Lauren L. Patton

Changing prevalence of oral manifestations of human immuno-deficiency virus in the era of protease inhibitor therapy☆☆☆

OBJECTIVE The purpose of this study was to determine temporal trends in the prevalence of oral manifestations of human immunodeficiency virus (HIV). STUDY DESIGN Five hundred seventy HIV-infected adults recruited consecutively were examined by using established presumptive clinical criteria for HIV-associated oral lesions. Prevalence of oral lesions before the widespread use of HIV protease inhibitors (February 1995 through August 1996, 8% of the early sample, n = 271) was compared with lesion prevalence in a more recent period of greater protease inhibitor use (December 1996 through February 1999, 42% of the late sample, n = 299). RESULTS Overall prevalence of oral lesions significantly decreased from early to late periods, 47.6% to 37.5%, respectively (P =.01), with some variation by lesion type. Prevalence of hairy leukoplakia (25. 8% to 11.4%; P <.01) and necrotizing periodontal diseases (4.8% to 1. 7%; P =.03) decreased, whereas HIV salivary gland disease increased (1.8% to 5.0%; P =.04). Changes in prevalence of oral candidiasis (20.3% to 16.7%), aphthous ulcers (3.7% to 3.0%), oral warts (2.2% to 4.0%), herpes simplex virus lesions (1.8% to 2.0%), and Kaposis sarcoma (1.1% to 0.3%) were not statistically significant (P >.20 for all comparisons). CONCLUSION The pattern of oral opportunistic infections is changing in the era of protease inhibitor use.

New developments and opportunities in oral mucosal drug delivery for local and systemic disease

The oral mucosas accessibility, excellent blood supply, by-pass of hepatic first-pass metabolism, rapid repair and permeability profile make it an attractive site for local and systemic drug delivery. Technological advances in mucoadhesives, sustained drug release, permeability enhancers and drug delivery vectors are increasing the efficient delivery of drugs to treat oral and systemic diseases. When treating oral diseases, these advances result in enhanced therapeutic efficacy, reduced drug wastage and the prospect of using biological agents such as genes, peptides and antibodies. These technologies are also increasing the repertoire of drugs that can be delivered across the oral mucosa to treat systemic diseases. Trans-mucosal delivery is now a favoured route for non-parenteral administration of emergency drugs and agents where a rapid onset of action is required. Furthermore, advances in drug delivery technology are bringing forward the likelihood of transmucosal systemic delivery of biological agents.

A systematic review of oral fungal infections in patients receiving cancer therapy

PurposeThe aims of this systematic review were to determine, in patients receiving cancer therapy, the prevalence of clinical oral fungal infection and fungal colonization, to determine the impact on quality of life and cost of care, and to review current management strategies for oral fungal infections.MethodsThirty-nine articles that met the inclusion/exclusion criteria were independently reviewed by two calibrated reviewers, each using a standard form. Information was extracted on a number of variables, including study design, study population, sample size, interventions, blinding, outcome measures, methods, results, and conclusions for each article. Areas of discrepancy between the two reviews were resolved by consensus. Studies were weighted as to the quality of the study design, and recommendations were based on the relative strength of each paper. Statistical analyses were performed to determine the weighted prevalence of clinical oral fungal infection and fungal colonization.ResultsFor all cancer treatments, the weighted prevalence of clinical oral fungal infection was found to be 7.5% pre-treatment, 39.1% during treatment, and 32.6% after the end of cancer therapy. Head and neck radiotherapy and chemotherapy were each independently associated with a significantly increased risk for oral fungal infection. For all cancer treatments, the prevalence of oral colonization with fungal organisms was 48.2% before treatment, 72.2% during treatment, and 70.1% after treatment. The prophylactic use of fluconazole during cancer therapy resulted in a prevalence of clinical fungal infection of 1.9%. No information specific to oral fungal infections was found on quality of life or cost of care.ConclusionsThere is an increased risk of clinically significant oral fungal infection during cancer therapy. Systemic antifungals are effective in the prevention of clinical oral fungal infection in patients receiving cancer therapy. Currently available topical antifungal agents are less efficacious, suggesting a need for better topical agents.

