Testing the accuracy of autofluorescence device in diagnosing oral potentially malignant disorders among people with HIV seeking dental care.

OBJECTIVES: Although many studies have assessed the diagnostic accuracy of autofluorescence in oral potentially malignant disorders (OPMDs), there has been a paucity of such information in high-risk populations. Our study thereby tested the accuracy of using autofluorescence in the oral examination of suspicious lesions among patients seeking care at an HIV-specialized dental clinic in Houston, Texas. MATERIALS AND METHODS: We performed a prospective single-arm design in which forty-four (44) HIV-infected individuals seeking dental care at a specialized-HIV dental clinic were recruited. Each subject had their oral cavity examined under conventional lighting and then used a fluorescence light-based handheld device (OralID®). Biopsy was obtained from unresolved suspicious OPMDs at the 15-day follow-up, and histopathological analysis was conducted. The oral lesions, not the patient, were treated as the unit of analysis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated using SPSS. RESULTS: The results showed that OPMDs could be identified with a sensitivity of 90%, a specificity of 18%, an NPV of 86%, a PPV of 24% using the fluorescence light-based handheld device, with a diagnostic accuracy of 55%. CONCLUSIONS: Despite the low specificity, fluorescence light can complement clinical oral cancer screening and aid identification of OPMDs during biopsy procedures. CLINICAL RELEVANCE: Our findings suggest that autofluorescence devices could supplement clinical oral examination and aid the identification of OPMDs during biopsy procedures, potentially improving oral cancer screening among HIV-positive patients seeking care.

Plasmablastic lymphoma: an HIV-associated entity with primary oral manifestations.

Plasmablastic lymphoma is a relatively new entity that is considered to be a diffuse large B-cell lymphoma with an unique immunophenotype and a predilection for the oral cavity. We present a 50 year-old HIV-positive, bisexual, white male with a CD4 count 300/mm(3) and a viral HIV-RNA polymerase chain reaction (PCR) load of 237 copies/ml, who developed a painful, purple-red mass in the edentulous area of the maxillary right first molar. Erythematous gingival enlargements of the interdental papillae were seen in three of the dental quadrants. In addition, the patient was being managed with antiretroviral therapy and liposomal doxorubicin for recurrent cutaneous Kaposi's sarcoma (KS). Although oral KS was suspected, the gingival lesions were biopsied because they were refractory to chemotherapy and a lymphoma could not be excluded. Histopathologic examination revealed a lymphoid malignant neoplasm, consistent with a plasmablastic lymphoma. Immunoreactivity with vs38c, CD79a, kappa light chain, and IgG was readily identified in tumor cells; while only focal cells expressed CD20 and LCA (CD45RB). CD56, CD3, lambda light chain, and EMA were non-reactive. EBV was detected in the tumor by Southern hybridization, PCR amplification, in situ hybridization for EBER-1 DNA, and immunohistochemistry for latent membrane protein-1. The same tumor was negative for HHV-8 by PCR. Recognition of plasmablastic lymphoma is important, because it represents an HIV-associated malignancy that predominantly involves the oral cavity, may mimic KS and has a poor prognosis.

Medication usage and dental caries outcome-related variables in HIV/AIDS patients.

The purpose of this study was to access current medication usage by HIV/AIDS patients and its effects on dental caries and on unstimulated salivary flow rates. Thirty females and 127 males (mean age = 39.6 +/- 7.4 years), of whom 46% were White/Non-Hispanic, 39% African-American, and 15% Hispanic, were examined and interviewed at the Bering Dental Clinic, Houston, Texas. The mean time in years after seroconversion was 5.4 +/- 4.1. Calibrated examiners performed dental caries examination (DMFS) with dental explorers and bitewing radiographs. Interviews were carried out with pretested questionnaires, and medication usage was assessed by illustrative examples of HIV/AIDS medications. Salivary flow rates were determined gravimetrically (mL/min). Bivariate analysis and analysis of variance (ANOVA) were used to analyze the data. Because there were no race or gender effects on dental caries outcome variables or salivary flow rates, separate logistic regression models for medication usage were generated, which were adjusted for age and CD4+ cell counts. Patients who, currently, were receiving antiretroviral therapy (ART) had a lower occurrence of dental caries than patients not taking these medications. An unexpected finding in the lower caries rate group was a decrease in salivary flow rates, which was a probable oral side effect of ART. It appears from this cross-sectional study that systemic medication for the management of HIV disease has no significant detrimental effect on the dentition.

Herpesviridae-associated persistent mucocutaneous ulcers in acquired immunodeficiency syndrome. A clinicopathologic study.

