The burden of oral malignancies in Zimbabwe 1988 to 1997: a population based study.

OBJECTIVE: Annual reports from the few cancer registries in Africa are the only reliable assessment of the burden of cancer using population-based data. Similar reports for oral malignancies have not been undertaken. The purpose of this study was to assess the burden of oral malignancies in Zimbabwe over a 10 year period using population-based data. DESIGN: A descriptive epidemiological study was undertaken to assess the burden of oral malignancies by determining the frequencies, incidence and cumulative rates, the lifetime risk and chances of developing an oral malignancy according to site (topography), gender, age, morphology and race/ethnic origin of the Zimbabwean population. A total of 873 incident cases of oral malignancies from the upper and lower lips, oral vestibule, retromolar area, floor of mouth, tongue, cheek mucosa, gums, hard and soft palate were accessed from the Zimbabwe National Cancer Registry (ZNCR). Cases from the skin, pharynx, larynx and the major salivary glands were excluded from the study. SETTING: This comprised the population of Zimbabwe during a 10 year period 1988 to 1997. The population figures used for this study were from the 1992 Census Zimbabwe National Report. The study population was standardised by the direct method against the world standard population to calculate the age standardized incidence rate (ASIR). The SPSS statistical software program (SPSS Inc.2001, USA) was used for the statistical analysis. RESULTS: Oral malignancies comprised 1.8% of total body malignancies with high histological confirmation of the diagnosis (77.3%). The 25 to 29 and 30 to 34 five-year age groups were the most and equally affected by oral malignancies. The mean age was 43.9 years and median age was 41 years [standard deviation (SD) = 17.7] excluding 53 cases of'unknown age'. Oral Kaposi's sarcoma (OKS) and oral squamous cell carcinoma (OSCC) were the predominant forms of oral malignancy. The palate was the most commonly affected site by oral malignancy followed by, in descending order, the tongue, mouth, floor of mouth and the gum. Blacks were affected more than whites and males more than females (sex ratio = 1.97:1). The palate and the tongue were the most commonly affected sites in blacks and whites respectively. OKS affected mostly young adults while OSCC was the commonest malignancy of the elderly. The tongue had more OSCC (60.4%) than OKS (31%). CONCLUSIONS: Lip cancer was three times more common in whites than in blacks and affected mostly the elderly, though females irrespective of race had a higher lifetime risk for malignancy of the lower lip. The high incidence of OKS among young adults was due to the HIV/AIDS epidemic.

Mechanisms of expression of HHV8, EBV and HPV in selected HIV-associated oral lesions.

Opportunistic DNA viruses, particularly members of the herpesvirus family, are frequently the aetiological agents of HIV-associated oral lesions. Oral lesions common to the early phase of the AIDS epidemic, including Kaposi's sarcoma (KS), oral aphthous ulceration, AIDS-associated oral lymphoma, and oral hairy leukoplakia (OHL), have been tested for the prevalence of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV). While EBV DNA is detected by PCR in all of these lesions, abundant viral replication can only be detected in OHL. In OHL, a novel state of EBV infection has been discovered with concurrent expression of replicative and transforming proteins, with all of these proteins contributing to the development of the lesion. Activation of signalling pathways and up-regulation of the viral receptor, proliferative and antiapoptotic genes by these proteins induce several of the histological features common to OHL, such as acanthosis and hyperproliferation. In contrast to other permissive herpesvirus infections, expression of EBV transforming proteins within the permissively infected OHL tissue enables epithelial cell survival and may enhance viral replication. Detection of KSHV in these HIV-infected individuals has been localized only to their saliva. Replicative and latent KSHV gene products have been detected in association with the development of oral KS lesions. EBV, but not human cytomegalovirus (HCMV), has been detected by PCR in minor salivary gland biopsies of HIV-associated salivary gland disease. Human papillomaviruses (HPV) are associated with oral warts in HIV-positive individuals; a diagnosis that appears to be increasing in frequency in the era of highly active antiretroviral therapy. To date, there appears to be little increase in the incidence of HPV-associated oral cancer. The mechanisms of interaction between HIV and HPV are not fully understood. Expression of viral gene products is clearly important and necessary for the development of multiple AIDS-associated oral lesions.

Intraoral myxoid nerve sheath tumour.

A case of an intraoral myxoid nerve sheath tumour of the dorsum of the tongue in a 73-year-old Caucasian male is reported. This case describes the oldest patient with this pathology to date. Immunoperoxidase staining for neuron-specific enolase (NSE) and epithelial membrane antigen (EMA) expression demonstrated the perineural origin of the lesion.

Mucoepidermoid carcinoma: a clinicopathologic study of 80 patients with special reference to histological grading.

