Screening HIV-positive individuals for early signs of anal cancer may lead to an earlier diagnosis and better survival, according to an observational Dutch cohort study.

Among men who have sex with men (MSM) living with HIV, anal cancer-related mortality was 3.7% in those who had been screened in the Netherlands compared with 24.0% in those who had not been screened (P=0.023), reported Jan Prins, PhD, of the University of Amsterdam, and colleagues.

While screening HIV-positive individuals detected more cases of anal cancer, tumor stage was more favorable for those diagnosed during screening (P=0.033), they noted in The Lancet HIV.

“We found that screened individuals were more likely to be diagnosed with anal cancer, but at an earlier stage than unscreened individuals, resulting in better survival. These data are an important justification to screen those most at risk of developing anal cancer,” Prins and team wrote.

Multivariable regression analyses suggested that the main factors associated with anal cancer-related mortality were screening participation (HR 0.31, P=0.051) and cumulative exposure to CD4 counts of <200 cells/μL (HR 1.11 per year, P=0.0022).

Prins’ group explained that starting in late 2007, screening and treatment to prevent anal cancer in the Netherlands was gradually implemented in some HIV treatment centers, with the main focus being on MSM.

Of the 227 individuals with HIV diagnosed with anal cancer in the study, 87 died — 70 within 5 years of their diagnosis. MSM were the least likely to die within 5 years (30.6%), followed by men who do not have sex with men (non-MSM; 37.3%) and women (62.5%).

Furthermore, women and non-MSM had more advanced tumor stages at the time of diagnosis (10% and 5.4%, respectively, were diagnosed at stage I), while 15.6% of MSM were diagnosed at stage I (P=0.0061).

“Our data support that healthcare professionals should not only be focused on MSM with HIV, but on the entire group of people living with HIV, as anal cancer incidence is rising in non-MSM and women,” Prins and colleagues wrote.

In an accompanying editorial, Elizabeth Ann Stier, MD, of Boston University Chobanian & Avedisian School of Medicine, noted that “although anal cancer is rare in the general population, its incidence is unacceptably high in people living with HIV.”

She said that prevention of anal cancer is still a work in progress. “Both cytology and human papillomavirus testing have limitations in accuracy for the detection of anal high-grade squamous intraepithelial lesions,” she wrote.

Stier also questioned whether efficacy of treatment can be improved, noting that the current study plus a previous study “showed that patients develop anal cancer despite treatment for anal high-grade squamous intraepithelial lesions.”

“The good news is that screening for anal cancer can decrease the incidence and mortality associated with anal cancer,” the editorialist concluded. “Optimization of the implementation of anal cancer prevention in people living with HIV is now needed.”

For this study, Prins and colleagues used data from the ongoing Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort from January 1996 through December 2020, and included 28,175 individuals with HIV, 59.7% of whom were MSM.

Crude incidence rates of anal cancer in MSM with HIV decreased over time in the country, from 107.0 per 100,000 person-years in 1996-2005 to 93.7 per 100,000 person-years in 2013-2020 (P=0.49). While crude incidence rates in non-MSM with HIV and in women with HIV were generally lower, they increased over time, from 51.08 to 67.82 per 100,000 person-years (P=0.52), and from 8.09 to 24.95 per 100,000 person-years (P=0.29), respectively.

The age-adjusted incidence rate in MSM with HIV from 2013-2020 was also lower compared with 1996-2005 (rate ratio 0.62, 95% CI 0.41-0.92), and likely due to changes in risk factors, including less smoking, cumulative exposure to CD4 count of <200 cells/μL, and plasma HIV-1 RNA of >1,000 copies/mL, Prins and team explained.

From 1996-2005 to 2013-2020, crude anal cancer-associated 5-year mortality rates in the country among people living with HIV decreased from 30.4% to 18.3%, though this difference was not statistically significant (P=0.070).

Of the 227 people diagnosed with anal cancer, 180 were MSM (median age 53), 37 were men who do not have sex with men (median age 50.4), and 10 were women (median age 48.3).

Nearly half were current smokers, median cumulative exposure to CD4 count of <200 cells/μL was 0.5 years, and median cumulative exposure to plasma HIV-1 RNA of >1,000 copies/mL was 1.2 years. Just over half had a previous diagnosis of AIDS.

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