In Vitro Toxicity Evaluation of Carrageenan on Cells and Tissues of the Oral Cavity.

Carrageenan is a highly potent anti-human papillomavirus (HPV) agent with the potential for formulation as a mouthwash against oral HPV infection. However, its toxic effect on tissues of the oral cavity is currently unknown. This study aims to evaluate the safety of carrageenan on human cells and tissues of the oral cavity. Human salivary gland cells and reconstructed human oral epithelium (RHOE) were used for this in vitro study. The cells were subjected to 0.005-100 µg/mL of carrageenan for 4, 12, and 24 h in quadruplicate. RHOE were exposed to 100 µg/mL of carrageenan for 24 h in triplicate and stained with hematoxylin/eosin for histological analyses. All experiments had saline and 1% sodium dodecyl sulphate (SDS) as negative and positive controls, respectively. Carrageenan tissue toxicity was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to quantify cell viability. Tissue toxicity was further evaluated histologically by an oral pathologist to assess morphological changes. Our data showed that carrageenan did not significantly decrease cell and tissue viability when compared to the positive control. The histological evaluation of the RHOE also showed no loss of viability of the carrageenan-treated sample compared to untreated tissue. In contrast, 1% SDS-treated RHOE showed extensive tissue destruction. Our experiments suggest that carrageenan is safe for use in the oral cavity.

HIV Modifies the Effect of Tobacco Smoking on Oral Human Papillomavirus Infection.

BACKGROUND: People living with HIV (PLWH) are more likely to smoke and harbor oral human papillomavirus (HPV) infections, putting them at higher risk for head and neck cancer. We investigated effects of HIV and smoking on oral HPV risk. METHODS: Consecutive PLWH (n = 169) and at-risk HIV-negative individuals (n = 126) were recruited from 2 US health centers. Smoking history was collected using questionnaires. Participants provided oral rinse samples for HPV genotyping. We used multivariable logistic regression models with interaction terms for HIV to test for smoking effect on oral HPV. RESULTS: PLWH were more likely to harbor oral HPV than HIV-negative individuals, including α (39% vs 28%), ß (73% vs 63%), and γ-types (33% vs 20%). HIV infection positively modified the association between smoking and high-risk oral HPV: odds ratios for smoking 3.46 (95% confidence interval [CI], 1.01-11.94) and 1.59 (95% CI, .32-8.73) among PLWH and HIV-negative individuals, respectively, and relative excess risk due to interaction (RERI) 3.34 (95% CI, -1.51 to 8.18). RERI for HPV 16 was 1.79 (95% CI, -2.57 to 6.16) and 2.78 for ß1-HPV (95% CI, -.08 to 5.65). CONCLUSION: Results show tobacco smoking as a risk factor for oral HPV among PLWH.

Effect of sodium lauryl sulfate on recurrent aphthous stomatitis: A systematic review.

The present systematic review sought to evaluate the effects of Sodium Lauryl Sulfate (SLS)-free compared to SLS-containing dentifrices on (Recurrent) aphthous stomatitis (RAS) in patients with this condition. Cochrane, Medline (PubMed) and Embase databases, and some trial registries were searched through December 2017. There was no language, nor publication year restrictions. We included double-blinded randomized controlled trials that compared the effects of dentifrices with and without SLS on RAS in humans. Data extraction was compliant with PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. PROSPERO 2018:CRD42018086001. Four trials were included in this review (all crossover studies; n = 124 participants) and two contributed to the main meta-analysis based on the random-effect model. SLS-free dentifrice, when compared to SLS-containing statistically significantly, reduced the number of ulcers, duration of ulcer, number of episodes, and ulcer pain. Sensitivity analysis of the four studies as parallel-group trials shows a consistent direction of effect in favor of SLS-free dentifrice usage. In conclusion, the qualitative and quantitative synthesis of the eligible trials for this review showed that use of SLS-free consistently reduced all four parameters of ulcers measured. The available evidence suggests that patients with RAS may benefit from using SLS-free dentifrices for their daily oral care. However, future well-designed trials are still required to strengthen the current body of evidence.

Protocol: carrageenan for the prevention of oral HPV infection - a feasibility randomised clinical trial.

