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HIV and Cancer

HIV and Cancer. Sarah Wilcox Jan 2006. Case Report. 36 yr old lady HIV +ve for 3 years (husband diagnosed at the same time) Not on treatment as CD4 count in normal range and low viral load 18 month history of metastatic adenocarcinoma ? Primary

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HIV and Cancer

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  1. HIV and Cancer Sarah Wilcox Jan 2006

  2. Case Report • 36 yr old lady • HIV +ve for 3 years (husband diagnosed at the same time) • Not on treatment as CD4 count in normal range and low viral load • 18 month history of metastatic adenocarcinoma ? Primary • Referred to palliative care clinic for symptom control

  3. Complex cancer diagnostic path • Presented with 9/12 of low back pain and suprapubic mass on USS • MRI: bilateral complex multilocular cysts in the pelvis (?ovarian origin and benign) and r hydronephrosis • Raised CA 125 and CA 19.9 • Upper GI investigations arranged

  4. Progress • admitted acutely with perforated DU • CT abdomen: soft tissue mass around the gastric pylorus, omental deposits, low volume ascites and hypodense region in neck of pancreas • Bx of omental mass: metastatic adenocarcinoma strongly +ve for CA 125

  5. Oncology Input • Differential diagnosis: • Pancreatic carcinoma • Gastric carcinoma • Gynaecological carcinoma • Had 6 cycles of ECCAP with PR (25% dose reduced). • Further 2 cycles then DP in pancreas • 20 Gy in 5# to pancreas

  6. Symptoms • Back pain • Low mood/anxiety • Questions around diagnosis and uncertainty of prognosis • Issues around HIV: son not aware of diagnosis “have I got cancer because of my HIV?”

  7. Unanswered Questions • Does HIV +ve status increase risk of developing a solid tumour? • Does treatment for cancer need to be modified by co-existent HIV? • Any guidelines for modifying treatments in HIV +ve patients?

  8. Overview of HIV and Cancer risk • Several studies have addressed the possible relationship between HIV infection, the resulting immune depression and incidence of non-AIDS defining tumours • Most are retrospective analyses which cross-link cancer registry databases with AIDS databases and look for patterns of cancer incidence in a period of time prior to AIDS diagnosis to a period of time afterwards • Most common malignant disorders have not been shown to have increased incidence in patients with HIV • Breast cancer is actually associated with a reduced incidence in HIV positive women

  9. AIDS-defining malignancies • caused by the severe immunodeficiency associated with advanced HIV infection (by definition) 1. Kaposi’s sarcoma 2. Non Hodgkin’s lymphoma (NHL) 3. Cervical cancer • Risk of NHL parallels degree of immunodeficiency and is associated with EBV infection

  10. Other malignancies associated with HIV infection • Hodgkin’s disease (HD) • Anogenital cancers • SCC of conjunctiva/skin • Increased rates of the above malignancies are also seen in transplant patients on immunosuppressants • increased incidence of leukaemia in HIV patients could be explained by leukaemoid transformation of AIDS-related NHL

  11. Non-Aids Defining Cancers(NADC) in HIV • RR of developing a non-AIDS defining cancer (NADC) in AIDS patients is quoted between 1.5 and 3.0 (cf 178 for KS and 73 for NHL in one study) • Estimates of RR for individual cancer types in HIV +ve patients are generally small and vary between papers • Other cancers which may have increased RR include primary brain tumours and soft tissue sarcomas but these may represent misclassified AIDS-related cancers [Relative risks (RR) is defined as the ratio of observed to expected cancers derived from population-based incidence]

  12. Confounding factors • Increased medical surveillance may be a bias in these estimates • sexual and other lifestyle variables e.g. smoking and lung cancer • ? Human herpes virus 8 infection linked to Kaposi’s and other cutaneous cancers including malignant melanoma • Anal and cervical cancers linked to HPV 16 and 18 infection and cigarette smoking

  13. HAART • Highly active anti-retroviral therapy (HAART) has dramatically decreased mortality rates for HIV-infected patients since 1996 • Cohort studies have shown a concomitant shift in causes of death in this population with an increase in malignant disease due to modification of competitive risks • NADCs accounted for <1% of all causes of death prior to HAART. The current figure is >10%

  14. Consequences of HAART • Improved survival of HIV infected patients • Reduced incidence of KS and NHL • Reduced rates of opportunistic infection • The fact that HAART has not reduced the overall incidence of NADCs suggests that they are not triggered by immune suppression alone • Difficult to study NADC due to small nos involved

  15. Possible Mechanisms • Chronicity of HIV infection / immunodeficiency • Ageing of the HIV-infected population • Higher level of exposure to risk factors eg tobacco use, alcohol use, viral co-infection, inadequate nutrition • Possible oncogenic role of Hep B,C and HIV virus