Persistent mucocutaneous ulcers in AIDS represent a variety of disease entities. The purpose of this study was to characterize clinicopathologic features of persistent oral ulcers associated with cytomegalovirus and herpes simplex virus in AIDS. Forty-seven persons infected with HIV with persistent ulcers (mean, 2.4 ulcers/person) were included in this study. A biopsy specimen from a representative ulcer was taken from each patient. Hematoxylin-eosin, periodic acid-Schiff, cytomegalovirus, and herpes simplex virus immunocytochemical stains were performed on tissue sections. The most common sites of involvement were the buccal/labial mucosa (27%), tongue (25%), and gingiva (18%). Mean ulcer size was 1.8 cm with a mean duration of 5.6 weeks. The ulcerogenic viral agents were cytomegalovirus alone in 53% of cases, cytomegalovirus and herpes simplex virus coinfection in 28% of cases, and herpes simplex virus alone in 19% of cases. Treatment response to ganciclovir with or without topical steroids resulted in lesion resolution in the cytomegalovirus and cytomegalovirus/herpes simplex virus groups; however, recurrence/resistance was relatively high (23%). Herpes simplex virus/cytomegalovirus ulcers responded to oral acyclovir in combination with systemic ganciclovir. Increasing the oral acyclovir dosage resulted in resolution of herpes simplex virus-only ulcers in all but one case. Cytomegalovirus and herpes simplex virus are associated with persistent mucocutaneous ulcers in AIDS. These lesions responded to systemic antiviral therapy but are difficult to differentiate from other ulcerogenic diseases such as aphthous major, necrotizing stomatitis, and ulcerations not otherwise specified without biopsy and histopathologic examination.

Intraoral squamous cell carcinoma in human immunodeficiency virus infection. A clinicopathologic study.

The purpose of this study was to characterize the clinical and histological features of intraoral squamous cell carcinoma in men who were seropositive for the human immunodeficiency virus and to evaluate viral cofactors (human papillomavirus, herpes simplex virus, Epstein-Barr virus), proliferative index (proliferating cell nuclear antigen), a factor associated with invasion (cathepsin D), and mutated tumor suppressor gene and proto-oncogene products (mutated p53, c-erbB-2). Four men who were seropositive for the human immunodeficiency virus and had acquired immunodeficiency syndrome presented with painful oral lesions of variable duration. Oral cancer risk factors included heavy tobacco use (four of four), heavy alcohol use (three of four), and previous radiotherapy (one of four). The lesions consisted of ulcers (two of four), a fungating mass (one of four), and papillary erythroplakia (one of four). Incisional biopsy specimens were obtained. High-stringency in situ hybridization was performed with DNA probes to the human papillomavirus (types 6/11; 16/18; 31/33/35) and Epstein-Barr virus: Immunocytochemical studies for the herpes simplex virus, proliferating cell nuclear antigen, cathepsin D, mutated p53, and c-erbB-2 were performed. Two lesions were moderately differentiated squamous cell carcinoma, one lesion was a basaloid squamous cell carcinoma, and one was carcinoma in situ. Stage of disease at diagnosis was II (one of four), III (two of four), and IV (one of four). Three cases were positive for the human papillomavirus, one case was positive for Epstein-Barr virus, and three cases were positive for the herpes simplex virus. C-erbB-2 was focally positive in one case, and mutated p53 was positive in a separate case.(ABSTRACT TRUNCATED AT 250 WORDS)

Kaposi's sarcoma-associated herpesvirus-like DNA sequences (KSHV/HHV-8) in oral AIDS-Kaposi's sarcoma: a PCR and clinicopathologic study.

Recently, a new human herpesvirus (KSHV/HHV-8) has been identified in classic, transplant, endemic, and AIDS Kaposi's sarcoma that may be involved in the pathogenesis of Kaposi's sarcoma. The purpose of this study was to evaluate oral AIDS-Kaposi's sarcoma for detection of KSHV/HHV-8 DNA. DNA extracted from 54 oral AIDS-Kaposi's sarcoma lesions (47 initial, 7 postvinblastine treated), 5 non-Kaposi's sarcoma HIV-positive lesions, and 3 non-Kaposi's sarcoma HIV-negative lesions was evaluated by polymerase chain reaction (KS330(233bp)amplicon) for KSHV/HHV-8. The AIDS-Kaposi's sarcoma study population consisted of 52 patients (51:1, men:woman; 92% men having sex with men, 8% heterosexual; mean age, 38 years; mean, CD4 59/mm3) Opportunistic infections occurred in 88% (candidiasis, 65%; Pneumocystis carinii pneumonia, 31%; nonoral Kaposi's sarcoma, 25%; mycobacterium avium-intracellulare (MAI), 16%; cytomegalovirus, 14%; herpes simplex virus, 14%). Sexually transmitted diseases occurred in 73% (gonorrhea, 37%; syphilis, 23%; condyloma, 22%; HSV, 16%). Most frequent lesion sites were palate (74%) and gingiva (17%). Most common lesion types were purple nodular (48%) and macular (42%). Histopathologic subtypes were nodular (71%), plaque (27%), and patch (2%). Polymerase chain reaction analysis detected KSHV/HHV-8 DNA in 53 of 54 AIDS-Kaposi's sarcoma lesions (47 of 47 initial, 6 of 7 postvinblastine treatment). KSHV/HHV-8 DNA was not detected in non-Kaposi's sarcoma lesions in HIV-positive or HIV-negative persons. KSHV/HHV-8 DNA sequence is present in a high proportion of oral AIDS-Kaposi's sarcoma lesions. Whether KSHV/HHV-8 is an etiologic agent or a cofactor in the development of this vascular neoplasm is uncertain and remains to be proven. Polymerase chain reaction analysis for KSHV/HHV-8 DNA sequence detection may be helpful in identifying Kaposi's sarcoma in early vascular proliferations, when the characteristic histopathologic features are not present.

