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    Website of the HIV Special Interest Group

    -as part of the College of Occupational Therapists Specialist Section - HIV/AIDs, Oncology & Palliative Care

This information is summarised from a chapter on HIV related cancers, to be published in Occupational Therapy in Cancer and Palliative Care by Jill Cooper, in 2006.

1. Research

2. Non-Hodgkin’s Lymphoma (NHL)

3. Hodgkin’s Disease (HD)

4. Kaposi’s Sarcoma

5. Multi-centric Castleman’s Disease (MCD) and Castleman’s Syndrome

6. Other HIV-related cancers

References

1. Research

A number of cancers occur more frequently in a HIV+ population than in the general population, with 30-40% or all PLWHA experiencing some kind of a malignancy in their lifetime. For positive people, the likelihood that they will develop a cancer in comparison to a non-HIV infected individual varies between two- to three-fold for some cancers up to over one hundred times or more likely for others. (Newcombe-Fernandez, 2003) The exact relationship between HIV and neoplastic activity are not fully understood, although a range of other  viruses have been implicated in having some kind of causative or catalyst role. This is discussed in more detail later in this section.

Whilst low CD4 counts correlate with higher rates of malignancy, malignancies still occur in individuals with comparatively high CD4 counts, in contrast to other opportunistic infections which only occur when CD4 counts are low. Since the advent of HAART (highly active antiretroviral therapy) malignancies have risen from being the cause of death in 10 – 15 % of HIV+ individuals to over one quarter. (Bonnet, Lewden, May et al., 2004) It is not clear why this is so although it is postulated that there may be some relationship between long term HIV infection and the risk of abnormal cell behaviour that precipitates the development of some malignancies. (Killebrew and Shiramizu, 2004; Newcombe-Fernandez, 2003)

Some of the otherwise relatively harmless viruses that have been linked to cancers in HIV infected individuals include:

Adapted from Gadd (ed) 2005

Some of the more common cancers seen in HIV are Kaposi’s Sarcoma, Primary CNS lymphoma, Hodgkin’s lymphoma, anal cancer and Burkitt’s lymphoma. It is worth noting that some common epithelial cancers such breast, prostate and colon cancer do not occur more commonly in an HIV infected population. (Cheung, Pantanowitz and Dezube, 2005)

Outside of countries where advanced treatment is widely available, and in particular in sub-Saharan Africa where over half the world’s HIV+ population lives, malignancies commonly seen in resource-rich countries in HIV+ populations in the pre-HAART era, such as Kaposi’s Sarcoma and Non-Hodgkin’s Lymphoma, are still increasing in incidence. Hodgkin’s Disease however does not appear to have become more prevalent. (Orem, Otieno and Remick, 2004)

Treatments for cancers in PLWHA often are similar to those in a non-infected individual, although some modifications may need to be made dependent on the underlying state of HIV health and possible drug interactions. Improvements in HAART mean that survival duration statistics are approaching those seen in HIV negative individuals, although are not consistent across all cancers. (Thirwell, Sarker, Stebbing and Bower, 2003)

2. Non-Hodgkin’s Lymphoma (NHL)

This is one of the most long-associated malignancies with HIV, having first been described in 1982. Most NHLs are B-cell in origin, with most of these being either a diffuse large-cell B-cell lymphoma or a Burkitt lymphoma. A small number are primary effusion lymphomas (PELs). When the primary site of the NHL is in the CNS, it is known as a primary CNS lymphoma (PCNSL), otherwise it is generally classified as systemic NHL. (Hoffman and Kamps, 2003; Gadd (ed), 2005)

Systemic NHLs tend to present as lymph node enlargement, with often a systemic extranodal focus, in any body region. The disease is often aggressive and although treatment has improved in the era of HAART, average prognosis still remains at around two years. Secondary CNS involvement is common. As there are drug interactions between antiretroviral therapy and conventional NHL treatments, the treatment protocol for NHLs in PLWHA is still considered experimental. Some researchers and clinicians advocate an interruption to ARV treatment to maximise the response to chemotherapy, seeing the NHL treatment as the priority; others advocate no interruption to HIV treatment. (Aboulafia, Pantanowitz and Dezube, 2004; Gadd (ed), 2005)

