Incidence of oral lesions in HIV-1-infected women: reduction with HAART.

Few studies assess the effectiveness of HAART on reducing the incidence and recurrence of oral lesions. We investigated such changes among 503 HIV+ women over six years in the Women's Interagency HIV Study. The incidence of erythematous candidiasis (EC), pseudomembranous candidiasis (PC), hairy leukoplakia (HL), and warts was computed over follow-up visits after HAART initiation compared with before HAART initiation. Analysis of our data demonstrates a strong decrease in candidiasis after HAART initiation. The incidence of EC fell to 2.99% from 5.48% (RR 0.545); PC fell to 2.85% from 6.70% (RR 0.425); and EC or PC fell to 3.43% from 7.35% (RR 0.466). No changes were seen in HL or warts. Higher HIV-RNA was associated with greater incidence of candidiasis and HL, but not warts. Analysis of these data indicates that recurrence and incidence of candidiasis are reduced by HAART, and that recurrence is reduced independently of CD4 and HIV-RNA.

A new device for measuring density of jaw bones.

OBJECTIVES: The purpose of this project was to develop a lightweight, simple device to evaluate alveolar process bone density using normal intraoral and extraoral imaging procedures. METHODS: A simple lightweight device was constructed using barium sulfate as the major radiopaque component. The 5 x 32 x 12 mm(3) resin block has eight segments with known densities ranging from 1.304 (g/cm(3)) to 1.982 (g/cm(3)). The device was integrated into an XCP unit for standard intraoral radiographs and placed between the jaws for computer aided tomographic imaging. The relationship between the device segment densities and the optical densities of the exposed film was plotted. RESULTS: A linear inverse relationship was found between the device segment densities and optical densities when segment densities were between 1.304 (g/cm(3)) to 1.882 (g/cm(3)). However, the relationship was non-linear for segment densities above 1.882 (g/cm(3)). CONCLUSIONS: Normal human bone density is 1.85 (g/cm(3)), and this densitometer is useful for determination of material densities from 1.304 (g/cm(3)) to 1.882 (g/cm(3)). The device may be useful for precise bone density assessment.

Accuracy of diagnoses of HIV-related oral lesions by medical clinicians. Findings from the Women's Interagency HIV Study.

OBJECTIVE: To determine if medical clinicians are as accurate as dental clinicians in recognizing diagnostic characteristics of HIV-related oral lesions. METHODS: In 355 HIV-infected participants at five Women's Interagency HIV Study sites, we paired oral examinations conducted within 7 days of each other by dental and medical clinicians. We used the former as a gold standard against which to evaluate the accuracy of the latter. We assessed the accuracy of the medical clinicians' findings based both on their observations of abnormalities and on their descriptions of these abnormalities. RESULTS: Dental clinicians diagnosed some oral abnormality in 38% of participants. When "abnormality" was used as the medical clinicians' outcome, sensitivities were 75% for pseudomembranous candidiasis and 58% for erythematous candidiasis, but only 40% for hairy leukoplakia. When a precise description of the abnormality was used as their outcome, sensitivities were 19%, 12% and 20%, respectively. CONCLUSIONS: Medical clinicians recognize that HIV-related oral abnormalities are present in 40-75% of cases, but less often describe them accurately. Low sensitivity implies that the true associations of specific oral lesions with other HIV phenomena, such as time until AIDS, must be stronger than the literature suggests.

Effect of highly active antiretroviral therapy on frequency of oral warts.

To investigate changes in the pattern of oral disease associated with highly active antiretroviral therapy (HAART), we assessed the frequency of these lesions in our clinic over 9 years. We retrospectively studied 1280 patients seen between July, 1990, and June, 1999, and related oral findings to medication use, immune function, and viral load. We found significant decreases in oral candidosis, hairy leucoplakia, and Kaposi's sarcoma over time, but no change in the occurrence of aphthous ulcers. There was an increase in salivary-gland disease and a striking increase in warts: three-fold for patients on antiretroviral therapy and six-fold for those on HAART (p=0.01). This pattern of oral disease in a referral clinic suggests that an increase in oral warts could be occurring as a complication of HAART.

Thalidomide for the treatment of esophageal aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group.