We sought to review our experience with salivary mucoepidermoid carcinoma (MEC) over two decades to confirm the validity and reproducibility of histologic grading and to investigate MIB-1 index as a prognosticator. Diagnosis was confirmed on 80 cases, and chart review or patient contact was achieved for 48 patients, with follow-up from 5 to 240 months (median 36 months). Immunohistochemistry with citrate antigen retrieval for MIB-1 was performed on a subset of cases. Kaplan-Meier survival curves were generated for each stage, site, and grade according to our proposed grading system. To address the issue of grading reproducibility, 20 slides were circulated among five observers, without prior discussion; slides were categorized as low-, intermediate-, or high-grade according to one's "own" criteria, and then according to the AFIP criteria proposed by Goode et al.10 Weighted kappa (kappa) estimates were obtained to describe the extent of agreement between pairs of rating. The Wilcoxon signed rank test or the Friedman test as appropriate tested variation across ratings. There was no gender predominance and a wide age range (15-86 years, median 49 years). The two most common sites were parotid and palate. All grade 1 MECs presented as Stage I tumors, and no failures were seen for this category. The local disease failure rates at 75 months for grades 2 and 3 MEC were 30% and 70%, respectively. Tumor grade, stage, and negative margin status all correlated with disease-free survival (DFS) (p = 0.0091, 0.0002, and 0.048, respectively). The MIB index was not found to be predictive of grade. Regarding the reproducibility of grading, the interobserver variation for pathologists using their "own" grading, as expressed by the kappa value, ranged from good agreement (kappa = 0.79) to poor (kappa = 0.27) (average kappa = 0.49). A somewhat better interobserver reproducibility was achieved when the pathologists utilized the standardized AFIP criteria (average kappa = 0.61, range 0.38-0.77). This greater agreement was also reflected in the Friedman test (statistical testing of intraobserver equality), which indicated significant differences in using one's own grading systems (p = 0.0001) but not in applying the AFIP "standardized" grading (p = 0.33). When one's own grading was compared with the AFIP grading, there were 100 pairs of grading "events," with 46 disagreements/100 pairs. For 98% of disagreements, the AFIP grading "downgraded" tumors. This led us to reanalyze a subset of 31 patients for DFS versus grade, for our grading schema compared with the AFIP grading. Although statistical significance was not achieved for this subset, the log rank value revealed a trend for our grading (p = 0.0993) compared with the Goode schema (p = 0.2493). This clinicopathologic analysis confirms the predictive value of tumor staging and three-tiered histologic grading. Our grading exercise confirms that there is significant grading disparity for MEC, even among experienced ENT/oral pathologists. The improved reproducibility obtained when the weighted AFIP criteria were used speaks to the need for an accepted and easily reproducible system. However, these proposed criteria have a tendency to downgrade MEC. Therefore, the addition of other criteria (such as vascular invasion, pattern of tumor infiltration [i.e., small islands and individual cells vs cohesive islands]) is necessary. We propose a modified grading schema, which enhances predictability and provides much needed reproducibility.

Age standardized incidence rates of oral cancer in South Africa, 1988-1991.

While numbers of papers on oral cancer in South Africa have been published, there have been very few studies on standardized morbidity rates. This paper has developed data collected by the National Cancer Registry from the entire country for the four year period 1988-1991 to present frequency, age standardized incidence rates (ASIRs) and life-time risk (LR) for histologically-diagnosed intra-oral cancers in female and male Asian, black, coloured and white South Africans. During this period 5396 cases of oral cancer were diagnosed in a total number of 157,307 cancer cases (3.4 per cent) excluding squamous cell carcinoma (SCC) and basal cell carcinoma (BSC) of the skin. Intra-oral cancer in all South African females and males accounted, respectively, for 1.8 per cent and 5.0 per cent of all cancers. There was a male preponderance in black, coloured and white groups but females were affected more frequently than men among Asians. The incidence in Asian women (6.66) was higher than those of the women in any of the other population groups, whereas the lowest incidence was found in black women (1.75). The incidence rate in coloured men was particularly high (13.13) whereas the incidence in white males (8.06) was not substantially lower than among black males (9.05). Differences between the eight groups were not significant (X2 = 6.24, df = 3, p > 0.1). The Cumulative Life Time Risk (LR) of developing intra-oral cancer for males and females in the four population groups ranged from 1:65 in coloured males to 1:455 for black females. Gender differences in LR in both black and coloured groups, signals substantial differences in exposure to known carcinogens for this disease. It is disturbing to note that the incidence in the period 1988-1991 was higher in Indian women that it was in 1964-1966, and that educative preventive measures have failed. Similarly, the incidence of intra-oral cancer in coloured men of 13.13 is substantially higher than the figure of 8.8 reported in 1979. If this is an accurately reflected trend, then a major educative programme needs to be pursued in this direction if the relative risk of one in 65 is to be reduced.

