Newell Walter Johnson

Risk factors for squamous cell carcinoma of the oral cavity in young people — a comprehensive literature review

There have been several reports of a rising incidence of oral cancer from many parts of the world. Although it is well known that oral cancer increases with age, recent trends for a rising incidence particularly relates to cancer of the tongue and mouth in young males. This review critically examines 46 publications devoted to oral cancer in the young adult. Most studies suggest that 4-6% of oral cancers now occur at ages younger than 40 years. Several studies examining risk factors for oral cancer in the young provide evidence that many younger patients have never smoked or consumed alcohol, which are recognised risk factors in older groups, or that duration of exposure may be too short for malignant transformation to occur. Information on many aspects of aetiology for this disease in the young implicating occupational, familial risk, immune deficits and virus infection are meagre. The spectrum of genetic abnormality disclosed is similar to older patients, there is paucity of specific studies involving younger cohorts, but predisposition to genetic instability has been hypothesised as a likely cause. Conflicting evidence is also reported on the sex distribution and outcome compared with older patients. Much work is required to understand the caveats related to global demography, risk factors and their diagnostic and prognostic markers for this disease which might be considered a disease distinct from that occurring in older patients.

Global Oral Health Inequalities in Incidence and Outcomes for Oral Cancer Causes and Solutions

The mouth and oropharynx are among the ten most common sites affected by cancer worldwide, but global incidence varies widely. Five-year survival rates exceed 50% in only the best treatment centers. Causes are predominantly lifestyle-related: Tobacco, areca nut, alcohol, poor diet, viral infections, and pollution are all important etiological factors. Oral cancer is a disease of the poor and dispossessed, and reducing social inequalities requires national policies co-ordinated with wider health and social initiatives – the common risk factor approach: control of the environment; safe water; adequate food; public and professional education about early signs and symptoms; early diagnosis and intervention; evidence-based treatments appropriate to available resources; and thoughtful rehabilitation and palliative care. Reductions in inequalities, both within and between countries, are more likely to accrue from the application of existing knowledge in a whole-of-society approach. Basic research aimed at determining individual predisposition and acquired genetic determinants of carcinogenesis and tumor progression, thus allowing for targeted therapies, should be pursued opportunistically.

Squamous cell carcinoma of the oral cavity in patients aged 45 years and under: a descriptive analysis of 116 cases diagnosed in the South East of England from 1990 to 1997

Background: there is, currently, much anecdotal and some epidemiological evidence for a rise in oral cancer rates amongst younger individuals, many of whom have had no exposure to traditional risk factors such as tobacco and heavy alcohol use, or at least not the exposure over decades usually associated with this disease. The probity of this assertion and the presence or absence of traditional risk factors needs further evidence. Objectives: this paper describes the demography and the exposure to potential risk factors amongst a cohort aged 45 years and younger, diagnosed with squamous cell carcinoma of the oral cavity between 1990 and 1997 from the South East of England. Materials and methods: eligible patients registered with a cancer registry were included in this retrospective study. Information was accessed from the database and by a postal questionnaire survey. The self-completed questionnaire contained items about exposure to the following risk factors: tobacco; alcohol; diet; frequency of dental visits and familial cancer. Results and conclusions: this is the largest UK epidemiological study so far to be undertaken on young subjects diagnosed with oral cancer. One-hundred and sixteen cases were recruited representing a response rate of 59%. Slightly over 90% of this cohort were classified as white European. A large proportion of cases (40%) were from social classes I & II suggesting either a true social class difference in young cases versus older oral cancer cases or a possible bias in responders or survivors. Risk factors of tobacco use and excessive alcohol consumption were present in the majority (75%) of patients. Significant differences in the pattern of alcohol consumption were found in female subjects, who were less likely to consume over the recommended amounts of alcohol compared with male subjects. Daily regular fresh fruit and vegetable consumption during the ten year period before cancer diagnosis was recorded to be low. There was a distinct subgroup of cases, 26% of the group, that showed little, if any, exposure to any major risk factors.

Role of p16/MTS1, cyclin D1 and RB in primary oral cancer and oral cancer cell lines.

