George Laskaris

High risk HPV types are frequently detected in potentially malignant and malignant oral lesions, but not in normal oral mucosa.

Studies on the involvement of the human papillomavirus (HPV) in initiation and progression of oral neoplasia have generated conflicting results. The observed discrepancy is attributable mainly to the varying sensitivity of the applied methodologies and to epidemiologic factors of the examined patient groups. To evaluate the role of HPV in oral carcinogenesis, we analyzed 53 potentially neoplastic and neoplastic oral lesions consisting of 29 cases of hyperplasia, 5 cases of dysplasia, and 19 cases of squamous cell carcinomas, as well as 16 oral specimens derived from healthy individuals. A highly sensitive nested polymerase chain reaction (PCR) assay was used, along with type-specific PCR, restriction fragment length polymorphism analysis, dot blotting, and nonisotopic in situ hybridization. Nested PCR revealed the presence of HPV DNA in 48 of the 53 (91%) pathologic samples analyzed, whereas none (0%) of the normal specimens was found to be infected. Positivity for HPV was independent of histology and the smoking habits of the analyzed group of patients. At least one “high risk” type, such as HPV 16, 18, and 33, was detected by type-specific PCR in 47 (98%) infected specimens, whereas only 1 (2%) squamous cell carcinoma was solely infected by a “low risk” type (HPV 6). HPV 16 was the prevailing viral type, being present in 71% of infected cases. Single HPV 16 and HPV 18 infections were confirmed by restriction fragment length polymorphism. HPV 58 was detected by dot blotting in three hyperplastic lesions. HPV positivity and genotyping were further confirmed, and the physical status of this virus was evaluated by nonisotopic in situ hybridization. Diffuse and punctate signals, indicative of the episomal and integrative pattern of HPV infection, were observed for low- and high-risk types, respectively. Our findings are suggestive of an early involvement of high-risk HPV types in oral carcinogenesis.

Bullous pemphigoid, cicatricial pemphigoid, and pemphigus vulgaris: A comparative clinical survey of 278 cases

The clinical features of bullous pemphigoid (BP), cicatricial pemphigoid (CP), and pemphigus vulgaris (PV), based upon examination of 278 patients during the years 1972 through 1981, are recorded. Data in relation to age, sex, site of onset, duration of the disease at the site of onset, distribution of oral, skin, and extracutaneous lesions, and time of final diagnosis are analyzed for each disease separately, and a detailed discussion in comparison with previous reports follows. Comparative evaluation of all the clinical data permitted identification of similarities and differences in the clinical manifestations within this disease group and provided an opportunity to increase our knowledge and understanding of the overall clinical behavior of these bullous diseases. Greater awareness of these entities, which very often involve the oral mucosa, in correlation with careful clinical observation is of particular importance and leads to early diagnosis and improved treatment.

Oral manifestations of HIV infection and their management. II. Less common lesions

This second of two articles reviews the many uncommon and rare oral lesions that have arisen in persons infected with human immunodeficiency virus (HIV). The various drug-related oral disorders of HIV disease are also considered.

Cicatricial pemphigoid: Direct and indirect immunofluorescent studies

Oral mucosa, skin tissue, and serum samples from thirty-three patients with cicatricial pemphigoid were studied by the direct and indirect immunofluorescent techniques to determine the presence of tissue-bound and circulating antibodies. A linear continuous basement membrane zone pattern was observed in 96.9 percent of the oral mucosa biopsy specimens studied. This pattern is indistinguishable from the pattern observed in bullous pemphigoid. In 97 percent of the cases clinically healthy skin biopsy specimens were negative for basement membrane zone staining. Circulating anti-basement membrane zone antibodies were present in 36.4 percent of thirty-three patients with cicatricial pemphigoid in low titer (1:10 to 1:40), when normal oral mucosa was used as substrate. The demonstration of tissue-bound and circulating basement membrane zone antibodies in cicatricial pemphigoid morphologically identical to those found in bullous pemphigoid provides further support for the concept that the two diseases may represent variants of the same entity.

Factors Associated with Delay in the Diagnosis of Oral Cancer

Early detection and treatment improve the prognosis for oral cancer. Delays from the onset of symptoms to clinical diagnosis are common. Our aim is to identify factors associated with this delay. Between 1995 and 1998, we interviewed 105 consecutive patients with histologically confirmed oral cancer in Greece. If 21 or more days elapsed from the time the patient noticed major symptoms to a definitive diagnosis, we called it a delay (52% of cases). We used logistic and linear regression to estimate odds ratios of delayed diagnosis and to identify correlates of length of delay, respectively. Former smokers had a 4.3 times greater risk of delayed diagnosis compared with current smokers (95% confidence interval: 1.1-17.1). The length of delay was greater among single patients, non-smokers, or those with stage IV tumors. Clinicians should be advised that delay in the diagnosis of oral cancer occurs frequently, even in individuals who do not smoke heavily.