2.1 Primary CNS Lymphoma (PCNSL)

PCNSL was previously a major cause of death in HIV infected individuals with a prevalence of up to 10% and poor average prognosis of only a few months from diagnosis. Since the advent of HAART the incidence has decreased considerably and mean survival time has increased to up to two years. (Hoffman and Kamps, 2003) PCNSL is almost always associated with the presence of Epstein-Barr Virus (EBV) in HIV infected individuals. Obtaining a differential diagnosis from other CNS pathology can be difficult; especially obtaining a differential diagnosis from the most common cerebral mass lesion, cerebral toxoplasmosis. (Newell et al., 2004) PCNSL is more likely to be a solitary mass than cerebral toxoplasmosis, although there may be two to four lesions. On CT scan lesions are usually enhancing with variable oedema. Frontal lobe lesions are most common, and lesions may cross the midline. Common presentations include confusion, personality changes, focal deficits, headaches and seizure activity. (Brew, 2001; Hoffman and Kamps, 2003; Newell et al., 2004) Treatment is not yet well defined and may include radiation, chemotherapy, HAART and treatment of the associated EBV. Current research results from multi-centre trials indicate that in future improved survival and long-term neurologic function in patients with PCNSL is likely. (Batara and Grossman, 2003) This may mean for therapists that these patients will be on the whole more appropriate for active rehabilitation rather than palliation as treatment options improve.

2.2 Burkitt Lymphoma

Unlike other common HIV related NHLs, the incidence of Burkitt Lymphoma has not decreased in the era of HAART. Burkitt lymphoma in HIV+ individuals may be the same as a classic Burkitt lymphoma or may have a plasmacytoid differentiation only seen in HIV. Peripheral blood and bone marrow are often involved. (Newcomb-Fernandez, 2003; Aboulafia, Pantanowitz and Dezube, 2004) The outcome is generally poor and poor outcome closely correlates with low CD4 counts. (Gadd (ed), 2005)

2.1 Primary Effusion Lymphoma (PEL)

This is a rare form of NHL also known as “body cavity based lymphoma”, and primarily seen in HIV populations. It is characterised by body cavity effusions in pleural and pericardial cavities, and ascites. PEL is aggressive, the outcome is generally poor and treatments experimental. (Noy, 2004; Newcomb-Fernandez, 2003; Aboulafia, Pantanowitz and Dezube, 2004; Gadd (ed) 2005)

3. Hodgkin’s Disease (HD)

Hodgkin’s Disease is a type of lymphoma found both in the general population and in HIV+ populations. Incidence is higher in HIV+ populations although not greatly so. In HIV negative populations HD tends to present earlier, is less aggressive and generally considered a treatable tumour. In contrast, HD in people with HIV is often aggressive, more likely to spread from the lymphatic system to other sites and mean prognosis is poor. HD is characterised by a Pel-Ebstein rising and falling fever, anaemia and weakness. Treatment in early stages is usually radiotherapy with chemotherapy being adopted in later stages. (Gadd (ed) 2005; Hoffman and Kamps, 2003; Lim and Levine, 2005)

4. Kaposi’s Sarcoma

Kaposi’s Sarcoma (KS) is a common malignancy in HIV+ populations and primarily presents as skin lesions although can also have visceral, oral, gastrointestinal (GI) or pulmonary manifestations. It was the emergence of KS amongst young gay men in San Fransisco and New York in 1981 that partially lead to the identification of HIV as a new disease. In early stages KS tends to present as purplish-black lesions that may appear anywhere on the body. Treatment in early stages is with HAART to address underlying immunosuppression; chemotherapy and local therapies may be indicated in more advanced disease. (Casper, 2004; Krown, 2003)

