Human immunodeficiency virus (HIV) related malignancies

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20 Human immunodeficiency virus (HIV) related malignancies

Introduction

Malignancies have a significant impact on the morbidity and mortality of people with human immunodeficiency virus (HIV) infection. 30–40% of HIV-infected patients develop malignancies during the course of their illness. Some of the malignancies are AIDS-defining conditions whereas others appear to be more common in HIV patients (Box 20.1). Although AIDS-defining malignancies may be caused mainly by progressive immunosuppression, the exact relationship between immunosuppression and non-AIDS-defining malignancies is yet to be established. The most common cancers in the general population such as breast, prostate and colon do not appear to increase in HIV infection.

Introduction of highly active antiretroviral therapy (HAART) has brought significant changes to the natural history of HIV-infection. The incidence of Kaposi’s sarcoma and NHL has generally declined whilst the incidence of Hodgkin’s lymphoma and non-AIDS-defining cancers has not changed. With the introduction of antiretroviral therapy, 28% of deaths in HIV infection are due to cancer compared with 10% before HAART.

Pathogenesis

Development of cancers in HIV-infected individuals may be similar to that occurring in patients with immunosuppression and immune-deficiency disorders. The possible mechanisms for increased incidence of various malignancies in HIV-infected people include:

• Immunosuppression – organ transplant recipients have an almost 100-fold increased risk compared with the general population.

• Though HIV is not generally considered as oncogenic, a possible direct role has been suggested recently.

• Increased risk of other viral infections – such as Epstein–Barr virus (Hodgkin’s disease), human papilloma virus (cervical cancer, anal cancer), human herpes virus (Kaposi’s sarcoma) and hepatitis virus (hepatocellular carcinoma).

AIDS-defining malignancies

Kaposi’s sarcoma

KS is one of the most common neoplasms in HIV-infected patients, associated with human herpes virus-8 (HHV-8). With the introduction of highly active anti-retroviral therapy (HAART), the risk of both visceral and cutaneous KS has decreased dramatically.

The clinical manifestation of KS varies from a mild to a fulminant course. Skin lesions appear mainly on the lower extremities, face and genitalia. Skin lesions are typically multifocal and papular (Figure 20.1), but can appear plaque-like or as a fungating mass. Extracutaneous lesions appear in the oral cavity (most commonly palate followed by gingiva), larynx, gastrointestinal tract and lung. Gastrointestinal lesions can be asymptomatic or can cause weight loss, abdominal pain, nausea, vomiting and bleeding. Pulmonary KS may be symptomatic with cough, dyspnoea, haemoptysis etc. or present with asymptomatic radiological features of infiltrates, isolated nodules, pleural effusion and hilar or mediastinal lymphadenopathy.

Figure 20.1 Kaposi’s sarcoma.

From Clutterbuck: Specialist Training in Sexually Transmitted Infections and HIV, with permission.

In the post HAART era, tumour burden and systemic illness are useful to categorize patients into two prognostic groups (Box 20.2). Diagnosis of KS is confirmed by biopsy.

Box 20.2
Staging of Kaposi’s sarcoma

	Good risk (all of the following)	Poor risk (any of the following)
Tumour (T)	Confined to skin and/or lymph nodes and/or non-nodular disease in palate	• Associated oedema or ulceration • Oral disease other than non-nodular disease in palate • Gastrointestinal KS • Non-nodal visceral KS

Systemic illness

No history of opportunistic infection or thrush

No B symptoms *

History of opportunistic infection or thrush

B symptoms present

Other HIV-related illness

* B symptoms – unexplained fever, night sweats, >10% involuntary weight loss or diarrhoea persisting more than 2 weeks

Treatment is aimed at symptom relief, preventing progression, cosmetic improvement, relief of oedema and avoiding organ compromise. For patients with limited cutaneous lesions and HIV viraemia, effective combination HAART is the initial management. Local therapy is indicated for bulky lesions and for cosmetic reasons. Local treatment options include external beam radiotherapy, laser therapy, cryosurgery, photodynamic therapy and intralesional vinblastine.