INTRODUCTION: Head and neck cancers (HNCs) are a significant health burden worldwide. Oral human papillomavirus (HPV) infection is a major risk factor for HNCs. Unfortunately, currently available prophylactic vaccines have limited coverage and potential for HPV type replacement. Carrageenan, a natural product extracted from marine red algae, has demonstrated potency as an HPV inhibitor and could offer a potential alternative to prevent HPV-related diseases, including oral HPV infection. However, there is a lack of clinical studies on the effect of carrageenan on oral HPV infections. As a first step to address this gap, we propose a randomised controlled trial (RCT) to evaluate the feasibility of conducting a larger multicentric RCT to investigate the effect of a carrageenan mouthwash on oral HPV infection. METHODS AND ANALYSIS: We will conduct a placebo-controlled triple-blinded feasibility RCT with two parallel arms, each arm consisting of 20 participants. Participants will complete a single in-person visit at baseline and conduct biweekly follow-ups from home by completing a web-based questionnaire and sending saliva self-samples via mail. During the 6-month period trial, participants will gargle with the mouthwash morning and night, and around sexual activities. The study will evaluate several factors including recruitment and retention rates, the feasibility of data collection procedures, compliance with study procedures, acceptability of RCT procedures and intervention and safety data on carrageenan use in the oral cavity. We will estimate the standard deviation of outcome measures, including time to the incidence of oral HPV infection and time to clearance of prevalent oral HPV infection. The trial primary outcome is whether to proceed to a definitive trial based on prespecified progression criteria. ETHICS AND DISSEMINATION: The protocol was approved by the McGill University institutional review board. Study results will be presented at scientific conferences and published in academic journals. TRIAL REGISTRATION NUMBER: NCT05746988.

Occupation as a measure of life course socioeconomic position and the risk of oral cancers in India.

OBJECTIVES: Evidence suggests that different indicators of socioeconomic position (SEP) contribute to oral cancer risk. Occupational status, as a measure of SEP, may be able to capture aspects of social hierarchy in societies in which employment is highly correlated with other social structures such as caste systems. Often in such societies, the life course of an individual is also influenced by this hierarchy. However, the influence of life course occupational status on the risk of oral cancer is not well understood. This study aims to identify the life course model that is best supported by the data using life course SEP-as represented by occupation-on oral cancer risk in a population in the South of India. METHODS: Data from the HeNCe Life study, Indian site were used. Incident oral cancer cases (N = 350) were recruited from two major referral hospitals in Kozhikode, Kerala, South India, from 2008 to 2012. Controls (N = 371), frequency-matched by age (5 years) and sex were recruited from the outpatient clinics at the same hospitals as the cases. Life grid-based structured interviews collected information on an array of exposures throughout the life course of the participant. Occupation was coded with the 1988 International Standard Classification of Occupations, transformed to the simplified European Socioeconomic Classification, and further dichotomized into advantageous and disadvantageous SEP at three different life periods (childhood, early adulthood and late adulthood). The analysis was conducted using the Bayesian relevant life course exposure model with a Dirichlet noninformative prior and a weakly informative Cauchy prior to the overall lifetime effect and confounders. RESULTS: Participants in disadvantaged SEP throughout their life had 3.6 times higher risk of oral cancer than those in advantaged SEP (OR = 3.6; 95% CrI = 1.6-7.2), after adjusting for potential confounders. While the crude and sex- and age-adjusted models showed a clear childhood sensitive period for this risk, the model further adjusted for behavioural factors could not distinguish the specific life course period best explained by data. CONCLUSION: Occupation status alone could provide a similar overarching risk estimate for oral cancer to those obtained from more complex measures of SEP.

Interaction of HPV16 and Cutaneous HPV in Head and Neck Cancer.

OBJECTIVES: Human papillomavirus 16 (HPV16) is an established risk factor for Head and Neck Cancer (HNC). Recent reports have shown that genotypes from the beta (ß) and gamma (γ) genera, also known as cutaneous HPV, can be found in the oral cavity, but their role is largely unidentified. We investigated the interaction between oral HPV16 and cutaneous HPV in HNC. METHODS: We use data on incident HNC cases (n = 384) and frequency-matched hospital-based controls (n = 423) from the HeNCe Life study in Montreal, Canada. Participants were tested for alpha HPV and cutaneous genera using oral mouth rinse and brush samples. We used unconditional logistic regression to obtain adjusted odds ratios (aOR) and 95% confidence interval (CI) as a measure of the effect between HPV and HNC and assessed the interaction between HPV genotypes on the multiplicative and additive scales. RESULTS: Prevalence of HPV infection was higher among cases (73%) than controls (63.4%), with cases more likely to be coinfected with more than a single genotype, 52.9% vs. 43.5%, respectively. Infection with HPV16 alone had a strong effect on HNC risk aOR = 18.2 [6.2, 53.2], while infection with any cutaneous HPV, but not HPV16, appeared to have the opposite effect aOR = 0.8 [0.6, 1.1]. The observed effect of joint exposure to HPV16 and any cutaneous HPV (aOR = 20.4 [8.3, 50.1]) was stronger than the expected effect based on an assumption of independent exposures but was measured with considerable imprecision. While the point estimate suggests a positive interaction between HPV16 and cutaneous HPV, results were imprecise with relative excess risk due to interaction (RERI) = 2.4 [-23.3, 28.2]. CONCLUSION: There could be biologic interaction between HPV16 and genotypes from cutaneous genera, which warrants further investigation. Although cutaneous HPVs are not usually found in tumor tissues, they are cofactors that could interact with HPV16 in the oral cavity and thus strengthen the latter's carcinogenic effect.

Life Course Tobacco Smoking and Risk of HPV-Negative Squamous Cell Carcinomas of Oral Cavity in Two Countries.

