Pharmacological suppression of the OTUD4/CD73 proteolytic axis revives antitumor immunity against immune-suppressive breast cancers.

Despite widespread utilization of immunotherapy, treating immune-cold tumors remains a challenge. Multiomic analyses and experimental validation identified the OTUD4/CD73 proteolytic axis as a promising target in treating immune-suppressive triple negative breast cancer (TNBC). Mechanistically, deubiquitylation of CD73 by OTUD4 counteracted its ubiquitylation by TRIM21, resulting in CD73 stabilization inhibiting tumor immune responses. We further demonstrated the importance of TGF-ß signaling for orchestrating the OTUD4/CD73 proteolytic axis within tumor cells. Spatial transcriptomics profiling discovered spatially resolved features of interacting malignant and immune cells pertaining to expression levels of OTUD4 and CD73. In addition, ST80, a newly developed inhibitor, specifically disrupted proteolytic interaction between CD73 and OTUD4, leading to reinvigoration of cytotoxic CD8+ T cell activities. In preclinical models of TNBC, ST80 treatment sensitized refractory tumors to anti-PD-L1 therapy. Collectively, our findings uncover what we believe to be a novel strategy for targeting the immunosuppressive OTUD4/CD73 proteolytic axis in treating immune-suppressive breast cancers with the inhibitor ST80.

Patterns of completion axillary dissection for patients with cT1-2N0 breast cancer undergoing total mastectomy with positive sentinel lymph nodes.

BACKGROUND AND OBJECTIVES: The ACOSOGZ0011 trial found that overall survival (OS) for patients with 1-2 positive nodes undergoing sentinel lymph node biopsy-alone (SLNB) was noninferior to completion axillary lymph node dissection (ALND), but excluded patients undergoing mastectomy. Our study examined patterns of ALND and its relationship with OS for SLNB-positive patients undergoing mastectomy. METHODS: The National Cancer Database was queried (2010-2017) for patients with cT1-2N0 breast cancer undergoing mastectomy with positive sentinel lymph nodes. Clinical data were compared. RESULTS: Of 20 001 patients, 11 574 (57.9%) underwent SLNB + ALND, and 8427 (42.1%) had SLNB-alone. The SLNB + ALND group had more positive nodes (mean 2.6 vs. 1.3, p < 0.001) and more frequently received nodal radiation (33.4% vs. 28.9%, p < 0.001). Patients diagnosed in later years were less likely to undergo ALND (2010: reference; 2017: odds ratio: 0.29, 95% confidence interval [CI]: 0.25-0.33, p < 0.001). ALND (hazard ratio [HR]: 0.97, 95% CI: 0.89-1.06, p = 0.49) and nodal radiation (HR: 0.92, 95% CI: 0.83-1.02, p = 1.06) were not independently associated with OS. Propensity-score matched 5-year OS was similar (SLNB + ALND: 90.9% vs. SLNB-alone: 90.3%, p = 0.65). CONCLUSION: For patients undergoing mastectomy for cT1-2N0 breast cancer with positive SLNB, SLNB-alone was common and increased over time. Axillary radiation was not routinely delivered in the SLNB-alone group. Completion ALND and nodal radiation were not associated with improved survival.

Impact of nodal status in determining multimodal treatment strategies in non-cardia gastric cancer.