The Oral HIV/AIDS Research Alliance: updated case definitions of oral disease endpoints.

The Oral HIV/AIDS Research Alliance (OHARA) is part of the AIDS Clinical Trials Group (ACTG), the largest HIV clinical trials organization in the world. Its main objective is to investigate oral complications associated with HIV/AIDS as the epidemic is evolving, in particular, the effects of antiretrovirals on oral mucosal lesion development and associated fungal and viral pathogens. The OHARA infrastructure comprises: the Epidemiologic Research Unit (at the University of California San Francisco), the Medical Mycology Unit (at Case Western Reserve University) and the Virology/Specimen Banking Unit (at the University of North Carolina). The team includes dentists, physicians, virologists, mycologists, immunologists, epidemiologists and statisticians. Observational studies and clinical trials are being implemented at ACTG-affiliated sites in the US and resource-poor countries. Many studies have shared end-points, which include oral diseases known to be associated with HIV/AIDS measured by trained and calibrated ACTG study nurses. In preparation for future protocols, we have updated existing diagnostic criteria of the oral manifestations of HIV published in 1992 and 1993. The proposed case definitions are designed to be used in large-scale epidemiologic studies and clinical trials, in both US and resource-poor settings, where diagnoses may be made by non-dental healthcare providers. The objective of this article is to present updated case definitions for HIV-related oral diseases that will be used to measure standardized clinical end-points in OHARA studies, and that can be used by any investigator outside of OHARA/ACTG conducting clinical research that pertains to these end-points.

The effectiveness of community-based visual screening and utility of adjunctive diagnostic aids in the early detection of oral cancer

A systematic review of community-based oral cancer screening programmes published between 1966 and March 2002 was undertaken. Data relating to study design, sampling and characteristics of the study group, interventions, and reported outcomes and diagnostic value of visual screening or adjunctive diagnostic aids were abstracted from 36 articles meeting inclusion and exclusion criteria. From these reports, there is insufficient evidence to demonstrate the effectiveness of community-based oral cancer visual screening in enhancing the early detection of oral cancer, due to small effect size. While the evidence is fair to support use of toluidine blue as an aid in diagnosis of oral cancer, there is insufficient evidence to determine whether the use of this or other adjunctive techniques will increase the detection of oral malignancies in community screening programmes. Targeted clinical examination of high-risk individuals may be more effective than mass screening in facilitating early detection of oral cancers.

Local drug delivery for oral mucosal diseases: challenges and opportunities

There are few topical formulations used for oral medicine applications most of which have been developed for the management of dermatological conditions. As such, numerous obstacles are faced when utilizing these preparations in the oral cavity, namely enzymatic degradation, taste, limited surface area, poor tissue penetration and accidental swallowing. In this review, we discuss common mucosal diseases such as oral cancer, mucositis, vesiculo-erosive conditions, infections, neuropathic pain and salivary dysfunction, which could benefit from topical delivery systems designed specifically for the oral mucosa, which are capable of sustained release. Each condition requires distinct penetration and drug retention profiles in order to optimize treatment and minimize side effects. Local drug delivery may provide a more targeted and efficient drug-delivery option than systemic delivery for diseases of the oral mucosa. We identify those mucosal diseases currently being treated, the challenges that must be overcome and the potential of novel therapies. Novel biological therapies such as macromolecular biological drugs, peptides and gene therapy may be of value in the treatment of many chronic oral conditions and thus in oral medicine if their delivery can be optimized.

