Aetiology of cancer

Are HIV infected patients more likely to develop Non-Hodgkin lymphoma than those without
it?

Non-Hodgkin lymphoma (NHL) is a form of cancer that originates in the lymphocytes. The
three main categories of HIV-associated NHL are; Burkitt’s lymphoma, Primary effusion
lymphoma and Plasmablastic lymphoma (Little, et al, 2001). Cancer research UK states it is
most common in males aged 70-74, with 1217 new patients contracting the cancer every year.
This age range in females also shows the greatest number of new cases per year with 972.
The highest incidence rate for females is in the age range of 80-84 with a rate of 85, this
differs from males, as the age group for largest incidence rate is 85-89 with a rate of 129.
Most patients when diagnosed with NHL are usually found to be in the later stages of the
disease, as 64% of patients diagnosed in 2014 were found to be at an advanced stage (stage
III or IV) compared to 36% that were found to be at an early stage (stage I or II). NHL is said
to be around 11 times higher in patients with HIV, but less and 1% of the total NHL cases are
caused by HIV. The survival rates for NHL are higher in women than in men, and the highest
five year net survival age range for both is 15-39 years old. Like most cancers the survival
rate decreases with age, the five year net survival rate for 80-99 year olds is significantly
lower. In men the rate decreases from 84% to 43%, and in women the rate decreases from
86% to 42% in the same age groups. 3% of all NHL cases in the UK are preventable. (Cancer
Research UK, 2017)

AIDs defining cancers can develop in the advanced HIV stages, this is because the immune
system is weakened and is vulnerable to infection. HIV targets CD4 cells and uses them to
make copies of itself. After this the cell swells and bursts and the new copies of the virus then
go on to find new CD4 cells and start the process over again. In response to this, the immune
system then makes new CD4 cells, but cannot make them fast enough so the CD4 count
drops. When the CD4 count is below 200, the disease has then progressed to AIDs. HIV is
diagnosable in three stages, acute HIV, chronic HIV and AIDs. Immediately after the patient
has contracted the disease, they are said to have acute HIV. This may appear in flu like
symptoms because of the increase in copies of HIV and infection around the body. The CD4
count in the body falls, then as a response the immune system makes more cells, increasing
the level again. There is the largest chance of transmission during this stage. The next stage is
chronic HIV. This is the latent stage where patients are asymptomatic and HIV numbers do
not increase as quickly as the acute phase. The final stage is AIDs, a patient has to have a
CD4 cell count of 200 or below. They can also be diagnosed if they’ve had an opportunistic
infection or a different AIDs defining condition. Patients at this stage can contract certain
cancers more easily, these include, lymphoma and cervical cancer. (Healthline 2018)

One form of lymphoma that is very common in HIV patients is Burkitt’s lymphoma, it is a B-
cell Hodgkin lymphoma which is very aggressive. The tumor itself is one of the fastest
growing in the body and was one of the first tumours to show ‘chromosomal translocation
that activates an oncogene’ (Molyneux, et al, 2012). Burkitt lymphoma can be divided into
three subgroups, Sporadic Burkitt lymphoma, immunodeficiency-associated Burkitt
lymphoma and Endemic Burkitt lymphoma. Each subgroup affects different types of patients.
Sporadic Burkitt lymphoma is sometimes found in patients who are also infected with
Epstein-Barr virus, and is the most common type of Burkitt lymphoma. Immunodeficiency-
associated Burkitt lymphoma is seen in HIV patients because their immune system has been
compromised. Finally, Endemic Burkitt lymphoma is found in patients where malaria is very
common. Patients infected with malaria and Epstein-Barr virus are the main suffers of this
disease. (Lymphoma Action, 2020)
Aetiology of cancer

Primary effusion lymphoma is another HIV-associated NHL. It is very unlikely that this type
of lymphoma is found in patients who are not HIV-positive. (Grogg, Miller, and Dogan,
2007) It is rare and mostly affects people with an immunodeficiency such as HIV. The tumor
is usually found in a body cavity such as the pericardial or peritoneal. Like Burkitt
lymphoma, primary effusion lymphoma is also found in patients who are coinfected with
Epstein-Barr virus. The cancer is also always associated with HHV-8, the human herpesvirus-
8. (Guillet, et al, 2015)

The third HIV-associated NHL is plasmablastic lymphoma (PBL). This is an unusual type of
NHL and normally is found in the oral cavity of HIV positive patients. Like both Burkitt
lymphoma and primary effusion lymphoma it is normally associated with the Epstein-Barr
virus. Tumours may be found as masses on the gingiva, palate or on the floor of the mouth.
PBL is also an AIDs-defining malignancy and as many as 80% patients who suffer from the
oral tumours are found to be HIV positive. (Orphanet, 2012)

