Kaposi sarcoma (KS) is a multicentric angioproliferative disorder of endothelial origin [
There are four clinicoepidemiological variants of KS: classic KS, endemic KS, iatrogenic KS, and HIV-associated KS (HIV-KS). These variants develop in distinct populations of subjects, and in all of them, the mouth may be affected. Human herpes virus 8 (HHV8) is a critical factor, although not on its own sufficient for the development of KS. Other cofactors including profound immune impairment, angiogenic mediators, or genetic predisposition appear to be necessary for the development of KS [
HIV-KS may develop at any stage of HIV infection including the stage of early HIV-seropositivity, but it is more prevalent at a lower CD4+ T-cell count [
It is estimated that in 22% of HIV-seropositive subjects with KS the initial presentation of HIV-KS is in the mouth, and that in up to 71% of subjects with HIV-KS, sooner or later the mouth will be affected [
HIV-KS is common in African countries where HHV8 infection is endemic, where HIV infection has reached epidemic proportions, and where antiretroviral medication is not always available [
Worldwide, HIV-KS affects males more commonly than females [
The aim of this retrospective study was to characterise the clinical features and course of oral HIV-KS in patients attending the oral medicine clinic at the School of Oral Health Sciences, University of Limpopo, Medunsa campus, South Africa, and to investigate differences between females and males with oral HIV-KS with regard to their CD4+ T-cell count, to the clinical presentation of oral HIV-KS and to survival rate.
Approval of the study was obtained from the Medical Research and Ethics Committee of the University of Limpopo, Medunsa campus, Pretoria, South Africa (MREC 0/212/2010 : PG). All the files of patients with histologically and clinically confirmed oral HIV-KS treated in the Department of Periodontology and Oral Medicine, School of Oral Health Sciences, University of Limpopo, Medunsa campus, from January 2004 until November 2010 were retrieved.
In this retrospective study, the diagnosis of KS was confirmed by microscopic examination of incisional biopsy specimens by an oral pathologist; the HIV-serostatus of the patients was determined by enzyme-linked immunosorbent assay (ELISA) and Western blot.
Data were recorded with regard to patient age, race, and gender; the oral site affected by HIV-KS; the clinical appearance of oral HIV-KS lesions; the period of HIV-seropositivity before a KS diagnosis was rendered; the CD4+ T-cell count at the time of HIV diagnosis and when HIV-KS was diagnosed; whether patients received highly active antiretroviral therapy (HAART) at the time of oral HIV-KS diagnosis, or thereafter; any KS involvement on the skin; the presence of facial lymphoedema; the presence of an immune reconstitution inflammatory syndrome (IRIS); the treatment modality used for oral HIV-KS; the course and response to treatment of oral HIV-KS disease; the survival period of patients from the time oral HIV-KS was diagnosed until the end of the observation period; for those who died during the observation period, the time that had elapsed from oral HIV-KS diagnosis to death.
IRIS-associated oral HIV-KS was diagnosed when there was worsening of pre-existing oral HIV-KS, or when there was development of new oral HIV-KS lesions, shortly after the introduction of HAART in parallel with an improvement in the immune status.
The presence of any pertinent medical information or HIV-associated oral diseases other than oral HIV-KS was also documented.
The clinical appearance of oral HIV-KS was categorised into macular, papular, nodular, and exophytic lesions. The lesions were classified into three size groups: smaller than 10 mm; between 10 mm and 50 mm and larger than 50 mm. The lesions of oral HIV-KS were categorised as solitary or multifocal. The oral site affected and the number of lesions per site was documented. Lesions affecting the upper and lower retromolar area and the soft palate were categorised as oropharyngeal lesions.
HAART comprised nevirapine, lamivudine, and stavudine. Local cytotoxic chemotherapy consisted of intralesional bleomycin. Systemic cytotoxic chemotherapy comprised combination of low-dose intravenous vincristine, bleomycin, and daunorubicin.
Differences between proportion were statistically tested using the Chi-squared test, two-sided
The study population comprised 37 patients diagnosed with oral HIV-KS, all of whom were black persons. The mean age at the time of oral HIV-KS diagnosis was 33.4 years (Table
Clinical and laboratory features of the patients at the time of oral HIV-KS diagnosis.