BACKGROUND: Patients with resectable noncardia gastric cancer may be subjected to perioperative chemotherapy (PEC), postoperative chemoradiation (POCR), or postoperative chemotherapy (POC). We analyzed these treatment strategies to determine optimal therapy based on nodal status. METHOD: The National Cancer Database was used to identify patients with resected noncardia gastric cancer (2004-2016). Patients were stratified based on clinical nodal status-negative (cLN-), positive (cLN+) and pathological nodal status (pLN-, pLN+). In cLN- patients who underwent upfront resection and were upstaged to pLN+, POC, and POCR were compared. Overall survival (OS) with PEC, POCR, and POC were compared in cLN- and cLN+. RESULTS: We identified 6142 patients (cLN-: 3831; cLN+: 2311). In cLN- patients who underwent upfront resection (N = 3423), 69% were upstaged to pLN+ disease (N = 2499; POCR = 1796, POC = 703). On MVA, POCR was associated with significantly improved OS when compared to POC (hazard ratio [HR]: 0.75; p < 0.001). In patients with cLN- disease (PEC = 408; POCR = 2439; POC = 984), PEC(HR: 0.77; p = 0.01) and POCR(HR: 0.81; p < 0.001) were associated with improved OS compared with POC. In cLN+ group (PEC = 452; POCR = 1284; POC = 575), POCR was associated with improved OS compared with POC (HR: 0.81; p < 0.01), and trend towards improved OS was noted when PEC(HR: 0.83; p = 0.055) was compared with POC. CONCLUSION: Postoperative chemoradiation may be the preferred treatment strategy over postoperative chemotherapy in non-cardia gastric cancer patients who receive upfront resection and are upstaged from clinically node negative to pathologically node positive disease.

Linking population-based cohorts with cancer registries in LMIC: a case study and lessons learnt in India.

OBJECTIVES: In resource-constrained settings, cancer epidemiology research typically relies on self-reported diagnoses. To test a more systematic alternative approach, we assessed the feasibility of linking a cohort with a cancer registry. SETTING: Data linkage was performed between a population-based cohort in Chennai, India, with a local population-based cancer registry. PARTICIPANTS: Data set of Centre for Cardiometabolic Risk Reduction in South-Asia (CARRS) cohort participants (N=11 772) from Chennai was linked with the cancer registry data set for the period 1982-2015 (N=140 986). METHODS AND OUTCOME MEASURES: Match*Pro, a probabilistic record linkage software, was used for computerised linkages followed by manual review of high scoring records. The variables used for linkage included participant name, gender, age, address, Postal Index Number and father's and spouse's name. Registry records between 2010 and 2015 and between 1982 and 2015, respectively, represented incident and all (both incident and prevalent) cases. The extent of agreement between self-reports and registry-based ascertainment was expressed as the proportion of cases found in both data sets among cases identified independently in each source. RESULTS: There were 52 self-reported cancer cases among 11 772 cohort participants, but 5 cases were misreported. Of the remaining 47 eligible self-reported cases (incident and prevalent), 37 (79%) were confirmed by registry linkage. Among 29 self-reported incident cancers, 25 (86%) were found in the registry. Registry linkage also identified 24 previously not reported cancers; 12 of those were incident cases. The likelihood of linkage was higher in more recent years (2014-2015). CONCLUSIONS: Although linkage variables in this study had limited discriminatory power in the absence of a unique identifier, an appreciable proportion of self-reported cases were confirmed in the registry via linkages. More importantly, the linkages also identified many previously unreported cases. These findings offer new insights that can inform future cancer surveillance and research in low-income and middle-income countries.

Outcomes of the same-day discharge following mastectomy before, during and after COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: The majority of patients undergoing mastectomy before the COVID-19 pandemic were admitted for 23-h observation to the hospital. Indications for observation included drain care education, pain control and observation for possible early surgical complications. This study compared the rates of outpatient mastectomy before, during, and after the COVID-19 pandemic and indirectly evaluated the safety of same-day discharge. METHODS: We retrospectively analyzed patients undergoing mastectomy using Current Procedural Terminology code 19303. RESULTS: A total of 357 patients were included: 113 were treated pre-COVID-19, 82 patients during COVID-19 and 162 post-COVID-19. The rate of outpatient mastectomies tripled during the pandemic from 17% to 51% (p < 0.001); after the pandemic remain high at 48%. The rate of bilateral mastectomies decreased during the pandemic to 30% from 48% prepandemic (p = 0.015). Pectoralis muscle block utilization increased during the COVID-19 period from 36% to 59% (p = 0.002). No difference in complication rates, including surgical site infections, hematomas, and readmissions, pre and during COVID. CONCLUSIONS: The rate of outpatient mastectomy increased during the COVID-19 pandemic. During this timeframe, perioperative complications did not increase, suggesting the safety of this practice. After the pandemic, the rate of outpatient mastectomy continued to be significantly higher than pre-COVID.

