• What is cancer?
• What causes cancer?
• What types of cancer affect people with HIV?
• Kaposi’s Sarcoma
• Lymphoma
• Anal cancer
• Melanoma
• Prostate cancer
• Bowel cancer

In the early years of the HIV epidemic there were a number of cancers associated with HIV and AIDS. The availability of HAART (Highly Active Anti HIV Treatment) in the late 1990's, and continued improvements in HIV treatment, have resulted a continuing decline in the diagnosis of many of these cancers.

However in recent years doctors are seeing other ‘non HIV related' cancers among people with HIV. This article aims to outline and describe this changing trend and to offer information and strategies to detect cancer early, and help prevent other cancers from developing.

What is cancer?

A cancer is an abnormal growth of cells that can grow in an uncontrolled way and, in some cases, spread to other parts of the body. Most cancers are named in relation to the part of the body in which they are found or start, or the type of body cell they arise from. Cancer may also be called a malignancy, a malignant tumor, or a malignant neoplasm - meaning literally, a ‘new growth'. Cancer is also the Latin word for crab, a term adopted by ancient practitioners of medicine.

Cancer is not a single disease - there are dozens of different types of cancer. The risk of developing certain types of cancer can depend on one's gender. While skin cancer is found in both men and women, prostate cancer is detected in men and cervical cancer in women. This might sound obvious but can be important for prevention and detection information, in relation to the different hormones and biology of men and women.

A diagnosis of cancer does not mean a death sentence. Many cancers are preventable, treatable and even curable. Science, research and treatment are improving constantly. Whilst treatment for cancer continues to improve in terms of effectiveness and side effects, prevention and early detection are also very important.

What causes cancer?

It is unclear how HIV contributes to increased rates of some cancers among people with HIV, but there are a number of theories.

Impaired immune surveillance

As well as ‘fighting infection', another important function of our immune system is to detect and fight cancer cells. This is called ‘Immune Surveillance'. If someone's immune system is unable to function well over a long period of time, some cancer cells may go undetected, or the immune system may not be operating well enough to respond to them. There are many different specialised functions of the immune system involved in this theory, however starting treatment at a CD4 count over 350, and perhaps even over 500, is thought to allow the immune system to continue to better detect and respond to cancer cells in their early stages of development, thereby reducing the risk of developing many cancers thought to be related to HIV.

Uncontrolled high Viral Load and low CD4 count

Having a low CD4 count or an untreated high viral load for a long time contributes to the incidence of many HIV/AIDS associated cancers. Examples of these cancers include Kaposi's sarcoma and non-Hodgkin lymphoma, which mostly occur at rather low CD4 counts. In Australia, the availability of quality medical care and treatment, as well as the high uptake of treatment, has been responsible for the marked decline in rates of these cancers.

Timely commencement of HIV treatment can help prevent a range of HIV related health issues in both the short and long term, including cancer. This is why doctors perform regular CD4 counts and viral load testing, and consider these results when recommending treatment. However the CD4 count is more important than viral load in considerations of when to start therapy; and in cancer prevention.

The presence of other virsuses

AIDS-defining cancers are often associated with oncogenic (cancer causing) viruses that are often sexually transmitted. Some of these viruses include:

• Epstein-Barr virus (EBV), also called human herpes virus 4 (HHV-4), which can cause non-Hodgkin lymphoma, and Hodgkin lymphoma
• Human herpes virus 8 (HHV-8), a herpes virus that causes Kaposi's sarcoma
• Hepatitis B (HBV) and Hepatitis C (HCV) that can cause liver cancer
• Human papillomavirus (HPV) - some types can cause genital warts, while others can, in a minority of cases, lead to cancers of the cervix, vulva, vagina, and anus in women or cancers of the anus and penis in men.