Males | Females | Total | |
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Number of patients (%) |
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Age (years) | |||
Mean |
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Tobacco usage (%) |
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Number of patients in whom the initial presentation of HIV-KS was in the mouth |
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Number of patients in whom the initial presentation of HIV-KS was concurrently in the mouth and skin |
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Number of patients who developed cutaneous HIV-KS before oral HIV-KS diagnosis |
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Other oral lesions present | |||
Pseudomembranous candidiasis |
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Hairy leukoplakia |
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Necrotizing gingivitis |
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Total number of patients |
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Average CD4+ T-cell count at KS diagnosis (data available for 33 patients) [cells/mm3] |
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Number of patients diagnosed with HIV infection and oral KS at the same time |
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Number of patients who were diagnosed with HIV infection before the diagnosis of oral KS |
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Number of patients with single oral HIV-KS lesions |
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Number of patients with multiple oral HIV-KS lesions |
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Lesion phenotype | |||
Number of macular lesions |
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Number of papular lesions |
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Number of nodular lesions |
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Number of exophytic lesions |
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Total number of lesions |
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Lesion size | |||
Number of lesions <10 mm |
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Number of lesions ≥10 mm ≤50 mm |
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Number of lesions >50 mm |
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Total number of lesions |
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In 21 patients (57%) the initial presentation of HIV-KS was in the mouth; in 6 patients the initial presentation of HIV-KS was concurrently in the mouth and on the skin; 10 patients (27%) developed cutaneous HIV-KS before the appearance of oral HIV-KS (Table
The CD4+ T-cell counts were obtained only for 33 patients, the mean CD4+ T-cell count being 107 cells/mm3 (Table
At the time of oral HIV-KS diagnosis, eight of the 37 patients had solitary oral lesions and 29 (78%) had multiple lesions affecting one or more oral sites (Table
Twenty-eight oral HIV-KS lesions (30%) affected the gingiva, 24 (26%) affected the hard palate, 22 (24%) affected the oropharynx (upper and lower retromolar areas, and the soft palate), 14 (15%) affected the alveolar mucosa, and five affected the dorsum of the tongue (Table
Oral sites affected by oral HIV-KS in relation to gender.
Males | Females | Total (%) | |
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Gingiva |
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Upper gingiva | 7 (16%) | 10 (21%) | 17 (18%) |
Lower gingiva | 6 (13%) | 5 (10%) | 11 (10.8%) |
Hard palate |
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Oropharynx |
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Alveolar mucosa |
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Upper alveolar mucosa | 4 (9%) | 3 (6%) | 7 (7.55%) |
Lower alveolar mucosa | 4 (9%) | 3 (6%) | 7 (7.55%) |
Dorsum of tongue |
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Total number of lesions |
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When the clinical features of oral HIV-KS and CD4+ T-cell counts of patients with HIV-KS at the time of oral HIV-KS diagnosis (Table
The CD4+ T-cell counts were available for only 33 of the 37 patients (Table
CD4+ T-cell counts (cells/mm3) of the participants.
CD4+ T-cell counts of the patients | Males | Females | Average |
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At the time of oral HIV-KS diagnosis (33 patients) |
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Who were simultaneously diagnosed with HIV and oral KS (14 patients) |
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Who were diagnosed with HIV infection before developing oral HIV-KS, at the time of HIV diagnosis (14 patients) |
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Who were diagnosed with HIV infection before developing oral HIV-KS, at the time of oral HIV-KS diagnosis (19 patients) |
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Receiving for some time HAART, at HIV-KS diagnosis (7 patients) |
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Who were HAART-naïve at oral HIV-KS diagnosis (26 patients) |
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Who had facial lymphoedema during their course of oral HIV-KS (8 patients) |
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Who did not have lymphoedema during the course of oral HIV-KS (25 patients) |
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Thirty patients (81%) were HAART-naïve, and seven patients had already been receiving HAART at the time of oral HIV-KS diagnosis. CD4+ T-cell counts were available for 26 of the 30 HAART-naïve patients at the time of oral HIV-KS diagnosis. Their average CD4+ T-cell count of 114 cells/mm3 was not statistically different (
Nine patients, five males, and four females had facial lymphoedema. Three patients presented with facial lymphoedema at the time their oral HIV-KS were diagnosed, and six patients subsequently developed facial lymphoedema on average 2.3 weeks after the diagnosis of oral HIV-KS. All patients with facial lymphoedema had multifocal exophytic oral HIV-KS lesions and their average CD4+ T-cell count at the time of oral HIV-KS diagnosis was 28 cells/mm3 (CD4+ T-cell counts were available for eight of the nine patients) compared to 133 cells/mm3 for those patients without such facial lymphoedema (Table
One patient had IRIS-associated HIV-KS. The CD4+ T-cell count of this female patient at the time of her HIV diagnosis was 9 cells/mm3, and she developed IRIS-associated HIV-KS, four weeks after she started HAART.
