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Human papillomavirus in oral premalignant lesions.

The aetiology of oral premalignant lesions is generally accepted to be multifactorial. Tobacco and alcohol are established as important cofactors in malignant development in the oral cavity, but in addition microorganisms, such as human papillomavirus (HPV), have gained much interest over the past decade. For many years, HPV has been accepted as an important cofactor in the development of cervical cancer, originating from a mucous membrane with similarities to the oral mucosa. 49 patients with oral premalignant lesions and 20 control patients with normal oral mucosa and no history of HPV infection were examined for the presence of HPV by immune histochemical staining using the peroxidase anti-peroxidase technique (PAP), DNA-DNA in situ hybridisation (ISH), and polymerase chain reaction (PCR) analysed by Southern blot hybridisation with an HPV 16 specific probe. The investigations revealed that HPV was found in 62.5% of the verrucous leucoplakias, 50.0% of the erythroplakias, 45.5% of the homogeneous leucoplakias, 33.3% of erythroleucoplakias and in 12.5% of the nodular leucoplakias. An overall HPV detection rate in the examined premalignant lesions was 40.8% and no patients in the control sample were positive. Concerning oral cancer development, it seems likely that HPV may be a cofactor, as 100% of patients who developed oral cancers within 4-12 years were all positive for HPV, one being positive for HPV 16.

Adult↗

Use of methylene blue as a diagnostic aid in early detection of oral cancer and precancerous lesions.

We assessed the sensitivity, specificity, and positive and negative predictive value of methylene blue staining in the diagnosis of oral cancer in 58 patients. The sensitivity was 90%, the specificity 69%, positive predictive value 74%, and negative predictive value 87%. Because of the number of false negatives and false positives we recommend that the diagnosis should always be confirmed by histopathological examination of a biopsy specimen. Methylene blue staining may, however, be useful as a screening tool for oral cancer in large, high-risk groups in a similar way to the more expensive toluidine blue.

Carcinoma, Squamous Cell↗

Oral erythroplakia--a review.

Oral erythroplakia (OE) is considered a rare potentially malignant lesion of the oral mucosa. Reports entirely devoted to OE are very few, and only two reviews none of which are of recent date have been published. Only the true, velvety, red homogeneous OE has been clearly defined while the terminology for mixed red and white lesions is complex, ill-defined and confusing. A recent case control study of OE from India reported a prevalence of 0.2%. A range of prevalences between 0.02% and 0.83% from different geographical areas has been documented. OE is predominantly seen in the middle aged and elderly. One study from India showed a female:male ratio of 1:1.04. The soft palate, the floor of the mouth and the buccal mucosa is commonly affected. A specific type of OE occurs in chutta smokers in India. Lesions of OE are typically less than 1.5 cm in diameter. The etiology of OE reveals a strong association with tobacco consumption and the use of alcohol. Histopathologically, it has been documented that in OE of the homogenous type, 51% showed invasive carcinoma, 40% carcinoma in situ and 9% mild or moderate dysplasia. Recently, genomic aberrations with DNA aneuploidy has been demonstrated. p53 mutations with different degrees of dysplasia may play a role in some cases of OE. Transformation rates are considered to be the highest among all precancerous oral lesions and conditions. Surgical excision is the treatment of choice. Data on laser excision are not available. Recurrence rates seem to be high, reliable data are, however, missing. More studies on OE are strongly needed to evaluate a number of so far unanswered questions. The natural history of OE is unknown. Do OEs develop de novo or are they developing from oral leukoplakia through several intermediate stages of white/red lesions? The possible role of fungal infection (Candida micro-organisms) is not clear as is the possible role of HPV co-infection in the development of OE. More data on incidence and prevalence, biological behaviour and adequate treatment are urgently needed.

Aged↗

Long-term treatment outcome of oral premalignant lesions.