Around 96% of people living with HIV are living with HPV (Human Papillomavirus), especially in the genitals ie penis, anus and vagina. Some specialists theorise that having HPV increases the risk of acquiring HIV, as the presence of HPV can compromise the mucosal lining of the part of the body that it lives in. Someone with HPV of the anus could be more likely to acquire HIV during unprotected receptive anal intercourse. Emerging theories also associate genital HPV with the sexual transmission of Hepatitis C (HCV).

A HPV vaccination has been available to young women through a national immunisation program in Australia since 2007. While this is mainly aimed at preventing cervical cancer, it has also resulted in substantial reductions in genital warts in women and in heterosexual men.

At the time of writing HPV vaccination is not subsidised by the PBS for young men. Although vaccination can be purchased from a doctor, it costs over AU$400. Recent Australian research has recommended that this vaccination be made available to all young boys and girls. Vaccination is unlikely to be helpful for adult gay men, as most will already be living with HPV.

Find out more: Cancer Aetiology and Prevention Group

Other infections

Some researchers think that repeated exposure to viruses and other infectious organisms may be related to the development of some cancers. Many cancers prevalent in people with HIV are found in body areas that are in contact with the outside environment (e.g. cervix, lung, mouth, skin, and anus).

The increased concentration of HIV at these sites could lead to compromised immunity, increasing the risk for cancer in these parts of the body. This suggestion relates to the theory of impaired immune surveillance outlined earlier.

Unprotected sex

Unprotected sex with multiple partners increases the risk of exposure to other Sexually Transmitted Infections (STI's). Repeated exposure to STI's, especially if untreated, is thought to increase the risk of some cancers, especially of the anus and genitals.

Cigarettes, alcohol and other drugs

It is well documented in various social research studies that people living with HIV tend to smoke, drink and sometimes take recreational drugs more than the general population. Studies show that quitting smoking is by far the most positive thing people living with HIV can do for their health as smoking is strongly related to increased risk of many cancers and other health issues.

What types of cancer affect people with HIV?

The following information has been compiled in reference to thebody.com, and full credit is given to them for their excellent resources on this health issue.

Kaposi's Sarcoma

Kaposi's sarcoma (KS) is a cancer that was originally known to affect elderly men of Eastern European or Mediterranean background. In people with HIV, KS develops on the skin, or the lining of the mouth, nose, or eye. KS is caused by a herpes virus called Human Herpes Virus 8 (HHV-8). KS affects about 20% of people with HIV/AIDS who aren't taking anti-HIV drugs. The rate of KS has dropped by over 80% since the introduction of HAART.

In 2007, in the US, scientists reported new cases of KS in people taking effective HAART with undetectable viral loads. These new cases were reported to be mild and non life-threatening, and were mostly seen in people who were injecting drug users, especially of crystal meth (also known as tina or ice).

How Is KS Treated?

HAART is the best treatment for active KS. For many people, HAART can stop the growth or even clear up skin lesions. In addition to HAART, there are different treatments for KS in the skin or in other parts of the body. KS of the skin may not require treatment if there are only a few lesions.

Other treatments for KS lesions include:

• Freezing with liquid nitrogen
• Radiation therapy - safe and very effective
• Surgical removal - a minor procedure much like having a mole removed
• Injection with anti-cancer drugs
• Treatment with medicated creams.

KS lesions can sometimes return after treatment, in which case repeated treatment is required.

Lymphoma

Lymphoma is cancer of the lymphatic system characterised by rapidly dividing white blood cells. One type of lymphoma, Hodgkin's lymphoma, presents differently to non-Hodgkin's lymphoma (see below) and responds well to recognised treatment. All other types are collectively termed non-Hodgkin's lymphoma (NHL) and are more often associated with HIV/AIDS.

The longer someone lives with a lower CD4 count and high viral load, the higher the risk of developing NHL. An association has been found between non-Hodgkin's lymphoma and certain infections including the Human T-lymphotropic virus Type I (HTLV-1), Epstein-Barr (EBV) virus, Hepatitis C virus (HCV), and Helicobacter pylori bacteria.

