Update on Oral and Oropharyngeal Cancers: A guide for oral health care providers.

Oral squamous cell carcinomas (OSCC) signs and symptoms may be first identified by dental hygienists during routine extra and intra-oral examinations. A comprehensive extra-oral and intra-oral examination during regular dental hygiene assessment is paramount to identifying oral potentially malignant disorders (OPMD) and cancerous lesions for timely referral and treatment. Integrating a systematic list of questions during the medical and dental assessment along with careful visual and tactile examinations is critical to identifying OPMDs and cancerous lesions. Understanding the relationship between oropharyngeal squamous cell carcinomas (OPSCC) and Human Papilloma Virus (HPV) and how vaccination can prevent HPV-related OPSCC is critical to providing evidence-based recommendations and care. The purpose of this report is to provide an update on current epidemiological trends of OSCC and OPSCC rates in the United States (US) and provide the latest evidence on what dental hygienists must know to improve health outcomes and mitigate the consequences of undiagnosed cancer. This report considers enduring challenges with the annual rise in OPSCC rates and the public health burden of HPV-related cancers in the US. Emphasis on regular, quality continuing education about OSCC and OPSCC is emphasized along with recommendations for evidence-based training.

Serologic Profiling Using an Epstein-Barr Virus Mammalian Expression Library Identifies EBNA1 IgA as a Prediagnostic Marker for Nasopharyngeal Carcinoma.

PURPOSE: The favorable prognosis of stage I and II nasopharyngeal carcinoma (NPC) has motivated a search for biomarkers for the early detection and risk assessment of Epstein-Barr virus (EBV)-associated NPC. Although EBV seropositivity is ubiquitous among adults, a spike in antibodies against select EBV proteins is a harbinger of NPC. A serologic survey would likely reveal which EBV antibodies could discriminate those at risk of developing NPC. EXPERIMENTAL DESIGN: Lysates from a new EBV mammalian expression library were used in a denaturing multiplex immunoblot assay to survey antibodies against EBV in sera collected from healthy individuals who later developed NPC (incident cases) in a prospective cohort from Singapore and validated in an independent cohort from Shanghai, P.R. China. RESULTS: We show that IgA against EBV nuclear antigen 1 (EBNA1) discriminated incident NPC cases from matched controls with 100% sensitivity and 100% specificity up to 4 years before diagnosis in both Singapore and Shanghai cohorts. Incident NPC cases had a greater IgG repertoire against lytic-classified EBV proteins, and the assortment of IgA against EBV proteins detected by the immunoblot assay increased closer to diagnosis. CONCLUSIONS: Although NPC tumors consistently harbor latent EBV, the observed heightened systemic and mucosal immunity against lytic-classified antigens years prior to clinical diagnosis is consistent with enhanced lytic transcription. We conclude that an expanding EBV mucosal reservoir (which can be latent and/or lytic) is a risk factor for NPC. This presents an opportunity to identify those at risk of developing NPC using IgA against EBNA1 as a biomarker.

Three-dimensional Models of the Nasopharynx for the Study of Epstein-Barr Virus Infection.

The ubiquitous and cancer-associated Epstein-Barr virus (EBV) is associated with nearly all cases of nasopharyngeal carcinoma (NPC). Nasopharyngeal tissue is comprised of both pseudostratified and stratified epithelium, which are modeled in three-dimensional (3-D) cell culture. The cellular origin of EBV-associated NPC is as yet unknown, but both latent and lytic infections are likely important for preneoplastic mechanisms and replenishing the compartmentalized viral reservoir. Conventional 2-D cultures of nasopharyngeal epithelial cells (as primary cells or immortalized cell lines) are difficult to infect with EBV and cannot mimic the tissue-specific biology of the airway epithelium, which can only be captured in 3-D models. We have shown that EBV can infect the pseudostratified epithelium in air-liquid interface (ALI) culture using primary conditionally reprogrammed cells (CRCs) derived from the nasopharynx. In this protocol, we provide a step-by-step guide for the (i) conditional reprogramming of primary nasopharyngeal cells, (ii) differentiation of CRCs into pseudostratified epithelium in ALI culture (known as pseudo-ALI), and (iii) EBV infection of pseudo-ALI cultures. Additionally, we show that nasopharyngeal CRCs can be grown as organotypic rafts and subjected to EBV infection. These nasopharyngeal-derived 3-D cell cultures can be used to study EBV latent and lytic infection in relation to cell type and donor variation, by immunostaining and single-cell RNA-sequencing methods ( Ziegler et al., 2021 ). These methods are useful for studies of EBV molecular pathogenesis, and can overcome many of the limitations associated with conventional 2-D cell cultures. Graphic abstract: Workflow of nasopharyngeal-derived conditionally reprogrammed cells grown into pseudostratified-ALI and organotypic rafts in 3-D cell culture. Created with Biorender.com.

A primary nasopharyngeal three-dimensional air-liquid interface cell culture model of the pseudostratified epithelium reveals differential donor- and cell type-specific susceptibility to Epstein-Barr virus infection.

Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus with latent and lytic cycles. EBV replicates in the stratified epithelium but the nasopharynx is also composed of pseudostratified epithelium with distinct cell types. Latent infection is associated with nasopharyngeal carcinoma (NPC). Here, we show with nasopharyngeal conditionally reprogrammed cells cultured at the air-liquid interface that pseudostratified epithelial cells are susceptible to EBV infection. Donors varied in susceptibility to de novo EBV infection, but susceptible cultures also displayed differences with respect to pathogenesis. The cultures from one donor yielded lytic infection but cells from two other donors were positive for EBV-encoded EBERs and negative for other lytic infection markers. All cultures stained positive for the pseudostratified markers CK7, MUC5AC, α-tubulin in cilia, and the EBV epithelial cell receptor Ephrin receptor A2. To define EBV transcriptional programs by cell type and to elucidate latent/lytic infection-differential changes, we performed single cell RNA-sequencing on one EBV-infected culture that resulted in alignment with many EBV transcripts. EBV transcripts represented a small portion of the total transcriptome (~0.17%). All cell types in the pseudostratified epithelium had detectable EBV transcripts with suprabasal cells showing the highest number of reads aligning to many EBV genes. Several restriction factors (IRF1, MX1, STAT1, C18orf25) known to limit lytic infection were expressed at lower levels in the lytic subcluster. A third of the differentially-expressed genes in NPC tumors compared to an uninfected pseudostratified ALI culture overlapped with the differentially-expressed genes in the latent subcluster. A third of these commonly perturbed genes were specific to EBV infection and changed in the same direction. Collectively, these findings suggest that the pseudostratified epithelium could harbor EBV infection and that the pseudostratified infection model mirrors many of the transcriptional changes imposed by EBV infection in NPC.

Late life alcohol use and gender differences among Former Soviet Union immigrants.

Immigrants from the Former Soviet Union tend to drink more frequently than other Israelis. However, little is known about alcohol consumption among older Former Soviet Union immigrants in Israel. In the current study, male and female Former Soviet Union immigrants residing in independent living facilities were studied to determine their patterns of alcohol use and attitudes toward drinking. Interviews were conducted using a modified version of the CAGE instrument. Findings show that men use alcohol more than women, believe they need to reduce consumption, and are more likely to be criticized and feel guilty about their drinking behavior. Additional research is needed to further understand the extent of improper alcohol use among late life immigrants and older people in the country. Such information should be applied to the development of policy and services that will address their quality of life needs.

Former Soviet Union immigrant and native-born adolescents in Israel: substance use and related problem behavior.

Studies on immigration and adolescence show that youth experience a variety of emotional and cognitive adjustments as well as conflicts related to acculturation and the realities of life in their new country. Such conditions place many of them at increased risk for psychosocial problems including personal stress, interpersonal conflicts, mental illness, school failure, delinquency, substance use, and other risk-taking behavior. This prospective study compares the patterns of substance use and problem behaviors among 365 at-risk adolescents born in Israel and those who immigrated to that country from the Former Soviet Union. Findings show that Former Soviet Union youth tend to have higher levels of last 30-day alcohol and ecstasy use and binge drinking. Multiple regression shows binge drinking behavior related to trading property to obtain drugs; deterioration of school achievement; selling drugs; and time spent when being absent from school and hanging around during the day. Country of origin was not found related to this behavior. Further research is needed to study substance use and related problem behavior among immigrant youth controlling for the impact of acculturation and other factors.

Late-life benzodiazepine use among Russian-speaking immigrants in Israel.

PURPOSE: In this prospective study, we examine the reasons for benzodiazepine use among Russian-speaking elderly people in Israel, and we discuss issues related to immigrants. We provide information that can be applied to the improvement of age-related health and social services. DESIGN AND METHODS: During a 6-month period, we interviewed late-life Russian-speaking immigrants in Israeli independent living facilities to determine benzodiazepine use among such individuals. RESULTS: Among individuals interviewed, 69% reported use; 45% of those who used the substance did so daily. Respondents aged 80 and older were more likely than those aged younger than 80 to use benzodiazepines. More men (78%) than women (67%) reported use, but we found no significant difference in a comparison of gender status and pattern of drug use. IMPLICATIONS: Although other studies of drug use show that patterns of use differ significantly among older men and women, this research indicates that gender status does not appear to influence the pattern of, and reasons for, benzodiazepine use. Additional studies are needed in order for researchers to further understand the nature and extent of benzodiazepine use. Such information should be applied to the development of policies and services that will address the quality-of-life needs of individuals who use or misuse this drug and others like it.

Brief report: Binge drinking among high-risk male and female adolescents in Israel.

A major factor attributed to the problem and consequences of underage alcohol use is binge drinking. The objective of this study was to examine binge drinking and other alcohol-related problem behaviour among high-risk male and female adolescents who were from alternative schools and programs because of learning and/or behaviour problems. Self-report data were collected from a purposive sample of 917 adolescents in Israel who ranged from 12 to 18 years. Binge drinking during the last 30 days prior to the survey was reported by 33% of males and 23% of females (p<.001). Results of other alcohol-related behaviour showed gender status not related to being in a car when the driver had been drinking (12%) or having driven a car or motorcycle after drinking (5%). Multiple regression analysis showed binge drinking related to what a youth does with time; a decline in relations with family members; selling drugs; and, having been in a serious fight during the last 12 months. Country of origin, i.e. born in Israel or the Former Soviet Union, was not found linked to binge drinking. Further research of binge drinking and alcohol-related problem behaviour among high-risk youth is important so that it can be applied to immediate and longstanding prevention efforts.