A survey conducted in India found that there were around 2.5 million people living in the
country with HIV/AIDs. After the AIDs epidemic there was an increase in NHL cases and the
two are thought to be linked. NHL was the second most common cancer amongst HIV
positive women, and the most common amongst men. 76% of patients were diagnosed with
HIV/AIDs at the same time as being diagnosed with NHL. Epstein-Barr virus was also found
to be involved in the HIV associated lymphomas. Each subtype was found to have a different
association to the virus; Hodgkin’s disease had 100% association, Burkitt’s lymphoma had
66.66% association and finally immunoblastic lymphoma was found to have 30%
association. Most patients are normally diagnosed when in an advanced stage, and diffuse
large B-cell lymphoma was found to be the most common. Treatment was given to over 50%
of the patients with NHL. They received chemotherapy and HAART, but some did not
receive treatment because of lack of funding. Non-AIDs defining cancers were also found
amongst the HIV-associated cancers, these include, anal cancer, head and neck cancer, and
Hodgkin’s disease. Some of these cancers have high risk factors from other causes like
tobacco or HPV. In India there is a lot of stigma around HIV, where most patients with HIV
and cancer belong to a lower socioeconomic class and treatment is expensive. There is only a
small number of patients who have access to clinical investigative tests such as the CD4 cell
count or viral load estimations. (Rangel, et al, 2015)

In conclusion, there is shown to be an association between HIV and NHL as HIV affects the
CD4 cells in the body, damaging the immune system. (Healthline, 2018) A patient is more
likely to develop an AIDs defining cancer when they are in the final stage of an HIV
infection. The main AIDs defining conditions have been reviewed and it is shown that the
immunodeficiency related lymphomas have the highest correlation with HIV-positive
patients. (Dhir, Sawant, 2008) The survey conducted in India found that a large number of the
population are living with AIDs, where NHL was the most common cancer in HIV-positive
males, and the second most common in HIV-positive females. HIV-positive patients in India
were also found to be in the later stages NHL when diagnosed, similarly to Cancer Research
UK who found that patients with NHL in England were more likely to be stage III or stage IV
when diagnosed. There were also other non-AIDs defining cancers found in HIV-positive
patients in India such as anal cancer and or Hodgkin’s disease. This is due to other risk
factors such as smoking tobacco or HPV. (Rangel, et al, 2015) When the AIDs epidemic was
at its peak there was a large increase in NHL, specifically central nervous system lymphoma,
another AIDs defining disease. Highly active antiretroviral therapy increases the CD4 cell
Aetiology of cancer

count in AIDs sufferers and with an increase in patients being treated for the disease, the risk
of lymphoma is reduced. Research into HIV has shown that infection is a random process and
is not thought to be itself oncogenic, however the compromise of the immune system is
thought to contribute to the development of lymphomas. Hodgkin’s lymphoma is not thought
to be as common in HIV-positive patients as the disease specific Reed-Sternberg cells have a
lack of interaction with the immune system. (Dhir, Sawant, 2008) Overall there is a
correlation between NHL and HIV, and further investigation should be carried out to see how
specifically the HIV infection leads to NHL.
Aetiology of cancer

Bibliography

Little, R.F., Gutierrez, M., Jaffe, E.S., Pau, A., Horne, M. and Wilson, W. (2001) HIV-
associated Non-Hodgkin Lymphoma Incidence, Presentation, and Prognosis. [online].

Cancer Research UK. (2017) Non-Hodgkin lymphoma statistics. Available from:

https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-
type/non-hodgkin-lymphoma#heading-Two, Accessed [December 2020].

Healthline. (2018) How does HIV affect the body? Available from:
https://www.healthline.com/health/hiv-aids/how-hiv-affects-the-body, Accessed [December
2020]

Molyneux, E., Rochford, R., Griffin, B., Newton, R., Jackson, G., Menon, G., Harrison, C.J.,
Israels, T. and Bailey, S. (2012) Burkitt's Lymphoma. The Lancet [online]. 379 (9822), pp.
1234-1244.

Lymphoma Action (2020) Burkitt lymphoma. Available from: https://lymphoma-

action.org.uk/types-lymphoma-non-hodgkin-lymphoma/burkitt-lymphoma, Accessed
[October 2020]

Guillet, S., Gerard, L., Meignin, V., Agbalika, F., Cuccini, W., Denis, B., Katlama, C.,
Galicier, L. and Oksenhendler, E. (2015) Classic and Extracavitary Primary Effusion
Lymphoma in 51 HIV‐infected Patients from a Single Institution. American Journal of
Hematology [online]. 91 (2), pp. 233-237.

Orphanet (2012) Primary effusion lymphoma. Available from:

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=48686. Accessed
[November 2020]

Rangel, J., Novoa, R., Morrison, C., Frank, D. and Kovarik, C. (2015) Fistulizing Epstein–
Barr Virus‐positive Plasmablastic Lymphoma in an HIV‐positive Man. British Journal of
Dermatology [online]. 174 (2), pp. 398-401.

Dhir, A.A. and Sawant, S.P. (2008) Malignancies in Hiv: The Indian Scenario. Current
Opinion in Oncology [online]. 20, pp. 517-521.

Grogg, K.L., Miller, R.F. and Dogan, A. (2007) Hiv Infection and Lymphoma. Journal of
Clinical Pathology[online]. 60 (12).