Mats Jontell

Human papillomaviruses in oral carcinoma and oral potentially malignant disorders: a systematic review

OBJECTIVES Human papillomavirus (HPV) in oral carcinoma (OSCC) and potentially malignant disorders (OPMD) is controversial. The primary aim was to calculate pooled risk estimates for the association of HPV with OSCC and OPMD when compared with healthy oral mucosa as controls. We also examined the effects of sampling techniques on HPV detection rates. METHODS Systematic review was performed using PubMed (January 1966-September 2010) and EMBASE (January 1990-September 2010). Eligible studies included randomized controlled, cohort and cross-sectional studies. Pooled data were analysed by calculating odds ratios, using a random effects model. Risk of bias was based on characteristics of study group, appropriateness of the control group and prospective design. RESULTS Of the 1121 publications identified, 39 cross-sectional studies met the inclusion criteria. Collectively, 1885 cases and 2248 controls of OSCC and 956 cases and 675 controls of OPMD were available for analysis. Significant association was found between pooled HPV-DNA detection and OSCC (OR = 3.98; 95% CI: 2.62-6.02) and even for HPV16 only (OR = 3.86; 95% CI: 2.16-6.86). HPV was also associated with OPMD (OR = 3.87; 95% CI: 2.87-5.21). In a subgroup analysis of OPMD, HPV was also associated with oral leukoplakia (OR = 4.03; 95% CI: 2.34-6.92), oral lichen planus (OR = 5.12; 95% CI: 2.40-10.93), and epithelial dysplasia (OR = 5.10; 95% CI: 2.03-12.80). CONCLUSIONS The results suggest a potentially important causal association between HPV and OSCC and OPMD.

Osteonecrosis of the jaw and bisphosphonate treatment for osteoporosis

A potential side effect associated with bisphosphonates, a class of drugs used in the treatment of osteoporosis, Pagets disease and metastatic bone disease, is osteonecrosis of the jaw (ONJ). The incidence of ONJ in the general population is unknown; this rare condition also may occur in patients not receiving bisphosphonates. Case reports have discussed ONJ development in patients with multiple myeloma or metastatic breast cancer receiving bisphosphonates as palliation for bone metastases. These patients are also receiving chemotherapeutic agents that might impair the immune system and affect angiogenesis. The incidence or prevalence of ONJ in patients taking bisphosphonates for osteoporosis seems to be very rare. No causative relationship has been unequivocally demonstrated between ONJ and bisphosphonate therapy. A majority of ONJ occurs after tooth extraction. Furthermore, the underlying risk of developing ONJ may be increased in osteoporotic patients by comorbid diseases. Treatment for ONJ is generally conservative.

Immune Defense Mechanisms of the Dental Pulp

Defense reactions of the dentin/pulp complex involve a variety of biological systems, in which the immune system plays a pivotal role. The knowledge of the organization and function of pulpal immunocompetent cells has been sparse, but in recent years a significant body of information of immune mechanisms in general has provided a footing for substantial new knowledge of the immune mechanisms of the dental pulp. The identification of pulpal dendritic cells (DCs) has generated research activities which have led to a concept of how an antigenic challenge may evoke a pulpal inflammatory response. Although DCs are not able to identify foreign antigens specifically, they provide necessary signals to activate T-lymphocytes which in turn will orchestrate other immunocompetent cells to mount the local immune defense of the dental pulp. The purpose of this review is to accent the organization and function of pulpal DCs and other tissue and cellular components and to provide a basis for how they may interact to instigate pulpal defense mechanisms.

Oral Lichen Planus and Malignant Transformation: Is a Recall of Patients Justified?