Background: Tobacco smoking remains one of the major risk factors for oral cavity cancers (OCC), a subgroup of head and neck cancer (HNC) less attributed to human papillomavirus (HPV) infection. Although a strong dose-dependent association between tobacco smoking and OCC exists, several important questions on the age-dependent effects of this habit remain unanswered. We investigated which life course hypothesis best describes the association between tobacco smoking and HPV-negative (HPV-ve ) OCC in Canada and India. Methods: We used data from the HeNCe Life study, a hospital-based case-control study conducted in Canada and India, using similar protocols. Cases were newly diagnosed subjects with primary squamous cell carcinomas of the head and neck region. Control subjects were patients with non-cancer selected from various outpatient clinics in a hospital located in the same catchment area as the cases and frequency-matched to cases according to age and sex. We collected information on an array of life course exposures using a structured questionnaire with the help of a life grid. Tobacco exposure (pack-years) during three life periods (≤ 30, 31-50, and >50 years of age) was calculated from the entire life course history of smoking. We used CDx brushes to collect oral exfoliated cells. Alpha HPV DNA detection and genotyping were performed for 36 HPV genotypes using the linear array. Participants who tested positive for HPV were excluded from the analysis. We used the Bayesian relevant life course exposure model (BRLM) to identify the life course hypothesis that best described the relationship between tobacco smoking and HPV-ve OCC. Results: We show evidence for a late-life sensitive period (>50 years of age) for tobacco smoking in relation to the risk of HPV-ve OCC in both Canada and India. An increase of 1 pack-year of tobacco smoking increased the risk of OCC by ~3% in both countries. Conclusion: Our findings from the Canadian and Indian data suggest that smoking tobacco after 50 years of age may carry a higher risk of developing oral cancer than earlier in life. Further studies are warranted to confirm the results.

Impact of abortion law reforms on health services and health outcomes in low- and middle-income countries: a systematic review.

While restrictive abortion laws still prevail in most low- and middle-income countries (LMICs), many countries have reformed their abortion laws, expanding the grounds on which abortion can be performed legally. However, the implications of these reforms on women's access to and use of health services, as well as their health outcomes, are uncertain. This systematic review aimed to evaluate and synthesize empirical research evidence concerning the effects of abortion law reforms on women's health services and health outcomes in LMICs. We searched Medline, Embase, CINAHL and Web of Science databases, as well as grey literature and reference lists of included studies. We included pre-post and quasi-experimental studies that aimed to estimate the causal effect of a change in abortion law on at least one of four outcomes: (1) use of and access to abortion services, (2) fertility rates, (3) maternal and/or neonatal morbidity and mortality and (4) contraceptive use. We assessed the quality of studies using the quasi-experimental study design series checklist and synthesized evidence through a narrative description. Of the 2796 records identified by our search, we included 13 studies in the review, which covered reforms occurring in Uruguay, Ethiopia, Mexico, Nepal, Chile, Romania, India and Ghana. Studies employed pre-post, interrupted time series, difference-in-differences and synthetic control designs. Legislative reforms from highly restrictive to relatively liberal were associated with reductions in fertility, particularly among women from 20 to 34 years of age, as well as lower maternal mortality. Evidence regarding the impact of abortion reforms on other outcomes, as well as whether effects vary by socioeconomic status, is limited. Further research is required to strengthen the evidence base for informing abortion legislation in LMICs. This review explicitly points to the need for rigorous quasi-experimental studies with sensitivity analyses to assess underlying assumptions. The systematic review was registered in PROSPERO database CRD42019126927.

Acceptability of HIV Screening in a Sample of International Students in the United States.

BACKGROUND AND OBJECTIVES: HIV transmission from persons unaware of their HIV status occurs more commonly than those who are aware of their status. Knowledge of one's HIV status may encourage preventive behaviors. Anecdotal evidence suggests that many international students may be willing to accept HIV screening, but empirical evidence to support this claim is lacking. We sought to determine the willingness of international students in the United States (US) to accept HIV screening, if offered. METHODS: We conducted a cross-sectional study using an online survey of international students at Western Illinois University, USA. The independent variable was the sociodemographic data of our participants; the dependent variable was the acceptance of HIV screening. The covariates were knowledge about HIV and the factors associated with the acceptance of the screening. Descriptive statistics and multivariate analysis were conducted. RESULTS: A total of 185 respondents out of 491 students participated in the online survey. Of these, 107 (57.8%) were males, and 78 (42.8%) were females. Most of the respondents were from Asian countries (64.9%) and African countries (24.9%). The prevalence of acceptance of HIV screening was 74%. Among participants willing to accept screening, if offered, 90% perceived screening would be beneficial to their health. Meanwhile, 83% of those who would refuse the screening were not sexually active. CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: Many international students may be interested in getting HIV screening if offered. Awareness of the benefits of HIV screening may influence the decision to screen. Findings may inform further studies that will lead to policy formulations for the health of international students in the US.