Anal cancer is one of the most common cancers among people living with HIV (PLWH), despite being rare in the general population. Anal cancer is caused by specific types of human papillomavirus (HPV), a very common sexually transmitted infection. While HPV vaccination can prevent anal cancer, for it to be effective, a person needs to be vaccinated before exposure to the types of HPV that cause anal cancer.
Another approach to preventing anal cancer has been shown effective among PLWH already exposed to the types of HPV that cause anal cancer. This involves screening for and treating anal dysplasia, a precancerous condition. If detected and treated, anal dysplasia can be prevented from progressing to cancer. However, many PLWH face significant barriers that delay or prevent diagnosis of anal dysplasia.
This article discusses the higher rates of anal cancer among PLWH, how testing for and treating anal dysplasia can prevent anal cancer, screening processes and challenges, and ways that service providers can help their clients overcome barriers to screening.
HPV, anal dysplasia and anal cancer
Human papillomavirus (HPV) is a very common sexually transmitted infection.1 Most HPV infections clear on their own and do not cause any symptoms. However, some HPV infections persist, which can lead to certain cancers, including anal cancer.2
There are many different types of HPV. Only some types cause anal cancer and other cancers. These are called high-risk types because they have a high risk of causing cancer.3
Persistent infection in the anal canal with high-risk types of HPV can cause cells there to become abnormal. These early changes are called anal dysplasia. Groups of the abnormal cells form areas of tissue called lesions, which can sometimes be seen by a healthcare provider using examination tools. Over time, these lesions can develop into cancer. Anal dysplasia is not cancer but it can become cancer.4,5
There are different grades of anal dysplasia, which indicate how close to cancer the abnormal cells/tissue are and how likely they are to become cancer. Low-grade anal dysplasia means there are some abnormal changes, but that these are unlikely to progress to cancer. High-grade anal dysplasia means the lesion is more advanced, is at higher risk of becoming cancer, and is less likely to go away on its own. A person with high-grade dysplasia has a risk of developing anal cancer if the lesion is not treated.5,6
Anal cancer among people living with HIV
Anal cancer is rare in the general population, at about one to two cases per 100,000 people per year.7,8
However, among PLWH, anal cancer rates are dramatically higher, on average 25–30 times higher than in the general population.9 Anal cancer is one of the most common cancers among PLWH.10
The increased risk of anal cancer among PLWH may be due to several factors, including the following:
- High-risk HPV is more common among PLWH.11
- Untreated HIV damages the immune system, which makes a person more susceptible to persistent infections and cancers.12
- Even with effective treatment, HIV causes chronic inflammation, which can also make a person more susceptible to persistent infections and cancers.12
Gay, bisexual and other men who have sex with men (gbMSM) living with HIV have a much higher incidence rate of anal cancer than other PLWH; it is estimated that there are 85 cases per 100,000 people per year in this population.13 This is largely because anal infection with high-risk HPV types is more common among gbMSM.11,14 This may be because receptive anal sex and sex with multiple partners, which are both risk factors for anal HPV infection, are more common among gbMSM.15
Prevention through HPV vaccination
The best way to prevent anal cancer is by preventing HPV infection, the number one cause of anal cancer. Vaccines are highly effective at preventing infection with the kinds of HPV that cause most cases of anal cancer.16 HPV vaccines protect only against types of HPV a person does not yet have, so it is best if a person gets the vaccine when they are young, ideally before they start having sex.17 Vaccination when a person is older and has had more sex can still prevent them from getting any HPV types they do not yet have, but the older and more sexually experienced they are, the more likely they are to already have one or more types of high-risk HPV.
