Oral Kaposi's Sarcoma Research Articles

A case series of acquired immunodeficiency syndrome patients with initial neoplastic diagnoses of intraoral Kaposi's sarcoma.

Oral Kaposi's sarcoma (KS) may represent the initial clinical manifestation of immunosuppression in human immunodeficiency virus disease. This article reviews the treatment provided to these patients and the outcome of the disease and provides the opportunity to assess the impact of improvements in the medical therapy of acquired immunodeficiency syndrome on disease outcome. A tumor registry was examined to identify patients in whom oral KS was the first neoplastic diagnosis. Thirty-seven cases of oral KS representing 1.9% of all cases of KS were identified as the first malignant diagnosis in patients with acquired immunodeficiency syndrome. Patients with oral KS have limited survival; the cause of death is either infection or malignancy. In our study, the palate was the most common site of primary involvement in the oral cavity. Recently diagnosed patients remained alive longer than those diagnosed earlier, and the patients with the most recently diagnosed cases were alive at the completion of the study, suggesting that medical management of human immunodeficiency virus has improved with new therapies.

Clinical and biological characteristics of human immunodeficiency virus-infected and uninfected intravascular drug users in Ho Chi Minh City, Vietnam.

To define the medical characteristics of intravascular drug users in Ho Chi Minh City, Vietnam, we examined 280 men, of whom 235 were infected with human immunodeficiency virus (HIV), being treated in a rehabilitation center. The patients used mainly opium, often in shooting galleries (50%). The prevalence of oral candidiasis (58%) and zoster infection (20%) was high in HIV-seropositive patients, whereas oral hairy leukoplasia and Kaposi's sarcoma were absent. The prevalence of acquired immunodeficiency syndrome was 24%. More than 80% of the patients had infections with hepatitis C virus, hepatitis B virus, cytomegalovirus, or human T cell lymphotropic virus type-1. The CD4+ cell counts correlated well with viral load. Only HIV-1 subtype E was detected in the 30 patients tested. A cohort study of HIV-infected subjects in this population seems feasible, and would permit introduction of anti-retroviral therapy The large number of HIV-seronegative subjects sharing the same at-risk practices as the HIV-infected subjects raises the possibility of natural protection in this population.

The burden of mucocutaneous conditions and the association with HIV-1 infection in a rural community in Uganda.

To determine the prevalence of mucocutaneous conditions and their association with HIV-1 infection in a rural community in Uganda. In a prospective cohort study, participants were recruited from a large population study and invited to attend a clinic every 3 months for a detailed medical interview and a thorough physical examination. All findings including mucocutaneous findings were coded onto a standard questionnaire. By the end of 1996, 436 participants had provided 1450 person years of observation (pyo); 646 pyo in HIV-positives and 804 pyo in HIV-negatives. Overall, 70% of participants had a skin condition during follow-up, and although skin conditions were significantly more common in HIV-positive subjects, the background level in HIV-negative subjects was high (77.3% and 63.6%, respectively). Herpes zoster, thin/sparse hair, maculo-papular rash and prurigo were significantly more common in the HIV-positives. Kaposi sarcoma, palmar/plantar rash and herpes zoster had positive predictive values for HIV infection of over 80%. Oral conditions were found in over 40% of participants and were significantly more common in HIV-positive subjects. Oral candidiasis and Kaposi sarcoma were significantly more frequent among HIV-positives. HIV infection increases the already high burden of mucocutaneous diseases in this rural population. We identified some conditions that are more common in HIV and others that can be used as indicators of HIV infection.

Shedding of cytomegalovirus and herpesviruses 6, 7, and 8 in saliva of human immunodeficiency virus type 1-infected patients and healthy controls.

We used the polymerase chain reaction to study the presence of DNA from cytomegalovirus (CMV) and human herpesvirus (HHV)-6, HHV-7, and HHV-8 in saliva from 44 human immunodeficiency virus (HIV) type 1-infected patients at different stages of disease and in 15 healthy HIV-seronegative controls. CMV DNA, HHV-6 DNA, and HHV-7 DNA were found in all groups, but HHV-8 DNA was found only in symptomatic HIV-1-infected patients (5 [17%] of 29). One of the patients with HHV-8 DNA in saliva had oral Kaposi's sarcoma at the time of sampling, and another later developed the tumor. CMV DNA was found most often in the patients with AIDS. HHV-6 shedding tended to be less frequent among HIV-1-infected patients than among healthy controls. HHV-7 DNA was detected least frequently in the group of patients with AIDS. The presence of viral DNA was not correlated either with antiherpesvirus drug therapy or with oral symptoms, apart from Kaposi's sarcoma.

