High-risk human papillomavirus (hrHPV) causes cervical cancer. In the United States, approximately 40% of women aged 14–59 years from all racial and ethnic groups are infected with HPV, and prevalence typically declines with age. However, American Indian (AI) women are insufficiently sampled to permit a population-specific estimate of hrHPV prevalence. Vaginal swabs were self-collected by 698 AI women aged 21–65 years from a tribal community in the Great Plains. We estimated the population prevalence of hrHPV and identified predominant genotypes. The combined prevalence of hrHPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 was 34.8%. HPV-51 (7.6%), HPV-58 (5.3%), HPV-52 (4.3%), HPV-18 (4.3%), and HPV-16 (3.9%) were most prevalent. hrHPV prevalence declined with age, from 42.2% in women aged 21–24 years to 27.9% in women aged 50–65 years. HPV-51 was the single most prevalent oncogenic genotype. The combined prevalence of hrHPV among AI women in our sample was high, particularly among women aged 50–65 years, for whom hrHPV prevalence was approximately triple that of other races. Cervical cancer screening efforts should be increased, particularly among women from the community aged 30 years and older.

Despite a global and nationwide decrease, Native Americans continue to experience high rates of cancer morbidity and mortality. Vaccination is one approach to decrease cancer incidence such as the case of cervical cancer. However, the availability of vaccines does not guarantee uptake, as evident in the Coronavirus 2019 pandemic. Therefore, as we consider current and future cancer vaccines, there are certain considerations to be mindful of to increase uptake among Native Americans such as the incidence of disease, social determinants of health, vaccine hesitancy, and historical exclusion in clinical trials. This paper primarily focuses on human papillomavirus (HPV) and potential vaccines for Native Americans. However, we also aim to inform researchers on factors that influence Native American choices surrounding vaccination and interventions including cancer therapies. We begin by providing an overview of the historical distrust and trauma Native Americans experience, both past and present. In addition, we offer guidance and considerations when engaging with sovereign Tribal Nations in vaccine development and clinical trials in order to increase trust and encourage vaccine uptake.

Vaginal dysbiosis is implicated in persistent human papillomavirus (HPV) infection and cervical cancer. Yet, there is a paucity of data on the vaginal microbiome in Native American communities. Here, we aimed to elucidate the relationships between microbiome, HPV, sociodemographic, and behavioral risk factors to better understand an increased cervical cancer risk in Native American women. In this pilot study, we recruited 31 participants (16 Native American and 15 non-Native women) in Northern Arizona and examined vaginal microbiota composition, HPV status, and immune mediators. We also assessed individuals’ sociodemographic information and physical, mental, sexual, and reproductive health. Overall, microbiota profiles were dominated by common Lactobacillus species (associated with vaginal health) or a mixture of bacterial vaginosis–associated bacteria. Only 44% of Native women exhibited Lactobacillus dominance, compared with 58% of non-Native women. Women with vaginal dysbiosis also had elevated vaginal pH and were more frequently infected with high-risk HPV. Furthermore, we observed associations of multiple people in a household, lower level of education, and high parity with vaginal dysbiosis and abundance of specific bacterial species. Finally, women with dysbiotic microbiota presented with elevated vaginal levels of proinflammatory cytokines. Altogether, these findings indicate an interplay between HPV, vaginal microbiota, and host defense, which may play a role in the cervical cancer disparity among Native American women. Future longitudinal studies are needed to determine the mechanistic role of vaginal microbiota in HPV persistence in the context of social determinants of health toward the long-term goal of reducing health disparities between non-Hispanic White and Native American populations. Prevention Relevance: Cervical cancer disproportionally affects Native American women. Sociodemographic and behavioral factors might contribute to this disparity via alteration of vaginal microbiota. Here, we show the association between these factors and vaginal dysbiosis and immune activation, which can be implicated in high-risk HPV infection among Native American and other racial/ethnic populations.

