Michele D. Mignogna

The World Cancer Report and the burden of oral cancer

The WHO has recently provided the most comprehensive global examination of cancer to date, through the publication of the World Cancer Report (WCR). According to IARC-WHO estimates, cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000, to 15 million in 2020. However, the report states that we have the opportunity to stem the predicted sharp increase in new cancer cases by taking action now, especially through planning effective cancer control strategies, such as reducing tobacco consumption, suggesting healthy lifestyle and diet, and performing early detection through screening. Although cancer of the oral cavity is largely related to lifestyle and can be easily detected and diagnosed at early stages through a 5 min visual inspection of the oral mucosa, actual figures concerning its prevention and early detection are dismal. Most oral cancers are detected at a late stage, requiring complex, costly and often ineffective therapies. Similarly, current research, educational and financial resources are focused on procedures burdened by high cost, high morbidity and unacceptable high mortality. Here we suggest that it is time to change this common point of view towards this disease and to alter this trend, stressing that there is no other oncologic specialty in which the WCR preventive guidelines could be applied in such an easy and effective manner, as in the field of oral cancer.

Oral lichen planus and HCV infection: a clinical evaluation of 263 cases

Background Hepatitis C virus (HCV) infection induces variable dermatologic manifestations. Our purpose was to determine whether there is an association between HCV infection and oral lichen planus (OLP).

Survivin expression in oral squamous cell carcinoma

A series of 110 cases of oral squamous cell carcinoma (SCC) together with six lymph node and one distant metastatic lesions was analysed for expression of survivin, a recent apoptosis inhibitor, by immunohistochemistry and Western blotting. In total, 91 cases (82.7%) of carcinoma and all metastasis (seven cases, 100%) were positive for survivin expression, with weighted survivin scores ranging from 1 to 4. In contrast, normal oral epithelium did not express survivin. There was no significant correlation between survivin expression and age, sex, tumour size, the presence of lymph node and distant metastases. Survivin expression was increased in poorly differentiated tumours, even if differences were not statistically significant. In contrast, when analysed for prognostic significance, patients with low survivin expression had statistically significant better survival rates than the group with high survivin expression (P<0.05). These data suggest that survivin expression may identify cases of oral SCC with more aggressive and invasive phenotype.

Survivin, a Potential Early Predictor of Tumor Progression in the Oral Mucosa

Survivin is a recently described apoptosis inhibitor selectively over-expressed in most tumors. Immunohistochemistry was used to investigate a potential role of survivin as an early predictor of malignant transformation in precancerous and cancerous lesions of the oral cavity. Survivin was present in 10/30 cases (33%) of oral precancerous lesions without malignant progression, and in 15/16 cases (94%) of oral precancerous lesions evolved into full-blown squamous cell carcinoma. Tumors that progressed from these precancerous lesions retained widespread survivin positivity (100%). Variations among group means were highly statistically significant (p < 0.001). No significant correlation was found between survivin expression and the degree of dysplasia. High expression of cytoplasmic/nuclear survivin is an early event during oral carcinogenesis and may provide a useful tool for the identification of precancerous lesions at higher risk of progression into invasive carcinoma.

Oral lichen planus: different clinical features in HCV-positive and HCV-negative patients.

Background Hepatitis C virus (HCV) infection induces variable dermatologic manifestations.

Oral pemphigus : Clinical significance of esophageal involvement: Report of eight cases

The extension of the blisters of pemphigus to the esophagus is relatively uncommon, especially in patients treated with corticosteroids who appear to be in clinical remission. The aim of this study was to evaluate the esophagus in eight patients affected by oral pemphigus in various stages of the disease. Upper gastrointestinal endoscopy revealed esophageal involvement in five patients (two men and three women); three had blisters or erosions in the upper esophagus, whereas two showed red longitudinal lines along the entire organ. Direct immunofluorescence was positive in all eight patients. It is suggested that endoscopic examination of esophageal mucosa is an objective criterion by which to judge the success of therapy of pemphigus vulgaris.

Anxiety, depression, and pain in burning mouth syndrome: first chicken or egg?

Background.— Burning mouth syndrome (BMS) is an idiopathic and chronic pain condition for which patients may experience high levels of pain, anxiety, and depression. So far, it has not yet been well investigated whether specific psychiatric features (anxious traits, personality disorder, or somatization) may play a role in the BMS pathogenesis or whether some BMS symptoms, or BMS itself, may cause secondary psychiatric symptoms.

