity rate (14.8%) and those with five to ten symptoms at 6.7%. Specific symptoms including muscle pain (OR = 21.04, p = 0.002), taste loss (OR = 24.20, p = 0.002), smell loss (OR = 15.25, p = 0.024), and fever (OR = 20.50, p = 0.016) were significantly linked to infection, while others such as headache and congestion were not. These findings underscore the utility of symptom-based monitoring in occupational health, though the single-site design, modest sample size, reliance on self-report, and early pandemic diagnostic limitations may have led to underestimation of true cases.

•V503-006 was a randomized safety and immunogenicity study in females 12–26 years of age.•V503-006 evaluated 9vHPV vaccine in those with previous qHPV vaccination.•9vHPV vaccine was generally well tolerated in prior qHPV vaccine recipients.•9vHPV vaccine was immunogenic for HPV 31/33/45/52/58 in prior qHPV vaccine recipients. To assess the safety and immunogenicity of the investigational 9-valent (6/11/16/18/31/33/45/52/58) HPV (9vHPV) vaccine in prior recipients of a 3-dose regimen of quadrivalent (6/11/16/18) HPV (qHPV) vaccine. V503-006 was a randomized, double-blinded, safety/tolerability and immunogenicity study of the 9vHPV vaccine in females 12–26 years of age who were previously vaccinated with qHPV vaccine. Subjects were randomized in a 2:1 ratio to receive 3 doses of 9vHPV vaccine (n=618) or saline placebo (n=306) at day 1, month 2, and month 6. Systemic, injection-site and serious adverse experiences (AEs) were monitored. Serum samples were collected at day 1, month 2, and month 7. Anti-HPV 6/11/16/18/31/33/45/52/58 titers were measured using the 9-valent HPV competitive Luminex Immunoassay (cLIA). The frequency of injection-site AEs (days 1–5 following any vaccination) was higher in the 9vHPV vaccine group than in the placebo group (91.1% and 43.9%, respectively). The frequencies of vaccine-related systemic AEs (days 1–15 following any vaccination) were generally comparable between the 2 groups (30.6% in the 9vHPV vaccine group, and 25.9% in the placebo group). One vaccine-related serious AE was reported in each of the 9vHPV vaccine and placebo groups. Few subjects (9vHPV=0.5%; placebo=0%) discontinued due to an AE. At 4 weeks post-dose 3, over 98% of subjects in the 9vHPV vaccine group were seropositive for HPV types 31/33/45/52/58, with marked elevations in cLIA geometric mean titers (GMTs) to these HPV types. Anti-HPV 31/33/45/52/58 GMTs were lower than in subjects administered 9vHPV vaccine who had not previously received qHPV vaccine (based on cross-study analyses); the clinical significance of this difference is unknown. Administration of a 3-dose regimen of 9vHPV vaccine to adolescent girls and young women 12–26 years of age who are prior qHPV vaccine recipients is highly immunogenic with respect to HPV types 31/33/45/52/58 and generally well tolerated.

Genital human papillomavirus (HPV) is the world's most commonly diagnosed sexually transmitted infection, and high-risk HPV types are strongly linked to cervical dysplasia and carcinoma. Puerto Ricans are among the US citizens with higher HPV prevalence and lower screening rates and access to treatment. This bleak statistic was as a motivation to detect biomarkers for early diagnosis of HPV in this population. We collected both urine and cervical swabs from 43 patients attending San Juan Clinics. Cervical swabs were used for genomic DNA extractions and HPV genotyping with the HPV SPF10-LiPA25 kit, and gas chromatography-mass spectrometry (GC-MS) was employed on the urine-derived products for metabolomics analyses. We aimed at discriminating between patients with different HPV categories: HPV negative (HPV-), HPV positive with simultaneous low and high-risk infections (HPV+B) and HPV positive exclusively high-risk (HPV+H). We found that the metabolome of HPV+B is closer to HPV- than to HPV+H supporting evidence that suggests HPV co-infections may be antagonistic due to viral interference leading to a lower propensity for cervical cancer development. In contrast, metabolites of patients with HPV+H were significantly different from those that were HPV-. We identified three urinary metabolites 5-Oxoprolinate, Erythronic acid and N-Acetylaspartic acid that discriminate HPV+H cases from negative controls. These metabolites are known to be involved in a variety of biochemical processes related to energy and metabolism and may likely be biomarkers for HPV high-risk cervical infection. However, further validation should follow using a larger patient cohort and diverse populations to confirm our finding.