  16. Oncogenic Role of HIV? • HIV infection results in chronic B cell stimulation due to HIV replication • This effect is magnified by co-infection with oncogenic viruses e.g. EBV, HPV • HIV interacts with cell cycling and growth mechanisms • HIV tat gene may modify the expression of certain proto-oncogenes in malignant cells • HIV may alter the expression of cytokines involved in promoting tumour growth

  17. Survey in CANCER Bonnet et al 2004 • Investigated all causes of death among HIV-infected patients in France in 2000 • Used ICD-10 to classify cause of death • Patients who died of solid, non-AIDS defining tumours were compared with those who died of non-malignancy related causes to identify comorbidities associated with fatal malignancies

  18. Results • 964 deaths were reported in 64,000 HIV-infected patients • Malignant disease accounted for 28% of deaths • 120 (12%) deaths were classified as NADC • Patients who died of solid tumours were more likely to be male, to smoke, to be older, to have longer duration of HIV infection and to have a higher CD4 count compared to patients dying of non-malignancy related causes

  19. HIV and lung cancer (LC) • An increased risk of LC in HIV patients cf general population was identified in the early 1990s • Adenocarcinoma is the most frequent histological type • Patients tend to be male, younger than the general population, have advanced stage at diagnosis (III or IV) and a poor prognosis (10% 1 yr survival cf 40%) • CD4 count/viral load do not appear to affect prognosis • LC is now the leading fatal NADC in the HIV-infected population

  20. HAART era • HAART has further increased the proportion of deaths due to LC in AIDS patients, although the degree of immunosuppression in these patients has actually decreased • One study of 8640 HIV +ve patients reported an incidence of lung cancer of 0.8% per 10,000 patient years in the pre-HAART era, similar to that in the general population. In the post-HAART era this figure rose to 6.7%, significantly above that for the general population. This equates to a RR of 9.

  21. Possible Explanations • Increase in life-expectancy conferred by HAART • Decline in deaths from AIDS may permit the expression of competing risks e.g. smoking • Smoking is a big confounding factor, but even when this is taken into account by assuming that all HIV patients smoke, the risk of LC compared to that in the general population was still 2.5 times higher • Increased susceptibility to carcinogens in cigarette smoke in the immunosuppressed has also been hypothesised but not proven

  22. Modification of treatment regimes in HIV patients • There are no published trials assessing efficacy and toxicity of chemoradiotherapy regimes in cancer patients with HIV • In general, HIV patients should be assessed and treated in the same way as the general population • Immunosuppression by HIV does not appear to influence surgical outcome or increase post-op complications • Chemotherapy is used less frequently in HIV-infected patients but this probably reflects their poorer performance status at presentation • CD4 count should be monitored monthly and 1 month after completion of chemo

  23. Chemotherapy in HIV +ve patients • Drug interactions and additive toxicity of cytotoxic and anti-retroviral drugs may explain poorer results in HIV positive patients. • Nadir neutrophil counts are often significantly lower and hence neutropenic sepsis more common • Therapeutic combinations carrying a high risk of toxicity and interactions should be avoided • Bone marrow toxicity and peripheral neuropathy can also be additive • No specific recommendations have been made on primary prophylaxis for opportunistic infections in HIV-infected patients receiving chemo

  24. Conclusions • Solid tumours are likely to become a major cause of morbidity and mortality among HIV-infected individuals in the coming years. • Progression of HIV infection may have a synergistic or additive effect with cancer in producing an increased mortality rate. • Solid tumours can affect patients with controlled HIV infection • Shorter survival in HIV-infected patients with cancer is influenced by the fact that such patients are often not clinically fit to undergo surgical resection, adjuvant chemo and/or DXT

  25. Prevention is better than cure • Controlling exposure to risk factors, particularly tobacco and alcohol use is a key factor in preventing HIV-infected patients from developing solid malignancies • Annual X ray screening for lung cancer and cytological screening for cervical and rectal malignancies has been advocated

  26. References • Risk of cancer in people with AIDS. Grulich et al 1999. AIDS 13: 839-43. • Spectrum of AIDS-associated malignant disorders. Goedert et al 1998. Lancet 351: 1833-9. • Malignancy-related causes of death in HIV infected patients in the era of HAART. Bonnet et al, Cancer 2004 101: 317-24. • Association of cancer with AIDS-related immunosuppression in adults. JAMA 2001 285 (13): 1737-45. • Incidence of Non-AIDS defining cancers before and during the HAART era in a cohort of HIV-infected patients. Herida et al 2003. Journal of Clinical Oncology 21(18): 3447-53. • Lung cancer, a new challenge in the HIV-infected population. Lavole et al 2006 Lung Cancer 51: 1-11. • HIV-related lung cancer in the era of highly active anti-retroviral therapy. Bower et al AIDS 2003 17: 371-5

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