Is Medicaid Expansion Associated with Improved Nonmetastatic Colon Cancer Survival? An Analysis of the National Cancer Database.

METHODS: This retrospective study of 86 413 patients (40-64 years old) undergoing surgical resection for a new diagnosis of invasive, nonmetastatic colon cancer included in the National Cancer Database (NCDB) from 2010 to 2015 compared overall survival (OS) in MES to NES. Cox proportional hazard models, fit for OS, and propensity score-matching (PSM) analysis were performed. RESULTS: In this sample, 51 297 cases (59.2%) lived in MES and 35 116 (40.8%) in NES. Medicaid expansion states had earlier pathological stage compared to NES (stage I 25.38% vs 24.17%, stage II 32.93 vs 33.4%, and stage III 41.69 vs 42.43%; P < .001). 5-year OS in MES was higher than NES (79.1% vs 77.3%; P < .001); however, on both multivariable analysis (MVA) and PSM analysis, MES did not have significantly different OS from NES (hazard ratio (HR), .99, 95% confidence interval (CI), .95-1.03; P = .570; HR, .99, 95% CI, .95-1.03; P = .68). CONCLUSION: Among NCDB patients with invasive, nonmetastatic colon cancer residing in MES at time of diagnosis was associated with earlier pathological stage. However, on both MVA and PSM analysis, OS was not significantly different in MES vs NES. Research on patient outcomes, such as receipt of guideline concordant care, can further inform the impact of insurance coverage expansion efforts on cancer outcomes.

Routine Implementation of Patient-Reported Outcomes Assessment Into Thoracic Surgery Practice.

BACKGROUND: Patient-reported outcomes (PROs) assessment is a necessary component of surgical outcome assessment and patient care. This study examined the success of routine PROs assessment in an academic-based thoracic surgery practice. METHODS: PROs, measuring pain intensity, physical function, and dyspnea, were routinely obtained using the National Institutes of Health-sponsored Patient-Reported Outcomes Measurement Information System (PROMIS) on all thoracic surgery patients beginning in April 2018 through January 2021. Questionnaires were administered electronically through a web-based platform at home or during the office visit. Completion rates and barriers were measured. RESULTS: A total of 9725 thoracic surgery office visits occurred during this time frame. PROs data were obtained in 6899 visits from a total of 3551 patients. The mean number of questions answered per survey was 22.4 ± 2.2. Overall questionnaire completion rate was 65.7%. A significant decline in survey completion was noted in April 2020, after which adjustments were made to allow for questionnaire completion through a mobile health platform. Overall monthly questionnaire completion rates ranged from 20% (April 2020) to 90% (October 2018). Mean T scores were dyspnea, 41.6 ± 12.3; physical function, 42.7 ± 10.5; and pain intensity, 52.8 ± 10.3. CONCLUSIONS: PROs can be assessed effectively in a thoracic surgery clinic setting, with minimal disruption of clinical activities. Future efforts should focus on facilitating PROs collection from disadvantaged patient populations and scaling implementation across programs.

Recovery of Patient-reported Quality of Life After Esophagectomy.