Indications for systemic chemotherapy (Box 20.3) include:

• widespread skin involvement (>25 lesions)

• extensive oral KS

• symptomatic oedema

• rapid progression

• symptomatic visceral KS

Box 20.3
Systemic treatment in KS

• Liposomal doxorubicin 20 mg/m² three-weekly

• Liposomal daunorubicin 40 mg/m² two-weekly

• Paclitaxel 100 mg/m² two to three-weekly

• Others: vinorelbine, alpha-interferon, thalidomide and imatinib

Cervical cancer

Cervical cancer in HIV-infected women is associated with advanced disease at diagnosis, high recurrence rate and frequent cytotoxicity. Oncological management is similar to seronegative patients with cervical cancer; however special consideration should be given for interaction between cytotoxics and antiretroviral agents

Non-Hodgkin’s lymphoma

Almost all of the HIV associated lymphomas are diffuse B cell (immunoblastic) or Burkitt’s like. Approximately two-thirds of the patients present with extranodal disease and up to 20% will have meningeal disease, necessitating CSF examination in all.

Optimal treatment of HIV-related lymphoma is not known. Patients are generally treated similarly to those who are seronegative (p. 302). The overall prognosis is poor with a less than 1 year median survival.

Primary CNS lymphoma is 15 times more common than in the general population. The histology is large cell or immunoblastic type of B cell origin. Treatment involves radiotherapy combined with steroids, which extend the median survival from 2–3 months to 6–8 months (p. 306).

Non-AIDS-defining malignancies

These account for the increased mortality in the HAART era. HIV-infected people have an increased risk of these cancers (RR 1.9), and these tumours occur at a relatively younger age. Apart from duration of immunosuppression, other contributing risk factors include HAART interruption, smoking, sun exposure, oncogenic viruses and family history. The diagnosis needs to be confirmed by biopsy and staging will be affected by the presence of reactive lymphadenopathy as well as unrelated imaging abnormalities. Treatment is based on performance status, co-morbidity and potential for surgery. Non-medical management is also challenging due to chemotherapy-enhanced immunosuppression, added cytotoxicity, drug interaction with HAART and severe radiation reactions. Patients need regular monitoring of their CD4 count. Continuation of HAART, prophylaxis of opportunistic infections and supportive medications such as G-CSF are important.

Anal cancer

The high-risk group includes patients who practice receptive anal intercourse, men who have sex with men and anal co-infection with HPV or syphilis. The clinical presentation and treatment is similar to that of the seronegative population (p. 170). Patients with high-grade anal intra-epithelial neoplasia (AIN), invasive anal margin cancer and those with severe drug reactions require surgical management. Although the response to treatment is equivalent to seronegative patients with anal cancer, there is a high risk of severe radiation toxicity.

Liver cancer

Hepatocellular cancer is increased by 8-fold in the HIV population. Tumours tend to be more symptomatic, advanced at presentation and have an aggressive course. Resection or transplantation is an option for early stage whereas systemic chemotherapy is used in advanced cancer (p. 147). Survival is not influenced by CD4 count.

Hodgkin’s disease

Patients present early in HIV infection with unfavourable histologic subtypes (mixed cellularity, lymphocyte depleted). There is a 5–15 fold increase in risk with a high rate of EBV co-infection (75–100%). Clinical presentation with B symptoms and extranodal disease are common. They are treated as seronegative patients (p. 298) and the median survival is 12–18 months.

Other cancers

Other cancers are treated similarly to seronegative patients.

Interactions between chemotherapy and HAART

There are interactions between some cytotoxic agents and antivirals due to cytochrome p450 enzymes and p-glycoprotein. These interactions may account for the better response rate and higher rates of survival seen with combinations of cytotoxics and antivirals compared with cytotoxics alone in patients with HIV associated malignancies. These interactions can also result in higher toxicities with treatment.

Further reading

Spano JP, Costagliola D, Katlama C, et al. AIDS-related malignancies: state of the art and therapeutic challenges. J Clin Oncol. 2008;26:4834-4842.

Deeken JF, Pantanowitz L, Dezube BJ. Targeted therapies to treat non-AIDS-defining cancers in patients with HIV on HAART therapy: treatment considerations and research outlook. Curr Opin Oncol. 2009;21:445-454.

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