Frequent detection of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) DNA in saliva of human immunodeficiency virus-infected men: clinical and immunologic correlates.

The prevalence, quantity, temporal pattern, and clinical and immunologic correlates of shedding of Kaposi's sarcoma (KS)-associated herpesvirus (KSHV; or human herpesvirus [HHV]-8) DNA in saliva were studied. KSHV DNA was detected in saliva from 18 (75%) of 24 human immunodeficiency virus (HIV)-positive patients with KS and from 1 of 1 HIV-negative patient with KS, 3 (15%) of 20 HIV-positive patients without KS, and none of 24 controls. KSHV DNA levels ranged from 10(2.4) to 10(6) copies/mL and were lower than levels for Epstein-Barr virus but comparable to those for HHV-6. Detection of KSHV DNA in saliva was not associated with oral KS or decreased peripheral blood CD4 cell counts. KSHV DNA was not detected in semen. Resistance of KSHV DNA from saliva to DNase treatment was consistent with the presence of virions. These data suggest that KSHV can replicate in the oropharynx and that salivary contact could contribute to KSHV transmission.

Epstein-Barr virus and human herpesvirus 8 prevalence in human immunodeficiency virus-associated oral mucosal lesions.

The prevalence of Epstein-Barr virus (EBV) and the recently identified Kaposi's sarcoma (KS)-associated herpesvirus (also designated human herpesvirus 8 [HHV-8]) was determined in oral lesions and oral neoplasms common to persons with human immunodeficiency virus (HIV) infection. Oral lesions were examined by polymerase chain reaction (PCR) for EBV and HHV-8 DNA and by Southern blot analysis for EBV clonality. EBV was detected by Southern blot in hairy leukoplakia lesions, in a subset of AIDS-related lymphomas, and in saliva from HIV-positive persons but not in pseudohairy leukoplakia lesions, oral aphthous ulcers, or oral KS lesions. EBV was detected, however, by PCR in most of the lesions, while HHV-8 was detected only in oral KSs. The absence of HHV-8 DNA in both the EBV-associated hairy leukoplakia lesions and in the EBV-associated AIDS-related lymphomas strengthens the etiologic relationship of EBV to these pathologies and the etiologic role of HHV-8 in KS.

Management of oral Kaposi's sarcoma and a proposal for clinical staging.

Kaposi's sarcoma (KS) is the most common neoplastic disease in patients with disease due to human immunodeficiency virus (HIV), and oral KS (OKS) is the commonest oral neoplasia. OKS has been managed by local excision, intralesional chemotherapy regional radiotherapy, and systemic chemotherapy. Comparison between studies is difficult as the severity of oral involvement is not well defined in most studies. This paper reviews the approach to the management of OKS and also presents a proposal for the clinical staging of OKS. Clinical staging of OKS will facilitate comparisons of outcomes of treatment of OKS and improve our understanding of the natural history of the neoplasia, which has varied presentation and rates of progression.

Detection of human herpesvirus-8 DNA in oral ulcer tissues of HIV-infected individuals.

To determine the frequency of detection of human herpesvirus-8 (HHV-8) in HIV-related oral ulcers. Analysis of archived biopsy material. Nested polymerase chain reaction of DNA extracts. HHV-8 DNA was detected in six of 10 oral ulcers of HIV-positive patients without oral Kaposi's sarcoma (KS) lesions and five of 11 oral KS lesions. The positive non-KS samples were derived from various oral sites. In HIV-positive people, HHV-8 can infect oral tissues that are not affected by KS.

Presence of human herpesvirus 8 variants in the oral tissues of human immunodeficiency virus-infected persons.