Nine patients were lost to follow-up. Of the remaining 28 patients, oral HIV-KS lesions increased in number and/or in size in 21 patients (75%), remained stable or shrunk in four patients, and resolved in three patients.
Twenty-one patients died during the observation period, on average 13.6 weeks from the time of oral HIV-KS diagnosis (Table
Mortality and survival in relation to oral HIV-KS.
Males | Females | Total | |
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Mortality | |||
Number of patients who died | 11 (85%) | 10 (66%) | 21 (75%) |
Average time of death from oral HIV-KS diagnosis | 15 weeks | 12.1 weeks | 13.6 weeks |
Average CD4+ T cell count (cells/mm3) at oral HIV-KS diagnosis | 75 | 54 | 64 |
Survival | |||
Number of patients who survived | 2 (15%) | 5 (33%) | 7 (25%) |
Average follow-up time | 76 weeks | 106 weeks | 91 weeks |
Average CD4+ T cell count (cells/mm3) at oral HIV-KS diagnosis | 258 | 129 | 166 |
Of those seven patients who survived, in three there was resolution of the oral HIV-KS (one had IRIS-associated HIV-KS and was treated with HAART in combination with systemic cytotoxic chemotherapy and surgery; one was treated with HAART and systemic cytotoxic chemotherapy; one with HAART and surgery). In the remaining four patients, the oral HIV-KS lesions remained unchanged or shrunk. These patients were treated with HAART or with HAART in combination with local cytotoxic chemotherapy.
The average CD4+ T-cell count of the patients who were alive at the end of the study observation period was 166 cells/mm3 at oral HIV-KS diagnosis (Table
There was a significantly higher number of patients with multiple oral lesions at the time of oral HIV-KS diagnosis than patients who had single lesions (Table
Exophytic oral HIV-KS lesions on the anterior maxillary and mandibular buccal gingiva of a 31-year-old male with a CD4+ T-cell count of 5 cells/mm3.
Exophytic confluent oral HIV-KS lesion on the hard palate in a 31-year-old male patient with a CD4+ T-cell count of 5 cells/mm3.
Exophytic oral HIV-KS lesion on the lower right retromolar area extending into the oropharynx in a 29-year-old female patient with a CD4+ T-cell count of 49 cells/mm3. The patient died six weeks after her oral HIV-KS diagnosis.
Exophytic oral HIV-KS lesions on the alveolar and labial mucosa in a 54-year-old male with a CD4+ T cell count of 258 cells/mm3. The patient died 15 weeks after his oral HIV-KS diagnosis.
Macular/nodular lesion on the dorsum of the tongue in a 44-year-old female patient with a CD4+ T-cell count of 13 cells/mm3. The patient died five weeks after the diagnosis of her oral HIV-KS.
Forty six percent (46%) of the patients with oral HIV-KS in this study cohort did not know their HIV-serostatus at the time of oral HIV-KS diagnosis, implying that oral KS in the Ga-Rankuwa area in South Africa may serve as an indicator of HIV infection. Although the prevalence of HHV8 infection in South Africa is relatively high [
Seven patients were on HAART at the time of oral HIV-KS diagnosis and although at this time their average CD4+ T-cell count (90 cells/mm3) was lower than the average CD4+ T-cell count of the HAART-naïve patients (114 cells/mm3) (Table
As a consequence of HAART being introduced only when the CD4+ T-cell count is already very low, there will be a lower level of reconstitution of the CD4+ T-cell number compared to the level of reconstitution when HAART is started at a higher CD4+ T-cell count [
It has been reported that in 22% of HIV-seropositive subjects with KS, the initial presentation of HIV-KS is in the mouth, and that in up to 70% of subjects with HIV-KS, the mouth will sooner or later be affected [
Facial lymphoedema may occur before, at the time of, or after oral HIV-KS is diagnosed. Facial lymphoedema which develops in parallel with the progression of oral HIV-KS disease is an indicator of poor prognosis [
The pathogenic mechanisms that cause facial lymphoedema in association with oral HIV-KS are obscure. However, as oral KS lesions and oral fluids of HIV-seropositive subjects carry a high HHV8 load, and as advanced exophytic oral HIV-KS lesions have a higher HHV8 load than initial maculopapular lesions [
To the best of our knowledge, this is the first report in the literature documenting the prevalence of IRIS-associated oral HIV-KS in a population of patients with oral HIV-KS regardless of whether they had extraoral KS. One patient in this case series had IRIS-associated HIV-KS. This patient was successfully treated with systemic cytotoxic chemotherapy and surgical excision. A comprehensive description of the case report of this patient has been published previously [