Kimura's disease--a benign condition that may be confused with malignancy. A case report.

A case of Kimura's disease is reported. The importance of this rare benign condition lies in the fact that it is clinically similar to malignant disease. The important principle of confirming the diagnosis by histological examination before embarking on major surgery is highlighted. Similarity to and differentiation from angiolymphoid hyperplasia with eosinophilia is discussed. The patient underwent resection with functional clearance of the neck nodes, and is free from disease after a 2-year follow-up period. Improper management of this rare head and neck lesion may lead to unnecessary cosmetic deformity and significant loss of function.

Candidal infection in oral lichen planus.

The prevalence of candidal infection in lichen planus (LP) and its possible association with ulceration were independently examined in two archived series of 108 and 77 cases derived from two separate populations. To ensure that similar material was being compared, each case was histopathologically reassessed and confirmed as LP or reclassified as nonspecific lichenoid stomatitis (NSLS), lichenoid dysplasia (LD), or other (O). Three further sections, cut at 25 microns intervals, were stained with periodic acid-Schiff reagent for the identification of intraepithelial candidal pseudohyphae. As control specimens, 61 normal and 59 hyperkeratotic mucosal samples were similarly processed and examined. Candidal infection was found in 17.4% and 16.4% of ulcerated and nonulcerated LP cases, respectively, and in 40.0% and 16.7% of ulcerated and nonulcerated NSLS cases, respectively. One case of LD was infected. Each control series contained one infected case. The results indicate that candidal infection occurs more readily in LP and NSLS, with no apparent association with ulceration in LP. The comparatively marked increase in the infection prevalence of ulcerated NSLS cannot be statistically confirmed, and its significance remains uncertain.

The causation of oral precancer and cancer.

Most cases of oral cancer result from the action of exogenic carcinogenic agents, some of which act synergistically in producing their effects. The evidence implicating tobacco and alcohol abuse is overwhelming and cannot be refuted. Other clearly identifiable aetiological agents include betel nut chewing and excessive exposure to sunlight. While there is increasing evidence of a viral causation, this is not yet clearly established. Similarly, the role of Candida albicans remains uncertain. Lichen planus and discoid lupus erythematosus may constitute important predisposing conditions, but the documentation remains inadequate and inconclusive, as does that implicating electrogalvanism. Tertiary syphilis is no longer considered a significant factor in oral cancer. Sideropenic dysphagia and haemoglobin and serum iron deficiencies may be of importance in the development of oral carcinoma, particularly in elderly women with no history of tobacco and alcohol abuse. The roles of poor oral hygiene and sharp edges of teeth and dentures have probably been overemphasized in the past.

Human papillomavirus infection related to oesophageal carcinoma in black South Africans. A preliminary study.

Oesophageal specimens derived from 70 patients with established invasive squamous cell carcinoma of the oesophagus were histologically reviewed with special reference to the morphological manifestations of human papillomavirus (HPV) infection. Epithelial changes fulfilling the criteria for HPV infection were noted in 23 cases (33%). The presence of HPV antigens was demonstrated by immunohistochemical staining in 7 of these 23 cases. Although acceptable for routine diagnostic purposes, histological typing and immunoperoxidase staining methods are not entirely conclusive of HPV infection. Electron microscopy for detection of viral particles and a molecular hybridization technique have to be used for absolute confirmation and viral subtyping. The results of this pilot study will be used for prospective studies to determine the role of HPV infection in the aetiology of oesophageal carcinoma.

Plexiform granular cell odontogenic tumor.

Two odontogenic tumors characterized by a previously undescribed histologic appearance are reported. Both lesions consisted of interlacing strands of odontogenic epithelium, with each strand being two cell layers thick. The cells were large and polyhedral in shape, with a granular eosinophilic cytoplasm. The nuclei were arranged "back to back" away from the basement membrane. One of the lesions seems to have originated, at least in part, from the basal layer of the oral epithelium. There is some evidence to suggest that these lesions may represent previously undescribed histologic variants of the ameloblastoma. However, the possibility that they represent a new entity cannot be excluded. For the time being the term plexiform granular cell odontogenic tumor is suggested.

A fruit-mouthwash chemical burn. Report of a case.

A case of an unusual chemical burn, confined to masticatory mucosa, produced by abusive fresh fruit ingestion and concommitant excessive use of mouthwashes, is reported. Clinical presentation, histopathological appearance and related factors are presented and discussed.