A multicenter, double-blind, randomized, placebo-controlled clinical trial was conducted to determine the safety and efficacy of thalidomide for treating esophageal aphthous ulceration in persons infected with human immunodeficiency virus (HIV). Twenty-four HIV-infected patients with biopsy-confirmed aphthous ulceration of the esophagus were randomly assigned to receive either oral thalidomide, 200 mg/day, or oral placebo daily for 4 weeks. Eight (73%) of 11 patients randomized to receive thalidomide had complete healing of aphthous ulcers at the 4-week endoscopic evaluation, compared with 3 (23%) of 13 placebo-randomized patients (odds ratio, 13.82; 95% confidence interval, 1.16-823.75; P=.033). Odynophagia and impaired eating ability caused by esophageal aphthae were improved markedly by thalidomide treatment. Adverse events among patients receiving thalidomide included somnolence (4 patients), rash (2 patients), and peripheral sensory neuropathy (3 patients). Thalidomide is effective in healing aphthous ulceration of the esophagus in patients infected with HIV.

Association of cutaneous and oral diseases in HIV-infected men.

OBJECTIVES: Mucocutaneous diseases are common in patients infected with human immunodeficiency virus (HIV). To identify cutaneous diseases for which HIV-infected people are at high risk, we sought those that are strongly associated with specific HIV-related oral lesions and with progression of HIV disease. DESIGN: A cross-sectional study of HIV-positive outpatients referred to a university stomatology clinic for diagnosis and treatment of oral diseases. Each subject underwent both complete oral and cutaneous examinations. RESULTS: Among 55 men, with a median age of 41 years and a median CD4 cell count of 125/microliter (range 0-950/microliter), 93% had active oral diseases or conditions, including candidiasis, hairy leukoplakia, ulcers, Kaposi's sarcoma (KS), and xerostomia, and 95% had skin conditions, including onychomycosis, dermatophytosis, seborrheic dermatitis, KS, folliculitis, xerosis, and molluscum contagiosum. Seborrheic dermatitis, xerosis, skin KS, and molluscum contagiosum were associated with oral HIV-sentinel lesions (oral candidiasis, hairy leukoplakia, and KS), with low CD4 cell counts, and with AIDS. CONCLUSION: Our results suggest that xerosis and seborrheic dermatitis may be early harbingers of HIV disease progression. Their roles as predictors warrant further study, based on their associations with low CD4 cell counts and AIDS and strong co-prevalence with one of the most common HIV-related oral lesions, oral candidiasis.

Comparison of cytopathic changes in oral hairy leukoplakia with in situ hybridization for EBV DNA.

OBJECTIVE: It has been observed that the cytopathic changes in hairy leukoplakia (HL) correlate with ultrastructural evidence of intra-keratinocyte herpes-type viral particles. In situ hybridization is considered to be the definitive confirmation of Epstein-Barr virus (EBV)-induced HL. This study evaluated the consistency of histopathological findings, which many believe to be diagnostic, with in situ hybridization for EBV-DNA in 60 patients with lesions clinically suggestive of HL. MATERIALS AND METHODS: Hematoxylin and eosin (H&E)-stained sections were reviewed independently by three oral pathologists who did not know the hybridization results. The presence in keratinocytes of nuclear inclusions and/or homogenization, believed to be specific for EBV in these lesions, was used as an indicator for infection. Cytoplasmic changes were evaluated separately. RESULTS: With in situ hybridization, 48 cases were positive and 12 were negative. When the two methods were compared, pathologist concurrence ranged from 83% to 92%. False negatives ranged from 6% to 19%, and false positives ranged from 8% to 25%. Cytoplasmic ballooning, homogenization, and perinuclear clearing were evident in all cases of hybridization-confirmed HL; however, these changes were also noted in 75% (9/12) of the cases with negative hybridization results. Most confirmed HL cases exhibited both nuclear homogenization and inclusions, although the former was more consistently seen. CONCLUSION: Cytoplasmic changes did not agree well with EBV-DNA hybridization results, whereas nuclear changes demonstrated good, but not complete, agreement. In appropriate clinical settings, the finding of nuclear inclusions and/or homogenization may be of diagnostic value. However, because the potential for false positives and negatives is high, H&E cytopathology should not be used as a substitute for in situ hybridization in the definitive diagnosis of oral hairy leukoplakia.

Expression of Epstein-Barr virus BMRF-2 and BDLF-3 genes in hairy leukoplakia.