A 210-bp DNA segment specific to the human herpesvirus 8 (HHV-8) genome was amplified by nested polymerase chain reaction from 10 of 14 archived oral biopsy samples of HIV-positive patients in London who had no evidence of oral Kaposi's sarcoma (KS). Various oral sites were represented. Oral tissues from 20 general dental patients not known to be HIV-infected were negative. When DNA sequences of these products were compared with sequences derived from 5 oral KS tissues of AIDS patients in London and 10 skin biopsies of Italian patients with Mediterranean KS (total number of positive tissues = 25), 11 were found to be unique. DNA and predicted peptide motifs of these sequences were also different from those in 28 of 36 HHV-8-positive lesions previously reported from American and African patients. HHV-8 is tropic for the oral mucosa of HIV-infected persons, and HHV-8 variants, though diverse, may be geographically restricted.

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.

Cytomegalovirus inclusions in HIV associated oral kaposi's sarcoma

Cytomegalovirus inclusions in HIV associated oral kaposi's sarcoma

Human herpesvirus-like sequence presence in oral kaposi's sarcoma: a preliminary PCR study

Human herpesvirus-like sequence presence in oral kaposi's sarcoma: a preliminary PCR study

Pathogenesis of oral Kaposi's Sarcoma in HIV-infection: relevance of endogenous glucocorticoid excess in blood and saliva.

Endogenous glucocorticoid excess with concomitant hypercortisolaemia and increased saliva levels of the free active hormone, is a common feature of HIV-infected/AIDS patients. Exposure of the oral tissues to virtually uninterrupted high burden of glucocorticoids through saliva may contribute to the high frequency of oral Kaposi's sarcoma (KS) in these patients. AIDS-KS cells contain unusually high levels of glucocorticoid receptor protein and recent studies indicate that growth of these cells in culture is significantly stimulated by glucocorticoids, particularly in the presence of growth factors, such as oncostatin-M. The suggestion that glucocorticoid excess may be important in the pathogenesis of KS in AIDS is not in conflict with the suspected aetiological role of newly reported KS-associated herpesviruses (KSHV), since steroid hormones may upregulate the expression of the viral gene. The latter is consistent with the observation that infection by specific oncogenic viruses does not necessarily result in cancers in the human, and does require the presence of other cellular factors or events.

Opportunistic oral infections in patients infected with HIV-1

Several organs are severely affected in human immunodeficiency virus type 1 (HIV-1) infection. One of these is the oral cavity, in which a variety of lesions of known and unknown causes are observed. The possible causes of some oral lesions and the presence of bacteria, virus and yeasts in saliva and gingival crevices have been investigated in patients infected with HIV-1. Common oral symptoms, which are strongly over-represented in adult patients infected with HIV-1, are Candida infection, necrotic periodontal disease, hairy leukoplakia, dry mouth problems, oral Kaposi's sarcoma and oral ulcers. These symptoms are seen mostly in immunocompromised HIV-1-infected patients with other HIV-1-related symptoms. Other less common oral lesions in adult patients infected with HIV-1 are infection with herpes simplex virus, varicella-zoster virus and papilloma virus, malignant lymphoma, salivary gland disease, drug-related ulcers or ulcers infected with microorganisms such as mycobacteria and cytomegalovirus. Changes in the bacterial flora and HIV-1 itself in the oral cavity do not explain the observed lesions. Fungal and viral infections are common in HIV-1-infected patients. Epstein-Barr virus is associated with oral hairy leukoplakia, and cytomegalovirus (CMV) may be correlated to some oral symptoms such as necrotizing gingivitis and dry mouth problems. The shedding of Epstein-Barr virus may indicate early deterioration of the cellular immune response, while CMV appears to be related to late HIV-1-induced symptoms.

Radiation treatment of oral epidemic Kaposi's sarcoma lesions: Potential adverse effects

Epidemic Kaposi's sarcoma, which has consistently been the most prevalent malignancy in people with HIV disease, frequently presents with lesions in the oral cavity. Guidelines for treating oropharyngeal lesions with radiotherapy are ubiquitous in the literature. Treatment indications include pain, dysphagia, and obstruction. Radiotherapy dosage and fractionation differ from that prescribed for non HIV-infected people. Current literature reveals better treatment outcomes for people infected with HIV if treatment is managed by practitioners experienced in HIV care. This article presents a review of the literature and a case study of a HIV-infected patient who experienced severe adverse effects of irradiation.

