Arecoline in buccal cells reflects Areca nut dose.

Areca nut (AN) is a carcinogen; its chewing cessation is, therefore, of worldwide interest. However, cessation biomarkers are lacking. We sought to establish arecoline in chewers' buccal cells (BCs) as a biomarker for AN dose. Self-reported AN doses, expressed as the average AN load ("AANL"), the product of AN amount, chewing time, and chewing frequency, were correlated by regression analysis with chewers' BC arecoline, measured by liquid chromatography mass spectrometry. We then determined whether associations differed between Class 1 chewers (who consume AN alone or with slaked lime, leaf, and/or spices) and Class 2 chewers (who consume any combination of the aforementioned ingredients plus tobacco). Among the 103 chewers, 28 Class 1 and 39 Class 2 chewers had detectable arecoline levels, which were used for analyses. A linear regression of cube-root transformed AANL on equally transformed BC arecoline levels provided the best model fit; resulting slopes and corresponding correlation coefficients were 0.86 and 0.40 (p < 0.01) for all; 1.09 and 0.51 (p < 0.01) for Class 1 chewers; 0.35 and 0.17 (p = 0.29) for Class 2 chewers; and 0.94 and 0.45 (p < 0.01), and 0.79 and 0.37 (p = 0.08), respectively, for those who included or excluded lime. Relationships between AANL and BC arecoline levels were similar between chewers who included or excluded lime (p = 0.76), but less between chewing classes (p = 0.14). This provides confidence that BC arecoline can generally act as a reliable biomarker for AN dose, useful for estimating efficacy in AN cessation studies and population-based chewing assessments.

Knowledge, Attitudes, Beliefs, Practices Regarding Human Papillomavirus (HPV), and Barriers to Vaccination Against HPV Infection: A Cross-Sectional Survey of Guam Residents.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States and is linked to several cancers. In Guam, the HPV vaccination rate falls short of the National Healthy People 2030 goal. Only half of eligible Guam teens have received the HPV vaccination series. Additionally, research on Guam HPV vaccination is limited. A cross-sectional survey was conducted, and a representative sample of Guam residents (n=775) was surveyed to examine their knowledge, attitudes, beliefs, practices regarding HPV, and barriers to HPV vaccination. Aggregated scores were calculated for these scale items: attitude, knowledge, subjective norms, and perceived behavioral control regarding HPV. One-way Analysis of Variance (ANOVA) was used to compare the means of the scores and check for significant differences. Binary logistic regression helped to identify significant predictors of HPV vaccination among respondents with children. Significant differences were found for sex, education, income, and ethnicity. Women and those with higher education and income demonstrated higher positive attitudes and knowledge about HPV vaccination. Also, those with health insurance and those who were advised by their physician were more likely to get their children vaccinated. These results will guide the implementation of effective strategies for developing targeted behavioral and other appropriate interventions to increase HPV vaccination in Guam.

The Betel Nut Intervention Trial (BENIT)-A Randomized Clinical Trial for Areca Nut and Betel Quid Cessation: Primary Outcomes.

BACKGROUND: Areca nut and betel quid (ANBQ) chewing is a widespread carcinogenic habit. The BENIT (ClinicalTrials-NCT02942745) is the first known randomized trial designed for ANBQ chewers. METHODS: We compared the intensive behavioral treatment intervention condition (IC) with the control condition (CC) in the BENIT and included a 5-stage early stopping rule. We report the primary analysis at stage 3. English-literate adults in Guam and Saipan who self-identified as ANBQ chewers with tobacco were enrolled between August 2016 and August 2020. IC participants (n = 88) received five in-person sessions over 22 days and a brochure containing quitting advice. CC participants (n = 88) received only the brochure. Participants were assessed at baseline and on day 22 of follow-up. Self-reported chewing status at day 22 was determined by a composite of two survey items with disparate wording and response options for cross-verification. RESULTS: Cessation rates were 38.6% (IC) and 9.1% (CC). Proportional hazards regression revealed a p = 0.0058, which met the Stage 3 criteria for significance, and an estimated reduction in ANBQ chewing for IC compared to the CC of 71% (95% CI: 41%-88%). CONCLUSIONS: Robust self-reported intervention effects at day 22 suggest that intensive cessation programs such as BENIT should be further developed and implemented on a larger scale.

Environmental Exposure to Cyanobacteria Hepatotoxins in a Pacific Island Community: A Cross-Sectional Assessment.