The high level of Epstein-Barr virus (EBV) replication found in hairy leukoplakia (HL) provides a unique opportunity to study EBV expression in the oral epithelium. Screening of a cDNA library from an HL biopsy revealed expression of two genes not previously described in vivo: BMRF-2 and BDLF-3. Sequence analysis of the cDNAs demonstrated several nucleotide changes from the B95-8 sequence. In all six different HL strains studied, only one amino acid change was found in BMRF-2 relative to B95-8 and two amino acid changes were found in the BDLF-3 ORF. mRNA expression of both genes was localized to the lower prickle cell layer of the tongue epithelium. BMRF-2 protein expression was primarily detected in the cell nuclei of the upper prickle cell layer; immunoelectron microscopy revealed that BMRF-2 was associated with the nuclear chromatin. BDLF-3 protein expression was observed in the perinuclear space and cytoplasm of the prickle cells. BDLF-3 has recently been identified as a virion-associated protein, but the functions of BMRF-2 and BDLF-3 have not been elucidated.

Epstein-Barr virus BMRF-2 and BDLF-3 expression in hairy leukoplakia.

Hairy leukoplakia (HL) is a lesion found on the side of the tongue of immunocompromised individuals, including those with human immunodeficiency virus (HIV) infection. The lesion has unique histopathologic features and is characterised by high-level Epstein-Barr virus (EBV) replication, multiple EBV strains, and extensive inter- and intra-strain recombination. Expression of EBV genes spanning the entire viral life cycle from latency-associated genes to late, replicative genes has been detected in the lesion. HL thus provides a unique opportunity to study EBV expression in oral epithelium, and to study expression of novel EBV genes. We therefore constructed a cDNA library from an HL biopsy and detected expression of two genes not previously described in vivo: BMRF-2 and BDLF-3. Sequence analysis of the cDNAs revealed few amino acid changes from the B95-8 sequence. Expression of both genes was localized to the lower prickle cell layer of the tongue epithelium. BMRF-2 protein expression was primarily detected in the cell nuclei of the upper prickle cell layer. BDLF-3 protein expression was observed in the peri-nuclear space and Golgi compartment. The function of these proteins is currently under investigation.

Oral ulceration in HIV infection: investigation and pathogenesis.

Oral ulcerations associated with HIV infection include recurrent aphthous ulcers (RAU). Whereas RAU prevalence is not increased, lesion severity is: among a group of HIV+ patients, 66% had the more severe herpetiform or major RAU. This increased severity suggests that HIV disease-related changes in the immune system may exacerbate RAU. In the peripheral blood of healthy subjects with RAU, CD4:CD8 cell ratios may be reversed and the proportion of T cell receptor-gamma delta + cells increased. HIV disease-related immune system changes are characterized by reversed CD4:CD8, lowered CD4 cell counts and an inverse correlation between CD4 cell counts and per cent activated gamma delta lymphocytes. Adhesion molecules and cytokines involved in lymphocyte homing may be important in RAU pathogenesis: ICAM-I and ELAM are strongly expressed, and TNF alpha production is increased in peripheral blood lymphocytes of healthy patients with RAU. In patients with active HIV disease/AIDS, serum TNF alpha levels are increased. Thalidomide, which inhibits TNF alpha production, is effective treatment for RAU. Some RAU patients have vitamin B12 or folate deficiencies, levels of which are commonly low in HIV+/AIDS patients. However, in a case control study of HIV+ patients, vitamin B12- or folate-deficiencies were not found to be significant risk factors for RAU.

Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group.

BACKGROUND: In patients with advanced human immunodeficiency virus (HIV) infection, aphthous ulceration of the mouth and oropharynx can become extensive and debilitating. Preliminary reports suggest that thalidomide may promote the healing of oral aphthous ulcers. METHODS: We performed a double-blind, randomized, placebo-controlled study of thalidomide as therapy for oral aphthous ulcers in HIV-infected patients. The patients received a four-week course of either 200 mg of thalidomide or placebo orally once per day. They were evaluated weekly for the condition of the ulcers, their quality of life, and evidence of toxicity. Assays were performed for plasma tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptors, and HIV RNA. RESULTS: Sixteen of 29 patients in the thalidomide group (55 percent) had complete healing of their aphthous ulcers after four weeks, as compared with only 2 of 28 patients in the placebo group (7 percent; odds ratio, 15; 95 percent confidence interval after adjustment for group sequential testing, 1.8 to 499; unadjusted P<0.001). Pain diminished and ability to eat improved with thalidomide treatment. The adverse effects noted with thalidomide included somnolence and rash (7 patients each), and 6 of the 29 patients discontinued treatment because of toxicity. Thalidomide treatment increased HIV RNA levels (median increase, 0.42 log10 copies per milliliter; increase with placebo, 0.05; P=0.04). With thalidomide treatment there were unexpected increases in the plasma concentrations of TNF-alpha and soluble TNF-alpha receptors. CONCLUSIONS: Thalidomide is an effective treatment for aphthous ulceration of the mouth and oropharynx in patients with HIV infection.

