Distribution of microbiota in cervical preneoplasia of racially disparate populations.

BACKGROUNDS: Microbiome dysbiosis is an important contributing factor in tumor development and thus may be a risk predictor for human malignancies. In the United States, women with Hispanic/Latina (HIS) and African American (AA) background have a higher incidence of cervical cancer and poorer outcomes than Caucasian American (CA) women. METHODS: Here, we assessed the distribution pattern of microbiota in cervical intraepithelial neoplasia (CIN) lesions obtained from HIS (n = 12), AA (n = 12), and CA (n = 12) women, who were screened for CC risk assessment. We employed a 16S rRNA gene sequencing approach adapted from the NIH-Human Microbiome Project to identify the microbial niche in all CIN lesions (n = 36). RESULTS: We detected an appreciably decreased abundance of beneficial Lactobacillus in the CIN lesions of the AA and HIS women compared to the CA women. Differential abundance of potentially pathogenic Prevotella, Delftia, Gardnerella, and Fastidiosipila was also evident among the various racial groups. An increased abundance of Micrococcus was also evident in AA and HIS women compared to the CA women. The detection level of Rhizobium was higher among the AA ad CA women compared to the HIS women. In addition to the top 10 microbes, a unique niche of 27 microbes was identified exclusively in women with a histopathological diagnosis of CIN. Among these microbes, a group of 8 microbiota; Rubellimicrobium, Podobacter, Brevibacterium, Paracoccus, Atopobium, Brevundimonous, Comamonous, and Novospingobium was detected only in the CIN lesions obtained from AA and CA women. CONCLUSIONS: Microbial dysbiosis in the cervical epithelium represented by an increased ratio of potentially pathogenic to beneficial microbes may be associated with increased CC risk disparities. Developing a race-specific reliable panel of microbial markers could be beneficial for CC risk assessment, disease prevention, and/or therapeutic guidance.

The Project ENABLE Cornerstone randomized controlled trial: study protocol for a lay navigator-led, early palliative care coaching intervention for African American and rural-dwelling advanced cancer family caregivers.

BACKGROUND: Family caregivers play a vital, yet stressful role in managing the healthcare needs and optimizing the quality of life of patients with advanced cancer, from the time they are newly diagnosed until end of life. While early telehealth palliative care has been found to effectively support family caregivers, little work has focused on historically under-resourced populations, particularly African American and rural-dwelling individuals. To address this need, we developed and are currently testing Project ENABLE (Educate, Nurture, Advise, Before Life Ends) Cornerstone, a lay navigator-led, early palliative care coaching intervention for family caregivers of African American and rural-dwelling patients with newly diagnosed advanced cancer. METHODS: This is a 2-site, single-blind, hybrid type I implementation-effectiveness trial of the Cornerstone intervention versus usual care. Cornerstone is a multicomponent intervention based on Pearlin's Stress-Health Process Model where African American and/or rural-dwelling family caregivers of patients with newly diagnosed advanced cancer (target sample size = 294 dyads) are paired with a lay navigator coach and receive a series of six, brief 20-60-min telehealth sessions focused on stress management and coping, caregiving skills, getting help, self-care, and preparing for the future/advance care planning. Subsequent to core sessions, caregivers receive monthly follow-up indefinitely until the patient's death. Caregiver and patient outcomes are collected at baseline and every 12 weeks until the patient's death (primary outcome: caregiver distress at 24 weeks; secondary outcomes: caregiver: quality of life and burden; patient: distress, quality of life, and healthcare utilization). Implementation costs and the intervention cost effectiveness are also being evaluated. DISCUSSION: Should this intervention demonstrate efficacy, it would yield an implementation-ready model of early palliative care support for under-resourced family caregivers. A key design principle that has centrally informed the Cornerstone intervention is that every caregiving situation is unique and each caregiver faces distinct challenges that cannot be addressed using a one-size-fits all approach. Hence, Cornerstone employs culturally savvy lay navigator coaches who are trained to establish a strong, therapeutic alliance with participants and tailor their coaching to a diverse range of individual circumstances. TRIAL REGISTRATION: ClinicalTrials.gov NCT04318886 . Registered on 20 March, 2020.

Evaluating the implementation and impact of navigator-supported remote symptom monitoring and management: a protocol for a hybrid type 2 clinical trial.