BACKGROUND: Esophagectomy is an important, but potentially morbid, operation used to treat benign and malignant conditions that may significantly impact patient quality of life (QOL). Patient-reported outcomes (PROs) are measures of QOL that come directly from patient self-report. This study characterizes patterns of change and recovery in PROs in the first year after esophagectomy. METHODS: Longitudinal QOL scores measuring physical function, pain, and dyspnea were obtained from esophagectomy patients during all clinic visits. PRO scores were obtained using the National Institutes of Health-sponsored Patient-Reported Outcomes Measurement Information System from April 2018 to February 2021. Mean PRO scores over 100 days after surgery were compared with baseline PRO scores using mixed-effects modeling with compound symmetry correlational structure. RESULTS: One hundred three patients with PRO results were identified. Reasons for esophagectomy were malignancy (87.4%), achalasia (5.8%), stricture (5.8%), and dysplasia (1.0%). When comparing mean PRO scores at visits ≤ 50 days after surgery with preoperative PRO scores, physical function scores declined by 27.3% (P < .001), whereas dyspnea severity and pain interference scores had increased by 24.5% (P < .001) and 17.1% (P < .001), respectively. Although recovery occurred over the course of the 100 days after surgery, mean physical function scores and dyspnea scores were still 12.7% (P = .02) and 26.4% (P = .001) worse, respectively, than mean preoperative levels. CONCLUSIONS: Despite declines in QOL scores immediately after esophagectomy, recovery back toward baseline was observed during the first 100 days. These findings are of considerable importance when counseling patients regarding esophagectomy, tracking recovery, and implementing quality improvement initiatives. Further long-term follow-up is needed to determine recovery beyond 100 days.

Impact of multi-agent systemic therapy on all-cause and disease-specific survival for people living with HIV who are diagnosed with non-Hodgkin lymphoma: population-based analyses from the state of Georgia.

For people living with HIV (PLWH) who are subsequently diagnosed with non-Hodgkin lymphoma (NHL), we investigate the impact of standard-of-care (SoC) cancer treatment on all-cause, NHL-specific, and HIV-specific survival outcomes. The focus is on a registry-derived, population-based sample of HIV + adults diagnosed with NHL within 2004-2012 in the state of Georgia. SoC treatment is defined as receipt of multi-agent systemic therapy (MAST). In multivariable survival analyses, SoC cancer treatment is significantly associated with better all-cause and NHL-specific survival, but not better HIV-specific survival across 2004-2017. Having a CD4 count <200 near the time of cancer diagnosis and Ann Arbor stage III/IV disease are associated with worse all-cause and HIV-specific survival; the effects on NHL survival trend negative but are not significant. Future work should expand the geographic base and cancers examined, deepen the level of clinical detail brought to bear, and incorporate the perspectives and recommendations of patients and providers.

Improved Adherence to ATA Medullary Thyroid Cancer Treatment Guidelines.

BACKGROUND: The 2009 American Thyroid Association (ATA) guidelines for medullary thyroid cancer (MTC) were created to unify national practice patterns. Our aims were to (1) evaluate national adherence to ATA guidelines before and after 2009, (2) identify factors that are associated with concordance with guidelines, and (3) evaluate whether there is an association between survival and concordant treatment. PATIENTS AND METHODS: Patients with MTC were identified from the 2009 to 2015 National Cancer Database. Adherence to ATA recommendations regarding extent of surgery (R61-R66) was analyzed. Logistic regression was used to determine predictors of discordance and propensity score matching was used to compare concordant treatment rates between time periods. Kaplan-Meier survival analysis was used to determine association between survival and concordant treatment. RESULTS: There were 3421 patients with MTC, and of these 3087 had M0 disease and 334 had M1 disease. We found that 72% of M0 cases adhered to R61-66, and 68% of M0 cases without advanced local disease were adherent to R61-63. Following propensity score matching, the adherence rate was 67% before 2009 and 74% after. Patient factors associated with discordant treatment were female gender, older age, treatment at a nonacademic facility, and living within 50 miles of the treatment facility. Adherence to guidelines was associated with improved overall survival (OS) (p < 0.01). CONCLUSIONS: Treatment of MTC was discordant from guidelines in 26% of cases from 2009 to 2015 compared with 33% prior to 2009 in a propensity matched analysis, and was most often in cases with localized, noninvasive disease. Improved adherence to guidelines may improve overall survival.

An overview of implementing an evidence based program to increase HPV vaccination in HIV community clinics.