Apoptosis-associated markers in oral lichen planus.

Hypothesizing that loss of basal cells in oral lichen planus is due to apoptosis, we evaluated LP specimens for apoptosis-regulating proteins [positive regulators Bcl-xS, Bax, Fas/Fas-ligand, p53, and negative regulators (anti-apoptotic) Bcl-2, Bcl-xL and compared results with reactions in normal mucosa and chronically inflamed gingiva. Also, sections were evaluated with an in situ TUNEL assay that identifies apoptotic DNA fragments. Basal keratinocytes in normal buccal mucosa, nonspecific gingivitis, and LP were negative for Bcl-2 protein, but melanocytes and lymphoid cells were positive. Keratinocyte staining for Bcl-x was negative to weak in normal buccal mucosa and gingivitis, and moderate in LP. Keratinocytes (especially upper prickle cells) in all tissues stained similarly for Bax at weak to moderate levels. Also, no differences in Fas and Fas-ligand staining were evident. Prominent p53-positive staining was seen in all LP biopsies (10-100% of basal keratinocytes) but not in normal buccal mucosa and gingivitis. Few basal keratinocytes in 5/10 LP cases exhibited a positive in situ signal for DNA fragment-associated apoptosis. That the Bcl-2 family of proteins and Fas/Fas-ligand were detected in normal and diseased tissues, and were occasionally expressed differently in oral LP, supports the notion that apoptosis is a potential mechanism of keratinocyte loss, especially in LP. The pattern of p53 staining in oral LP suggests over-expression of wild-type protein; a phenomenon that would arrest the cell cycle to allow repair of damaged DNA, or trigger apoptosis. While immunohistochemical evidence for apoptosis-associated basal keratinocyte death in LP was slight, it appeared that it may be p53 protein, and possibly Bcl-x associated.

Macrophages and vascular adhesion molecules in oral Kaposi's sarcoma.

Kaposi's sarcoma (KS) is a heterogeneous tumor where spindle cells are predominant and macrophages and factor XIIIa positive dendrocytes are abundant. The origin of the macrophages and dendrocytes is unclear, although their numbers suggest a critical role in KS pathogenesis. To determine if KS macrophages are recruited from the blood stream or proliferate on-site, we examined biopsy specimens 1) for expression and distribution of vascular adhesion molecules (PECAM-1, ELAM-1, ICAM-1, VCAM-1, P-selectin, L-selectin) and the macrophage-associated adhesion-molecule ligand, VLA-4; 2) for dual expression of proliferation (Ki-67) and lineage-associated markers (KP-1, CD34, factor XIIIa, LCA); and 3) for dual expression of macrophage (KP-1) and endothelial cell (CD34) associated markers. Avidinbiotin peroxidase techniques were used. Resident vessels were found to strongly express PECAM-1, ELAM-1, ICAM-1, P-selectin, and moderately express VCAM-1 and VLA-4. Tumor spindle cells showed less intense expression of ELAM-1, ICAM-1 and P-selectin. The most frequent double-stain combination was Ki-67 + CD34+. In contrast, the combinations of Ki-67 + KP-1+, Ki-67 + XIIIa+ and Ki-67 + LCA+ were rarely seen. The enhanced expression of adhesion molecules on resident vessels and the lack of evidence of macrophage proliferation suggest that the abundant macrophages in KS are recruited from the blood stream.

Altered expression of epithelial integrins and extracellular matrix receptors in oral erythema multiforme.

