At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the UK issues related to terminology, definitions and classification of oral precancer were discussed by an expert group The consensus views of the Working Group are presented here The term, 'potentially malignant disorders', was recommended to refer to precancer as it conveys that not all disorders described under this term may transform into cancer Critically evaluating all definitions proposed so far for oral leukoplakia, the Working Group agreed that the term leukoplakia should be used to recognize 'white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer' An outline was proposed for diagnosing oral leukoplakia that will prevent other oral white disorders being misclassified as leukoplakia The Working Group discussed the caveats involved in the current use of terminology and classification of oral potentially malignant disorders, deficiencies of these complex systems, and how they have evolved over the past several decades The terminology presented in this report reflects our best understanding of multi-step carcinogenesis in the oral mucosa, and aspires to engender consistency in use

https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1600-0714.2007.00582.x

Nomenclature and classification of potentially malignant disorders of the oral mucosa

Two hundred fifty-seven patients with oral leukoplakia were studied and followed for an average period of 7.2 years. All lesions were more than one cm in size and had been present and observed for a minimum of 6 months. Of the initial biopsies, 235 revealed a benign hyperkeratosis and 22 others contained some degree of epithelial dysplasia. Seventy-three percent of the patients used tobacco, with cigarette usage being the predominant form. Forty-five patients (17.5%) subsequently developed squamous carcinomas in the hyperkeratotic epithelial site in an average time of 8.1 years. Eight of these malignant transformations came from patients who originally had epithelial dysplasia. High risks for malignant transformation also included non-smoking patients, the clinical presence of erythroplasia (erythroleukoplakia), and a clinical verrucous-papillary hyperkeratotic pattern. Duration of the leukoplakia progressively increased the total number of malignant transformations, with the largest rate occurring in the second year. This study confirms that oral leukoplakia is a precancerous lesion and that certain characteristics indicate greater risks and warrant consideration of more aggressive management.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819840201%2953%3A3%3C563%3A%3AAID-CNCR2820530332%3E3.0.CO%3B2-F

Oral leukoplakia and malignant transformation. A follow-up study of 257 patients.

Carcinogenesis research is increasingly focused on chemicals that are not genotoxic and yet, at high doses, can induce cancer, apparently by increasing cell proliferation. We hypothesize that increased cell division per se stimulated by external or internal factors is also associated with the development of many human cancers. Although this hypothesis is well substantiated in the experimental literature, it has not been generalized as an important mechanism for carcinogenesis in human populations. Under this increased cell division model, the pathogenesis of cancer may result from molecular genetic errors induced during the process of cell division and from altered growth control of malignant or premalignant cells. Molecular genetic analysis of human cancers has shown that tumor cells contain multiple genetic defects including mutations, translocations, and amplifications of oncogenes and are reduced to homozygosity for putative tumor suppressor genes; these phenomena all require cell division for their occurrence and fixation. Increased cell division increases the risk of such events occurring. An accumulation of a combination of such genetic errors leads to a neoplastic phenotype. Examples are discussed of human cancers in which increased cell division, which drives the accumulation of genetic errors and can lead to neoplastic transformation, is caused by hormones, drugs, infectious agents, chemicals, physical or mechanical trauma, and other chronic irritation.

https://cancerres.aacrjournals.org/content/canres/50/23/7415.full.pdf

Increased cell division as a cause of human cancer

Background
Lay health workers (LHWs) are widely used to provide care for a broad range of health issues. Little is known, however, about the effectiveness of LHW interventions.

Objectives
To assess the effects of LHW interventions in primary and community health care on maternal and child health and the management of infectious diseases.