NHL can sometimes occur in people with a high CD4 count who are not on treatment. HAART can cut the rate of NHL by about 50%, especially in the Central Nervous System (CNS).

Download: Continuing declines in some but not all HIV-associated cancers in Australia after widespread use of antiretroviral therapy

How is NHL diagnosed?

The following is taken from the Cancer Council NSW website and full credit is given to the Cancer Council NSW for their work in this field.

• Tests - If non-Hodgkin's lymphoma is suspected, your doctor will feel the lymph nodes in your neck, underarm or groin for signs of swelling. An initial blood test and chest x-ray may also be recommended. Even if you have never had symptoms you should ask your doctor if any results from your regular blood tests might indicate the early stages of NHL. You might like to ask your doctor to show you where your lymph nodes are located so that you can monitor them yourself.
• Biopsy - A biopsy involves the removal of a piece of a lymph node for a diagnostic study, and is a quick and simple procedure performed with a local or general anaesthetic. A small piece of the inflamed lymph node is removed using a small needle. The sample is examined under a microscope to make a diagnosis.

How Is NHL treated?

NHL is treated with a combination of drugs (chemotherapy or chemo). NHL in the central nervous system can be more difficult to treat. Radiation therapy may be used instead of, or in addition to, chemotherapy for NHL of the Central Nervous System (CNS) which is considered rare among people taking HAART.

Since HAART, the types of NHL seen in people with HIV are easier to treat. HAART also makes it easier for HIV patients to tolerate strong chemotherapy for NHL. As a result, the rate of death among people diagnosed with NHL has dropped by over 80%. In a recent study (Ill-7.pdf located at end of article), 74% of people recovered from NHL using a new combination of chemotherapy drugs known as EPOCH. Emerging research suggests that the new groups of HIV treatments known as CCR5 antagonists, or entry blockers, may have a role in the prevention and treatment of NHL.

Starting treatment with a CD4 count of 350 or higher, drugs that have a high CNS penetration score will drastically reduce your chances of developing NHL.

Anal cancer
Anal cancer is a form of cancer affecting the anus. The anus includes the external part that you can see, as well as the inch-and-a-half-long end portion of the large intestine that is internal. Anal cancer is seen at much higher rates among gay, bisexual or MSM men with HIV and HPV.

In Australia the incidence of anal cancer has remained high among people with HIV since the introduction of HAART suggesting that HAART has not had an impact on anal cancer. Anal cancer has become the third most diagnosed cancer among people with HIV.

Like cervical cancer in women, anal cancer is usually preceded by pre-invasive lesions called ‘anal dysplasia'. If detected early, anal dysplasia can be treated with minor surgical procedures. However anal cancer often goes unnoticed in its early stages, and by the time it is diagnosed people might require chemotherapy and/or radiation therapy and/or surgery. There is no widely available screening test used to detect anal cancer, although researchers in Sydney are currently investigating this in a large study called the SPANC study (Study of the Prevention of Anal Cancer).

Signs of anal cancer include itching or swelling of the anus, the presence of a lump, noticing blood in your bowel movements or on toilet paper after wiping, experiencing pain not previously felt during receptive anal intercourse or during bowel movements. The risk of anal cancer rises with age, and is very uncommon in people with HIV under the age of 35.

Melanoma

A melanoma is a form of skin cancer that is caused by melanocytes - the cells that produce pigment, or skin colour. Melanoma's can often begin as a mole. Melanocytes produce a pigment called melanin that gives the skin its colour and protects it from sun damage. Darker skin has more melanin and therefore more protection from developing melanomas. Melanocytes often cluster together and form moles (medically called nevi). Most moles are benign, but some may go on to become cancerous.

Recent research from the US found that neither HIV, nor HIV-related immune suppression, increases the risk of melanoma. Whilst the research found a moderate increase in the rate of melanoma in MSM with HIV, they suggested the link was most likely due to "recreational sun exposure or the use [of] tanning beds."

