Oral/oropharyngeal "selfies" in gay and bisexual men: a pilot study exploring oropharyngeal screening for HPV-related possible malignancies.

Objectives: This study aims to determine the potential uptake and quality of oropharyngeal "selfies" taken by gay/bisexual men as a screening approach for HPV-associated oropharyngeal cancer. Methods: From 1,699 gay/bisexual men in the US, surveyed about knowledge and attitudes to HPV-associated oropharyngeal cancer, a random sample of 320 men were invited to take an oropharyngeal "selfie" by smartphone and send it to the study website: 113 (35.5%) did so. Images were rated for quality by three healthcare professional raters blinded to each other's rating, with an otolaryngologist as the gold standard. In the second wave, those whose images were rated as unacceptable were sent a short instructional video and asked to send another image. Of the 65 invited, 46 did so. An additional 15.2% sent acceptable images, and a total of 28.3% of the sample was acceptable. Results: A total of 1,121 men willing to participate in the future study who believed they could take a quality "oral selfie" were potentially eligible for this activity. A random sample of 320 participated: 153 participants started (47.8%) and 113 participants (35.3%) submitted an image. Responders were more likely to be younger, have higher knowledge scores on oropharyngeal HPV-related cancer, and have had HPV vaccination. There was high agreement between the three raters. Images of good/acceptable quality were 22.1%; oropharynx partially occluded images were 29.2%; oropharynx not visible images were 18.6%; images too dark were 21.2%; and images too small were 8.8%. From the second wave of requests with instructional videos, an additional 15.2% sent in quality images, with the remaining issues being partial occlusion of the tonsils by the tongue. Conclusion: One-third of the invited gay and bisexual men sent oropharyngeal selfie images to the study website and a total of 28.3% were of clinically acceptable quality. Following an instructional video on poorer-quality images, additional quality images were received. One barrier, i.e., partial occlusion of the oropharynx by the tongue remained. Quality oropharyngeal "selfies" are obtainable online.

HPV-related oropharyngeal cancer early detection in gay and bisexual men is an "orphan" practice: A qualitative analysis among healthcare providers.

Introduction: Among US men, oropharyngeal cancer (cancer of the back of the mouth and throat) is the 8th most common cancer. If detected early, human papillomavirus (HPV)-16-associated oropharyngeal cancer has a high 5-year survival rate. Risk factors such as high numbers of oral sex partners, disparities in smoking and drinking, and low rates of HPV vaccination may put gay and bisexual men at even higher risk for oropharyngeal cancer. Methods: We recruited 21 healthcare providers in Minneapolis-St. Paul, Minnesota and Houston, Texas to participate in semi-structured interviews. Nurses, physician assistants, dental hygienists, and dentists were asked about their clinical experiences serving gay and bisexual men and opinions on potential interventions for the early detection of oropharyngeal cancer. Results: Providers typically did not tailor health screenings and examinations for gay and bisexual men. Participants lacked confidence in their ability to effectively implement routine screening for oropharyngeal cancer. The extent to which oropharyngeal cancer screening was incorporated into clinical practice varied by specialty, and practices necessary to detect it were scattered across clinical environments. HIV- and LGBTQ-focused healthcare providers were more aware of HPV-associated oropharyngeal cancer in gay and bisexual men, and appeared readier to act and lead on this issue. Discussion: Further studies should (1) evaluate protocols for oropharyngeal cancer detection; (2) identify and assess the acceptability of screening in the community; and (3) study how to best close gaps in health services for gay and bisexual men which might contribute to low early detection rates of oropharyngeal cancer.

Epstein-Barr virus infection of Langerhans cell precursors as a mechanism of oral epithelial entry, persistence, and reactivation.