There has been a continuous debate regarding the possible malignant potential of oral lichen planus (OLP). Based on the results from follow-up studies, OLP is regarded by several authors as a pre-malignant condition, and patients with OLP have been recommended to have their lesions monitored two to four times annually. This recommendation needs reconsideration, because a recall system of all patients with OLP requires substantial economic resources. In a reality where such resources are limited, a recall system must be weighed against other benefits and the fact that the malignant potential of OLP is most likely very low. The present review focuses on the diagnostic criteria for OLP, the pre-malignant potential of OLP, and the extent to which the available information can be used to reduce morbidity and mortality of oral cancer related to OLP.

Effects of Unpolymerized Resin Components on the Function of Accessory Cells Derived from the Rat Incisor Pulp

Monomeric resin components from dental composites are toxic to fibroblasts in culture and thus may interfere with the local immune system of the pulp, reducing its effective defense potential, either by cytotoxicity or by a more specific immune mechanism. Therefore, the present study was undertaken to observe the cytotoxic effects elicited by certain unpolymerized components of resin composites upon the function of accessory pulp cells in mitogen-induced proliferation of T-lymphocytes. Accessory cells from the rat incisor pulp were released following enzymatic digestion with collagenase. The assay included incubation of these cells with purified T-lymphocytes from cervical lymph nodes for 72 h in the presence of different concentrations of the resin components. The proliferative T-lymphocyte response was monitored by 3H-thymidine incorporation. Initially, we conducted experiments on spleen cells to determine the proper concentration intervals for suitable testing of the resin components. To assess the individual susceptibility of accessory cells and T-lymphocytes, we pre-treated each of these cells with some of the test materials prior to assay. At low concentrations, urethane dimethacrylate (UDMA), bisglycidyl methacrylate (bis-GMA), triethylene glycol dimethacrylate (TEGDMA), and bis-phenol A (BPA) increased spleen cell proliferation to concanavalin A (con A). Purified T-lymphocytes stimulated by pulpal cells did not show enhanced responses to UDMA, bis-GMA, glycidyl methacrylate (GMA), or N,N-dihydroxyethyl-p-toluidine (DHEpT). At higher concentrations, all substances except camphoroquinone (CAMP) showed inhibitory effects in both test systems. The in vitro study shows that resin components can evoke either immunosuppression or immunostimulation on mitogen-driven proliferation of purified T-lymphocytes and spleen cells.

Cancer and oral lichen planus in a Swedish population.

Oral lichen planus (OLP) is generally regarded as a premalignant condition. The objective of the present study was to assess the number of oral malignant tumours in a retrospective analysis of 1028 patients (mean age=55 years; range=18-86; female, n=667; men, n=351) who between 1978 to end of 1993 were diagnosed with OLP at the Faculty of Odontology, Goteborg University, Sweden. Patients with malignant tumours were identified through the Swedish Cancer Registry at the National Board of Health and Welfare, which annually reports the incidence of malignant neoplasms in the Swedish population. The incidence of oral squamous cancer (OSCC), other malignant tumours and survival in the study group was compared to the Swedish population. The total time with OLP in the study group amounted to 7009 person years, with a mean follow up of 6.8 years (SD=4.9). The observed incidence of OSCC was higher than the expected incidence in the study group. The difference was statistically significant (P<0.001). No statistically significant difference was found for any other malignant tumours than OSCC. Also, no statistically significant difference could be identified in survival between study group and the population. The results from the present study gives further support to the concept of a small but increased risk for development of squamous cell carcinoma in patients with OLP.

Isoelectric focusing of the phosphoprotein of rat-incisor dentin in ampholine and acid pH gradients : Evidence for carrier ampholyte—protein complexes

Rat-incisor phosphoprotein (RIP) has been subjected to isoelectric focusing at 4 degrees in (a) an Ampholine pH gradient of 2.5-4 and (b) an acid pH gradient created by electrolysis of a system of acids and acidic ampholytes and covering the pH range 0.5-3.5. In the Ampholine gradient, the RIP unexpectedly formed several adjacent and strongly opalescent bands in the pH range 2.5-3.1. These bands, which migrated slowly toward the anode on prolonged focusing, are interpreted as being the result of an interaction between the amino groups of the Ampholine and the numerous phosphate groups of the protein. In the acid pH gradient, the RIP focused into one narrow zone corresponding to an isoelectric pH of 1.1 at 4 degrees. This value is consistent with the amino-acid composition and the phosphate content of the protein,