BACKGROUND: Symptoms in patients with advanced cancer are often inadequately captured during encounters with the healthcare team. Emerging evidence demonstrates that weekly electronic home-based patient-reported symptom monitoring with automated alerts to clinicians reduces healthcare utilization, improves health-related quality of life, and lengthens survival. However, oncology practices have lagged in adopting remote symptom monitoring into routine practice, where specific patient populations may have unique barriers. One approach to overcoming barriers is utilizing resources from value-based payment models, such as patient navigators who are ideally positioned to assume a leadership role in remote symptom monitoring implementation. This implementation approach has not been tested in standard of care, and thus optimal implementation strategies are needed for large-scale roll-out. METHODS: This hybrid type 2 study design evaluates the implementation and effectiveness of remote symptom monitoring for all patients and for diverse populations in two Southern academic medical centers from 2021 to 2026. This study will utilize a pragmatic approach, evaluating real-world data collected during routine care for quantitative implementation and patient outcomes. The Consolidated Framework for Implementation Research (CFIR) will be used to conduct a qualitative evaluation at key time points to assess barriers and facilitators, implementation strategies, fidelity to implementation strategies, and perceived utility of these strategies. We will use a mixed-methods approach for data interpretation to finalize a formal implementation blueprint. DISCUSSION: This pragmatic evaluation of real-world implementation of remote symptom monitoring will generate a blueprint for future efforts to scale interventions across health systems with diverse patient populations within value-based healthcare models. TRIAL REGISTRATION: NCT04809740 ; date of registration 3/22/2021.

HPV Vaccination Champions: Evaluating a Technology-Mediated Intervention for Parents.

Human papillomavirus (HPV) vaccination prevents 6 HPV-related cancers in men and women. Yet, rates of HPV vaccination among adolescents in the United States lag behind other developed nations, revealing a significant public health issue. This feasibility study tested a collaborative online learning environment to cultivate HPV vaccination champions. A 3-month training program recruited parents to serve as proponents and social media influencers to identify solutions to overcome barriers to HPV vaccination. A mixed methods study design included a pretest survey, three online asynchronous focus groups, a posttest survey, as well as a longitudinal follow-up survey at 6 months. Participants included 22 parents who self-identified as female (95.4%) and white (90.9%). Overall, there was a statistically significant difference in knowledge of HPV and HPV vaccination between pretest and posttest (p = 0.0042). This technology-mediated intervention increased parents' confidence and motivated them to speak more freely about HPV vaccination in-person and online with others in their social networks. Participants identified prevalent misinformation about HPV vaccination and learned how to effectively craft messages to address concerns related to safety and side effects, gender, understanding of risk, and sexual activity. Objective measures and qualitative open-ended assessment showed high intervention engagement and treatment satisfaction. All participants (100%) indicated that they enjoyed participating in the intervention. The effectiveness of this feasibility study suggests that social media is an appropriate platform to empower parents to counter vaccine hesitancy and misinformation through HPV vaccination information that is simple and shareable in-person and online.

Correcting HPV Vaccination Misinformation Online: Evaluating the HPV Vaccination NOW Social Media Campaign.

The human papillomavirus (HPV) vaccine provides protection from six HPV-related cancers. Approximately half of South Carolina adolescents have not completed the vaccination series, representing a missed opportunity to prevent cancer. The HPV Vaccination NOW: This is Our Moment social media campaign is an initiative of the South Carolina Cancer Alliance (SCCA) and Hollings Cancer Center at the Medical University of South Carolina (MUSC). This statewide social media campaign aimed to increase parental awareness of and build vaccine confidence around HPV vaccination in S.C. The ten-week campaign was strategically implemented between June and August 2019 to encourage HPV vaccination at back-to-school medical appointments. A process evaluation showed that the campaign resulted in over 370,000 total impressions, reached over 33,000 individuals, and culminated with over 1122 followers. There were over 2700 engagements on Facebook and Twitter. A qualitative content analysis indicated that pro-vaccine and anti-vaccine comments were dominated by personal stories. Comments promoting misinformation about the HPV vaccine were often countered through peer-to-peer dialogue. Findings suggest that creating opportunities for the target audience to engage with campaign messages effectively corrected misinformation.