Treating Kaposi's lesions in the HIV-infected patient.

Kaposi's sarcoma is the most frequent malignant neoplasm in AIDS, occurring in about 10 percent of all risk groups. This study evaluates the effect of intralesional vinblastine on intraoral Kaposi's sarcoma in 24 HIV-positive, homosexual males with 82 lesions. Complete resolution occurred in nearly 70 percent of the cases.

Multiple herpesviruses in saliva of HIV-infected individuals.

Oral infections with human herpesviruses cause increased morbidity in patients infected with HIV. In this study, multiple HHVs were often isolated from the saliva of HIV-seropositive dental patients, but their isolation rate did not differ substantially from rates reported for the general population, except for human cytomegalovirus.

Role of dentinal carious lesions in the pathogenesis of oral candidiasis in HIV infection.

The authors describe a clinicopathologic study that evaluated whether dentinal carious lesions are colonized by candidal organisms--and if so, whether there is a relationship between dentinal carious lesion colonization and clinical oral candidiasis, or OC, in HIV infection. Using light microscopy, the authors examined 30 extracted teeth with dentinal carious lesions from people in each of two groups: 30 consecutively treated HIV-positive patients and 30 consecutively treated HIV-negative patients. OC was diagnosed only in HIV-positive patients (40 percent). The dentinal carious lesion pattern in both groups was similar in occlusal, root and proximal caries. Candidal colonization of carious dentinal tubules was more frequent in HIV-positive subjects than it was in HIV-negative subjects. This research shows that it may be important to restore dentinal caries in HIV-infected patients to remove a protected niche for candidal organisms.

An overview of the oral manifestations of AIDS-related Kaposi's sarcoma.

Acquired immunodeficiency syndrome-associated Kaposi's sarcoma (AIDS-KS) is the most common malignancy in human immunodeficiency virus infection and is seen most often in homosexual men. The oral cavity is frequently involved by AIDS-KS and may represent the initial site of this malignancy in up to 60% of patients. A number of treatment modalities, including systemic and localized chemotherapy and radiotherapy, are available for AIDS-KS. The initial diagnosis of AIDS-KS requires microscopic evaluation of biopsy material because this disease can mimic a number of intraoral lesions, including atrophic candidiasis, erythroplakia, pyogenic granuloma, bacillary angiomatosis, median rhomboid glossitis, hemangioma, and lymphoma. Overall, treatment of AIDS-KS does not significantly affect the prognosis or survival of AIDS patients, however, treatment can alleviate aerodigestive and/or respiratory dysfunction, allow for adequate nutritional intake, and improve the quality of life for these patients.

Cystoscopic confirmation of inadvertent ureteral catheterization during cystometry.

A patient in whom the right ureter was inadvertently catheterized at the time of cystometry is described. Upon filling, the patient immediately developed severe colicky right flank pain and the vesical pressure of 150 cmH(2)O triggered the pump's automatic shut-off mechanism. Cystoscopy was performed and confirmed the inadvertent placement of the microtip catheter in the right ureteral orifice. After the catheter was repositioned, symptoms resolved and the remainder of the examination was performed routinely, with normal vesical and urethral pressures.

Role of intralesional vinblastine administration in treatment of intraoral Kaposi's sarcoma in AIDS.