The purpose of the present retrospective study was to learn the long-term outcome of oral premalignant lesions, leukoplakia and erythroplakia, with or without surgical intervention and to relate the outcome to factors supposed to be significant for malignant development including clinical type, demarcation, size, site, presence of epithelial dysplasia, smoking and surgery. A total of 269 lesions in 236 patients were included. Ninety-four lesions were surgically removed, 39 lesions (41%) being homogenous and 46 (49%) non-homogenous leukoplakias whereas nine (5%) were erythroplakias. Seventy-three percent of the lesions were associated with tobacco habits. The mean size of the lesions was 486 mm(2), and 71% of the lesions showed a degree of epithelial dysplasia. After excision the defects were closed primarily by transposition of mucosal flaps or they were covered by free mucosal or skin grafts. A few defects were left for secondary healing. After surgical treatment the patients were followed (mean 6.8 yrs, range 1.5-18.6 yrs), and new biopsies taken in case of recurrences. One hundred and seventy five lesions had no surgical intervention, 149 lesions (85%) being homogenous and 20 (11%) non-homogenous leukoplakias, and 6 (3%) erythroplakias. Eighty-one percent of the lesions were associated with smoking. The mean size of the lesions was 503 mm(2) and 21 of the lesions (12%) exhibited epithelial dysplasia. Sixty-five lesions were not biopsied. These patients were also followed (mean 5.5 yrs, range 1.1-20.2 yrs), and biopsies taken in case of changes indicative of malignant development. All patients were encouraged to quit smoking and candidal infections were treated. The possible role of different variables for malignant development was estimated by means of logistic regression analysis. Following surgical treatment 11 lesions (12%) developed carcinoma after a mean follow-up period of 7.5 yrs. Non-homogenous leukoplakia accounted for the highest frequency of malignant development, i.e. 20%, whereas 3% of the homogenous leukoplakias developed carcinomas. Surgically treated lesions with slight, moderate, severe and no epithelial dysplasia developed carcinoma with similar frequencies, i.e. 9-11%. Without surgical intervention 16% of the 175 lesions disappeared whereas seven lesions (4%) developed carcinoma after a mean observation period of 6.6 yrs. The highest frequency of malignant development (15%) was seen for non-homogenous leukoplakias, this figure being 3% for homogenous leukoplakias. Fourteen percent of lesions with slight epithelial dysplasia developed malignancy and 2% of lesions with no dysplasia showed malignant transformation. Logistic regression analysis showed a seven times increased risk (OR = 7.0) of non-homogenous leukoplakia for malignant development as compared with homogenous leukoplakia and a 5.4 times increased risk for malignant development for lesions with a size exceeding 200 mm(2). No other examined variables including presence of any degree of epithelial dysplasia, site, demarcation, smoking and surgical intervention were statistically significant factors for malignant development.

Adult↗

Cancerisation within the oral cavity: the use of 'field mapping biopsies' in clinical management.

Field cancerisation within the oral cavity risks multiple primary tumour development. Whilst multi-focal disease may ultimately affect up to 24% of oral cancer patients, a particular management problem is encountered with those patients presenting with pan-oral dysplasia. In an attempt to characterise the extent of dysplasia and to quantify the risk of malignant change, examination under anaesthesia (EUA) and multiple, 'field mapping biopsies' were carried out for 16 consecutive patients presenting with pan-oral disease. Seventy lesions, predominantly homogenous leukoplakias, were biopsied primarily showing hyperkeratosis or mild dysplasia histologically. More significant dysplasia was seen to affect the faucial pillars, floor of mouth and ventral tongue. Interventional CO(2) laser surgery was used to excise 11 severely dysplastic lesions in six patients. Field mapping appears effective in the initial identification and treatment of the most significant areas of dysplasia in patients with multi-focal precancer. Longitudinal, multi-centre trials are now required.

Adolescent↗

Pathology of malignant and premalignant oral epithelial lesions.

Oral mucous membranes and the surrounding structures are largely composed of stratified squamous epithelium that is supported by a fibrous connective tissue lamina propria and a submucosa of fibroadipose tissue. Minor salivary glands, nerves, and capillaries course abundantly throughout the supporting collagen and fibro-fatty submucosa. Premalignant and malignant lesions arise most frequently from epithelium, and these epithelial lesions ultimately account for 95% of all cancers of the oral cavity. Malignant neoplasia of bone, cartilage, salivary glands, and connective tissue and those of lymphoproliferative derivatives are far less common occurrences in the oral cavity. Malignant neoplasms can and do arise from the tooth germ apparatus, but neoplasms of odontogenic elements are rare and are not included in this discussion.

Carcinoma in Situ↗

Erythroplastic lesion on the mandibular marginal gingiva.

Carcinoma of the gingiva is a significant risk to patients because the asymptomatic characteristics of erythroplastic lesions are not always readily identified. This case report shows the similarity in clinical appearance of squamous cell carcinoma of the gingiva to the common inflammatory changes associated with periodontal disease. A similar clinical presentation might be seen in any lesion with increased vascularity, including Kaposi's sarcoma associated with human immunodeficiency virus infection. Any erythroplastic change involving the oral mucosa should be viewed with suspicion and, if not resolved after removal of local sources of irritation, must be biopsied to establish a definitive diagnosis.

Aged↗

Balanitis circumscripta plasmacellularis.

A patient is presented with a recalcitrant penile lesion which demonstrated the clinical and histologic features of the balanitis originally described by Zoon. The status of this disease and its relationship to similar disorders are discussed.

Aged↗

Vulvitis circumscripta plasmacellularis.

