Yi-Shing Lisa Cheng

A review of research on salivary biomarkers for oral cancer detection

Using saliva for disease diagnostics and health surveillance is a promising approach as collecting saliva is relatively easy and non-invasive. Over the past two decades, using salivary biomarkers specifically for early cancer detection has attracted much research interest, especially for cancers occurring in the oral cavity and oropharynx, for which the five-year survival rate (62%) is still one of the lowest among all major human cancers. More than 90% of oral cancers are oral squamous cell carcinoma (OSCC) and the standard method for detection is through a comprehensive clinical examination by oral healthcare professionals. Despite the fact that the oral cavity is easily accessible, most OSCCs are not diagnosed until an advanced stage, which is believed to be the major reason for the low survival rate, and points to the urgent need for clinical diagnostic aids for early detection of OSCC. Thus, much research effort has been dedicated to investigating potential salivary biomarkers for OSCC, and more than 100 such biomarkers have been reported in the literature. However, some important issues and challenges have emerged that require solutions and further research in order to find reliable OSCC salivary biomarkers for clinical use. This review article provides an up-to-date list of potential OSCC salivary biomarkers reported as of the fall of 2013, and discusses those emerging issues. By raising the awareness of these issues on the part of both researchers and clinicians, it is hoped that reliable, specific and sensitive salivary biomarkers may be found soon—and not only biomarkers for early OSCC detection but also for detecting other types of cancers or even for monitoring non-cancerous disease activity.

Optical axial scanning in confocal microscopy using an electrically tunable lens

This paper presents the use and characterization of an electrically focus tunable lens to perform axial scanning in a confocal microscope. Lateral and axial resolution are characterized over a >250 µm axial scan range. Confocal microscopy using optical axial scanning is demonstrated in epithelial tissue and compared to traditional stage scanning. By enabling rapid axial scanning, minimizing motion artifacts, and reducing mechanical complexity, this technique has potential to enhance in vivo three-dimensional imaging in confocal endomicroscopy.

Diagnosis of oral lichen planus: a position paper of the American Academy of Oral and Maxillofacial Pathology

Despite being one of the most common oral mucosal diseases and recognized as early as 1866, oral lichen planus (OLP) is still a disease without a clear etiology or pathogenesis, and with uncertain premalignant potential. More research is urgently needed; however, the research material must be based on an accurate diagnosis. Accurate identification of OLP is often challenging, mandating inclusion of clinico-pathological correlation in the diagnostic process. This article summarizes current knowledge regarding OLP, discusses the challenges of making an accurate diagnosis, and proposes a new set of diagnostic criteria upon which to base future research studies. A checklist is also recommended for clinicians to provide specific information to pathologists when submitting biopsy material. The diagnostic process of OLP requires continued clinical follow-up after initial biopsy, because OLP mimics can manifest, necessitating an additional biopsy for direct immunofluorescence study and/or histopathological evaluation in order to reach a final diagnosis.

FGFR2 in the dental epithelium is essential for development and maintenance of the maxillary cervical loop, a stem cell niche in mouse incisors

Constant supplies of dental epithelial cells from stem cell niches in the cervical loop enable mouse incisors to grow continuously through life. Fibroblast growth factor 10 (FGF10) has been shown to be essential for development of mouse incisors and maintenance of incisor cervical loops during prenatal development. Whether its cognate receptor, FGFR2IIIB, in the dental epithelium is required for postnatal tooth development remains unknown because Fgfr2IIIb ablation causes neonatal lethality. Here we report that tissue‐specific ablation of Fgfr2 in the dental epithelium led to defective maxillary incisors that lacked ameloblasts and the enamel, and had poorly developed odontoblasts. Although the cervical loop in Fgfr2 null maxillary incisors was formed initially, it failed to continue to develop and gradually diminished soon after birth. The results suggest that the FGFR2 signaling axis plays a role in maintaining the stem cell niche required for incisor development and lifelong growth. Developmental Dynamics 238:324–330, 2009.

Salivary endothelin-1 potential for detecting oral cancer in patients with oral lichen planus or oral cancer in remission.

Endothelin-1 (ET-1) is a potent vasoconstrictor involved not only in vascular biology but also in carcinogenesis. Results of a study in 2007 suggested salivary ET-1 as a potential biomarker for oral squamous cell carcinoma (OSCC), but a later study showed conflicting results. The purpose of our pilot study was to investigate feasibility of using salivary ET-1 as a biomarker for OSCC in two groups: oral lichen planus (OLP) patients and patients with OSCC in remission. Saliva samples were collected from five groups of subjects: patients with newly diagnosed, active OSCC (Group A); patients with OSCC in remission (Group B); patients with active OLP lesions (Group C); patients with OLP in remission (Group D); and normal controls (Group E). Salivary ET-1 levels were determined by enzyme-linked immunosorbent assay, and the results were analyzed by the Mann-Whitney U test. The mean salivary ET-1 level in Group A was significantly higher than that found in Group C (p=0.001), Group D (p=0.015) or Group E (p=0.004). There were no significant differences (p>0.05) in the mean salivary ET-1 levels between Groups A and B; Groups B and C; Groups B and D; Groups B and E; Groups C and D; Groups C and E; or Groups D and E. Salivary ET-1 could be a good biomarker for OSCC development in OLP patients regardless of the degree of OLP disease activity. However, it appeared not to be a good biomarker for detecting recurrence of OSCC in patients in remission.

Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer

Abstract. Optical imaging techniques using a variety of contrast mechanisms are under evaluation for early detection of epithelial precancer; however, tradeoffs in field of view (FOV) and resolution may limit their application. Therefore, we present a multiscale multimodal optical imaging system combining macroscopic biochemical imaging of fluorescence lifetime imaging (FLIM) with subcellular morphologic imaging of reflectance confocal microscopy (RCM). The FLIM module images a 16×16  mm2 tissue area with 62.5 μm lateral and 320 ps temporal resolution to guide cellular imaging of suspicious regions. Subsequently, coregistered RCM images are acquired at 7 Hz with 400 μm diameter FOV, <1  μm lateral and 3.5 μm axial resolution. FLIM-RCM imaging was performed on a tissue phantom, normal porcine buccal mucosa, and a hamster cheek pouch model of oral carcinogenesis. While FLIM is sensitive to biochemical and macroscopic architectural changes in tissue, RCM provides images of cell nuclear morphology, all key indicators of precancer progression.

Flexible endoscope for continuous in vivo multispectral fluorescence lifetime imaging

Fluorescence lifetime imaging (FLIM) offers a noninvasive approach for characterizing the biochemical composition of biological tissue. There has been an increasing interest in the application of multispectral FLIM for medical diagnosis. Central to the clinical translation of FLIM technology is the development of compact and high-speed endoscopy systems. Unfortunately, the predominant multispectral FLIM approaches suffer from limitations that impede the development of endoscopy systems that are suitable for in vivo tissue imaging. We present a compact wide-field time-gated FLIM flexible endoscope capable of continuous lifetime imaging of up to three fluorescence emission bands simultaneously. This endoscope design will facilitate the evaluation of FLIM for in vivo applications.

Salivary Interleukin-6 and -8 in Patients With Oral Cancer and Patients With Chronic Oral Inflammatory Diseases

BACKGROUND Previous research has indicated that salivary interleukin (IL)-6 and IL-8 are potential biomarkers for oral squamous cell carcinoma (OSCC). However, their levels have been found to be significantly elevated in patients with chronic periodontitis (CP) or oral lichen planus (OLP). The data also showed wide variations in levels among the different studies, and no standardization procedure was ever performed. Therefore, the objective of this study is to determine whether CP or OLP confounds the use of IL-6 or IL-8 for OSCC detection. METHODS Saliva samples were collected from five groups: OSCC before treatment (n = 18); CP (n = 21); disease-active OLP (n = 21); disease-inactive OLP (n = 20); and healthy controls (n = 21). IL-6 and IL-8 concentrations (determined by enzyme-linked immunosorbent assays) were compared, using total salivary protein-standardized levels to validate the data. The Kruskal-Wallis test (α = 0.05) followed by pairwise Mann-Whitney U (post hoc) tests with Bonferroni adjustments (α = 0.00625) were used for statistical analysis. RESULTS Salivary IL-6 levels were significantly higher in patients with OSCC than in patients with CP (P <0.001), disease-active OLP (P = 0.001), disease-inactive OLP (P <0.001), and healthy controls (P <0.001). Salivary IL-8 levels were significantly higher in patients with OSCC than in patients with CP (P <0.001), but only marginally significantly higher than in healthy controls (P = 0.014). Statistical results of standardized IL-6 and IL-8 levels were consistent with the non-standardized levels in all pairs except one. CONCLUSION Salivary IL-6 may be a useful biomarker in the detection of OSCC, unconfounded by CP or OLP.

Salivary basic fibroblast growth factor in patients with oral squamous cell carcinoma or oral lichen planus

OBJECTIVE The objective of this study was to gather preliminary data concerning the feasibility of using salivary basic fibroblast growth factor (bFGF) for detecting development of oral squamous cell carcinoma (OSCC) in patients with oral lichen planus (OLP), and in patients with OSCC whose disease was in remission. STUDY DESIGN Saliva samples were collected from 5 patient groups: patients with newly diagnosed OSCC, patients with OSCC whose disease was in remission, patients with OLP in disease-active state, patients with OLP in disease-inactive state, and healthy controls. Salivary bFGF levels were determined by enzyme-linked immunosorbent assay, and data were analyzed using the Mann-Whitney U test. RESULTS Salivary bFGF levels were significantly elevated in patients with newly diagnosed OSCC compared with patients with OSCC in remission, patients with disease-active OLP, and healthy controls. No significant difference was found between patients with newly diagnosed OSCC and patients with disease-inactive OLP. CONCLUSIONS Our results suggested that salivary bFGF might be a potential biomarker for detecting OSCC development in patients with OSCC in remission, but not in patients with OLP.

Advances in Diagnostic Adjuncts for Oral Squamous Cell Carcinoma

Oral cancer is the 8 th most common cancer in males and the 15 th most common in females in the United States. Each year, it affects approximately 22,000 Americans and results in approximately 5300 deaths. The five-year survival rate of oral cancer remains low (53% to 60%) for the past three decades and delayed diagnosis has been suggested to be one of the major reasons. The detection and diagnosis of oral cancer is currently based on clinical visual examination and histopathological evaluation of the biopsy material. In responding to the need for early detection of oral cancer, several diagnostic adjuncts have been developed over the years. The purpose of this article is to review the current knowledge about the commercially available diagnostic adjuncts as well as to review the research on the development of the promising tools for the early detection of oral cancer.