Inflammation and ulceration at the epithelium-connective tissue interface, a characteristic of erythema multiforme (EM), may be associated with altered molecular attachment of basal keratinocytes. To determine the expression of basal keratinocyte-associated integrins and their basement membrane ligands in oral EM, specimens of clinically and microscopically confirmed EM (n = 12) and mucosal controls (n = 7) were stained immunohistochemically for the integrins alpha 3, beta 6, beta 1, and beta 4 and for extracellular matrix proteins laminin 1, laminin 5, collagen IV, and collagen VII using a standard avidin-biotin-peroxidase technique. In EM, results showed increased staining intensity for all integrins studied in basal and suprabasal keratinocytes. Basement membrane-associated staining of a6 and b4 was intense, but disrupted and fragmented. In EM, integrin staining was most marked at the summit of the connective tissue papillae. Laminin 5 staining was more intense than in controls, was frequently fragmented, and extended into the lamina propria. Laminin 1 staining was discontinuous and was frequently less intense than in controls. Collagen IV staining in EM was interrupted along the basement membrane. Collagen VII staining was fragmented but unchanged in intensity. These alterations in interface adhesion molecules suggest that hemidesmosome-associated molecules are important in the pathogenesis of EM. The staining intensities and patterns of expression of these adhesion molecules suggest that oral EM is initially focused in the connective tissue papillae.

Altered interface adhesion molecules in oral lichen planus.

OBJECTIVE: To evaluate expression of key epithelial-connective tissue interface adhesion molecules (basal keratinocyte integrins and extracellular matrix receptors) in oral lichen planus (LP). DESIGN: Integrins alpha 3, alpha 6, beta 1, beta 4 and basement membrane proteins laminin 1, laminin 5, collagen IV, and collagen VII were immunohistochemically identified in frozen biopsy specimens (14 oral LP and II matched controls) using a standard avidin-biotin-peroxidase technique. RESULTS: An increased staining intensity of all antigens in LP was shown, as compared to controls. Integrin expression by LP keratinocytes was generally more intense and appeared on more upper level cells. Staining for basement membrane-associated extracellular matrix proteins was also generally more intense, although fragmentation and gaps were typically seen. Reactions for alpha 6, beta 4, laminin 5, and collagen VII stains were particularly intense along the basement membrane. In LP, strands of laminin 5, collagen IV, and collagen VII appeared in the submucosa approximating or duplicating the basement membrane. CONCLUSIONS: The apparent increased expression of the interface-associated adhesion molecules may be reflective of a keratinocyte compensatory response (due to lymphocyte-mediated damage) that would functionally help resist epithelial separation (ulceration). Expression of alpha 3 beta 1 and alpha 6 beta 4 would also assist in epithelial migration associated with wound repair. We interpret the submucosal extensions and deposits of basement membrane proteins as representing remnants of basement membrane, indicating recent remodeling or atrophy of epithelial rete ridges.

Prophylaxis with nystatin pastilles for HIV-associated oral candidiasis.

To determine whether daily use of nystatin pastilles can prevent initial outbreak or recurrence of oral candidiasis in HIV-infected patients and to identify factors associated with outbreaks during 20-week follow-up, a randomized, double-blind, placebo-controlled clinical trial was conducted. Subjects were 128 HIV-infected men (aged 27-60 years) who either had had no documented episode of oral candidiasis in the previous year or had been clinically clear of oral candidiasis for at least 72 h before randomization. Study arms were two placebo pastilles, one nystatin (200,000 U) and one placebo pastille, or two nystatin pastilles daily for 20 weeks. The main outcome measure was time to oral candidiasis, as determined by potassium hydroxide (KOH) smear and fungal culture. A multivariate proportional hazards model showed that four factors were significant (p < 0.001) in predicting time to oral candidiasis: nystatin treatment (hazard ratio 0.59), history of oral candidiasis (3.58), Candida albicans carriage (2.79), and CD4 count at randomization (0.65). In this small group of subjects, nystatin appeared to be effective in delaying onset of oral candidiasis. Patients with CD4 counts < 200 who are carriers of C. albicans and have a history of oral candidiasis may be most likely to benefit from antifungal prophylaxis.

Expression of laminin 5, fibronectin, and epithelium-associated integrins in recurrent aphthous ulcers.

