Anal cancer is being diagnosed less often in gay and bisexual men with HIV in the Netherlands since 2013, but rates of diagnosis have hardly changed in other groups of people living with HIV over several decades, and Dutch HIV specialists say that screening and treatment for anal precancers should be offered to all people living with HIV.
Although the researchers attribute the decline in anal cancers in gay and bisexual men to earlier initiation of HIV treatment and less smoking rather than screening of gay and bisexual men with HIV, they note that screening enabled earlier diagnosis of anal cancer, resulting in better survival.
Anal cancer is rare in the general population. One or two people per 100,000 are diagnosed with anal cancer each year but incidence is much higher in people living with HIV. Around 85 gay and bisexual men with HIV and 22 women with HIV per 100,000 are diagnosed with anal cancer each year, according to a meta-analysis of studies.
Anal cancer is the most common non-AIDS-defining cancer among people living with HIV. Most anal cancers are squamous cell cancers caused by specific strains of human papillomavirus. The risk of anal cancer increases with age and in people with persistently low CD4 counts. There is some evidence that anal cancer rates are stabilising or falling due to earlier HIV treatment.
Screening gay and bisexual men for anal cancer or anal lesions that might develop into anal cancer takes place in some clinics and health systems but evidence that it reduces the risk of developing or dying from anal cancer has been lacking.
Researchers in the Netherlands carried out a retrospective analysis of anal cancer incidence and mortality in people enrolled in ATHENA, the national HIV cohort study.
The ATHENA cohort consists of 98% of people with HIV receiving care at HIV clinics in the Netherlands. This study looked at the incidence of anal cancer and screening for the condition in 28,175 people with HIV in the ATHENA cohort who received care between 1996 and 2020. Screening for, and treatment of, anal precancerous lesions began in some HIV clinics in 2007.
The analysis compared the incidence of anal cancer by HIV exposure category. Fifty-nine percent of the cohort were gay and bisexual men, 18% women and 21% men who do not have sex with men.
During the follow-up period, 227 cases of anal cancer were diagnosed, 79% in gay and bisexual men, 4% in women and 16% in men who do not have sex with men. The age-adjusted incidence rate in gay and bisexual men had declined by almost 40% by 2013-20 compared to 1996-2005 (relative risk 0.62) whereas the incidence rates remained unchanged over time in the two other groups.
In a multivariable model controlling for known risk factors for anal cancer (older age, HIV transmission category, AIDS diagnosis, duration of CD4 count below 200, duration of viral load above 1,000 copies/ml), the decline in anal cancer incidence ceased to be significant. The decline was largely explained by a decrease in smoking and less time spent with a CD4 count below 200 or viral load above 1,000 copies/ml (due to earlier diagnosis and treatment initiation).
The investigators also looked at the impact of screening (testing as part of a health check) on anal cancer diagnosis and survival. Fourteen percent of cohort members had been screened at least once and screening was more common among gay and bisexual men (23%) than women (0.8%) or men who do not have sex with men (2.6%).
"Men's risk of dying of anal cancer within five years of diagnosis was lower in those who had participated in screening (3% vs 24%)."
Few people diagnosed with anal cancer (19%) had been screened for precancerous lesions or anal cancer. Twenty-five people diagnosed with anal cancer had previously been diagnosed with a precancerous lesion (anal intraepithelial neoplasia or AIN) as a result of screening and 11 had undergone treatment for AIN. People who had undergone screening were almost two-and-a-half times more likely to be diagnosed with anal cancer (RR 2.4). However, anal cancers diagnosed in those who had undergone screening were less advanced (p=0.033).
Thirty-eight percent of those diagnosed with anal cancer died within five years of diagnosis. Women had more advanced tumours at diagnosis and the risk of dying within five years was higher in women (62% vs 30% in gay and bisexual men).
In men, the risk of dying of anal cancer within five years of diagnosis was lower in those who had participated in screening (3% vs 24%, p=0.024). Participation in screening reduced the risk of dying by 69% in a multivariable analysis (hazard ratio 0.31, p =0.051). The risk of death increased by 11% for each year of follow-up spent with a CD4 count below 200 (HR 1.11, p=0.0022).
The study investigators say that screening of the entire anogenital area is needed to reduce anal cancer mortality, especially for women.
In an accompanying editorial comment, Professor Elizabeth Ann Stier of Boston University says that along with the findings of the ANCHOR study (presented in March 2022), the Dutch findings support screening people living with HIV for anal cancer.
ANCHOR was a large randomised control trial which showed that screening and treatment for high-grade anal intrepithelial lesions reduced the risk of progression to anal cancer compared with monitoring of AIN alone.
But Professor Stier highlights several issues that need to be addressed to enable the incorporation of screening into routine care. Both ANCHOR and ATHENA used high resolution anoscopy, which is costly, cannot be carried out in all clinics and is not recommended in screening guidelines. Other tests used to diagnose AIN may not be sufficiently accurate and it is unclear if any biomarker can be used to identify which patients ought to undergo high resolution anoscopy. More information is also needed about the acceptability of anal cancer screening, especially in women.
But she also notes that the best method of preventing anal cancer is human papillomavirus vaccination. The vaccine is recommended for girls around 12 years old in most high-income countries, with around half the countries also recommending it for boys. In the United Kingdom, it is also recommended for gay and bisexual men up to age 45 in the United Kingdom.
A UK clinical trial comparing methods of screening for anal precancer in gay and bisexual men or transgender women living with HIV, aged 40 and over, is recruiting participants at five HIV clinics in London. You do not need to be receiving your regular HIV care at one of these clinics to take part in the study.
You can learn more about the scientific background to anal cancer screening and treatment in people living with HIV from a British HIV Association webinar on the results of the ANCHOR study presented in 2022.
Van der Zee RP 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, published online 11 January 2023.
Stier EA. How do we prevent anal cancer in people living with HIV? Lancet HIV, published online 11 January 2023.