Prevention through screening for and treating anal dysplasia
Another approach to preventing anal cancer is screening for and treating anal dysplasia before it can become cancer. For a long time, it was unclear whether treating high-grade anal dysplasia was effective at preventing anal cancer. However, in 2022, a landmark study with PLWH diagnosed with high-grade anal dysplasia showed that those who received treatment had a 57% lower chance of developing anal cancer than those who did not receive treatment.18
Conservative approaches to treating anal dysplasia include applying topical treatments to lesions to slow or reverse the progression of dysplasia. More aggressive approaches involve destroying lesions (ablation) using an electric probe, freezing, laser, infrared or a sharp metal instrument (scalpel).4
Anal cancer screening guidelines
Following the landmark study, in 2024 the International Anal Neoplasia Society (IANS) released new anal cancer screening guidelines focused on screening for high-grade anal dysplasia, as a means of preventing anal cancer.19 The IANS guidelines recommend that this screening be offered to the groups at highest risk of anal cancer:
- HIV-positive gbMSM and trans women 35 years of age or older
- all other HIV-positive people 45 years of age or older
There are currently no national guidelines for anal cancer screening in Canada, although some provincial and local guidance is available.20,21
Screening procedures
There are several screening tests for anal dysplasia and early anal cancer. When available in an area, these tests can be done by a primary care provider who is familiar with them. Like all screening tests, these tests do not provide a final diagnosis, but they can help a provider decide who needs diagnostic testing.
Each screening test has its own uses and limitations. Sometimes multiple tests are used, to more accurately identify people with early anal cancer, or at high risk of anal cancer.
Two tests, the anal Pap test and high-risk HPV test (hrHPV), are recommended in regions where access to a procedure called high-resolution anoscopy (HRA) is available for follow-up examination (see section on HRA below). If HRA is not available, only the digital anal rectal exam (DARE) is recommended.19
Digital anal rectal exam (DARE)
The digital anal rectal exam (DARE) is used to find lumps (tumours) that might be cancerous. A healthcare provider inserts a finger into the anal canal and feels around. DARE is a valuable tool because it can sometimes detect early cancer and does not require special equipment, lab work or extensive training. As a result, DARE is widely available and easy to include in routine screening. However, DARE is unable to detect anal dysplasia because the lesions are flat and often small so they cannot be felt.22,23
If lumps are found during DARE, the provider will generally refer a person to a surgeon for further investigation, and additional tests as needed.
Anal Pap test
In Canada, the most widely available screening test for precancerous anal lesions is anal cytology, commonly called the anal Pap test. The anal Pap test can find microscopic signs suggesting anal dysplasia. A swab is inserted into the anal canal to collect a cell sample, which is then sent to a lab for examination. If dysplastic cells are found, the sample is graded as low grade or high grade.21 A primary care provider can conduct an anal Pap test with minimal training. A patient whose anal Pap test suggests high-grade dysplasia can then be referred to a specialist for a careful examination using high-resolution anoscopy (HRA) with biopsy (see below).
Although anal Pap tests can identify signs that a person may have high-grade dysplasia, they are not perfect. Approximately 20% of people who test negative for high-grade dysplasia with anal Pap testing actually do have it.24 This means that some people who need closer investigation and possible biopsy using HRA may not be referred for it. Conversely, about 40% of people who test positive for high-grade anal dysplasia on a Pap test do not have it. 24 This means that many people are referred unnecessarily for HRA. This can create long wait times and can delay diagnosis for people who urgently need these services.
High-risk HPV test (hrHPV)
High-risk HPV (hrHPV) is a screening test used to assess a person’s risk for anal dysplasia and anal cancer by detecting anal infection with high-risk HPV types. This test is currently not available in most areas of Canada. A swab sample is collected from the anal canal and then tested in a lab for genetic material from high-risk HPV types. People who test positive for high-risk HPV can then have an anal Pap test done for further triage, or they may be referred to a specialist for closer investigation using HRA.
HrHPV tests are more sensitive than anal Pap tests: only about 10% of people who test negative for high-grade dysplasia actually do have it.24 However, approximately 60% of people who test positive on hrHPV actually do not have high-grade anal dysplasia.24 Like anal Pap tests, hrHPV tests can result in unnecessary referrals to HRA, contributing to long wait times and delayed diagnoses for people at higher risk of anal cancer.
High-resolution anoscopy (HRA)
People with suspected anal dysplasia may be referred for a procedure called high-resolution anoscopy (HRA), if it is available. During HRA, a healthcare provider with specialized knowledge and equipment inserts a hollow tube called an anoscope into the anal canal to view it. They then examine the anal canal through a magnifying device called a colposcope to provide very close, detailed images. A solution is also applied to the tissue being examined, to make any lesions more visible. If the provider sees areas that they suspect might be high-grade dysplasia, they take a tissue sample (biopsy) using tiny pincers. They may decide to treat any suspicious lesions at the same time.