Recurrent aphthous ulceration (RAU) is characterized by an ulcerated lesion that persists longer than traumatic ulcers of similar size. This delayed healing phase of the lesion was investigated for extracellular matrix components and matrix receptors (integrins). The hypothesis tested was that aphthous ulcers may lack key extracellular matrix components, or their receptors, that are necessary for the migration of marginal keratinocytes from the ulcer edge. We immunocytochemically stained biopsy specimens of RAUs and non-involved mucosal specimens from HIV+ and non-infected individuals to investigate the presence and distribution of molecules reported to be associated with reepithelialization of mucosal and cutaneous wounds. Fibronectin, laminin type 5 (kalinin), and integrin subunits beta 1, beta 4, alpha 6, and alpha v were consistently found at the margins of RAU, as they are in traumatic ulcers. The alpha 5 and beta 6 subunits were not always present. We also found alpha v in the intact stratified squamous epithelium adjacent to ulcers. Immunohistochemical stains showed distruption in the deposition of laminin 5 and an apparent lack of fibronectin at the edges of some ulcers. Although these tissue results do not determine which integrin subunits are paired with each other, they do show some alterations in their expression in RAU. Absence of one or more of these molecules at the migrating front may contribute to delayed epithelial regeneration. It is likely that the absence or inappropriate expression of keratinocyte integrins or their extracellular matrix receptors occurs after the causative factors (currently unknown) of the lesion are gone. The reason for the altered expression of these molecules may be related to the secretory products (including lymphokines and proteinases) of the lymphocytic infiltrate.

Vascular adhesion molecules in oral lichen planus.

OBJECTIVE: Because recruitment and retention of lymphoid cells appear to be critical components of the pathogenesis of lichen planus, we have compared the expression and distribution of a panel of vascular adhesion molecules (ELAM-1, P-selectin, ICAM-1, VCAM-1, PECAM-1, CD34) and leukocyte adhesion molecule ligands (LFA-1, Mac-1, VLA4, L-selectin) in biopsies of this disease. STUDY-DESIGN: Frozen sections of 12 clinically and histologically confirmed cases of lichen planus and 9 normal control tissues were evaluated immunohistochemically with a standard 1-day avidin-biotin peroxidase technique. Staining intensity of vascular endothelium was evaluated semiquantitatively. Three microvascular zones or compartments were defined and evaluated separately. RESULTS: Generally, different staining patterns were observed in association with the various endothelium-associated adhesion molecules. In normal controls, PECAM was intensely expressed and VCAM-1 was weakly expressed. Intermediate staining was associated with ELAM-1, P-selectin, ICAM-1, and CD34. Staining within the three microvascular compartments frequently showed variations in intensity. In lichen planus, increased staining for ELAM-1, P-selectin, ICAM-1, and VCAM-1 was evident in one or more of the microvascular compartments. In the subepithelial vascular compartment where the infiltrate was the most dense, VCAM-1 appeared to show the greatest positive change. Almost all cells in the lichen planus infiltrates stained positive for ICAM-1, L-selectin, LFA-1, and VLA4, and large numbers of cells also exhibited VCAM-1, PECAM-1, and Mac-1 immunoreactivity. CONCLUSIONS: It appears that upregulation of ELAM-1, ICAM-1, and VCAM-1 (especially by endothelial cells in the subepithelial vascular plexus) could play a role in the pathogenesis of lichen planus. The expression of leukocyte receptors L-selectin, LFA-1, and VLA4 by most of the cells in the lichen planus infiltrate suggest that these molecules may be responsible for recruitment as well as retention in the active lichen planus lesion.

Direct immunofluorescence vs. culture for detecting HSV in oral ulcers: a comparison.

Diagnostic tests may be necessary to determine the cause of oral ulcers. Direct immunofluorescence staining of oral smears supplies results much more quickly than viral culture, the "gold standard" for diagnosing HSV lesions. This study compares the sensitivity and specificity of direct immunofluorescence staining vs. viral culture and evaluates the usefulness of the two techniques for the general dental practitioner.

HPV-associated epithelial atypia in oral warts in HIV+ patients.

Reported are oral mucosal warts (HPV common antigen-positive) from 7 adult HIV+ patients in which there was cytologic atypia and disordered growth. Lesions were papillary, white to red in color, and were located on the lip, gingiva, palate, tongue, and buccal mucosa. Histologically, the keratinocytes in the lesions exhibited atypical features in the form of hyperchromatism and karyomegaly. Koilocytes were frequently seen in the upper level keratinocytes where HPV common antigen was identified. The dysplastic areas, which ranged from mild to severe, typically showed abrupt limiting margins. All lesions exhibited intense PCNA reactivity from basement membrane to surface. Nuclei of mid-level and basal keratinocytes of 3 specimens stained positively for p53 protein. We believe that the atypia found in these lesions represents cytologic change that has malignant potential. The subtype of the HPV in these lesions has not yet been determined.