In this study, we evaluate the association between vaginal and cervical human papillomavirus infections high-risk types (HPV+H), negative controls (HPV−), the bacterial biota, and urinary metabolites via integration of metagenomics, metabolomics, and bioinformatics analysis. We recently proposed that testing urine as a biofluid could be a non-invasive method for the detection of cervical HPV+H infections by evaluating the association between cervical HPV types and a total of 24 urinary metabolites identified in the samples. As a follow-up study, we expanded the analysis by pairing the urine metabolome data with vaginal and cervical microbiota in selected samples from 19 Puerto Rican women diagnosed with HPV+H infections and HPV− controls, using a novel comprehensive framework, Model-based Integration of Metabolite Observations and Species Abundances 2 (MIMOSA2). This approach enabled us to estimate the functional activities of the cervicovaginal microbiome associated with HPV+H infections. Our results suggest that HPV+H infections could induce changes in physicochemical properties of the genital tract through which niche partitioning may occur. As a result, Lactobacillus sp. enrichment coincided with the depletion of L. iners and Shuttleworthia, which dominate under normal physiological conditions. Changes in the diversity of microbial species in HPV+H groups influence the capacity of new community members to produce or consume metabolites. In particular, the functionalities of four metabolic enzymes were predicted to be associated with the microbiota, including acylphosphatase, prolyl aminopeptidase, prolyl-tRNA synthetase, and threonyl-tRNA synthetase. Such metabolic changes may influence systemic health effects in women at risk of developing cervical cancer. Overall, even assuming the limitation of the power due to the small sample number, our study adds to current knowledge by suggesting how microbial taxonomic and metabolic shifts induced by HPV infections may influence the maintenance of microbial homeostasis and indicate that HPV+H infections may alter the ecological balance of the cervicovaginal microbiota, resulting in higher bacterial diversity.

: Cervical cancer is primarily caused by the human papillomavirus (HPV), with persistent infections progressing to low- (LGSIL) and high-grade (HGSIL) lesions. Emerging evidence indicates that the cervicovaginal microbiota influences HPV persistence and disease progression, although the underlying metabolic mechanisms remain unclear. Therefore, we assessed the relationship between the cervicovaginal microbiota and the metabolic milieu in women with cervical dysplasia and HPV infections. : We recruited 36 non-menopausal, non-pregnant women who were classified as negative, LGSIL, or HGSIL based on pathology and HPV results. Cervical swabs were collected for genomic DNA extraction to characterize bacterial communities using 16S rRNA sequencing and to perform HPV genotyping. Cervical lavages were collected for untargeted metabolomic profiling using Gas Chromatography-Mass Spectrometry. Integrative multiomic analysis was performed using the MIMOSA2 pipeline. : Although bacterial community structure was not different between groups, women with HGSIL had higher richness and exhibited a higher abundance of , , and . Lesion-positive samples had shifts in tyramine and putrescine, biogenic amines linked to cancer development. Specifically, was identified as a potential contributor to tyramine oxidation. : Cervical lesions and HPV risk are associated with shifts in the cervicovaginal microbial metabolic milieu, highlighting the role of low-abundant anaerobic bacteria. Despite the small sample size, biogenic amines were associated with anaerobic taxa and microbial dysbiosis. These findings warrant further assessment of microbial-derived metabolites and their potential to promote tumor progression by driving a pro-inflammatory, metabolically altered microenvironment.