Minority participation in phase 1 gynecologic oncology clinical trials: Three decades of inequity.

OBJECTIVES: It is important to develop effective therapies in minorities to ensure equity in cancer care. Underrepresentation of minorities in early phase trials may cause therapies that are effective only in majority populations. We evaluated minority participation in gynecologic oncology phase 1 clinical trials. METHODS: In peer-reviewed published articles of gynecologic oncology phase 1 clinical trials from years 1985 to 2018, we manually abstracted racial distribution of enrolled participants, cancer type, and year published. We calculated expected and observed ratios of racial participation on the basis of age-adjusted cancer incidence for race from the United States Centers for Disease Control and Prevention. RESULTS: We identified 357 articles of phase 1 trials (total, 9492 participants), including 213 articles on ovarian cancer (60%). Racial distribution of participants was available in 84 articles (23%) that included 2483 participants (26%): 1950 white (79%), 140 black (5%), and 393 other participants (16%). Other nonwhite races exceeded black enrollment in 46 of 84 trials (55%) that listed race. Enrollment of black participants was less than expected from disease incidence for ovarian (incidence-to-enrollment ratio, 18.5; P < .001), endometrial (3.6; P < .001), and cervical cancer (6.8; P < .001). No phase 1 study met expected enrollment for black participants. Frequency of black participants decreased 1.8-fold from 1995 to 1999 (8 of 70 participants [11%]) to 2015-2018 (55 of 892 participants [6%]; P < .025). CONCLUSIONS: Major racial underrepresentation exists in gynecologic oncology phase 1 clinical trials. Enrollment of more black participants is needed to achieve racial equity.

Looking at cancer health disparities without the colored lenses.

Cancer health disparities (CHDs), defined as the adverse differences in cancer incidence and mortality, are prevalent in certain racial and ethnic groups. Underlying causes of CHDs are multi-factorial and debatable. While low socioeconomic status, geographical location, lifestyle and behavioral factors are mostly believed to contribute to CHDs, regardless of ethnic and racial background, significant data now also exist to support a genetic basis of such disparities as well. Clearly, CHDs could best be understood by studying the interplay of multiple (genetic and non-genetic) factors and then translating the resulting knowledge into effective approaches for reducing the existing disparity gaps. This review article highlights these aspects in brief and calls the people of different expertise to work together to make an impact and tackle the challenges associated with CHDs.

A reproductive justice approach to understanding women's experiences with HPV and cervical cancer prevention.

Cervical cancer is a preventable disease. HPV infection has been linked to more than 90% of cervical cancers. A vaccine to prevent the acquisition of HPV has been available since 2006. The purpose of this study was to investigate women's perceptions of cervical cancer prevention, including HPV vaccination. A reproductive justice framework guided data collection and analysis. In 2016, researchers conducted 70 in-depth, semi-structured qualitative interviews with women aged 19-78 years in South Carolina. A purposive sampling approach was employed to maximize requisite variety based on social, economic, and environmental axes of inequality. Participants self-identified as white (53%), African American (33%), and Hispanic (9%). Data analysis included an inductive constant comparative method to identify patterns and themes across the interviews. Misinformation about the prevalence and risk of HPV and cervical cancer led to "othering" of women with HPV-related diagnoses based on the flawed assumption of not being at risk. Participants described a lack of knowledge about the effectiveness and safety of the HPV vaccine. Social norms influenced participants' perceptions of HPV vaccination and cervical cancer, including concerns about sexual activity and intergenerational communication. Participants' social construction of identity, including race/ethnicity, socioeconomic position, ability, age, gender, sexual orientation, and immigration status, impacted their perceptions of cervical cancer screening and the HPV vaccine. In particular, participants believed that the HPV vaccine was "only for girls" and identified gender norms that limited uptake. Participants described barriers to accessing health care and cervical cancer screening, including cost, health insurance, and life changes (e.g., pregnancy, relocating). Many participants experienced an abnormal Papanicolaou test and described follow-up care, including biopsies and treatment for cervical dysplasia. Findings from this study offer insight into women's identity and perceptions of cervical cancer prevention. Results provide practical recommendations to increase women's agency in the development of successful public health interventions.

Why do we continue to overtreat stage Ia carcinoma of the cervix?