Intralesional vinblastine injections for the treatment of oral Kaposi's sarcoma: Report of 10 patients with 2-year follow-up

Purpose: This study evaluated the use of intralesional vinblastine injections for the treatment of the intraoral lesions of Kaposi's sarcoma. Patients and Methods: Eighteen patients were treated with up to three intralesional injections of 0.1 mg/cc vinblastine. Results: All lesions responded to the local injections; 40% required one injection; 31%, two injections; and 29%, three injections. Large, exophytic lesions usually required the multiple injections. No complications were encountered, and the patients tolerated the protocol well. Ten patients were followed for 24 months. Eight died of their general disease during this period. Four patients developed new intraoral lesions, which were treated with, and responded favorably to, the three-injection protocol. Conclusion: Intralesional vinblastine injections are an effective and useful treatment alternative for human immunodeficiency virus (HIV)-associated intraoral Kaposi's sarcoma.

Intralesional vinblastine injections for the treatment of oral Kaposi's sarcoma: Report of 10 patients with 2-year follow-up

Intralesional vinblastine injections for the treatment of oral Kaposi's sarcoma: Report of 10 patients with 2-year follow-up

Presence of human herpesvirus-like DNA sequence in oral Kaposi's sarcoma: A preliminary PCR study

DNA sequences closely related to herpesvirus-like sequences have been found in AIDS-associated Kaposi's sarcoma. Subsequent studies indicate that these DNA sequences may be consistently found in AIDS Kaposi's sarcoma and non-AIDS Kaposi's sarcoma from different geographic regions. Oral Kaposi's sarcoma is rare and the specificity of this viral DNA in oral Kaposi's sarcoma and in other oral neoplasms has not been examined. A total of 77 oral neoplasms, including 3 Kaposi's sarcoma specimens from 2 patients with AIDS, were analyzed by polymerase chain reaction for the presence of this herpesvirus-like DNA sequence with the 330-233 primers. All three specimens of oral AIDS-Kaposi's sarcoma from two patients were positive for this DNA sequence. All of the other intraoral lesions including hemangioma, pyogenic granuloma, and various types of epithelial neoplasms, however, had negative reactions. Our results further confirm that oral Kaposi's sarcoma appears to be associated with this herpesvirus-like DNA sequence.

HIV-ASSOCIATED LESIONS

Oral lesions are common in HIV infection and may be the first sign of AIDS. This article reviews the oral fungal and viral infections commonly detected in HIV-infected patients, particularly candidiasis, deep fungal infections, herpes simplex virus infections, cytomegalovirus infections, and oral hairy leukoplakia. The neoplasms associated with AIDS such as oral Kaposi's sarcoma and lymphoma are related periodontal diseases. Each disorder is discussed by clinical appearance, diagnosis, and management. Recent advances in therapy are stressed.

Urgency of Medical Care

<h3>Background:</h3> To assess the agreement between patients and physicians about the appropriate time to seek medical attention for symptom complexes commonly encountered in human immunodeficiency virus (HIV) disease, identifying potential suboptimal utilization of health care services. <h3>Methods:</h3> A questionnaire consisting of 25 clinical problems commonly encountered in the ambulatory care of patients with HIV infection was developed to survey opinions regarding the most appropriate time to seek medical attention. Participants included 70 anonymous HIV-positive patients attending a health department's early intervention clinic and 104 physicians recruited at academic conferences in 1992. <h3>Results:</h3> Clinically and statistically (<i>P</i>&lt;.05 after Bonferroni correction) significant disagreement between physicians and HIV-positive patients regarding perceived urgency to seek medical care was found in 22 of the 49 possible responses. In seven of these scenarios, patients perceived greater urgency to seek care than physicians, especially for relatively discrete complaints, such as oral lesions, lymphadenopathy, and Kaposi's sarcoma. Conversely, in 15 scenarios, physicians were more concerned than patients, especially for serious complaints, such as those associated with meningitis, retinitis, sinusitis, pneumonia, infectious diarrhea, and urinary tract infection. <h3>Conclusions:</h3> Substantial differences regarding the urgency to seek care exist between physicians and HIV-positive patients. Patients focused on the physical aspects of their disease and had difficulty appreciating important symptom complexes associated with serious but potentially reversible conditions. A need exists for health professionals to educate patients about the appropriate urgency to seek care for a number of common symptom complexes. (Arch Intern Med. 1994;154:1857-1862)