Occurrence of papillomavirus structural antigens in oral papillomas and leukoplakias

Six oral papillomas and 7 oral leukoplakias were studied with genus-specific antibodies against detergent-disrupted papillomaviruses. Indirect immunofluorescence staining was applied to frozen sections. Distinct nuclear staining of superficial keratinocytes was seen in 5 of 6 oral papillomas, 2 of 5 homogenous leukoplakias, and in 2 cases of nodular leukoplakia, one of these showing transition into an invasive carcinoma. Papillomavirus antibodies offer a new way to detect and localize papillomaviruses in epithelial hyperplasias. The relevance of the immunomorphological identification of papillomavirus-associated antigens is discussed with special reference to the molecular hybridization technique.     

In situ DNA hybridization analysis of oral papillomas, leukoplakias, and carcinomas for human papillomavirus.

Twenty-one papillomas, 23 ordinary benign keratoses, 13 smokeless tobacco keratoses, 10 verrucous hyperplasias, 10 verrucous carcinomas, 17 squamous cell carcinomas, 3 epithelial dysplasias, and 6 lichen planus lesions were evaluated for human papillomavirus (HPV) types 6/11, 16/18, and 31/33/35, with biotinylated double-stranded DNA probes by in situ hybridization. Sixty-two percent (13/21) of oral squamous papillomas were positive for HPV DNA. HPV DNA types 6 and 11 demonstrated the strongest reactivity. Of the 13 cases, 10 also showed some reactivity with HPV-16/18 and -31/33/35. None of the cases of keratoses, epithelial dysplasia, squamous cell carcinoma, verrucous hyperplasia, verrucous carcinoma, or lichen planus were positive for HPV DNA. This study confirms the consistent and frequent finding of HPV DNA in oral squamous cell papillomas and the inconsistency of being able to identify HPV DNA in keratotic, premalignant, or cancerous lesions of the oral mucous membranes.     

Quantitative analysis of immunocompetent cells in human normal oral and uterine cervical mucosa, oral papillomas and leukoplakias

Using monoclonal antibodies reacting with T-cell subpopulations, Langerhans cells and macrophages, the number and distribution of cells of the immune system in normal oral and cervical mucosa was determined and statistically compared with that in oral papillomas and oral leukoplakias. Increased numbers of labelled cells were found in oral leukoplakias and particularly in oral papillomas. In the epithelium of all specimens, Langerhans cells and T-lymphocytes of the suppressor/cytotoxic phenotype as well as of the helper phenotype were seen. Suppressor/cytotoxic and helper T-lymphocytes were in equal numbers in the epithelium of oral papillomas, but were about 2:1 in all other lesions. In normal oral epithelium, macrophages were rare but were in greater numbers in leukoplakias and papillomas. In the connective tissue of all lesions, more labelled cells were present than in epithelium with T-lymphocytes predominant. Although Langerhans cells were rare in connective tissue, many were seen in oral papillomas.     

Human papillomavirus (HPV) in oral squamous cell papillomas

One hundred and forty oral squamous cell papillomas (SCPs) were subjected to immunocytochemical staining for papillomavirus antigen using the immunoperoxidase-PAP method 41% of the oral squamous papillomas showed positive intranuclear staining, 50% were negative and the remaining 9% showed both intranuclear and cytoplasmic staining. In view of these findings it is suggested that a review of the etiology of lesions diagnosed as oral SCPs should be considered.     

Human papillomavirus (HPV) in oral squamous cell papillomas

One hundred and forty oral squamous cell papillomas (SCPs) were subjected to immunocytochemical staining for papillomavirus antigen using the immunoperoxidase-PAP method 41% of the oral squamous papillomas showed positive intranuclear staining, 50% were negative and the remaining 9% showed both intranuclear and cytoplasmic staining. In view of these findings it is suggested that a review of the etiology of lesions diagnosed as oral SCPs should be considered.     