The current recommended treatment for stage Ia2 cervical cancer is a radical or modified radical hysterectomy. Although in the United States the incidence of cervical cancer is low and declining, almost 50% of the >4000 new cases will present in early stages. An estimated 2200 women each year will undergo radical hysterectomy and many will have both early- and late-onset complications. The purpose of this review is to examine if there is still a role for radical hysterectomy in the proper treatment of stage Ia2 cervical cancer given most recent data. Sufficient histological evidence suggests that although parametrial involvement and lymph node metastases can increase the risk for recurrence, they are relatively uncommon at early stages. Worldwide data that challenge radical hysterectomy as standard of care have shown that conservative management of stage Ia2 cervical cancer results in similar survival and recurrence rates. It is the recommendation based on all reviewed data that radical hysterectomy should no longer be considered standard of care in all cases of stage Ia2 cervical cancer.

Rates of human papillomavirus vaccine uptake amongst girls five years after introduction of statewide mandate in Virginia.

BACKGROUND: The Commonwealth of Virginia enacted statewide school-entry human papillomavirus vaccine mandate in 2008 requiring all girls to receive the vaccine before starting the 6th grade. The mandate, one of very few in the country, has been in effect for 5 years. This study assesses the impact that it has had on the rates of human papillomavirus uptake. OBJECTIVE: The purpose of this study was to evaluate the uptake of the human papillomavirus vaccine among girls seeking well-child care 5 years after the introduction of a statewide mandate in Virginia in October 2008. STUDY DESIGN: This prospective cohort study used the Clinical Data Repository at the University of Virginia to identify girls 11-12 years old who was seen for well-child care from January to December 2014. Billing and diagnosis codes were used to establish human papillomavirus vaccine administration. Those girls who were identified through the Clinical Data Repository were then contacted by advance letter followed by a representative from the University of Virginia Center for Survey Research who invited the responsible parent or guardian to complete a 50-item telephone questionnaire. Questionnaire results were used to inform objective findings and to assess parental attitudes that were related to human papillomavirus vaccination. Findings were compared against those of Pierce et al (2013), who evaluated human papillomavirus vaccination levels in a similar cohort of patients in 2008, before mandate enactment, to assess relative change attributable to vaccine mandate. RESULTS: Nine hundred eight girls were identified through the Clinical Data Repository; 50.9% of the girls received at least 1 dose of human papillomavirus vaccine. White race and private insurance coverage were found to be associated negatively with human papillomavirus vaccine uptake (relative risk, 0.74 and 0.71; 95% confidence interval, 0.64-0.85 and 0.62-0.81, respectively). Black race and public insurance coverage were found to be associated positively with vaccine uptake (relative risk, 1.35 and 1.39; 95% confidence interval, 1.17-1.55 and 1.22-1.58, respectively). In comparison with the previous study, there has been no change in human papillomavirus vaccine uptake or distribution of uptake after the introduction of the statewide mandate for human papillomavirus vaccination. CONCLUSION: The statewide human papillomavirus vaccine mandate has had no impact on the overall rate of human papillomavirus vaccination, nor has it diminished the previously described racial or payer disparities in vaccine uptake in school-aged girls being seen for well-child care in the state of Virginia.

Morbidity and mortality of vulvar and vaginal cancers: Impact of 2-, 4-, and 9-valent HPV vaccines.

Vaginal and vulvar cancers do not account for a large proportion of gynecologic malignancies but their impact is significant. Both vaginal and vulvar lesions have precursors and display levels of dysplasia before progression to invasive disease. Human Papillomavirus (HPV) is a known causative agent of such dysplasia and can be detected now more readily than ever with adequate recognition techniques and provider awareness. Although HPV vaccination is still lagging compared to other recommended childhood vaccinations, the impact on lower genital tract neoplasia is promising. The bivalent and quadrivalent vaccines have been shown to be efficacious and the newest nonavalent vaccine should add even more of impact on coverage of cancer-causing HPV types. Although it is still early to show true clinical and population-based disease reduction due to low disease incidence and relatively short time of vaccine availability, the potential is noteworthy.

Increasing HPV vaccination through policy for public health benefit.