(1) Background: Cyanobacteria produce a wide range of secondary metabolites, including tumor-promoting hepatotoxins. We recently reported evidence of an independent association between oral cyanobacteria and hepatocellular carcinoma in a U.S. population. We sought to characterize the nature, sources, and health correlates of cyanotoxin exposure in the U.S. Pacific Island territory of Guam, which has a high incidence of liver cancer. (2) Methods: Seventy-four adult males and females were enrolled in a cross-sectional study to quantify cyanotoxins in saliva, urine, and blood and their correlation with health behaviors, medical history, and environmental exposures. Plant samples were collected from locations throughout the island. Microcystin/nodularin (MC/NOD), cylindrospermopsin (CYN), and anabaenopeptin (AB) were measured in biospecimens and in plant extracts by ELISA. (3) Results: Overall, among study participants MC/NOD were detected in 53.9% of saliva, 7.5% of urine, and 100% of serum.; CYN in 40.0% of saliva, 100.0% of urine, and 70.4% of serum; AB in 30.8% of saliva, 85% of urine, and 92.6% of serum. Salivary MC/NOD levels were significantly higher in individuals using municipal tap water as their primary source of drinking water; both salivary and urinary MC/NOD levels were higher in those not using store-bought/commercial water. Urine MC/NOD levels were highest among individuals consuming fruits and vegetables exclusively from local sources. Urine MC/NOD levels were elevated in individuals with hypertension and hyperlipidemia and salivary MC/NOD in those with recent alcohol consumption. Cyanotoxins were prevalent in plant samples including MC/NOD (46.6%), CYN (35.1%), and AB (51.7%). (4) Conclusions: Our study provides evidence that exposure to cyanobacterial hepatotoxins, including tumor promoters, may be prevalent in Guam and may originate from environmental sources. Population-based epidemiologic studies are needed to investigate the role of cyanotoxins in liver cancer development.

Using a Short Message System to Increase Cervical Cancer Screening Uptake among Chuukese Women in Guam: Lessons Learned from Linking Distance Technology Between Carriers and Using Telehealth Communication in a Cross-Cultural Context.

This paper reports on a project aimed at using a short message system (SMS) to increase cervical cancer screening uptake among Chuukese women in Guam. It documents the process and identifies the unexpected challenges which led to the early termination of the study. Although the original aims of the project were not met, there were some lessons learned about technology incompatibility in the context of Guam's and the United States' cell phone technology interface, the cultural nuances of cell phone use in the study population, and the necessity to follow a protocol for the termination of a project.

Rationale and design of a randomized, controlled, superiority trial on areca nut/betel quid cessation: The Betel Nut Intervention Trial (BENIT).

BACKGROUND: Areca nut (AN) is the seed endosperm of the Areca catechu L. palm and a Group 1 carcinogen chewed by 10-20% of the world population. AN is often chewed with Piper betle L. leaf, slaked lime, and tobacco to form a betel quid (BQ). The negative health effects associated with AN/BQ consumption warrant the need for an evidence-based cessation program. However, systematic research on AN/BQ cessation is rare. METHODS/DESIGN: The Betel Nut Intervention Trial (BENIT; trial #NCT02942745) is a randomized controlled trial designed to test the efficacy of an intensive AN/BQ cessation program. The trial is ongoing in Guam and Saipan with adult chewers who include tobacco in their BQ. Enrolled participants are assessed for their primary (chewing status) and secondary (saliva bio-verification) outcome at baseline, 22 days, and 6 months. Participants randomized into the control arm receive an educational booklet while those randomized into the intervention arm receive the educational booklet and a 22-day cessation program modeled after a smoking cessation program and led by trained facilitators. Information on chewing behavior (history, reasons for chewing, and AN/BQ composition and dependency) are collected. The intervention effectiveness is assessed using the logistic mixed model to compare cessation status between randomization groups. DISCUSSION: AN/BQ chewing affects a large population of people, many of whom live in low and moderate income countries in the Asia-Pacific region. Although the BENIT focuses on chewers in Guam and Saipan, it has the potential for greater regional and global importance.

Composition of betel specific chemicals in saliva during betel chewing for the identification of biomarkers.

Betel nut chewing causes cancer in humans, including strong associations with head and neck cancer in Guam. In the search for biomarkers of betel chewing we sought to identify chemicals specific for the 3 most commonly consumed betel preparations in Guam: nut ('BN'), nut + Piper betle leaf ('BL'), and betel quid ('BQ') consisting of nut + lime + tobacco + Piper betle leaf. Chemicals were extracted from the chewing material and saliva of subjects chewing these betel preparations. Saliva analysis involved protein precipitation with acetonitrile, dilution with formic acid followed by LCMS analysis. Baseline and chewing saliva levels were compared using t-tests and differences between groups were compared by ANOVA; p < 0.05 indicated significance. Predominant compounds in chewing material were guvacine, arecoline, guvacoline, arecaidine, chavibetol, and nicotine. In chewing saliva we found significant increases from baseline for guvacine (BN, BQ), arecoline (all groups), guvacoline (BN), arecaidine (all groups), nicotine (BQ), and chavibetol (BL, BQ), and significant differences between all groups for total areca-specific alkaloids, total tobacco-specific alkaloids and chavibetol. From this pilot study, we propose the following chemical patterns as biomarkers: areca alkaloids for BN use, areca alkaloids and chavibetol for BL use, and areca alkaloids plus chavibetol and tobacco-specific alkaloids for BQ use.