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus associated with many malignant and nonmalignant human diseases. Life-long latent EBV persistence occurs in blood-borne B lymphocytes, while EBV intermittently productively replicates in mucosal epithelia. Although several models have previously been proposed, the mechanism of EBV transition between these two reservoirs of infection has not been determined. In this study, we present the first evidence demonstrating that EBV latently infects a unique subset of blood-borne mononuclear cells that are direct precursors to Langerhans cells and that EBV both latently and productively infects oral epithelium-resident cells that are likely Langerhans cells. These data form the basis of a proposed new model of EBV transition from blood to oral epithelium in which EBV-infected Langerhans cell precursors serve to transport EBV to the oral epithelium as they migrate and differentiate into oral Langerhans cells. This new model contributes fresh insight into the natural history of EBV infection and the pathogenesis of EBV-associated epithelial disease.

Short-term success of osseointegrated dental implants in HIV-positive individuals: a prospective study.

PURPOSE: Except for the occasional case report, there are no studies evaluating the success rate of osseointegrated dental implants in individuals infected with the human immunodeficiency virus (HIV). This study investigated the short-term clinical outcome of implant placement in a group of HIV-positive and HIV-negative individuals who required complete dentures. METHODS AND MATERIALS: Edentulous subjects were recruited from an HIV-dedicated clinic and a dental school clinic. Two BioHorizons dental implants were placed in the anterior mandible to support an overdenture opposing a maxillary denture. Outcome measurements obtained six months after activation of implants were presence of pain, mobility, soft tissue status, and radiographic bone level. Descriptive statistics were used. RESULTS: Twenty-nine edentulous adults, including 20 HIV-positive subjects (test) and nine HIV-negative subjects (control), participated. The test group had six females, 14 males; 13 Whites, four African-Americans, and three Hispanics with a mean age of 48.9 years (range: 35-59). The mean CD4 count was 467 cells/mm3 (range: 132-948). The control group had six females, three males; seven Whites, and two Hispanics with a mean age of 65.3 years (range: 50-82). Short-term success rate was 100% for both groups. No difference in clinical outcome was found between the groups. CONCLUSION: This study demonstrated dental implants are well tolerated and have predictable outcomes for HIV-infected individuals for the duration of the study and probably over an even longer term.

The effect of complete dentures with a metal palate on candida species growth in HIV-infected patients.

PURPOSE: This in vivo investigation compared the oral candidal population between heat-cured acrylic resin and nickel-chromium-beryllium alloy in maxillary complete dentures in HIV-infected patients. MATERIALS AND METHODS: Split-palate maxillary complete dentures were fabricated for 19 HIV-infected patients: one-half of the palate was made in acrylic resin and the other half in nickel-chromium-beryllium. Patients were divided into low or high CD4+ lymphocyte count groups. Dentures were worn for 5 months. Palatal mucosa was clinically evaluated at baseline, 1, 3, and 5 months after denture insertion. Specimens were collected at 1, 3, and 5 months using a modified imprint culture method. Speciation of Candida was performed using a chromogenic culture medium. Two-sample t-test was employed to determine effects and significant interactions between the control and test groups and the low and high CD4+ lymphocyte groups. A chi(2) test analyzed and compared the results of the clinical evaluation (p < 0.05). RESULTS: Significant differences were observed in the colony counts between both materials during the third (p= 0.046) and fifth months (p= 0.039). The low CD4+ group demonstrated significant differences during the third (p= 0.03) and fifth months (p= 0.05). There were no significant differences between the species of Candida that colonized either material with the exception of Candida dubliniensis (p < 0.001) and "Others" (p < 0.001) during the first and fifth months. There were no significant differences on the clinical appearance of the palatal mucosa between both materials (p= 1.00). CONCLUSIONS: The metal base proved to be effective in decreasing the fungal growth typically present in complete dentures. Although overt clinical manifestations were not present, colony counts of Candida species were high in the acrylic resin denture bases of these patients. This investigation demonstrated that metal base complete dentures provide an important alternative dental service for edentulous HIV-positive and other patients who are particularly prone to higher incidences of fungal infections.

Retrospective clinical and radiologic evaluation of nonsurgical endodontic treatment in human immunodeficiency virus (HIV) infection.