Search methods
For the current version of this review we searched The Cochrane Central Register of Controlled Trials (including citations uploaded from the EPOC and the CCRG registers) (The Cochrane Library 2009, Issue 1 Online) (searched 18 February 2009); MEDLINE, Ovid (1950 to February Week 1 2009) (searched 17 February 2009); MEDLINE In-Process & Other Non-Indexed Citations, Ovid (February 13 2009) (searched 17 February 2009); EMBASE, Ovid (1980 to 2009 Week 05) (searched 18 February 2009); AMED, Ovid (1985 to February 2009) (searched 19 February 2009); British Nursing Index and Archive, Ovid (1985 to February 2009) (searched 17 February 2009); CINAHL, Ebsco 1981 to present (searched 07 February 2010); POPLINE (searched 25 February 2009); WHOLIS (searched 16 April 2009); Science Citation Index and Social Sciences Citation Index (ISI Web of Science) (1975 to present) (searched 10 August 2006 and 10 February 2010). We also searched the reference lists of all included papers and relevant reviews, and contacted study authors and researchers in the field for additional papers.

Selection criteria
Randomised controlled trials of any intervention delivered by LHWs (paid or voluntary) in primary or community health care and intended to improve maternal or child health or the management of infectious diseases. A 'lay health worker' was defined as any health worker carrying out functions related to healthcare delivery, trained in some way in the context of the intervention, and having no formal professional or paraprofessional certificate or tertiary education degree. There were no restrictions on care recipients.

Data collection and analysis
Two review authors independently extracted data using a standard form and assessed risk of bias. Studies that compared broadly similar types of interventions were grouped together. Where feasible, the study results were combined and an overall estimate of effect obtained.

Main results
Eighty-two studies met the inclusion criteria. These showed considerable diversity in the targeted health issue and the aims, content, and outcomes of interventions. The majority were conducted in high income countries (n = 55) but many of these focused on low income and minority populations. The diversity of included studies limited meta-analysis to outcomes for four study groups. These analyses found evidence of moderate quality of the effectiveness of LHWs in promoting immunisation childhood uptake (RR 1.22, 95% CI 1.10 to 1.37; P = 0.0004); promoting initiation of breastfeeding (RR = 1.36, 95% CI 1.14 to 1.61; P < 0.00001), any breastfeeding (RR 1.24, 95% CI 1.10 to 1.39; P = 0.0004), and exclusive breastfeeding (RR 2.78, 95% CI 1.74 to 4.44; P <0.0001); and improving pulmonary TB cure rates (RR 1.22 (95% CI 1.13 to 1.31) P <0.0001), when compared to usual care. There was moderate quality evidence that LHW support had little or no effect on TB preventive treatment completion (RR 1.00, 95% CI 0.92 to 1.09; P = 0.99). There was also low quality evidence that LHWs may reduce child morbidity (RR 0.86, 95% CI 0.75 to 0.99; P = 0.03) and child (RR 0.75, 95% CI 0.55 to 1.03; P = 0.07) and neonatal (RR 0.76, 95% CI 0.57 to 1.02; P = 0.07) mortality, and increase the likelihood of seeking care for childhood illness (RR 1.33, 95% CI 0.86 to 2.05; P = 0.20). For other health issues, the evidence is insufficient to draw conclusions regarding effectiveness, or to enable the identification of specific LHW training or intervention strategies likely to be most effective.

Authors' conclusions
LHWs provide promising benefits in promoting immunisation uptake and breastfeeding, improving TB treatment outcomes, and reducing child morbidity and mortality when compared to usual care. For other health issues, evidence is insufficient to draw conclusions about the effects of LHWs.

/pdf/lay-health-workers-in-primary-and-community-health-care-for-561d75zkrw.pdf

Lay health workers in primary and community health care for maternal and child health and the management of infectious diseases.

Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management

Incidence rates of oral cancer and natural history of oral precancerous lesions in a 10-year follow-up study of Indian villagers.

A case-control study to elucidate the etiology of oral submucous fibrosis was conducted in Bhavnagar, Gujarat. Sixty consecutively arriving oral submucous fibrosis patients at a dental clinic were selected as cases. An equal number of controls matched for age, sex, religion and socioeconomic status were selected from individuals who did not exhibit any oral mucosal lesion or condition. Among cases, 98% chewed areca nut regularly in one form or the other whereas among controls 35% chewed areca nut, giving an overall relative risk of 109.6. Areca nut chewing was practiced most commonly in the form of mawa: a mixture containing mainly areca nut (over 90% by weight), some tobacco, and a few drops of lime. Mawa chewers and those who chewed mawa along with other chewing habits showed very high relative risks. The relative risks increased with increase in the frequency as well as the duration of chewing habits. In a bivariate analysis the effect of frequency and duration of chewing appeared to be multiplicative. The present findings confirm areca nut as the most important etiologic factor in oral submucous fibrosis.