Oropharyngeal candidiasis in head and neck cancer patients treated with radiation: update 2011

BackgroundOropharyngeal candidiasis (OPC) is a major cause of morbidity in patients with malignancies. It is a common complication of head and neck radiation therapy and can result in pain, dysgeusia (taste changes), anorexia, malnutrition, and esophageal or systemic dissemination. Clinicians should be aware of current epidemiology, elements of diagnosis, and therapeutic trials guiding the recent recommendations for prophylaxis and management of OPC, a disease often incorrectly perceived as benign.MethodsThis review discusses OPC with focus in head and neck cancer patients receiving radiotherapy.ResultsLocal treatments are recommended as first-line therapy in milder forms of OPC. In the setting of local therapy, products that provide prolonged contact time and are not sucrose sweetened may result in successful prevention and management with low risk of oral/dental complications.ConclusionDiagnosis and management of OPC is required in head and neck cancer patients treated with radiation. Local therapy is suggested as first-line treatment for OPC, unless severe clinical infection or high risk immune suppression necessitate systemic therapy. The availability of effective locally delivered (topical) medications may provide potential for prophylaxis for carriers of Candida species in head and cancer patients during radiation therapy.

National prevalence of oral HPV infection and related risk factors in the US adult population reply

Dear Editor, We appreciate these readers’ interest in our paper (Sanders et al, 2012) and confine our response to comments in their letter that address the methods, results, and interpretation of findings of our study. In their letter, Prabhu et al state that our work extrapolates data from 4846 adult subjects’ and they caution against over-interpretation. It is not necessary to study all people in a population to estimate prevalence and in practice that almost never happens. In our paper, oral HPV infection prevalence was estimated from the 2009–2010 National Health and Nutrition Examination Survey (NHANES). NHANES uses probability sampling methods to select people and to produce prevalence estimates that are generalizable to the community dwelling US population. In fact, the ability to estimate prevalence is the primary purpose of NHANES. Because prevalence estimates in NHANES are from a sample of study participants, it is essential that the estimates be interpreted in view of sampling error that is inherent in such surveys, which is why we report 95% confidence intervals throughout the paper. We made no attempt to extrapolate beyond the data. Prabhu et al express concern about the use of the word infection’ in the title. Throughout themanuscript, our use of infection’ is consistent with Stedman’s Medical Dictionary (28th edition; Stedman, 2006), which defines infection as Invasion of the body with organisms that have the potential to cause disease.’ In accordance with this definition, we do not imply the presence of disease. Prabhu et al note that saliva is not recognized as a vehicle for transmission. While this consideration is beyond the scope of the objectives of our paper, we point out that in this study, DNA was purified from oral exfoliated cells, not from saliva. A fourth criticism concerns our interpretation of attributable risk for oral squamous cell carcinoma (OSCC) associated with HPV infection. Last defines attributable risk as the rate or proportion of a disease or other outcome of interest among exposed persons that can be attributed to an exposure of interest’(Last, 2007). This conventionalmeasure can be readily calculated using two pieces of information: (1) the prevalence of exposure to a risk factor in a defined population; and (2) the strength of association between that risk factor and an outcome of interest in that population. In the context of this study, the exposure is oncogenic oral HPV infection and the outcome is OSCC. We combined the estimate of oncogenic oral HPV infection prevalence of 3.1% (95% CI: 2.4, 3.9) observed in the 2009–2010 NHANES with published findings from a case–control study of OSCC that estimated the strength of association between oral HPV infection and OSCC (Smith et al, 2004). Of note, that study used the same methods as used in 2009–2010 NHANES to evaluate oral HPV infection, yielding an odds ratio of 2.6 (95% CI: 1.5, 4.2) as the estimate of the association after adjusting for age, tobacco use, and alcohol consumption. If the measure of HPV exposure was either a necessary or sufficient cause of oral cancer (as might be the case, for example, if the study had measured altered protein expression in the host as a consequence of HPV integration into DNA), the corresponding odds ratio would be infinity. The attenuated odds ratio of 2.6 reflects, in part, the fact that HPV infection of oral exfoliated cells is an upstream marker of causal events contributing to cancer, as Prabhu et al explain. Its usefulness is as a practical measure to gauge excess risk in the population. Such markers need not be necessary or sufficient causes, and in practice, they almost never are. When we used the estimated association from Smith et al (2004) with our own estimate of prevalence, the point estimate for population attributable risk was 4.7%. The significance of this contribution to public health is that it permits interpretation that there would be a 4.7% reduction in incidence of head and neck cancer in the USadult population (exposed andunexposed) if exposure to oncogenic types of oral HPV infection was eliminated. Given that this estimate is based on the best quality data presently available, we respectfully disagree with Prabhu et al who suggest that this finding is premature. We thank these readers for the opportunity to clarify these points.We trust that our replymight help to enhance a fuller understanding of epidemiologic principles and methods for the diverse readership ofOral Diseases.