Direct immunofluorescence in oral lichen planus

Direct immunofluorescent staining (DIF) was performed on biopsy specimens from thirty-five patients with oral lichen planus. The results showed fibrin deposition in all cases at the mucosal-submucosal interface, within colloid bodies (fourteen of thirty-five) and within vascular walls (five of thirty-five). Deposition of IgG, IgA and IgM was detected to a lesser extent, while complement (C3) could not be identified in any case. The significance of these findings was assessed by comparison with the IF results obtained in thirty-five biopsies from various oral diseases other than lichen planus and ten healty persons. Although the presence of fibrin deposition at the mucosal-submucosal junction, within vessels and cytoid bodies, was found to be highly characteristic of lichen planus, these findings were not specifically diagnostic. Morphologically identical deposits were also seen in lupus erythematosus. It is known at present whether immunologic reactions may play a role in the pathogenesis of lichen planus. However, the immunopathologic findings may occasionally be additional suggestive markers in the diagnosis of the disease.

Smoking and alcohol in the etiology of oral cancer: gender-specific risk profiles in the south of Greece

Oral and pharyngeal cancer (OC) mortality is very low in Greece, especially among men, compared to other European countries. We conducted a case-control study of OC in Athens, and obtained information on tobacco, alcohol use and other potential risk factors and confounding variables for 110 incident cases and 115 hospital-based controls. We used multivariate logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Tobacco smoking (pack years, P(trend)=0.01) and alcohol use (drinks/week, P(trend)=0.07) were independent risk factors, with a multiplicative effect for combined exposures (OR, 8.3; 95% CI, 2.4-29.1, for >28 alcohol drinks/week and >50 pack years of cigarette smoking). The type of alcoholic beverage also seemed important: drinking ouzo and tsipouro (liquors of high ethanol concentration) was associated with greater increased OC risk than drinking comparable amounts of wine, beer or dark spirits. While alcohol drinking is more common for male cases versus controls, few men reported regularly consuming large quantities of ethanol associated with highest risk of OC in other studies. This may partially explain the low rates of male OC mortality in Greece. Among the 38% of our cases who were women, however, neither smoking nor alcohol drinking frequencies were significantly elevated compared to controls, and so the etiology of OC risk in females requires further investigation.

Interaction between a single nucleotide polymorphism in the alcohol dehydrogenase 3 gene, alcohol consumption and oral cancer risk†

We investigated effects on oral cancer (OC) risk of an interaction between a single nucleotide polymorphism (SNP) in the alcohol dehydrogenase 3 (ADH3) gene and alcohol consumption levels using a hospital‐based study of 93 cases and 99 controls conducted in Athens, Greece. This SNP affects ethanol metabolism in vitro and appeared to interact with alcohol consumption in a previous OC study. We also evaluated a SNP in CYP2E1, another gene involved in ethanol metabolism, reported to be associated with OC risk in a European population. Data on genotypes and risk factors obtained from interviews were analyzed using multivariate logistic regression, accounting for potential confounders. No overall (marginal) association was found between OC risk and ADH3 genotypes. An interaction between ADH3 genotypes and alcohol consumption levels, however, was suggested. In non‐drinkers, the ADH31‐1 genotype has higher risk than ADH31‐2 or ADH32‐2 genotypes, but for subjects consuming alcohol, lower risk was observed for ADH3 We fit a logistic regression model to estimate the increase in OC risk associated with each alcohol drink consumed per week. We estimated that OC risk increased by 31.5% per drink/week for the ADH32‐2 genotype, 4.1% for the ADH31‐2 genotype and 1.6% for the ADH31‐1 genotype. Evidence of genotype‐environment interaction was suggestive (p = 0.048, Wald χ p = 0.145, likelihood ratio). This finding is opposite to that reported for a population in Puerto Rico, where the ADH31‐1 genotype seemed more sensitive to ethanol exposure. In Greece, genetic variation at the CYP2E1 SNP is almost entirely absent, with only 1 case and 1 control heterozygous for the variant. By contrast, in a population in France where an OC association was reported, the frequency of CYP2E1 heterozygotes was 5% in controls and 9% in OC cases. These findings illustrate the importance of replicating SNP associations both within and between different racial and ethnic groups and geographic regions. Published 2001 Wiley‐Liss, Inc.

Epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia) in the oral mucosa: A case report and review of the literature

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign uncommon entity whose aetiology and pathogenesis is under debate. Clinically, it is characterised by cutaneous papules or nodules. Cases of this entity reported in the oral mucosa are very rare. We describe such a case, discuss the problems of histological differential diagnosis between ALHE and other diseases of the region and review the literature.

Frequency of desquamative gingivitis in skin diseases

In an attempt to determine the frequency of desquamative gingivitis (DG) in pemphigus vulgaris (PV), bullous pemphigoid (BP), cicatricial pemphigoid (CP), and lichen planus (LP), a large series of patients examined and classified in each group during the years 1972 to 1981 were included in this study. Analysis of the clinical data revealed that, of the four skin diseases, CP manifests as DG in 63.6 percent of the cases. Desquamative gingival lesions are less frequent in LP (25 percent) and in PV (18.4 percent). The great majority of DG patients were females (72.9 percent). Identification of the underlying causes of desquamative gingivitis is of utmost importance and is dependent upon clinical, histologic, and immunologic criteria.