Overexpression of cyclin-D1, bcl-2, and bax proteins, proliferating cell nuclear antigen (PCNA), and DNA-ploidy in squamous cell carcinoma of the oral cavity

The prognostic role of the expression of bcl-1, bcl-2, bax, PCNA, and DNA-ploidy in a series of 25 oral squamous cell carcinoma (SCC) was investigated. The average age of the patients was 62.04 years (range, 27 to 81 years), with a sex ratio (M/F) of 23:2. The follow-up mean time was 2.24 years (range, 8 months to 8 years from surgery). Immunohistochemistry for PCNA, bcl-2, bcl-1, and bax proteins was carried out on 5-microm serial sections from formalin-fixed, paraffin-embedded tissue. The findings were compared with clinicopathologic data and with follow-up. The statistical evaluation of the results of the current study suggests that the low positivity for PCNA with a high positivity for bcl-2 protein are related to a better clinical behavior of the tumors. By converse, a high expression of PCNA, bax, and bcl-1 appears to correlate with a worse prognosis. All of our cases of SCC showed the presence of aneuploid populations, which was not correlated with the clinicopathologic parameters or with the overexpression of bcl-1, bcl-2, bax, and PCNA. Therefore, the aneuploidy per se did not predict the clinical evolution for the single cases of cancers. Nevertheless, once the parameters considered for the evaluation of DNA were examined in detail, it appeared that some of them, individually or combined with each other or with the expression of bcl-1, bcl-2, and bax, gained statistical significance in predicting the clinical evolution of SCC of our series. Particularly, high values of 2cDI and DNA-MG and the absence or reduction of the euploid population were associated with a short interval between surgery and recurrence or death, and this significance persisted when the simultaneous presence of overexpression of bcl-1 was considered.

Effectiveness of small-volume, intralesional, delayed-release triamcinolone injections in orofacial granulomatosis: A pilot study

BACKGROUND Orofacial granulomatosis (OFG) is an idiopathic disorder characterized by chronic orofacial swellings causing significant cosmetic and functional problems. Treatment with high-volume triamcinolone injections has been shown to be effective but requires nerve block anesthesia and causes a dramatic temporary increase of lip swelling. OBJECTIVE We have performed a noncomparative open-label pilot study in 7 patients with OFG in order to evaluate the effectiveness of small volumes of extended-release high-concentrate triamcinolone injections in reducing lip swelling and preventing recurrences. METHODS Seven patients with OFG were studied. Small-volume, intralesional, high-concentrate, extended-release triamcinolone was injected on the basis of a weekly schedule. A standard cycle consisted of 2 or 3 injection sessions over 14 or 21 days, depending on the clinical response. RESULTS After cycle completion, all patients remained without recurrences or with cosmetically acceptable slight lip enlargement for a mean time of 19 months (range, 8-30 months). No side effects were observed, except in one patient with hypopigmentation of the skin of the upper lip. CONCLUSIONS Slow-volume, intralesional, high-concentrate, extended-release triamcinolone injections appear to be effective in reducing lip enlargement in patients with OFG and do not require nerve block anesthesia or cause a temporary troublesome increase of swelling. A long disease-free period is generally obtained.

Oral cancer screening: 5 minutes to save a life

colleagues report the first solid evidence that periodic examination of the oral cavity can reduce mortality from oral cancer in high-risk individuals. These results come from the Kerala screening trial, a cluster randomised trial, designed to have 80% power to detect a 35% reduction in oral cancer mortality within 12 years of enrolment between the intervention and control group, through rounds of screening every 3 years. The investigators report that, 9 years after the start of screening, there was a significant 32% reduction in mortality in high-risk individuals in the intervention group (42% when only male tobacco/alcohol users are considered). Overall, these data suggest that oral visual screening in high-risk patients could prevent about 40 000 deaths from oral cancer worldwide. The reported data could be read in two ways. The first is the methodological evaluation of oral cancer screening itself. From this point of view, are the outcomes reported by Sankaranarayanan and colleagues adequately supported by the study design or do limitations exist? For example, the restricted-block randomisation can be potentially imbalanced when the number of clusters is small. Also, the recruitment of non-medical health workers raises concerns about the sensitivity and specificity to detect lesions and patients’ compliance with referral. A screening interval of 3 years is long and the percentage of patients who did not get biopsy was high. Finally, clinical and histopathological diagnostic criteria were not clearly reported and variations in definitions and management of oral lesions can influence screening outcomes. On the other hand, the data suggest perhaps the right perspective in the fight against oral cancer—supporting prevention through screening as a potential major target of every health organisation worldwide. Oral cancer is a significant public-health threat, accounting for 270 000 new cases annually and with one of the lowest survival rates (fewer than 50% of patients surviving more than 5 years). Furthermore, in the past few decades despite advances in the detection and treatment of many other malignancies, this rate has remained disappointingly low and relatively constant. Rather than prevalence, the most peculiar characteristic of oral cancer is the apparently unexplainable imbalance between its global burden and the potential theoretical ease in decreasing morbidity and mortality with early detection. Oral cancer is almost always preceded by visible changes in the oral mucosa (figure, A and B), which allows clinicians to detect and treat effectively early intraepithelial stages of oral carcinogenesis. Nevertheless, most oral cancers are currently detected at a late stage, when treatment is complex, costly, and has poor outcomes (figure, C and D). Paradoxically, the percentage of oral cancers diagnosed in the early stages is similar to that of colon cancers (36%). Lack of awareness in the public of the signs, symptoms, and risk factors for oral cancer, as well as a disappointing absence of prevention and early detection by health-care providers, are both believed to be responsible for the diagnostic delay. It is strange to think that, at present, pelvic examination and Pap smears appear more acceptable than looking in the mouth, for both patients and physicians. Current research mainly focuses on therapies for advanced oral cancers. As a result we have been spending hundreds of millions of dollars in treating patients, two-thirds of whom will die within 3–5 years, consuming educational Comment