Longitudinal studies in oral leukoplakias

Abstract. Follow-up examinations of 520 patients with oral leukoplakia during a 25-ycar period showed cancer development in 31 cases, i.e. 5.9 %. The mean observation period was 8.7 years. The age distribution of leukoplakia showed that the highest frequency occurred in the age group 51–60 years; carcinoma was most frequency in the age group 61–70 years. Females had a higher prevalence for malignant transformation of oral leukoplakia (7.2 %). The tongue was the site of predilection for malignant transformation (in 38.8 % of the eases). Among etiological factors, smoking, mechanical irritation, alcohol consumption and electrical potential differences could be correlated with oral leukoplakia. Certain factors seemed to favor the development of cancer. Carcinoma originated in 26 % of verrucous leukoplakias and in 74 % of erosive leukoplakias. The highest risk for malignant transformation of leukoplakia occurs in the erosive type, whereby 28 % of all eases developed into cancer.     

Historadiographic study of oral leukoplakias

Abstract— Sections of seven typical grayish-white leukoplakias from the gingiva of the hard palate. the inside of the lip, and of the cheek have been studied by means of ultra-soft X-ray historadiography. Conspicuous differences in keratinization were observed in the different biopsies. Apart from orthokeratinization and regular parakeratinization, two types of incomplete parakeratinization were observed. Historadiographs of paraffin sections have been compared with hematoxylineosin and van Gieson-Hansen stained adjacent sections. The highest dry weight was found in orthokeratosis and regular parakeratosis. In incomplete parakeratosis flattened cells of the keratinized layer showed, in most cases, considerably higher dry weight than unflattened cells. No correlation was found between the thickness of the stratum granulosum and the radiopacity of the stratum corneum. The investigation indicates that the process of keratinization of oral mucosa is not only a chemical process but comprises a loss of water and/or water-soluble substances as well.     

Dark cells in human oral leukoplakias

Dark basal keratinocytes, characterized by a strong affinity for basic dyes and by electron density of cytoplasm and nucleus, could be recognized in eleven oral leukoplakias. The percentage of dark cells was higher in the group comprising leukoplakias verrucosa, and erosiva (28% of the basal cells) than in the leukoplakia simplex group (10%). The presence of these cells is a good indicator of the degree of histological dysplasia and correlates well with the preneoplastic potential of these lesions.     

口腔鳞状细胞乳头状瘤组织中HPV DNA的原位杂交研究

目的 探讨人乳头瘤病毒（ｈｕｍａｎ ｐａｐｉｌｌｏｍａｖｉｒｕｓ,ＨＰＶ）感染与口腔鳞状细胞乳头状瘤（ｓｑｕａｍｏｕｓ ｃｅｌｌ ｐａｐｉｌｌｏｍａ,ＳＣＰ）的发生之间的关系。方法 应用地高辛标记的ＨＰＶ６／１１和ＨＰＶ１６／１８核酸探针分别在３０例口腔ＳＣＰ组织上进行原位杂交,检测口腔ＳＣＰ组织中ＨＰＶ ＤＮＡ的特征。结果 ＨＰＶ６／１１ ＤＮＡ阳性１６例（５３％）,ＨＰＶ１６／１８ＤＮＡ未检出,ＨＰＶ６／１１ＤＮＡ阳性细胞多数分布在鳞状上皮的表层、中层和基底层。结论 原位杂交方法可以检测口腔ＳＣＰ组织中ＨＰＶ ＤＮＡ的存在并能准确组织定位,进一步支持ＨＰＶ６／１感染与口腔ＳＣＰ的发生密切相关。     

A quantitative microradiographic study of oral leukoplakias

abstract — Biopsies from 13 oral leukoplakias and from normal tissue specimens in the contralateral region of each patient were examined histologically and microradiographically. Microradiographs of freeze-sectioned and freeze-dried sections were made and quantitative photometric analyses of the distribution of the dry mass concentration in different epithelial cell layers of both normal and pathologic specimens were performed. In each microradiograph, the thickness of the stratum corneum was determined. The results indicated that in oral leukoplakia two main changes occur in the epithelial surface layer, i.e. an increase of the thickness of the surface epithelial cell layer, and a formation of an epithelial surface zone of cell layers with different degrees of keratinization and varying dry mass concentrations.     