Dendritic Cells and Macrophages Expressing Class II Antigens in the Normal Rat Incisor Pulp

This study has identified and characterized class II (Ia) antigen-expressing cells in the normal rat incisor pulp by immunohistochemistry and flow cytometry. Two types of la-expressing cells occurred: one with a pronounced dendritic appearance located primarily in the periphery of the pulp, and one with morphological characteristics similar to those of macrophages. The latter cells were mainly observed in the central portion of the pulp. A numerical ratio of 1 :4 was established between the two cell types. The existence of la-expressing cells suggests an inherent capacity of the pulp to process and present foreign antigens.

Effect of replacement of dental amalgam on oral lichenoid reactions

OBJECTIVES The objectives of this study were to investigate (i) healing of oral lichenoid reactions (OLR) following the selective replacement of restorations of dental amalgam, (ii) whether there were differences in healing between contact lesions (CL) and oral lichen planus (OLP), and (iii) whether there was a difference in healing potential when different materials were selected as a substitute for dental amalgam. METHODS Patients included in the study presented with OLR confined to areas of the oral mucosa in close contact with amalgam restorations (CL; n = 142) or with OLR which involved other parts of the oral mucosa as well (OLP; n = 19). After examination, restorations of dental amalgam which were in contact with OLR in both patient groups were replaced. The effect of replacement was evaluated at a follow-up after 6-12 months. RESULTS In the CL group, the lesions showed a considerable improvement or had totally disappeared in 95% of the patients after replacement of the restorations of dental amalgam (n = 474). This effect was paralleled by a disappearance of symptoms, in contrast to patients with persisting CL (5%) who did not report any significant improvement. The healing response was not found to correlate with age, gender, smoking habits, subjective dryness of the mouth or current medication. However, the healing effect in patients who received gold crowns was superior compared to that of patients treated with metal-ceramic crowns (MC; P < 0.05). In the OLP group (n = 19), 63% of the patients with amalgam-associated erosive and atrophic lesions showed an improvement following selective replacement. OLP lesions in sites not in contact with amalgams were not affected. Most of the patients (53%) with OLP reported symptoms also after replacement. CONCLUSION From these data it can be concluded that the vast majority of CL resolve following selective replacement of restorations of dental amalgam, provided that a correct clinical diagnosis is established. It is also noteworthy that MC crowns did not facilitate healing of CL to the same extent as gold crowns.

Langerhans cells and T cells in oral graft versus host disease and oral lichen planus.

Chronic graft versus host disease (cGVHD) of the oral mucosa, following allogeneic stem cell transplantation, and oral lichen planus (OLP) are both mucosal diseases where the immune system is involved in the pathogenesis. Although the aetiology of the two conditions is different, they present with a similar clinical appearance. This study compares the two diseases regarding the distribution of cells, which are expressing cell surface markers of interest for inflammatory responses. Monoclonal antibodies (MoAbs) were used in standard immunohistochemical procedures. CD1a+, CD80+ and CD86+ cells in the epithelium of OLP‐ and cGVHD lesions had the dendritic morphology of Langerhans cells (LC). Higher frequencies of CD1a+ LC as well as CD25+ cells were observed in the OLP epithelium than in the cGVHD epithelium. The OLP lesions showed higher frequencies of subepithelial cells expressing CD1a, CD86, CD4, CD8 and CD25 than the cGVHD lesions. Notably there was a significantly higher frequency of CD25+ cells in the epithelium and the connective tissue of OLP than in cGVHD. These cells might represent regulatory T cells. In conclusion, cGVHD and OLP show marked differences at the cellular level despite similar clinical appearance. Hence, the findings indicate differences in the regulation of the inflammatory response between the two conditions.