PURPOSE: This retrospective study evaluated the clinical and radiographic status of nonsurgical endodontic treatment (ET) of anterior and posterior teeth in HIV-seropositive patients. METHODS: ET was analyzed in 26 anterior and 34 posterior teeth from 54 consecutive HIV patients (gender ratio 3 Male : 1 Female, mean age 40.2 years, mean CD4 240, CD4<500 in 88%, 12 with AIDS) over a six year period with a minimum of six months follow-up. ET was evaluated as successful, questionable, or failure based upon clinical factors (palpation, mobility, sinus tract, percussion, function, infection/swelling, occlusion, symptoms) and radiographic factors (periodontal ligament space, rarefaction, lamina dura, root resorption, obturation) during post-treatment examinations with a mean follow up of 26 months. RESULTS: Clinical evaluation at follow up found ET outcome was successful in 88%, questionable in 10% (tenderness with percussion, mobility, widened ligament), and a failure in 2% (developed lesion after ET). Periapical lesions were present in 37% of cases (mean lesion size 6.2 mm). Following ET, mean lesion size (1.8 mm) had decreased by 71%. Obturation was evaluated as optimal or acceptable in 68%. Radiographic evaluation was considered successful in 80%, no change in 15%, and a failure in 5%. CONCLUSIONS: Despite obturation deficiencies and the immunocompromised state of the patients, endodontic therapy has a relatively high degree of success in the majority of HIV/AIDS patients. HIV infection and AIDS should not be considered as a contraindication to endodontic therapy in this patient population.

Molecular markers of clonality and identity in Epstein-Barr virus-associated B-cell lymphoproliferative disease.

Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disease may be polyclonal, oligoclonal, or monoclonal. The degree of tumor clonality reflects the disease pathogenesis and may have implications for disease diagnosis, prognosis, and treatment. In this study, specimens of EBV-associated B-cell lymphoproliferative disease obtained from immunocompromised hosts were analyzed for molecular markers of cellular and virologic clonality and virologic identity. Each tumor specimen was assessed for immunoglobulin gene JH region rearrangement, the structure of the EBV genome termini, and the EBV genotype(s) present using a new EBV genotyping assay based upon LMP-1 gene sequence variation. The results of the JH rearrangement and EBV termini assays were generally concordant in their assessment of tumor specimen clonality, and both assays contributed to establishing clonal identity between different tumor specimens. The EBV genotyping assay did not significantly contribute to the assessment of tumor clonality but did established clear virologic identity between different tumor specimens obtained from the same individual. In one individual, these three assays together characterized a multi-focal, monoclonal tumor that may have arisen through clonal selection after sequential infections with two different EBV genotypes. In summary, the JH rearrangement and EBV termini assays each provided different but complementary information on tumor clonality, while the EBV genotyping assay proved most useful for establishing virologic identity among tumors. Utilization of these three assays together may provide new insight into the pathogenesis of EBV-associated B-cell lymphoproliferative disease.

Persistence and transition of Epstein-Barr virus genotypes in the pathogenesis of oral hairy leukoplakia.

This prospective study examined the persistence and transition of Epstein-Barr virus (EBV) in human immunodeficiency virus (HIV)-seropositive subjects with and without oral hairy leukoplakia, a replicative EBV-associated epithelial disease. The intrahost molecular epidemiology of EBV infection was characterized in subjects treated with valacyclovir to suppress EBV replication. Tongue epithelial tissues of HIV-seropositive subjects were found to support not only EBV replication but also persistent, nonproductive EBV infection. EBV appeared to enter the tongue from the blood reservoir of infection and, possibly, from exogenous sources as well. EBV transition from the blood to the tongue appeared to occur even during valacyclovir-mediated suppression of EBV replication, suggesting EBV entry into tongue epithelial tissue as a cell-associated latent infection. In conclusion, these results describe the persistence and transition of EBV as a dynamic interaction between the blood and epithelial reservoirs of EBV infection and suggest a role for entry, persistence, and reactivation of oral epithelial EBV in the pathogenesis of oral hairy leukoplakia.

