Dutch HIV study finds implementing anal cancer screening and treatment saves lives

Some strains of human papillomavirus (HPV) are sexually transmitted and can cause abnormal development of cells in the following places:

anus
cervix
lips
mouth and/or throat
penis
vulva

In some cases, abnormal cells can eventually transform into pre-cancer and cancer.

Due to persistent HPV infection and a degree of immunological weakness, people with HIV as a group are at heightened risk for HPV-related abnormal cellular development and cancer. For this population, regular screening to detect pre-cancer and cancer of the affected body parts mentioned is needed.

A team of researchers in the Netherlands has conducted a study monitoring the health of more than 28,000 people with HIV. The study collected data from 1996 to 2020. In that country, screening programs for anal pre-cancer and cancer were gradually expanded beginning in 2007. People in the program who had pre-cancer or cancer are referred for treatment.

In their most recent analysis, researchers found that over the course of the study 227 new cases of anal cancer were diagnosed. Over time, rates of anal cancer among a subgroup in the study—men who have sex with men (MSM)—fell, though the risk of anal cancer remained higher than in HIV-negative people. Furthermore, among MSM who underwent anal cancer screening, when anal cancer was diagnosed it tended to be found in the early stages before multiple tumours had appeared and spread. Deaths due to complications from anal cancer occurred in 4% of men who were screened vs. 24% of men who had not been screened.

The results from the Netherlands support programs for people with HIV that offer screening for anal pre-cancer/cancer and treatment when it is found.

Study details

A study called Athena enrolled many people with HIV from 28 clinics across the Netherlands.

In December 2007, anal cancer screening using high-resolution anoscopy (HRA) was gradually made available for people with HIV. As part of that screening, abnormal cells found in the anus were biopsied. If pre-cancer or cancer was found, treatment was offered (surgery, radiation and/or chemotherapy). Most people targeted for screening in the study were MSM.

In general, screening was offered every two years. However, if abnormal cells were detected, screening could occur more often. After treatment for pre-cancer/cancer, people were reassessed six months later to be sure that treatment was effective.

During the study period, 28,175 people with HIV were enrolled. They were divided into the following groups; note that gender at birth was used and sexual orientation was provided by participants. As such, MSM may include trans women and non-binary people:

MSM – 60%
non-MSM – 22%
women – 19%

Note that numbers here and elsewhere in this report may not total 100 due to rounding.

During the study, 227 cases of anal cancer were diagnosed. Here is a brief average profile of participants at the time this cancer was diagnosed:

age – 52 years
time since HIV diagnosis – 14 years
current CD4+ cell count – 480 cells/mm³
lowest-ever CD4+ count – 110 cells/mm³
74% had an undetectable viral load (in this case, less than 40 copies/mL)
time on ART – 10 years
13% of participants were in the anal cancer screening program at the time this cancer was diagnosed

Analysis of anal tumours revealed that the vast majority (99%) were squamous cell carcinoma.

Results

Over time, the risk of anal cancer fell significantly among MSM but not among other populations. This is noteworthy because MSM would have been aging and the immune system’s ability to detect and destroy pre-cancers and cancers decreases with age as the immune system slowly degrades.

To explore why the risk for anal cancer decreased among MSM relative to other groups, the researchers conducted further analyses. They found that MSM as a group tended to have the following:

less likely to smoke over time; that is, as new participants entered the study they were less likely to be smokers and people who entered the study as smokers were more likely to quit
less likely to have had low CD4+ cell counts and high viral loads, probably due to earlier initiation of ART
less likely to have viral loads greater than 1,000 copies thanks to initiation of ART and good adherence

Screening

During the study, 14% of all participants were screened at least once for anal cancer.

Of the 227 people diagnosed with anal cancer, 81% (184 people) had never been screened and were distributed as follows:

MSM – 142
non-MSM – 34
women – 8

People who were screened were more likely to have been diagnosed with anal cancer. This should not be misconstrued as screening having caused cancer. Rather, doctors were actively looking for such cancers so they were more likely to be found in people who were screened.

Furthermore, such screening would be more likely to uncover anal cancer early in the course of disease compared to people who did not undergo screening.

Survival

Among 227 people diagnosed with anal cancer, 38% ultimately died. A total of 31% of deaths (from any cause) occurred within five years of diagnosis of anal cancer, distributed as follows:

MSM – 31%
non-MSM – 38%
women – 63%

In general, there were more tumours found at the time of diagnosis of anal cancer among non-MSM than among MSM.

When researchers analyzed the deaths within five years of diagnosis, they found a connection between screening and survival:

4% of people who had undergone anal cancer screening and who had been diagnosed with anal cancer died from complications associated with anal cancer
24% of people who had not undergone anal cancer screening and who had been diagnosed with anal cancer died from complications associated with anal cancer

This difference underscores the impact and importance of screening.

Bear in mind

The Dutch researchers stated that new cases of anal cancer in MSM peaked in 2004 and then slowly decreased. However, the risk of this cancer occurring is still relatively high in this population.

The researchers stated that the decrease in anal cancer risk among MSM was driven by decreased rates of smoking and early initiation of ART. Minimizing the time with low CD4+ counts and high viral loads was found to reduce people’s subsequent anal cancer risk.

People in the anal cancer screening program were more likely to have been diagnosed early with this cancer vs. people who were not in the screening program and who developed anal cancer. What’s more, people in the screening program were much less likely to die from anal cancer–related complications than people who were not screened.

The Dutch study found that anal cancer risk is elevated in some non-MSM and women with HIV compared to people without HIV. Researchers found that this was not due to poor responses to ART. Some researchers in the Netherlands suspect that part of the reason for the elevated risk of anal cancer among some non-MSM might be due to what they described as “undisclosed sexual contact with other men.”

For the future

The widespread use of ART has greatly increased life expectancy. However, as ART users grow older, they require monitoring so that any health issues are detected and treated early.

In the present study, anal cancer screening saved lives. Such screening needs to be more available to people with HIV in other countries. Research is needed to find out which subset of people with HIV are most in need of such screening.

Resources

Canadian Cancer Society

Cancer – Government of Canada

Cancer – Government of Quebec

Second cancer risk after surviving Hodgkin’s lymphoma in people with HIV – CATIE News

French researchers investigate second cancers in people with HIV who survived a first cancer – CATIE News

Ontario study looks at trends in cancer in people with HIV – CATIE News

—Sean R. Hosein

REFERENCES:

van der Zee RP, Wit FWNM, Richel O, et al. Effect of the introduction of screening for cancer precursor lesions on anal cancer incidence over time in people living with HIV: a nationwide cohort study. Lancet HIV. 2023; in press.
Stier EA. How do we prevent anal cancer in people living with HIV? Lancet HIV. 2023; in press.