BACKGROUND: HPV-related anal cancer occurs in excess rates among people living with HIV (PLWH) and has been increasing in incidence. The HPV vaccine is an effective and safe approach to prevent and reduce the risk of HPV-related disease. Yet, HPV vaccine programs tailored and implemented in the HIV population are lagging for this high-risk group. METHODS: A pre-post intervention study design will be used to tailor, refine, and implement the 4 Pillars™ Practice Transformation Program to increase HPV vaccination among PLWH. Guided by the RE-AIM framework, the CHAMPS study will provide training and motivation to HIV providers and clinic staff to recommend and administer the HPV vaccination within three HIV clinics in Georgia. We plan to enroll 365 HIV participants to receive HPV education, resources, and reminders for HPV vaccination. Sociodemographic, HPV knowledge, and vaccine hesitancy will be assessed as mediators and moderators for HPV vaccination. The primary outcome will be measured as an increase in uptake rate in initiation of the HPV vaccine and vaccine completion (secondary outcome) compared to historical baseline vaccination rate (control). DISCUSSION: The proposed study is a novel approach to address a serious and preventable public health problem by using an efficacious, evidence-based intervention on a new target population. The findings are anticipated to have a significant impact in the field of improving cancer outcomes in a high-risk and aging HIV population. TRIAL REGISTRATION: NCT05065840; October 4, 2021.

Surgical resection for adrenocortical carcinoma: Current trends affecting survival.

INTRODUCTION: Adrenocortical carcinoma (ACC) is associated with a poor prognosis. We reviewed the National Cancer Database (NCDB) to analyze the prognostic factors in surgically resected ACC patients and the association of surgical approaches with overall survival (OS). METHODS: A retrospective NCDB (2004-2014) review of patients undergoing curative-intent surgical resection for ACC was performed. Effects of patient demographics, tumor characteristics, histopathology, and perioperative course on OS were analyzed. Log-rank statistics were used to associate clinical variables with OS. The multivariable Cox proportional hazard model included only statistically significant variables. RESULTS: A total of 1599 patients with ACC were included. A majority of patients were female (60.73%) and presented with a Charlson-Deyo score of zero (75.42%). A majority of the ACC cases were Grade 3 (45.69%), and almost a third (30.64%) underwent margin-positive resections. Univariate analysis demonstrated a decrease in OS associated with increasing age and comorbidities. A negative resection margin and lack of lymphovascular invasion predicted better OS. Multivariable analysis showed that age, grade, surgical resection margins, and hospital length of stay were associated with OS. CONCLUSIONS: Advanced age, grade, presence of lymphovascular invasion, and positive surgical margins predicted a worse overall survival for adrenocortical cancer in our analysis. Resection with negative margins improves outcomes.

A dose-escalation clinical trial of intranasal ketamine for uncontrolled cancer-related pain.

STUDY OBJECTIVE: The objective of our study was to determine safety and pharmacology (pharmacokinetics and preliminary efficacy) of intranasal (IN) ketamine for uncontrolled cancer-related pain. DESIGN: Dose escalation clinical trial. SETTING: Outpatient. PATIENTS: Ten adult patients with uncontrolled cancer-related pain. INTERVENTION: Each patient received escalating doses of ketamine over four visits, each 2-5 days apart: 10 mg IN at visit 1, 10 mg intravenous (IV) at visit 2, 30 mg IN at visit 3, and 50 mg IN at visit 4. MEASUREMENTS: Pain was measured before and after drug administration for up to 4 h using the 11 point (0-10) Numerical Pain Rating Scale (NPRS). MAIN RESULTS: All subjects had advanced cancer, with intractable pain, despite being on moderate dosage of opioids. There was a statistically significant reduction in median NPRS by 1.5 (1-4), 3 (2-3), and 4 (3-5) points at 60 min after receiving the medication and remained decreased by 1.5 (1-2), 2 (1-2) and 1 (1-4) points at the end of the study visit (240 min) with the 10 mg, 30 mg and 50 mg IN dosage, respectively. The median percentage of maximal pain relief being 22.5 (16.6-71.5), 65.5 (40-100), and 69.25 (50-100) for 10 mg, 30 mg and 50 mg IN dosage, respectively and 100 (75-100) with 10 mg IV dose. All side effects (nausea and feeling of unreality) resolved by the end of each study visit. No severe adverse events occurred. CONCLUSION: In this single-institution study, all dosages of IN ketamine administered in the study (10, 30, and 50 mg) provided significant pain relief for intractable cancer-related pain and were well tolerated. The 50 mg dose provided maximal pain relief without major side effects. Further study focused on repeated administration efficacy and safety for cancer-related pain is warranted.