Vaccines against specific types of human papillomavirus (HPV) linked to cancer and other diseases have been met with mixed acceptance globally and in the United States. Policy-level interventions have been shown to be effective in increasing public health benefit. Government policies and mandates may result in improved HPV vaccination coverage and reduced disease burden, and alternative policies that improve unhindered access to HPV vaccination may allow success as well. The purpose of this commentary is to summarize policy efforts to maximize the public health benefit of HPV vaccination. We examine selected examples of HPV vaccination policy in global contexts and in the United States.

Transcriptional suppression, DNA methylation, and histone deacetylation of the regulator of G-protein signaling 10 (RGS10) gene in ovarian cancer cells.

RGS10 regulates ovarian cancer cell growth and survival, and RGS10 expression is suppressed in cell models of ovarian cancer chemoresistance. However, the mechanisms governing RGS10 expression in ovarian cancer are poorly understood. Here we report RGS10 suppression in primary ovarian cancer and CAOV-3 ovarian cancer cells compared to immortalized ovarian surface epithelial (IOSE) cells, and in A2780-AD chemoresistant cells compared to parental A2780 cells. RGS10-1 and RGS10-2 transcripts are expressed in ovarian cancer cells, but only RGS10-1 is suppressed in A2780-AD and CAOV-3 cells, and the RGS10-1 promoter is uniquely enriched in CpG dinucleotides. Pharmacological inhibition of DNA methyl-transferases (DNMTs) increased RGS10 expression, suggesting potential regulation by DNA methylation. Bisulfite sequencing analysis identified a region of the RGS10-1 promoter with significantly enhanced DNA methylation in chemoresistant A2780-AD cells relative to parental A2780 cells. DNA methylation in CAOV-3 and IOSE cells was similar to A2780 cells. More marked differences were observed in histone acetylation of the RGS10-1 promoter. Acetylated histone H3 associated with the RGS10-1 promoter was significantly lower in A2780-AD cells compared to parental cells, with a corresponding increase in histone deacetylase (HDAC) enzyme association. Similarly, acetylated histone levels at the RGS10-1 promoter were markedly lower in CAOV-3 cells compared to IOSE cells, and HDAC1 binding was doubled in CAOV-3 cells. Finally, we show that pharmacological inhibition of DNMT or HDAC enzymes in chemoresistant A2780-AD cells increases RGS10 expression and enhances cisplatin toxicity. These data suggest that histone de-acetylation and DNA methylation correlate with RGS10 suppression and chemoresistance in ovarian cancer. Markers for loss of RGS10 expression may identify cancer cells with unique response to therapeutics.

Post Approval Human Papillomavirus Vaccine Uptake Is Higher in Minorities Compared to Whites in Girls Presenting for Well-Child Care.

Since introduction of the human papillomavirus (HPV) vaccine, there remains low uptake compared to other adolescent vaccines. There is limited information postapproval about parental attitudes and barriers when presenting for routine care. This study evaluates HPV vaccine uptake and assesses demographics and attitudes correlating with vaccination for girls aged 11-12 years. A prospective cohort study was performed utilizing the University of Virginia (UVA) Clinical Data Repository (CDR). The CDR was used to identify girls aged 11-12 presenting to any UVA practice for a well-child visit between May 2008 and April 2009. Billing data were searched to determine rates of HPV vaccine uptake. The parents of all identified girls were contacted four to seven months after the visit to complete a telephone questionnaire including insurance information, child's vaccination status, HPV vaccine attitudes, and demographics. Five hundred and fifty girls were identified, 48.2% of whom received at least one HPV vaccine dose. White race and private insurance were negatively associated with HPV vaccine initiation (RR 0.72, 95% CI 0.61-0.85 and RR 0.85, 95% CI 0.72-1.01, respectively). In the follow-up questionnaire, 242 interviews were conducted and included in the final cohort. In the sample, 183 (75.6%) parents reported white race, 38 (15.7%) black race, and 27 (11.2%) reported other race. Overall 85% of parents understood that the HPV vaccine was recommended and 58.9% of parents believed the HPV vaccine was safe. In multivariate logistic regression, patients of black and other minority races were 4.9 and 4.2 times more likely to receive the HPV vaccine compared to their white counterparts. Safety concerns were the strongest barrier to vaccination. To conclude, HPV vaccine uptake was higher among minority girls and girls with public insurance in this cohort.