Genomic instability and tumor-specific DNA alterations in oral leukoplakias

Leukoplakias, clinically identifiable premalignant lesions, often precede oral squamous cell carcinoma (OSCC). Identification of leukoplakias that have the potential for transformation to malignancy is a key clinical problem. The aim of this study was to assess genomic instability, and to detect tumor-specific genomic alterations, in leukoplakias. Genomic instability was analyzed by comparing the DNA fingerprints of 32 leukoplakias with those of paired normal tissue. In addition, the mutational status of the p53 gene was analyzed using polymerase chain reaction–single-stranded conformational polymorphism (PCR-SSCP) and polymerase chain reaction–heteroduplex DNA (PCR-HET), and the mutations were subsequently confirmed by DNA sequencing. Moderate-to-significant genomic instability was detected in all leukoplakias analysed. Nine unique amplicons, present in leukoplakias but not in normal tissue, were retrieved and successfully characterized. The p53 gene was mutated in 40.6% of patients. Four patients with moderate instability and mutated p53 developed OSCC. The data obtained in this study support and concretize the thesis that premalignant lesions possess many of the alterations found in cancer before the development of a malignant phenotype. Inactivation or mutation of the p53 tumor-suppressor might be an early event contributing to genomic instability and increasing the risk of malignant transformation.     

Risk of preneoplastic and neoplastic events in operated oral leukoplakias

We retrospectively analysed 167 consecutive patients with oral leukoplakias operated on by CO₂ laser resection in the Day Hospital of the Istituto Nazionale Tumori in Milan from January 1981 to December 1988, with post-operative histological examination negative for cancer. Within 5 years there were 69 patients with at least one unfavourable event. First unfavourable events were: 31 local relapses, 27 new leukoplakias, 5 oral carcinomas and 6 other neoplasms elsewhere. To identify possible prognostic factors we recorded age, sex and history of previous oral leukoplakias or head and neck cancers; also number, site, size and type of lesion; as well as tobacco and alcohol consumption and oral hygiene. The Cox regression model was employed to compare disease-free survival between different patient groups, both by univariate and multivariate analysis. From this analysis it emerges that age of operated patients and size of resected lesion are significantly predictive for development of relapses, new leukoplakias and carcinomas.     

A study of Danish snuff-induced oral leukoplakias

Abstract. In a sample of 450 patients with oral leukoplakias, 32 used snuff, which was a Danish wet variety, Göteborg snus ® (Gothenburg Snuff). The group of snuff users consisted of males only, with a mean age of 58.4 years. The mean life exposure time lo snuff was 197,000 hours, the equivalent of 22 years of constant use. Patients with leukoplakia due lo the use of snuff experienced fewer symptoms than did patients with leukoplakia due to other unknown causes. The snuff users also tended to be older at first examination, and to have a higher alcohol intake. Histological changes characteristic of snuff-users' leukoplakias were: (1) vacuolated cells in the upper part of the spinous cell layers of the epithelium with intervening streaks of parakeratinized cells, (2) epithelial hyperplasia, and (3) hyalinized, eosinophilic deposits around salivary glands. However, statistically significant differences were not found between snuff-induced leukoplakias and other leukoplakias either as lo dysplasia observed histologically or as to malignant development.     

DNA-ploidy rates in oral leukoplakias determined by flow-cytometry

In 11 patients with histologically confirmed benign (n = 4) precancerous (n = 7) oral leukoplakias, the nuclear DNA distribution patterns were analyzed by flow-cytometry. In two of three precancerous lesions exhibiting severe dysplasia, monoclonal hyperdiploid (aneuploid) cell populations were demonstrated. Aneuploidy was not observed in early or moderate dysplasias. To fully assess the diagnostic significance of flow cytometry in oral premalignancies, a larger quantity of specimens must be examined.     

Candida in oral leukoplakias A histologic and exfoliative cytologic study

Abstract— Oral leukoplakias and clinically normal mucosa of 226 patients were examined by smear or biopsy or both. From the biopsies eleven consecutive sections were evaluated, the first section being stained with hematoxylin-eosin and the following ten with PAS. Clinically normal mucosa did not show Candida , whereas Candida was present in 31 % of the biopsied leukoplakias. Eight of the 30 Candida -invaded biopsies did not contain the hyphae in all ten PAS-stained sections. Had only one section been evaluated per biopsy, the risk of arriving at a false negative diagnosis was estimated to be 13 %. 40% of leukoplakia biopsies invaded by Candida showed atypia and 67 % of all atypias were associated with Candida. No relationship between intensity of Candida invasion and presence of atypia could be demonstrated.