The purpose of this clinical study was to determine the effect of intralesional vinblastine administration on intraoral Kaposi's sarcoma (KS) in AIDS patients. One hundred and forty-four KS lesions in 50 HIV-positive homosexual males (mean CD4 count 64/mm3) were treated periodically with intralesional vinblastine injection (0.1 mg/cm2) until lesion resolution or no further reduction in lesional area. The most common lesion sites were: palate 56% (hard palate 42%, soft palate 14%); gingiva 22% (maxillary 15%, mandibular 7%); and maxillary tuberosity 6%. The mean lesion area was 4.6 cm2 (range = 0.1-35 cm2). Complete resolution occurred in 74%. The mean reduction in lesional area was 93% for all lesions. Lesions with only a partial response (26%) to vinblastine had a mean reduction in the lesional area of 69%. The mean number of treatments was 2.4 (range = 1-6). The recurrence rate was 26% with a mean disease-free period of 12.9 weeks. Recurrence rates were highest for nodular (40%) and purple macular lesions with focal nodularity (36%). The most frequent complications were transient pain (72%), superficial mucosal ulceration (22%) and transient paresthesia (12%). Intralesional vinblastine administration produced complete resolution in a substantial number of intraoral KS lesions and represents a well-tolerated treatment regimen for localised control of intraoral KS lesions. Owing to a 25% recurrence rate, re-evaluation is necessary for treatment of recurrent and new Kaposi's sarcoma lesions.

Intraoral presentation of anaplastic large-cell Ki-1 lymphoma in association with HIV infection.

Persons infected with human immunodeficiency virus have an increased risk for development of high-grade, non-Hodgkin's lymphomas. Anaplastic large-cell Ki-1 lymphoma is a recently described lymphoid neoplasm characterized by cellular pleomorphism, a sinusoidal growth pattern, and Ki-1 epitope reactivity. This type of lymphoma is often mistaken for metastatic carcinoma, melanoma, or malignant histiocytosis. Although persons with acquired immunodeficiency syndrome frequently have non-Hodgkin's lymphoma at extranodal sites, the oral cavity and mandible, in particular, are unusual locations. We report two cases of anaplastic large-cell Ki-1 lymphoma that occurred in persons with the human immunodeficiency virus and with initial presentation as soft tissue masses of the posterior mandible. Immunocytochemical studies were positive for Ki-1 (CD30) in both cases. In situ hybridization for Epstein-Barr virus-deoxyribonucleic acid was positive with tumor cells in both cases. Flow cytometry on paraffin, formalin-fixed tissue revealed tetraploidy and high proliferative fractions that are characteristic of high-grade lymphomas. Intraoral presentation of rapidly enlarging, soft tissue masses may represent a high-grade non-Hodgkin's lymphoma in persons with the human immunodeficiency virus. Although rare, anaplastic large-cell Ki-1 lymphoma should be considered and requires immunocytochemical study to eliminate the possibility of other malignant conditions associated with the acquired immunodeficiency syndrome.

The molecular epidemiology and evolution of Epstein-Barr virus: sequence variation and genetic recombination in the latent membrane protein-1 gene.

The phylogeny and evolution of Epstein-Barr virus (EBV) genetic variation are poorly understood. EBV latent membrane protein-1 (LMP-1) gene sequences are especially heterogeneous and may be useful as a tool for EBV genotype identification. Therefore, LMP-1 sequences obtained directly from EBV-infected human tissues were examined by PCR amplification and cloning. EBV genotypes were defined as "strains" from among 22 identified LMP-1 sequence patterns. Three molecular mechanisms were identified by which genetic diversity arises in the LMP-1 gene: point mutation, sequence deletion or duplication, and homologous recombination. The rate of LMP-1 gene evolution was found to be accelerated by coinfection with multiple EBV strains. The results of this study refine our understanding of LMP-1 sequence variation and enable accurate discrimination between independent EBV infection events and the consequence of intrahost EBV evolution. Thus, this LMP-1 sequence-based approach to EBV molecular epidemiology will facilitate the study of intrahost EBV infection, coinfection, and persistence.

Persistent productive Epstein-Barr virus replication in normal epithelial cells in vivo.

Productive Epstein-Barr virus (EBV) replication characterizes hairy leukoplakia, an oral epithelial lesion typically occurring in individuals infected with human immunodeficiency virus (HIV). Serial tongue biopsy specimens were obtained from HIV-infected subjects before, during, and after valacyclovir treatment. EBV replication was detected by Southern hybridization to linear terminal EBV genome fragments, reverse-transcriptase polymerase chain reaction amplification of EBV replicative gene transcripts, immunohistochemical detection of EBV replicative protein, and in situ hybridization to EBV DNA. EBV replication was detected in both hairy leukoplakia and normal tongue tissues. Valacyclovir treatment completely abrogated EBV replication in vivo, resulting in resolution of hairy leukoplakia when it was present. EBV replication returned in normal tongue epithelial cells after valacyclovir treatment. These data suggest that normal oral epithelium supports persistent EBV infection in individuals infected with HIV and that productive EBV replication is necessary but not sufficient for the pathogenesis of oral hairy leukoplakia.