Find out more: HIV doesn't increase risk of melanoma, but immune suppression associated with risk of rarer skin cancers

Recent Australian researchers found that:

‘For two cancers not increased in the pre-HAART period, melanoma and prostate cancer incidence declined significantly and by the late-HAART period, was lower than in the general population'.₁

The research also stated:

‘Curiously, incidence of melanoma was significantly lower than in the general population during the late-HAART period. Although the risk of melanoma is slightly raised overall in people with HIV, most studies reporting data in the post-HAART period have not observed excess risk'.

While these research results can't tell us that treatment ‘protects' against melanoma, they don't take into account other known risk factors including genetics, smoking, ethnicity, age or the impact of highly successful public health information programs. These public health messages may also be responsible for the lower rates of melanomas.

The best tools are prevention by protecting against the harmful effects of the sun, and early detection and treatment of any new or changing moles, freckles or other skin pigmentations.

In Australia, Medicare funds free melanoma screening by doctors. Your HIV doctor can also check your skin for any changes or moles that might require monitoring or removal.

Web: Cancer Council Australia

Prostate cancer

The prostate is a gland in the male reproductive system that is located just below the bladder. The prostate is roughly slightly larger than a walnut and surrounds the beginning of the urethra, the tube inside your penis that empties the bladder, or that you urinate and cum out of.

While the exact cause of prostate cancer is not known, it is diagnosed more often in older men. In regard to HIV and prostate cancer, recent Australian research previously cited in this article states:

‘Prostate cancer incidence was the same, or lower, (for those with HIV) than for the general population and declined significantly after HAART. For reasons unclear, reduced prostate cancer risk has been repeatedly documented in HIV-infected men. Lower rates of prostate cancer screening and complications of HIV infection including lower androgen (hormone) levels and diabetes mellitus, each believed to be associated with reduced prostate cancer risk, may be possible explanations. In addition, there has been a single report of an inhibitory effect of protease inhibitors on prostate cancer cell lines'.

Researchers do not recommend lowering testosterone levels, developing diabetes or changing HIV treatments, as any of these may result in a range of other health issues. These findings might help future research to help prevent prostate cancer among PWH.

Symptoms of prostate cancer (from the Cancer Council NSW website)

Early curable prostate cancer rarely causes symptoms. This is because the cancer is not large enough to put pressure on the urethra. If the cancer is larger, it may cause the following problems:

• Pain or burning when urinating
• Increased frequency (needing to pass urine more often)
• Difficulty urinating
• Blood in urine or semen
• Pain in the lower back, hips or upper thighs

These symptoms are common to many conditions and may not be a sign of prostate cancer. However early detection is important, so if you are experiencing any of these symptoms you should discuss them with your doctor.

Causes of prostate cancer (from the Cancer Council NSW website)

While the causes of prostate cancer are unknown, the chance of developing prostate cancer increases:

• As you get older - it mainly affects men over 65
• If your father or brother has had prostate cancer
• If there is a history of breast cancer in your family

In 5-10% of men with prostate cancer, their family medical history may indicate they have an inherited gene that contributed to the cancer's development. You may have an inherited prostate cancer gene if you have:

• Many relatives with prostate cancer or breast cancer on the same side of the family (either the mother's or father's side)
• Younger male relatives (under 50) with prostate cancer

If you are concerned about your family history of prostate cancer, you may wish to ask your doctor for a referral to a family cancer clinic or a urologist to advise you on suitable testing for you and your family.

Bowel cancer

Bowel cancer, also called colorectal cancer, describes cancerous growths in the colon, rectum and appendix. Most bowel cancers develop from tiny growths or lumps called ‘polyps', however not all polyps become cancerous.

In relation to symptoms the following has been taken from www.bowelcanceraustralia.org, and full credit is given to Bowel Cancer Australia for this information and their ongoing work in this field.