Amphipathic peptides with amino acids arranged in alternating patterns of hydrophobic and hydrophilic residues efficiently self‐assemble into β‐sheet bilayer nanoribbons. Hydrophobic side chain functionality is effectively buried in the interior of the putative bilayer of these nanoribbons. This study investigates consequences on self‐assembly of increasing the surface area of aromatic side chain groups that reside in the hydrophobic core of nanoribbons derived from Ac‐(XKXE)₂‐NH₂ peptides (X = hydrophobic residue). A series of Ac‐(XKXE)₂‐NH₂ peptides incorporating aromatic amino acids of increasing molecular volume and steric profile (X = phenylalanine [Phe], homophenylalanine [Hph], tryptophan [Trp], 1‐naphthylalanine [1‐Nal], 2‐naphthylalanine [2‐Nal], or biphenylalanine [Bip]) were assessed to determine substitution effects on self‐assembly propensity and on morphology of the resulting nanoribbon structures. Additional studies were conducted to determine the effects of incorporating amino acids of differing steric profile in the hydrophobic core (Ac‐X₁KFEFKFE‐NH₂ and Ac‐(X_1,5KFE)‐NH₂ peptides, X = Trp or Bip). Spectroscopic analysis by circular dichroism (CD) and Fourier transform infrared (FT‐IR) spectroscopy indicated β‐sheet formation for all variants. Self‐assembly rate increased with peptide hydrophobicity; increased molecular volume of the hydrophobic side chain groups did not appear to induce kinetic penalties on self‐assembly rates. Transmission electron microscopy (TEM) imaging indicated variation in fibril morphology as a function of amino acid in the X positions. This study confirms that hydrophobicity of amphipathic Ac‐(XKXE)₂‐NH₂ peptides correlates to self‐assembly propensity and that the hydrophobic core of the resulting nanoribbon bilayers has a significant capacity to accommodate sterically demanding functional groups. These findings provide insight that may be used to guide the exploitation of self‐assembled amphipathic peptides as functional biomaterials.

The fungal disease Valley fever causes a significant medical and financial burden for affected people in the endemic region, and this burden is on the rise. Despite the medical importance of this disease, little is known about ecological factors that influence the geographic point sources of high abundance of the pathogens Coccidioides posadasii and C. immitis, such as competition with co-occurring soil microbes. These “hot spots”, for instance, those in southern Arizona, are areas in which humans are at greater risk of being infected with the fungus due to consistent exposure. The aim of this study was to isolate native microbes from soils collected from Tucson, Arizona (endemic area for C. posadasii) and characterize their relationship (antagonistic, synergistic, or neutral) to the fungal pathogen with in vitro challenge assays. Secreted metabolites from the microbes were extracted and described using analytical techniques including high-performance liquid chromatography (HPLC) and mass spectrometry. Bacteria belonging to the genus Bacillus and fungi in the Fennellomyces and Ovatospora genera were shown to significantly decrease the growth of Coccidioides spp. In vitro. In contrast, other bacteria in the Brevibacillus genus, as well as one species of Bacillus bacteria, were shown to promote growth of Coccidioides when directly challenged. The metabolites secreted from the antagonistic bacteria were described using HPLC and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The microbes identified in this study as antagonists to Coccidioides and/or the metabolites they secrete have the potential to be used as natural biocontrol agents to limit the amount of fungal burden at geographic point sources, and therefore limit the potential for human infection.

Indigenous and American Indian Alaskan Native (AI/AN) community members are systematically underrepresented in clinical trial research. This paper focuses on exploratory steps to partner with Native Nations of Arizona to engage Community Health Representatives (CHR) as a trusted source for building COVID-19 clinical trial research, including vaccine trials awareness. CHRs are frontline public health workers who apply a unique understanding of the experience, language, and culture of the population served. This workforce has entered the spotlight as essential to the prevention and control of COVID-19. Methods: Three Tribal CHR programs were engaged to develop and refine culturally centered educational materials and a pre-post survey using a consensus-based decision-making approach. CHRs used these materials in brief education sessions during regular client home visits and community events. Results: At 30 days post CHR intervention, participants (N = 165) demonstrated significantly increased awareness about and ability to enroll in COVID-19 treatment and vaccine trials. Participants also described a significant increase in trust in researchers, decreased perceived barriers related to cost for participation in a clinical trial, and improved belief that participation in a COVID-19 clinical trial for treatment was considered a benefit to American Indian and Alaskan Native people. Conclusion: CHRs as trusted sources of information, coupled with culturally centered education materials designed by CHRs for CHR clients, demonstrated a promising approach to improved awareness of clinical trial research generally and COVID-19 trials specifically among Indigenous and American Indian community members of Arizona.