A case-control study of oral submucous fibrosis with special reference to the etiologic role of areca nut.

The malignant potential of oral lichen planus was assessed on the basis of observations in 722 patients found among 27,599 individuals examined in various epidemiologic studies in Kerala, Ernakulam district, India. Seven hundred and two patients with oral lichen planus were re-examined annually over a 10-year period with a mean observation period of 5.1 years. Most of the lesions (93%) were observed among tobacco users. Carcinoma developed in 3 (0.4%) patients with oral lichen planus. Clinically, all 3 had atrophic components in their lesions, and all were tobacco users. The relative risk of a lichen planus developing oral cancer compared to a tobacco user was estimated as 3.3. However, this relative risk was not significant. Histologically, 74% of the 94 biopsies from oral lichen planus showed epithelial atrophy. Two of the 3 in whom cancer developed also showed epithelial atrophy. It is felt that epithelial atrophy probably renders the mucosa more vulnerable to the carcinogenic action of tobacco. Although this study could not confirm the precancerous nature of this disease with a high degree of certainty, the disease did not appear to be innocuous either.

Malignant potential of oral lichen planus: observations in 722 patients from India.

OBJECTIVE: To study the effect of cessation of tobacco use on the incidence of lichen planus, leukoplakia and other oral mucosal lesions.



DESIGN: A 10–yr cohort study in a rural population of Ernakulam district, Kerala, India.



MATERIAL AND METHODS: Some 12 212 tobacco users were interviewed and examined in a basetine survey and re-examined annually for 10 years. At each examination they were exposed to health educational programs to encourage them to quit their tobacco use. The incidence rates were calculated using person-years method among those who stopped their tobacco use and all others.



RESULTS: A total of 77 681 person-years of observation accrued among men and 32 544 among women. Among men 6.5% of these and among women 14.4% were in the stopped category. The incidence of oral lichen planus did not show any consistent association with cessation of tobacco habits (incidence ratio I.35) but for leukoplakia there was a substantial drop in the incidence after cessation (incidence ratio 0.3I). Several other tobacco-associated oral mucosal lesions such as oral lichen planus-like lesion, smoker's palate, preteukoplakia, central papillary atrophy of the tongue and leukoedema showed either zero, or very small incidence, after cessation. CONCLUSION: The reported association between tobacco use and lichen planus appears to be indirect but for all other lesions it is direct. The cessation of tobacco use led to a substantial fall in the incidence of leukoplakia and other lesions implying a reduced risk for oral cancer after cessation of tobacco use.

Effect of cessation of tobacco use on the incidence of oral mucosal lesions in a 10-yr follow-up study of 12,212 users.

Oral cancer is caused by chewing and smoking of tobacco. To assess the feasibility of primary prevention of oral cancer, two cohorts were studied in base-line surveys and then followed up annually for 10-yr in Ernakulam district of Kerala state. The intervention cohort consisted of 12212 tobacco users aged 15 yr and over, who were exposed to a concentrated program of education against tobacco use. The control cohort was a non-concurrent cohort of 6075 tobacco users studied using similar methods but with a minimal amount of advice against tobacco use. The stoppage of tobacco use increased and the incidence rate of leukoplakia decreased significantly and substantially in the intervention cohort compared to the control cohort. The decrease in the incidence of leukoplakia was indicative of the decrease in the risk of oral cancer since the two were intimately related. This study demonstrated feasibility of primary prevention of oral cancer.

F. S. Mehta

Papers

Incidence rates of oral cancer and natural history of oral precancerous lesions in a 10-year follow-up study of Indian villagers.

A case-control study of oral submucous fibrosis with special reference to the etiologic role of areca nut.

Malignant potential of oral lichen planus: observations in 722 patients from India.

Effect of cessation of tobacco use on the incidence of oral mucosal lesions in a 10-yr follow-up study of 12,212 users.

Primary prevention trial of oral cancer in india: a 10-year follow-up study.