Mucous membrane and visceral complications may occur with skin lesions or independently. Mild cases of skin lesions that are neither painful or restrict function may not be treated and patients may be given just advice on camouflaging lesions until they resolve. As skin lesions may occur anywhere they can lead to functional problems, for example lesions on the foreskin or glans penis may cause difficulty managing urination. GI Kaposi’s Sarcoma is often asymptomatic but may lead to pain or bleeding. Oral lesions may cause difficulty with eating and speaking. Most serious is pulmonary KS and this can be fatal, particularly as it is more prevalent in patients with advanced HIV disease. (Krown, 2003; Gadd, 2005)

Until the advent of HIV, Kaposi’s Sarcoma was rare and occurred in various forms in older Mediterranean men, African children and people who had been treated with immunosuppressive drugs. Epidemic form of KS, which is the form associated with HIV, is thought to be linked to the HHV-8 virus, which is sexually transmitted. HIV-associated KS varies widely in extent and how aggressive the disease process is. Since the advent of HAART, Kaposi’s Sarcoma is far less prevalent in countries where antiretroviral medication is widely available. In the rest of the world, KS remains a significant problem. (Gadd, 2005; Orem, Otieno and Remick, 2004)

The role of the therapist with individuals with HIV-related KS depends on the extent of the disease and the nature of any functional or cosmetic impairment. For people with advanced disease a palliative approach may be appropriate; with recovering pulmonary disease a rehabilitative approach may be indicated; for skin lesions causing functional problems novel problem solving may be required.

5. Multi-centric Castleman’s Disease (MCD) and Castleman’s Syndrome

These relatively rare and poorly understood lymphoproliferative disorders are associated with the Human Herpes Virus (HHV-8) and Kaposi’s Sarcoma. Hepatomegaly, anaemia and respiratory symptoms are common and MCD appears to lead to NHLs in many instances, thus rendering the outcome of MCD often poor. Treatment may be chemotherapy and splenectomy in advanced disease. (Hoffman and Kamps, 2003; Gadd (ed) 2005)

6. Other HIV-related cancers

6.1 Lung cancer

Although there is some variation in the literature, in the UK the rate of lung cancer amongst HIV+ individuals is much higher than in the general population. Although there may be some links to non-HIV related well-proven risks (e.g. higher rates of smoking amongst young gay and bisexual men) there has also been observed differences in  the histological presentation, age at presentation and progression of the disease, and low CD4 count has also been linked with higher incidence of lung cancer. This would all suggest there is some link between lung cancer and HIV that is not yet fully understood. Given that lung cancer is one of the most prevalent serious illnesses in the UK this may have implications as people with HIV live longer secondary to HAART. (Northfelt, 2003; Gadd (ed) 2005; ; Lim and Levine, 2005)

6.2 Ano-rectal cancers

Studies demonstrate that people with HIV are between thirty and fifty times more likely to develop an anal carcinoma than HIV negative individuals. A link between these carcinomas and the Human Papillomavirus (HPV) has been established, although no correlation between levels of immunosupression and incidence of anal cancer has been shown. Outcomes are often poor in HIV infected individuals. Rates are higher amongst gay and bisexual men, however a history of anal sex is no longer implicated as being a predisposing factor in the presence of HPC or the development of a anal carcinoma. (Newcomb-Fernandez, 2003; Lim and Levine, 2005)

6.3 Cervical cancer

Although cervical cancer is listed on the CDC stages B and C as defining illnesses, the relationship between invasive cervical cancer (ICC) and HIV is somewhat inconsistent in the literature. As with anal carcinomas, there is a strong link between HPV and the development of ICC. (Newcomb-Fernandez, 2003)

6.4 Multiple myeloma

Evidence is emerging that plasma cell neoplasms are being reported with increasing incidence within HIV+ populations, and that multiple myelomas (MM) have features that differentiate it from MMs in non-HIV populations. At present treatment remains as for MM in non-HIV populations. (Cheung, Pantanowitz and Dezube, 2005)