Exploring the Anal Microbiome in HIV Positive and High-Risk HIV Negative Women.

This exploratory study sought to characterize the anal microbiome and explore associations among the anal microbiome, risk factors for anal cancer, and clinical factors. A pilot sample of 50 HIV infected and high-risk HIV negative women were recruited from the former Women's Interagency HIV Study. Microbiome characterization by 16S rRNA gene sequencing and datasets were analyzed using QIIME 2™. Composition of the anal microbiome and its associations with anal cancer risk factors and clinical factors were analyzed using linear decomposition model and permutational multivariate analysis of variance. Composition of the anal microbiome among HIV positive and high-risk negative women was dominated by Bacteroides, Prevotella, and Campylobacter. The overall taxonomic composition and microbial diversity of the anal microbiome did not significantly differ by HIV status. However, the abundance of Ruminococcus 1 belonging to the Rumincoccaceae family was associated with HIV status (q = .05). No anal cancer risk factors were associated with the anal microbiome composition. Clinical factors marginally associated with the anal microbiome composition included body mass index (BMI; p = .05) and hepatitis C virus (HCV; p = .05). Although HIV and risk factors for anal cancer were not associated with the composition of the anal microbiome in this pilot sample, other clinical factors such as BMI and HCV, may be worth further investigation in a larger study. Future research can build on these findings to explore the role of the microbiome and HIV comorbidities in women.

Influencers of Immediate Postmastectomy Reconstruction: A National Cancer Database Analysis.

BACKGROUND: The literature examining decision-making related to treatment and reconstruction for women with breast cancer has established that patient, clinical, and facility factors all play a role. OBJECTIVES: The aim of this study was to use the National Cancer Database to determine how patient, clinical, and facility factors influence: (1) the receipt of immediate breast reconstruction; and (2) the type of immediate breast reconstruction received (implant-based, autologous, or a combination). METHODS: A total of 638,772 female patients with breast cancers (Tis-T3, N0-N1, or M0) who between 2004 and 2017 received immediate reconstruction following mastectomy were identified in the National Cancer Database. Univariate and multivariate logistic regression models were applied to identify characteristics associated with immediate breast reconstruction and type of reconstruction. RESULTS: Immediate breast reconstruction was more frequently associated with patients of White race, younger age, with private insurance, with lesser comorbidities, who resided in zip codes with higher median incomes or higher rates of high-school graduation, in urban areas, with Tis to T2 disease, or with involvement of <4 lymph nodes (all odds ratios [ORs] > 1.1). Negative predictors of immediate breast reconstruction were insurance status with Medicaid, Medicare, other government insurance, and none or unknown insurance (all ORs < 0.79). Implant-based reconstruction was associated with non-Black race, uninsured status, completion of higher education, undifferentiated disease, and stage T0 disease (all ORs > 1.10). CONCLUSIONS: These findings confirm some previous studies on what patient, clinical, and facility factors affect decision-making, but also raise new questions that relate to the impact of third-party payer on receipt and type of reconstruction postmastectomy for breast cancer.

Lymph node involvement in gastric adenocarcinoma.