Background/Objective: Cervical cancer incidence is rising in Puerto Rico (PR) despite being preventable through HPV vaccination, Pap smear screening, and the timely treatment of dysplasia. This study evaluated the presence of single-nucleotide polymorphisms (SNPs) in Toll-like receptors (TLR4 and TLR9) among women with cervical dysplasia and HPV infection, as potential immune-related susceptibility factors. Methods: Cervicovaginal samples from 210 Hispanic women in PR were analyzed for dysplasia severity and HPV genotype. Demographic data were collected. Seven SNPs (four in TLR4, three in TLR9) were examined using PCR-RFLP and AS-PCR. Associations between SNP frequency, dysplasia severity, and high-risk HPV (HR-HPV) were assessed. Results: HR-HPV was found in 64% of severe dysplasia cases versus 46% of mild/negative cases (p < 0.025). The TLR4 AG (rs4986790) and CT (rs1927911) genotypes were more frequent in severe dysplasia. For TLR9, CT heterozygotes (rs187084) and the TC genotype (rs5743836) were also enriched in severe dysplasia. Conclusions: This first PR-based study shows that TLR4 and TLR9 SNPs significantly correlate with HR-HPV infection and dysplasia severity, supporting further research on their potential as biomarkers for cervical cancer prevention.

With the expansion of human microbiome studies in the last 15 years, we have realized the immense implications of microbes in human health. The human holobiont is now accepted, given the commensal relationships with bacteria, fungi, parasites, viruses, and human cells. The cervicovaginal microbiota is a specific case within the human microbiome where diversity is lower to maintain a chemical barrier of protection against infections. This narrative review focuses on the vaginal microbiome. It summarizes key findings on how native bacteria protect women from disease or predispose them to damaging inflammatory processes with an emphasis on the role of HPV infections in Latin America, one of the world’s regions with the highest cervical cancer prevalence.

The relationship between SARS‐CoV‐2 infection and the oral microbiome remains poorly understood, particularly in the Hispanic population. Oral samples from 62 individuals (38 SARS‐CoV‐2 positive, 24 negative) were analyzed using 16S rRNA sequencing, comparing diversity and taxa by infection and symptoms. Longitudinal data from 11 participants assessed microbiome changes as the infection resolved over time. To assess the impact of vaccination, we further examined 68 consistently SARS‐CoV‐2–negative individuals with paired samples collected before and after vaccination. SARS‐CoV‐2 infection was not significantly associated with alpha diversity, while beta diversity showed a non‐significant but marginal trend (p = 0.051). Prevotella nanceiensis was consistently depleted in infected individuals, even after excluding recent antibiotic users, suggesting a reproducible association with infection status rather than a diagnostic marker. Among infected participants, mucosa‐related symptoms were associated with lower Veillonella parvula abundance. Longitudinal data revealed stable microbiome profiles with slightly reduced variance in alpha diversity following viral clearance. In contrast, COVID‐19 vaccination in consistently negative individuals was associated with significant increases in Shannon (p = 0.050) and Simpson diversity (p = 0.017), indicating greater evenness without expansion of richness. Beta diversity analyses showed vaccination‐related shifts in community composition (PERMANOVA p = 0.026), with increases in Treponema, Campylobacter, Oribacterium, and Selenomonas, and a decrease in Haemophilus. The oral microbiome of Hispanics with mild SARS‐CoV‐2 infection appeared resilient, with only subtle taxonomic alterations. In contrast, COVID‐19 vaccination was associated with short‐term increases in diversity and compositional shifts, highlighting its influence on oral microbial ecology. The oral microbiome in Hispanics remains largely resilient during mild SARS‐CoV‐2 infection, showing minimal diversity changes, while COVID‐19 vaccination induces increased microbial evenness and compositional shifts. These findings highlight limited infection impact but suggest vaccination transiently reshapes oral microbial ecology.