6.5 Other cancers

Some other cancers do appear to have a slightly to moderately increased incidence within HIV populations although in some instances other factors such as smoking rates, gender and aging populations may have an impact. Cancers that have been described as having increased incidence within a positive population include leiomyosarcoma, germ cell malignancies, nonmelanoma skin cancers and a range of systemic cancers e.g. stomach, liver, kidney. More research is required with these conditions. (Newcomb-Fernandez, 2003; Northfelt, 2003)

Authors:       

Will Chegwidden, Senior Occupational Therapist, Royal London and St. Bartholomew’s Hospital NHS Trust, London

Camilla Hawkins, Senior Occupational Therapist, Mildmay Hospital, London

June 2006

References

Aboulafia, DM, Pantanowitz, L, and Sezube, BJ. (2004). AIDS-related Non-Hodgkin Lymphoma: still a problem in the era of HAART. AIDS Reader. 14(11):605-617.

Batara, JF, and Grossman, SA. (2003). Primary central nervous system lymphomas. Current Opinion in Neurology. 16:671-675.

Bonnet, F, Lewden, C, May, D, Heripret, L, Jougla, E, Costagliola, D, Salmon, D, Chêne, G, and Morlat, P. (2004). Malignancies-related causes of death of HIV-infected patients in the era of Highly Active Antiretroviral Therapy. Poster Presentation at 11^th Conference on Retroviruses and opportunistic Infections.

Brew, BJ. (2001). HIV Neurology. Sydney: Oxford University Press.

Casper, C. (2004). Human Herpesvirus-8, Kaposi Sarcoma and AIDS-associated neoplasms. HIV InSite Knowledge Base Chapter.  Accessed online 06.07.2005 at http://hivinsite.ucsf.edu  

Cheung, M.C. (2005) AIDS-related malignancies: emerging challenges in the era of Highly Active Antiretroviral Therapy. The Oncologist. 10(6):412-426.

Gadd, C. (ed) (2005) National AIDS Manual: HIV & AIDS Treatments Directory (24^th edition). London: National AIDS Manual.

Hoffman, C, and Kamps, BS. HIV Medicine 2003. Accessed online 06.07.2005 at http://www.hivmedicine.com/index.htm

Killebrew, D, and Shiramizu, B. (2004) Pathogenesis of HIV-associated non-Hodgkin lymphoma. Current HIV Research. 2(3):215-21.

Krown, SE. (2003). Clinical characteristics of Kaposi Sarcoma. HIV InSite Knowledge Base Chapter.  Accessed online 06.07.2005 at http://hivinsite.ucsf.edu

Lim, ST, and Levine, AM. (2005). Non-AIDS-defining cancers and HIV infection. Current Infectious Diseases Reports. 7:227-234.

Newell, ME, Hoy, JF, Cooper, SG, DeGraaff, B, Grulich, AE, Bryant, M, Millar, JL, Brew, BJ, Quinn, DI. (2004). Human Immunodeficiency Virus-related primary central nervous system lymphoma: factors influencing survival in 111 patients. Cancer. 100(12):2627-2636.

Newcomb-Fernandez, J. (2003) Data Review: Cancer in the HIV-infected population. Research Initiative Treatment Action. 9(1) Accessed online 06.07.2005 www.centerforaods.org/rita/0903/epi.htm

Northfelt, DW. (2003). Other malignancies associated with HIV. HIV InSite Knowledge Base Chapter.  Accessed online 06.07.2005 at http://hivinsite.ucsd.edu

Orem, J, Otieno, MW, and Remick, S. (2004) AIDS-associated cancer in developing nations. Current Opinion in Neuology. 16:468-476.

Thirwell, C, Sarker, S, Stebbing, J and Bower, M. (2003). Acquired Immunodefficiency Related Lymphoma in the Era of Highly Active Antiretroviral Therapy. Clinical Lymphoma. 4(2):86-92.

Send mail to will.chegwidden@bartsandthelondon.nhs.uk with questions or comments about this web site.                           
Last modified: 16 May 2007