National prevalence of oral HPV infection and related risk factors in the U.S. adult population: Oral HPV prevalence in the US

This article reviews the rapidly growing evidence that oral human papilloma viruses (HPV) infection contributes to the risk of oral squamous cell carcinoma. It also reports the first nationally representative estimates of oral HPV prevalence in the United States adult population. An estimated 7.3% (95% CI: 6.0, 8.9) of the U.S. population had one or more oral HPV types detected in oral rinse; 3.1% (95%CI: 2.4, 3.9) of the U.S. population had one or more oncogenic HPV types. A substantial excess risk of HPV infection in men is not explained by education, smoking, age of sexual debut, or number of lifetime sex partners. Based on the published finding from a case-control study, where there was an odds ratio of 2.6 (95% CI: 1.5, 4.2) for the association of head and neck cancer oncogenic oral HPV infection, the estimated population attributable risk for head and neck cancer in the U.S. population was 4.7%. In other words, there would be a 4.7% reduction in incidence rate of head and neck cancer in the United States if oncogenic HPV infection could be prevented. The results also provide population data that help evaluate the likely public health benefits of prophylactic vaccination against oral HPV acquisition.

Salivary Secretory Leukocyte Protease Inhibitor and Oral Candidiasis in Human Immunodeficiency Virus Type 1-Infected Persons

ABSTRACT Oropharyngeal candidiasis, typically caused by Candida albicans, is the most common oral disease associated with human immunodeficiency virus type 1 (HIV-1) infection. Secretory leukocyte protease inhibitor (SLPI), a 12-kDa antiprotease, suppresses the growth of C. albicans in vitro. To determine whether the mucosal protein plays a role in protecting oral tissues against fungal infection, we conducted a cross-sectional study investigating the oral and systemic health and salivary SLPI levels in 91 dentate HIV-1-infected adults receiving medical care in the southeastern United States. Participants with a self-reported history of clinical oropharyngeal candidiasis during the previous 2 years constituted the test group (n = 52), while the comparison group (n = 39) had no oropharyngeal candidiasis during that period. Data collected from medical records, oral examination, and SLPI enzyme-linked immunosorbent assay quantitation of whole saliva were analyzed by t test, analysis of variance, linear regression, and unconditional logistic regression. The test group had a significantly higher mean salivary SLPI level than the comparison group (1.9 μg/ml versus 1.1 μg/ml, P < 0.05). Linear regression modeling identified CD4 cell count and history of oropharyngeal candidiasis as key predictors of salivary SLPI and revealed a significant interaction (P < 0.05) between immunosuppression (CD4 cell count below 200 cells/μl) and positive history of oropharyngeal candidiasis in predicting salivary SLPI level. By logistic regression modeling, a salivary SLPI level exceeding 2.1 μg/ml, low CD4 count, antiretroviral monotherapy, and smoking were key predictors of oropharyngeal candidiasis. These data support a key role for SLPI in the oral mucosal defense against C. albicans. The antimicrobial mucosal protein may serve as an indicator of previous oropharyngeal candidiasis infection among immunosuppressed persons.