One of the most important components of G1 checkpoint is the retinoblastoma protein (pRB110). The activity of pRB is regulated by its phosphorylation, which is mediated by genes such as cyclin D1 and p16/MTS1. All three genes have been shown to be commonly altered in human malignancies. We have screened a panel of 26 oral squamous cell carcinomas (OSCC), nine premalignant and three normal oral tissue samples as well as eight established OSCC cell lines for mutations in the p16/MTS1 gene. The expression of p16/MTS1, cyclin D1 and pRB110 was also studied in the same panel. We have found p16/MTS1 gene alterations in 5/26 (19%) primary tumours and 6/8 (75%) cell lines. Two primary tumours and five OSCC cell lines had p16/MTS1 point mutations and another three primary and one OSCC cell line contained partial gene deletions. Six of seven p16/MTS1 point mutations resulted in termination codons and the remaining mutation caused a frameshift. Western blot analysis showed absence of p16/MTS1 expression in 18/26 (69%) OSCC, 7/9 (78%) premalignant lesions and 8/8 cell lines. One cell line, H314, contained a frameshift mutation possibly resulting in a truncated p16/MTS1 protein. pRB was detected in 14/25 (56%) of OSCC but only 11/14 (78%) of these contained all or some hypophosphorylated (active) pRB. In premalignant samples, 6/8 (75%) displayed pRB, and all three normal samples and eight cell lines analysed contained RB protein. p16/MTS1 protein was undetectable in 10/11 (91%) OSCCs with positive pRB. Overexpression of cyclin D1 was observed in 9/22 (41%) OSCC, 3/9 (33%) premalignant and 8/8 (100%) of OSCC cell lines. Our data suggest p16/MTS1 mutations and loss of expression to be very common in oral cancer cell lines and less frequent in primary OSCC tumours. A different pattern of p16/MTS1 mutations was observed in OSCC compared to other cancers with all the detected p16/MTS1 mutations resulting in premature termination codons or a frameshift. The RB protein was expressed in about half (44%) of OSCCs and its expression inversely correlated with p16/MTS1 expression. In conclusion, we show that abnormalities of the RB pathway are a common mechanism of oral carcinogenesis.

Advanced dental disease in people with severe mental illness: systematic review and meta-analysis

BACKGROUND Psychiatric patients have increased comorbid physical illness. There is less information concerning dental disease in this population in spite of risk factors including diet and psychotropic side-effects (such as xerostomia). Aims To compare the oral health of people with severe mental illness with that of the general population. METHOD A systematic search for studies from the past 20 years was conducted using Medline, PsycINFO, Embase and article bibliographies. Papers were independently assessed. The primary outcome was total tooth loss (edentulousness), the end-stage of both untreated caries and periodontal disease. We also assessed dental decay through standardised measures: the mean number of decayed, missing and filled teeth (DMFT) or surfaces (DMFS). For studies lacking a control group we used controls of similar ages from a community survey within 10 years of the study. RESULTS We identified 21 papers of which 14 had sufficient data (n = 2784 psychiatric patients) and suitable controls (n = 31 084) for a random effects meta-analysis. People with severe mental illness had 3.4 times the odds of having lost all their teeth than the general community (95% CI 1.6-7.2). They also had significantly higher scores for DMFT (mean difference 6.2, 95% CI 0.6-11.8) and DMFS (mean difference 14.6, 95% CI 4.1-25.1). Fluoridated water reduced the gap in oral health between psychiatric patients and the general population. CONCLUSIONS Psychiatric patients have not shared in the improving oral health of the general population. Management should include oral health assessment using standard checklists that can be completed by non-dental personnel. Interventions include oral hygiene and management of xerostomia.

A systematic review of medical interventions for oral submucous fibrosis and future research opportunities.

Oral Diseases (2011) 17 (Suppl. 1), 42-57 Oral submucous fibrosis (OSF) is a chronic, insidious disease caused by areca nut use, and is associated with both significant morbidity (including pain and reduced oral opening) and an increased risk for malignancy. This systematic review explored and updated the current medical (i.e., non-surgical) interventions available for the management of OSF. Of the 27 published medical interventions, there were four randomized controlled trials. The overall quality of these randomized controlled studies was assessed using the GRADE approach and significant limitations that challenged the conclusions were found. However, this review was valuable in terms of identifying opportunities to provide recommendations for future research, in terms of the populations to research, the types of interventions needed, the types of outcomes to be measured, the study designs needed, and the infrastructure required to conduct studies. The next step is to initiate a pathway for a low-cost research plan leading to the development of a brief protocol for future clinical trials in this field, with an emphasis on conducting studies in regions of the world where OSF is prevalent.