BACKGROUND: Endoscopic management of early gastric cancer is limited by the risk of lymph node metastasis. We aimed to examine the incidence and predictors of nodal metastasis in early gastric adenocarcinoma in a large national US cohort. METHODS: Cases were abstracted from the National Cancer Database from 2004 to 2016. The incidence and predictors of lymph node involvement for patients with Tis, T1a, and T1b tumors were examined. RESULTS: A total of 202,216 cases of gastric adenocarcinoma were identified in the NCDB. Cases with unknown patient or tumor characteristics, presence of other cancers, and prior neoadjuvant chemotherapy or radiotherapy were excluded. 1839 cases of Tis, T1a, and T1b tumors were identified. Lymph node metastases were present in 18.1% of patients. Lymphovascular invasion (LVI), high-grade histology, stage T1b, and larger size (> 3 cm) were independently associated with an increased risk of nodal metastasis on multivariate analysis (P < 0.05). The presence of LVI was the strongest predictor of nodal metastasis with an OR (95% CI) of 5.7 (4.3-7.6), P < 0.001. No lymph node metastasis was found in any Tis tumors. Small T1a low-grade tumors with no LVI had a low risk of nodal metastasis (0.6% < 2 cm and 0.9% < 3 cm). CONCLUSION: In this large national cohort, size, lymphovascular invasion, higher grade histology, and T stage were independently associated with lymph node metastasis. For patients with low-grade tumors, < 3 cm, without lymphovascular invasion, the risk of nodal involvement was very low, suggesting that this Western cohort could be considered for endoscopic resection.

Feasibility of investigating the association between bacterial pathogens and oral leukoplakia in low and middle income countries: A population-based pilot study in India.

BACKGROUND: Certain oral bacterial pathogens may play a role in oral carcinogenesis. We assessed the feasibility of conducting a population-based study in India to examine the distributions and levels of Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia in relation to oral leukoplakia (a potentially malignant disorder) and other participant characteristics. METHODS: This exploratory case-control study was nested within a large urban Indian cohort and the data included 22 men and women with oral leukoplakia (cases) and 69 leukoplakia-free controls. Each participant provided a salivary rinse sample, and a subset of 34 participants (9 cases; 25 controls) also provided a gingival swab sample from keratinized gingival surface for quantitative polymerase chain reaction (qPCR). RESULTS: Neither the distribution nor the levels of pathogens were associated with oral leukoplakia; however, individual pathogen levels were more strongly correlated with each other in cases compared to controls. Among controls, the median level of total pathogens was the highest (7.55×104 copies/ng DNA) among persons of low socioeconomic status. Salivary rinse provided better DNA concentration than gingival swab for qPCR analysis (mean concentration: 1.8 ng/µl vs. 0.2 ng/µl). CONCLUSIONS: This study confirms the feasibility of population studies evaluating oral microbiome in low-resource settings and identifies promising leads for future research.

Willingness of Latinx and African Americans to Participate in Nontherapeutic Trials: It Depends on Who Runs the Research.

Background: Inclusion of racial/ethnic minorities in cancer-related research remains inadequate, continuing to impact disparate health outcomes. Data regarding enrollment of racial/ethnic minorities in nontherapeutic, health-related research is sparse, and even less is known about enrollment of those with a double disparity of racial/ethnic minorities in rural settings. Objective: To examine perspectives of Latinx and African American (AA) healthy volunteers from rural and urban settings in five southern US states and Puerto Rico regarding their trust in research and their willingness to participate in nontherapeutic research trials based on who conducts the research. Methods: This study was conducted in 2013 in rural and urban communities across Alabama, Florida, Georgia, Mississippi, Louisiana, and Puerto Rico. A 38-item questionnaire based on the Tuskegee Legacy Project Questionnaire assessed willingness, motivators, and barriers to participation in nontherapeutic cancer-related research. The sample was segmented into four subgroups by urban/rural location and race/ethnicity. Results: Of 553 participants (rural Latinx=151, urban Latinx=158, rural AA=122, urban AA=122), more than 90% had never been asked to participate in research, yet 75% of those asked agreed to participate. Most had positive views regarding health-related research. Trust in who conducted research varied by subgroup. Personal doctors and university hospitals were most trusted by all subgroups; for-profit and tobacco companies were least trusted. Both Latinx subgroups trusted pharmaceutical companies more than AAs; local hospitals and for-profit businesses were more trusted by AAs. Both rural subgroups trusted research by insurance companies more than their urban counterparts. Conclusions: If asked, rural and urban AA and Latinx healthy volunteers were willing to participate in health-related research, with personal doctors and university hospitals considered the most trusted sources to encourage/conduct research.