Possible signs of bowel cancer include a change in bowel habit or blood in the stool. In its early stages, bowel cancer often has no symptoms. This is why it is important to screen. Like most diseases, bowel cancer can often cause symptoms which are similar to other unrelated conditions. If you experience any of the following symptoms, you should consult your doctor.

• A recent, persistent change in bowel habit to looser, more diarrhoea-like motions, going to the toilet more often, or trying to go (ie. irregularity in someone whose bowels have previously been regular)
• Blood (either bright red or very dark) in the stool
• Diarrhoea, constipation, or feeling that the bowel does not empty completely
• Frequent gas pains, bloating, fullness or cramps
• Stools that are narrower than usual
• A lump or mass in your tummy
• Weight loss for no known reason
• Persistent, severe abdominal pain, which has come on recently for the first time (especially in an older age group)

If you have any of these symptoms, it does not mean that you have bowel cancer, but it is very important you discuss them with your doctor as soon as possible.

What causes bowel cancer?

Although the causes are not fully known, bowel cancer is associated with a diet low in fruit, vegetables and fibre, and high in red meat, sugar, alcohol and other animal fats. People living with illnesses that cause chronic inflammation of the bowel, are at higher risk.

Bowel cancer is also associated with people who have a close relative diagnosed with bowel cancer (such as parents, brothers or sisters), especially if their relative was diagnosed at under 50 years of age. Bowel cancer is more common in people over 50 than in younger people and among people who do little exercise, drink excessive amounts of alcohol and smoke.

Previously cited Australian research correlated a reduced incidence of bowel cancer in people with HIV taking HAART:

‘Incidence of colorectal cancer was consistently lower than in the general population.

However the authors state in their conclusion:

‘Reasons for the reduced incidence of colorectal (bowel cancer) . . . . . . are unclear.

How can I prevent bowel cancer?

As well as modifying lifestyle issues such as diet and exercise, monitoring and early detection are vital in the early diagnosis and treatment of bowel cancer.

Bowel Cancer Australia free home screening test kits

There is a free home test that you can order online at Bowel Cancer Australia. You will be sent a kit for a test called a Faecal Occult Blood Test (FOBT). The test looks for small amounts of blood in your bowel motion. This is a simple test that you do at home and involves placing small samples of stool on special cards included in the kit, then sending them to a pathology laboratory for analysis.

The results are then sent back to you and your doctor, so you will need to include the address of your Doctor's clinic in the information. If the test comes back positive for blood it does not mean that you have bowel cancer, but will prompt you and your doctor to talk about having more detailed tests to further explore the cause of the findings.
This test is only recommended to people over 50 or with a family history of bowel cancer.

Conclusion

With more people taking improved treatment combinations, the rates of cancers previously related to HIV/AIDS are declining, and continue to decline. Whilst this is excellent news for people living with HIV, prevention and monitoring are still the most important strategies that we have to even further reduce the impact that cancer can have on us individually and as a community.

Whilst we have long known that lifestyle factors such as smoking, poor diet, lack of exercise, untreated STI's and excessive alcohol and drug use can cause a range of health issues, there is growing evidence that these ‘behaviours' can carry an extra risk of cancer developing for people with HIV.

The timely commencement of tailored combinations of HIV treatment is also associated with a reduced risk of a range of cancers, and these health issues should be considered by people with HIV considering commencing treatment.

Find out more

Download: Continuing declines in some but not all HIV-associated cancers in Australia after widespread use of antiretroviral therapy

1. Continuing declines in some but not all HIV-associated cancers in Australia after widespread use of antiretroviral therapy. Marina T. van Leeuwen, Claire M. Vajdic, Melanie G. Middleton, Ann M. McDonald, Matthew Law, John M. Kaldor and Andrew E. Grulich. AIDS. 2009 Oct 23; 23(16): 2183-90