Evaluation of multiple micronutrient supplementation in the management of oral submucous fibrosis in Karachi, Pakistan

Oral submucous fibrosis (OSF) is an oral precancerous condition characterized by symptoms such as intolerance to spicy food, altered salivation, progressive difficulty in opening the mouth, and signs like vesiculation, ulceration, blanching, rigidity, and stiffening of the oral mucosa and depapillation and altered mobility of the tongue. It is seen mostly among people of Indian subcontinent origin. The major structural change is extensive fibroelastic scarring of the lamina propria and deeper connective tissues. A combination of micronutrients (vitamins A, B complex, C, D, and E) and minerals (iron, calcium, copper, zinc, magnesium, and others) was evaluated for its efficacy in controlling the symptoms and signs of OSF in 117 compliant subjects in Karachi, Pakistan, in a single-arm preliminary study. The subjects received supplementation for one to three years. Significant improvement in symptoms, notably intolerance to spicy food, burning sensation, and mouth opening, was observed at exit. The interincisor distance deteriorated in 11 subjects (10%) at exit; it was stable in 56 subjects (49%) and improved in 48 (41%). The mean interincisor distance was 19.1 +/- 10.8 (SD) mm at exit compared with 16.2 +/- 7.5 mm at baseline. A significant proportion of concomitant lesions like leukoplakia also regressed at exit. The major outcome from this study was a beneficial clinical response in subjects with OSF to multiple micronutrient intervention, which justifies its further evaluation in well-designed randomized controlled trials in other settings in South Asia.

Prevalence of human papillomavirus infection in premalignant and malignant lesions of the oral cavity in U.K. subjects : a novel method of detection

To evaluate the possible role of human papillomavirus (HPV) in oral neoplasms, 28 oral squamous cell carcinomas (SCC) and 12 potentially malignant lesions were analysed for the presence of HPV DNA. A nested polymerase chain reaction (PCR) approach, using two sets of HPV consensus primers to the L1 region, was used, which was able to detect a broad spectrum of HPV types. HPV DNA was detected in 14/28 (50%) carcinomas and 4/12 (33%) precancerous lesions. A novel approach based on labelling the PCR products with 32P and the separation of radioactively labelled products on an 8% polyacrylamide gel increased the sensitivity of the detection and enabled the identification of the HPV types. The typing of HPV was subsequently confirmed by direct DNA sequencing. HPV 6 and HPV 16 were the only HPV types detected and seven tumours harboured both types. Our results suggest that HPVs may be an important aetiological factor in the development of oral cancer. The detection procedure ensured sensitivity and consistency of the detection of low copy numbers of the virus DNA. The presence of HPV in 33% of premalignant tissues suggests that HPV infection may be an early event in the malignant transformation of oral SCC. There was no statistically significant association between viral infection and tumour grade or stage.

Oral cancer in India continues in epidemic proportions: evidence base and policy initiatives.

OBJECTIVES India has the highest number of cases of oral cancer in the world and this is increasing. This burden is not fully appreciated even within India, despite the high incidence and poor survival associated with this disease. Because the aetiology of oral cancer is predominantly tobacco-related, the immense public health challenge can be ameliorated through habit intervention. METHODS We reviewed current rates of incidence, mortality and survival, and investigated the determinants of disease and current prevention strategies. RESULTS In addition to tobacco smoking and the myriad other forms of tobacco use prevalent in India, risk factors include areca nut consumption, alcohol consumption, human papillomavirus, increasing age, male gender and socioeconomic factors. Although India has world-leading cancer treatment centres, access to these is limited. Further, the focus of health care services remains clinical and is either curative or palliative. CONCLUSIONS Although the efforts of agencies such as the Ministry of Health and Family Welfare and the Indian Dental Association are laudable, enhanced strategies should be based on common risk factors, focusing on primary prevention, health education, early detection and the earliest possible therapeutic intervention. A multi-agency approach is required.

Expression of p53 in oral squamous cell carcinoma is associated with the presence of IgG and IgA p53 autoantibodies in sera and saliva of the patients.

Around 50% of head and neck cancers are known to have aberrations of the p53 gene. Overexpression of the mutant p53 protein can induce a specific humoral response in cancer patients. Matched saliva, serum, and tissue samples from 26 patients with histologically confirmed oral squamous and verrucous carcinoma were investigated. p53 protein expression was evaluated by immunohistochemistry and antibodies specific for 53 protein were analysed in sera and whole mouth saliva by ELISA, immunoprecipitation, and competition assays; 16/25 (64%) samples demonstrated the stabilized p53 protein in tissues and 7/26 (27%) had a high level of p53 antibody in serum. In samples where matching saliva was available, p53 antibody was also present in saliva. In some tumours, only IgA‐type p53 antibody was detected. p53 antibodies were found only in the serum and saliva of patients who showed p53 overexpression in their tumour tissues. These results demonstrate that detection of p53 antibodies can offer a specific and non‐invasive method for the detection of a subset of tumours with p53 aberrations. Copyright