Can the CD4/CD8 ratio be used to predict the risk of anal cancer in HIV-positive people?

• HIV-positive people are at increased risk for certain cancers, including anal cancer
• The ratio of CD4 to CD8 cells can provide an overall picture of the health of the immune system
• Researchers have found that the CD4/CD8 ratio may be useful in predicting anal cancer risk

Some strains of the common sexually transmitted infection HPV (human papillomavirus) can cause the development and growth of abnormal cells in parts of the body. Eventually, some of these abnormal cells can transform into precancer and the following cancers:

• anal cancer
• cervical cancer
• head and neck cancers (affecting the throat, tonsils and tongue)
• penile cancer
• vaginal cancer
• vulvar cancer

Prevention of HPV and related disease

A vaccine called Gardasil-9 is approved in Canada and other high-income countries for preventing infection with strains of HPV that are associated with anogenital warts, precancer and cancer. Gardasil-9 is approved for use in males and females between the ages of nine to 45 years. Some provinces and territories in Canada subsidize the cost of Gardasil-9. Your pharmacist can tell you more about the availability of these subsidies.

Anal cancer and HIV

Initiating HIV treatment (ART) helps to reduce the amount of HIV in the blood and allows the immune system to begin the process of repairing itself. Continued use of ART reduces the risk of AIDS-related complications. Furthermore, the power of ART is so tremendous that scientists expect that many ART users will have near-normal life expectancy. However, despite the use of ART exactly as directed, the immune system is able to only partially repair itself. As a result, ART users remain at heightened risk (compared to HIV-negative people) for some infection-related cancers, such as those caused by HPV. Some major clinics in large cities have anal cancer screening programs for HIV-positive people.

Key parts of the immune system in HIV

HIV-positive people who are in care regularly get blood drawn for analysis of the levels of important T-cells—CD4+ and CD8+ cells—and the ratio of these cells (CD4/CD8). In cases of untreated HIV infection, the level of CD4+ cells and the CD4/CD8 ratio fall over time. Once ART is initiated, the level of CD4+ cells and the CD4/CD8 ratio rise. In general, the earlier that ART is initiated, the faster that CD4+ cells can increase—and the same goes for the CD4/CD8 ratio.

The CD4/CD8 ratio provides an overall picture of the health of the immune system. In healthy HIV-negative people, the ratio is generally 1.0 or greater. In HIV-positive people who have a ratio less than 1.0, research suggests that there is some degree of persistent immunological injury.

Anal cancer, HIV and the CD4/CD8 ratio

A team of researchers at the University of Wisconsin has conducted a study on anal cancer. The researchers reviewed health-related information collected from HIV-positive people over about nine years. The researchers divided participants into two groups:

• 266 people – had anal precancer and/or anal cancer
• 111 people – did not have any anal abnormalities

The two groups had a similar balance of people with key features, including age (mid-40s), gender (91% males, 9% females), ethno-racial background, history of sexually transmitted infections (STIs) and history of receptive anal intercourse. Participants were taking ART and had a current average CD4+ cell count between 560 and 680 cells/mm³. They were monitored for about nine years.

Key findings

The researchers found that there were factors linked to an increased risk for developing anal precancer and cancer, as follows:

• being female
• having a history of anal warts
• having a CD4/CD8 ratio of less than 0.5 at some point in the past or having a CD4/CD8 ratio of less than 1.0 around the last time they had anal cancer screening

In contrast, people who had a CD4/CD8 ratio greater than 1.0 around the time of their last anal cancer screening were at significantly reduced risk for anal precancer and cancer.

Bear in mind

1. The study is based on data collected in the past for one purpose and then reanalysed for another purpose. Such retrospective study designs, while relatively low in cost, can inadvertently introduce hidden bias when researchers are reanalysing the data. Also, this study only recruited people from one clinic. Taken together, these issues mean that the findings are suggestive, not definitive. However, the Wisconsin researchers may have come across a relatively simple way to monitor the risk of anal precancer and cancer with CD4/CD8 ratios in HIV-positive people. Therefore, it would be useful if other clinical centres that specialize in anal cancer screening could also analyse their data for similar trends.

2. Achieving and maintaining a relatively high CD4+ cell count and a normalized CD4/CD8 ratio is important for overall health. Recent research from Canada and other countries suggests that such normalization is more likely to occur sooner if HIV treatment is initiated earlier rather than later in the course of infection.

3. Despite the use of ART, chronic HIV infection can cause lasting immunologic dysfunction and researchers are studying ways to try to reverse this. Scientists in Canada and other countries have conducted research that suggests that co-infection with CMV (cytomegalovirus), a member of the herpes virus family, appears to contribute to persistent immunological dysfunction, including less-than-optimal CD4/CD8 ratios. Future research is needed to find a safe and effective way to minimize CMV in people who are co-infected with HIV and CMV.

Reducing the risk of cancer

As many ART users are now living into their senior years, it is important to maximize activities that can help further good health and quality of life at all ages. Here are some general tips:

• Early initiation of ART will help to preserve the immune system. Research has found that initiating ART early in the course of HIV disease significantly helps to reduce the risk of cancer. Leading international HIV treatment guidelines recommend that doctors offer initiation of ART as soon as possible after HIV infection has been diagnosed.
• Quitting or cutting down on smoking. Smoking is associated with many harms and causes several cancers mentioned in this bulletin, including cancers of the lungs, cervix, kidneys, liver and mouth/throat. It is therefore important to help people who smoke come to the realization that they need to quit and to provide support when they do attempt to quit.
• Getting screened for cancer. Different regions, clinics and some hospitals have cancer-screening programs, including the use of low-dose X-ray scans for lung cancer, Pap tests and other assessments for abnormal growths in the anus and cervix, colonoscopy for colon cancer, and so on. Speak to a doctor or nurse about your options for cancer screening.
• Screening for co-infection with hepatitis B and C viruses (which can cause liver cancer). If active infection with these viruses is detected, doctors and nurses can offer treatment. In cases where there is no active infection with hepatitis B and a person has no immunity against this virus, vaccination can be an option.
• Discussion with a doctor about vaccination against HPV (human papilloma virus) is a useful first step to take, as this virus can cause cancers of the anus, cervix, mouth/throat, penis and vulva. Doctors and pharmacists will know if HPV vaccination is subsidized in your region.
• Exercising regularly. Research suggests that regular physical activity can reduce the risk of some cancers in HIV-negative people. It is likely that exercise also contributes to reduced cancer risk in HIV-positive people. Speak to a doctor or nurse about what forms of regular physical activity are right for you.
• Maintaining a healthy weight. Research suggests that obesity is associated with an increased risk for cancer and that intentional weight reduction is associated with a reduced risk. Speak to a doctor or nurse about safe ways to achieve and maintain a healthy weight.
• Eating a wholesome diet. Eating a diet rich in colourful fruit and vegetables as well as fibre is associated with a reduced overall risk for cancer. Some large hospitals offer subsidized access to nutritional counselling.

—Sean R. Hosein

Resources

Canadian researchers point to CMV as a problem for the immune system – CATIE News

Changes in CD4+ cell count after cancer treatment linked to survival among HIV-positive people – CATIE News

Delays in cervical cancer screening among some HIV-positive Canadian women – CATIE News

Large study finds advanced stage cancer more common in HIV-positive people – CATIE News

Study finds shift in cancers as HIV-positive people age – CATIE News

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