During the study observation period, 21 of the 37 patients (57%) died, on average within 13.6 weeks from the time of oral HIV-KS diagnosis; nine were lost to follow-up; 7 patients survived (average period of follow-up of 91 weeks). The average CD4+ T-cell counts of the patients who were alive at the end of the study observation period was 166 cells/mm3 at oral HIV-KS diagnosis and the CD4+ T-cell counts of the patient who died was 64 cells/mm3, at oral HIV-KS diagnosis. The difference in these CD4+ T-cell counts was statistically significant (
Of those who survived, in three patients oral HIV-KS completely resolved following various treatment modalities. One of these patients was treated with HAART in combination with systemic cytotoxic chemotherapy and surgery, one with HAART in combination with cytotoxic chemotherapy, and one patient with HAART and surgery. In four patients, the oral HIV-KS remained unchanged or shrunk. These patients were treated with HAART or with HAART in combination with local cytotoxic chemotherapy.
HAART is used to treat HIV infection. Even though effective HAART does not directly influence HHV8 replication, by reducing HIV load with subsequent improvement in the host-immune status, it indirectly brings about a decrease in the incidence and prevalence of HIV-KS and an improvement in the clinical manifestation of pre-existing HIV-KS disease [
In this study, seven patients have been on HAART at least four weeks before their oral HIV-KS diagnosis, confirming that HIV-seropositive subjects on HAART may develop KS. Eight of the 21 patients who died during the observation period were on HAART as a sole modality of treatment. These patients died on average 4.4 weeks after their oral HIV-KS diagnosis. During this period, they experienced worsening of their oral HIV-KS disease. This suggests that although introduction of HAART should be the first line of therapy for HAART-naïve HIV-seropositive subjects with oral KS, HAART by itself may not be effective in controlling oral HIV-KS disease. Two of the 21 patients who died were concurrently treated with HAART and with local cytotoxic chemotherapy.
Eleven of the 21 patients (52%) who died during the observation period received neither HAART nor any other treatment for their oral HIV-KS. The average time from oral HIV-KS diagnosis to their death was 20 weeks. The paradoxical finding that in this study HAART-naïve patients lived longer than patients on HAART might be attributed to skewed statistics associated with the small number of patients, or to ineffective HAART that was started late in the course of oral HIV-KS disease when the CD4+ T-cell count had already fallen very low.
The small number of patients who received treatment for HIV-KS in this study prevents drawing conclusions regarding what is the best treatment approach to control the progression of oral HIV-KS and to improve the prognosis of the patients. However, as reported elsewhere [
In developed countries, HIV-KS predominantly affects males. However, in many resource poor countries in sub-Saharan Africa where HIV infection is endemic and young females aged 15–24 years are more frequently infected with HIV than males, there is almost an identical incidence of HIV-KS in males and females [
In spite the fact that the CD4+ T-cell counts of females were lower than males at oral HIV-KS diagnosis, the differences between the percentage of males and females who survived or died were not statistically significant. Other reports in the literature also note that gender differences do not influence survival of patients with HIV-KS [
Two patients were children. Both were boys, aged 10 and 11 years. This supports data reported from other areas of sub-Saharan Africa, that children are not uncommonly affected by HIV-KS. In fact, in Zimbabwe, the most frequent malignancy in children between 1 and 14 years of age is HIV-KS [
Thirty-eight percent (38%) of the patients in this study had common HIV-associated oral diseases which presented concurrently with oral HIV-KS (Table
In the Ga-Rankuwa area of South Africa where HIV-KS is prevalent, oral KS affects similarly males and females. In this population, a low CD4+ T-cell count at the time of oral HIV-KS diagnosis is associated with a poor prognosis. The development of facial lymphoedema during the course of HIV-KS disease portends a very poor prognosis. Owing to the small number of patients who received treatment, it was not possible to determine what the best treatment modality was for oral HIV-KS.