After a provider takes a biopsy during HRA, they send the tissue to a lab to be examined. If anal dysplasia is found, it is graded as high grade or low grade. The examination of the biopsy is used to confirm a diagnosis of anal dysplasia.21 After diagnosis by biopsy, the provider and patient can decide on next steps, which can include (further) treatment, follow-up examination or more tests.
HRA can be used to see very subtle or small lesions and can distinguish between low-grade and high-grade lesions. This makes it the gold standard for identifying tissue needing biopsy and for accurately targeting these areas during the biopsy procedure. For these reasons, HRA is a critical tool for preventing anal cancer by treating high-grade dysplasia.25–27
There is a major drawback to HRA, however. Access to it is extremely limited, because it requires specialized expertise, takes a long time to master and uses expensive equipment, which means that very few healthcare providers perform it.25,27 In Canada, only a few clinicians in a few major urban centres perform HRA.28
Anal cancer screening uptake among PLWH
Many PLWH who meet the IANS recommendations for routine anal cancer screening are not being screened.
A large 2020 study in Ontario with men aged 45–59 living with HIV (mostly gbMSM) found that 70% had previously completed a DARE test, and most of them had done so within the previous year. However, the study found that only 40% reported ever having been screened using techniques that can detect anal dysplasia.29
Similarly, a large 2024 study in the United States of PLWH aged 35 or older found that only 4.8% had received an anal Pap test in the previous 12 months. The proportion among gbMSM and trans women age 35 or older was slightly higher (7.7%) than the proportion among all other PLWH age 45 years or older (1.9%).30
Implications for service providers
PLWH are at much higher risk for anal cancer than the general population. Diagnosing and treating high-grade anal dysplasia can help prevent anal cancer, and early anal cancer treatment can improve outcomes. The biggest barrier to preventing anal cancer by treating anal dysplasia is the low availability of HRA, which is by far the best way to identify the lesions most likely to become cancer. Improving this requires multi-pronged strategies at the level of health systems. In the meantime, service providers can support clients to overcome the barriers to accessing screening services available in their area.
Competing priorities, challenges with coordinating care and lack of clear guidance can discourage healthcare providers from recommending and initiating screening with PLWH.31–37 Despite these challenges, it is important for anal cancer screening to stay on the agenda for PLWH. Community-based providers can play an important role by educating and motivating clients to get screened and facilitating their access to screening and follow-up services.
Many PLWH lack critical information on anal cancer and anal cancer screening. This can lead them to underestimate their risks for anal cancer and undervalue screening, which in turn undermines their motivation to get screened and follow through as needed.38–41 Service providers can help to address this lack of knowledge by clearly communicating key information to clients, including the heightened risk for anal cancer among PLWH, of HPV and its role in causing anal cancer, and basic anal cancer screening tests, including when screening tests are indicated and how to access them.
Screening can bring up fear and anxiety about possible pain and discomfort, test results and the possibility of cancer.38,42–45 Service providers can help to support PLWH before and throughout the screening process by helping them understand what to expect, including providing information on how others have perceived the experience, coping strategies and what different test results mean. These steps may help to reduce fear, increasing the chances that PLWH will initiate screening and follow through with subsequent steps as needed. Support from peers who have undergone the process may also help to increase confidence and reduce fear.
Overlapping layers of stigma and discrimination make the screening process more difficult and can discourage PLWH from screening.42,46–48 Service providers can help by connecting PLWH with healthcare providers experienced in providing stigma-free care for PLWH from the communities to which a client belongs. Additionally, they can provide support and information to help PLWH advocate for the care they need.
Resources
HPV, anal dysplasia and anal cancer – CATIE fact sheet
Human papillomavirus (HPV): Symptoms and treatment – Public Health Agency of Canada
Ontario study looks at trends in cancer in people with HIV – CATIE News
Preventing anal cancer: The importance of HPV vaccination for gay, bisexual and other men who have sex with men – Prevention in Focus
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Externally reviewed by: Mathieu L'Heureux, Manuel Murillo, Ahmed Muslimani & Dr. Alexandra de Pokomandy
About the author(s)
Dan Miller is CATIE’s knowledge specialist, HIV care and STI. He completed a master’s degree in public health at the University of Toronto and is an experienced health services researcher and communicator.