In this paper we present what is apparently the tenth published case of vulvitis circumscripta plasmacellularis (Zoon). The patient had eroded, red-brown, asymptomatic vulvar lesions that were recalcitrant to treatment. The characteristic histopathology--dense plasma cell infiltrate and deposition of hemosiderin--was present.

Adult↗

Management of potentially malignant oral mucosal lesions by consultant UK oral and maxillofacial surgeons.

This paper describes the results of a recent survey carried out under the auspices of the Professional Education and Evaluation Subgroup of the UK Working Group on Screening for Oral Cancer and Precancer. The aim of this survey was to assimilate information regarding currently used management options of potentially malignant oral lesions as a basis from which to rationalise our future approach to their management. The survey has confirmed that variation exists among oral and maxillofacial consultants in their approaches and a more formal approach to management may therefore be indicated.

Data Collection↗

Oral cancer: a retrospective study of 100 Danish cases.

One hundred Danes with oral cancer who were collected consecutively from 1986 to 1991 were evaluated retrospectively. The study included subjective and objective observations in 56% men and in 44% women. M:F ratio was 1.2:1. Fifty percent of the patients were non-smokers. Nine percent were women who did not drink alcohol. Ten percent of the patients were between 40 and 49 years of age, 20% between 50 and 59 years, 35% were between 60 and 69 years and 20% between 70 and 79 years of age. This may reflect a tradition of early drinking and smoking. Doctor's delay was the cause of delayed referral in 14% of the cases while 72% of the patients were the cause themselves for the delayed referral.

Adult↗

Surgical treatment of premalignant lesions of the oral mucosa.

Oral premalignant lesions were treated by surgical excision in 61 patients. Criteria for inclusion in the study were epithelial dysplasia varying from slight to carcinoma in situ, or a non-dysplastic lesion located sublingually or on the tongue. The clinical diagnosis of the treated lesions were: erythroplakia 10, erythroleukoplakia 15, nodular leukoplakia 9, verrucous leukoplakia 9, homogeneous leukoplakia 13, and lichen planus 5. The surgically created defects were closed by direct approximation of the wound edges in 25 patients, transposition by a local mucosal flap in 9, covered with a free mucosal graft in 3, and by a free split skin transplant in 24 patients. The patients have been followed for an average period of 3.9 years after the operation. A recurrence rate of 20% was found, and 3 carcinomas developed in the follow-up period. The importance of using a surgical technique permitting histological examination of the entire lesion was documented by the finding of 4 superficial carcinomas in the excision specimen, undiagnosed in the preoperative biopsy.

Adult↗

Prevalence of Epstein-Barr virus in oral squamous cell carcinomas, premalignant lesions and normal mucosa--a study using the polymerase chain reaction.

Epstein-Barr virus (EBV) prevalence was assessed in 12 clinically normal oral mucosas, nine premalignant lesions, 36 oral squamous cell carcinomas (OSCCs) and a human papillomavirus (HPV) 16 positive cell line, derived from an OSCC studied. The polymerase chain reaction (PCR) with two pairs of primers with different sensitivities was used. With primers specific for the BamHIW repeat, EBV was found in 100% of OSCCs, in 77.8% of premalignant lesions and in 8.3% of clinically normal oral mucosas (P = 0.0001). Using primers specific for the single copy BNLF-1 gene, EBV was detected in 50% of OSCC and in none of the premalignant lesions. No statistically significant associations could be established among EBV presence and clinico-pathological data of OSCC. The cell line derived from an HPV/EBV-positive carcinoma did not reveal EBV DNA. The higher prevalence of EBV in OSCCs and premalignant lesions may be due to increased EBV shedding, possibly due to associated immunodepression in these patients, rather than its clonal presence in the neoplastic cells.

Adult↗

Oral epithelial dysplasia and the development of invasive squamous cell carcinoma.

Oral epithelial dysplasia, the histopathologic marker of a premalignant disorder of the mouth mucosa, may present clinically as leukoplakia, erythroplakia, or leukoerythroplakia. Its presence in lesions of the oral mucosa is predictive by a variable rate (6.6% to 36%) of transformation to invasive squamous cell carcinoma. We studied the clinical features and microscopic slides of 308 case of oral epithelial dysplasia in our biopsy service and retrospectively evaluated 44 of these with follow-up data for transformation to invasive squamous cell carcinoma. Forty-four patients had follow-up of more than 6 months with a mean follow-up time of 18.4 months. Twenty (45%) were clinically free of disease and 15 (34%) had recurrence of the dysplasia. An additional two cases of lower grades of the disease recurred as carcinoma in situ. Invasive squamous cell carcinoma developed in seven (16%) in a mean transformation time of 33.6 months.

Adult↗