Expression of Epstein-Barr virus latent genes in oral epithelium: determinants of the pathogenesis of oral hairy leukoplakia.

This retrospective study examined expression of Epstein-Barr virus (EBV) latent genes in oral epithelium from human immunodeficiency virus-seropositive subjects, to identify genes associated with the pathogenesis of oral hairy leukoplakia (HLP). Transcription of EBV latent genes was detected in tissues with productive EBV replication and, also, in normal oral epithelial tissues without EBV replication. Expression of the EBV EBNA-2 open-reading frame in oral epithelium was identified as an important cofactor associated with the pathogenesis of HLP. In vitro experiments suggested that a recombinant variant of the EBNA-2 gene may play a role in the pathogenesis of HLP, through modulation of EBNA-2 protein function.

Effect of Epstein-Barr virus replication on Langerhans cells in pathogenesis of oral hairy leukoplakia.

Epstein-Barr virus (EBV) replicates productively in oral hairy leukoplakia (HLP). One characteristic of human immunodeficiency virus (HIV)-associated HLP is a decreased oral epithelial Langerhans cell count. This prospective study tested the hypothesis that oral epithelial EBV replication decreases oral Langerhans cell counts. EBV replication in HLP was highly correlated with decreased oral Langerhans cell counts. Inhibition of EBV replication restored oral Langerhans cell counts to normal control levels, and the return of EBV replication after treatment resulted in a recurrent decline in oral Langerhans cell counts. Decreased oral Langerhans cell counts occurred independently of HIV infection, as demonstrated in HLP of otherwise healthy HIV-seronegative individuals. These results support the tested hypothesis and suggest that EBV manipulates and evades the mucosal immune response in oral epithelial infection. This novel EBV strategy for eliminating oral Langerhans cells may facilitate the persistence of oral epithelial EBV and may contribute to the pathogenesis of HLP.

Epstein-Barr virus replication in oral hairy leukoplakia: response, persistence, and resistance to treatment with valacyclovir.

Nineteen cases of human immunodeficiency virus (HIV)-associated oral hairy leukoplakia (HLP) and Epstein-Barr virus (EBV) replication were treated with high-dose oral valacyclovir to inhibit productive EBV replication. The clinical, histopathological, and molecular viral responses to treatment were assessed in surgical biopsy specimens obtained before, during, and after treatment. In the majority of treated cases, HLP was resolved, and EBV replication was terminated. In many cases, the initial response to inhibition of replication was a persistent, nonproductive, EBV infection of the oral mucosa, characterized by limited expression of replicative EBV genes, especially BZLF1. In some cases, productive EBV replication recurred after discontinuation of treatment with valacyclovir. In a few treated cases, treatment failed, and productive EBV replication persisted, possibly because of the evolution of acyclovir-resistant EBV. In summary, safe treatment of HLP and of EBV replication, with valacyclovir, provides new insight into the mechanisms of EBV persistence in oral mucosa.

A non-invasive technique for studying oral epithelial Epstein-Barr virus infection and disease.

Oral Epstein-Barr virus (EBV) infection is associated with hairy leukoplakia and possibly other oral diseases. Many studies of oral EBV infection utilize surgical specimens. This study tested a non-invasive brush biopsy technique as an alternative to surgical biopsy to study oral EBV infection and disease. Paired, same-site, samples of tongue epithelium were obtained from research subjects, first by brush and then by surgical biopsy. Brush cells and surgical specimens were fixed and prepared for histologic sectioning and/or processed for nucleic acid extraction. Brush cell pellet sections proved equivalent to surgical specimen tissue sections for hairy leukoplakia diagnosis by routine histologic staining and EBV immunohistochemistry or in situ hybridization. Amplification of EBV sequences demonstrated superiority of the brush cells over surgical specimens for both sensitivity (90% vs. 73%) and negative predictive value (93% vs. 82%). This non-invasive brush biopsy technique should facilitate larger, prospective studies of oral EBV infection and pathogenesis.