TY - JOUR
T1 - Effect of the introduction of screening for cancer precursor lesions on anal cancer incidence over time in people living with HIV
T2 - a nationwide cohort study
AU - van der Zee, Ramon P.
AU - Wit, Ferdinand W. N. M.
AU - Richel, Olivier
AU - van der Valk, Marc
AU - ATHENA national observational HIV cohort
AU - Reiss, Peter
AU - de Vries, Henry J. C.
AU - Prins, Jan M.
N1 - Funding Information: The authors received no specific funding for this work. The ATHENA database is maintained by SHM and financed by the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment. The funding source of the ATHENA database did not have any influence on the design of the study, data collection, data analysis, interpretation of the data, in writing the manuscript, or in the decision to submit the article for publication. Publisher Copyright: © 2023 Elsevier Ltd
PY - 2023/2/1
Y1 - 2023/2/1
N2 - Background: Incidence of anal cancer is high in people living with HIV, particularly in men who have sex with men (MSM). Screening for and treatment of precursor lesions might prevent progression to anal cancer in people living with HIV. We examined trends in incidence of and mortality after anal cancer diagnosis in people living with HIV, including the effect of screening from 2007 onwards, in the Netherlands. Methods: In this observational cohort study, we analysed data from the ongoing open nationwide Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort. We included all consenting adults living with HIV and identified all primary anal squamous cell carcinoma. We reported temporal trends in incident anal cancer cases from Jan 1, 1996, to Dec 31, 2020, and all-cause and anal cancer-related mortality in individuals diagnosed with anal cancer. Multivariable Poisson regression was used to explore risk factors for incident anal cancer and multivariable Cox regression was used to explore risk factors for anal cancer-related mortality. Findings: Among 28 175 individuals in HIV care (59·7% MSM), 227 primary anal cancer cases were diagnosed. Despite the increasing average age of the cohort, crude incidence rates of anal cancer in MSM declined slowly over time, from 107·0 (95% CI 75·7–147·0) per 100 000 person-years in 1996–2005 to 93·7 (75·3–115·0) per 100 000 person-years in 2013–20 (p=0·49). Crude incidence rates in men who do not have sex with men (non-MSM) and women were generally lower than in MSM, but increased slightly over time, from 51·08 (95% CI 20·54–105·25) to 67·82 (40·83–105·91; p=0·52) per 100 000 person-years in non-MSM and from 8·09 (0·20–45·06) to 24·95 (10·03–51·40; p=0·29) per 100 000 person-years in women. The age-adjusted incidence rate in MSM in 2013–20 was significantly lower (rate ratio 0·62 [95% CI 0·41–0·92]) compared with in 1996–2005. Changes in risk factors (less smoking, cumulative exposure to CD4 count of <200 cells per μL, and plasma HIV-1 RNA of >1000 copies per mL) mostly explained the decrease in anal cancer risk over time in MSM. 3866 (23·0%) of 16 819 MSM participated in anal cancer screening at least once. TNM tumour staging was more favourable (Cochrane-Armitage test for trend p=0·033) in individuals diagnosed during screening. Crude anal cancer-associated 5-year mortality in people living with HIV decreased from 30·4% (1996–2005) to 18·3% (2013–20; odds ratio 0·48; p=0·070). Anal cancer-related mortality was 3·7% (95% CI 0·5–23·5) in all men who had been screened and 24·0% (95% CI 18·1–31·3) in men who had not been screened (p=0·023). In men, screening participation (hazard ratio [HR] 0·31, p=0·051) and cumulative exposure to CD4 counts of less than 200 cells per μL (HR 1·11 per year; p=0·0022) were independently associated with anal cancer-related mortality. Interpretation: As anal cancer incidence is slowly declining in MSM but not in non-MSM and women, health-care professionals should not focus only on MSM for anal cancer prevention. Men diagnosed with anal cancer during screening had improved survival, probably because they were diagnosed at an earlier disease stage. Next to preventing anal cancer, these data are an important justification to screen those most at risk of anal cancer. Funding: None.
AB - Background: Incidence of anal cancer is high in people living with HIV, particularly in men who have sex with men (MSM). Screening for and treatment of precursor lesions might prevent progression to anal cancer in people living with HIV. We examined trends in incidence of and mortality after anal cancer diagnosis in people living with HIV, including the effect of screening from 2007 onwards, in the Netherlands. Methods: In this observational cohort study, we analysed data from the ongoing open nationwide Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort. We included all consenting adults living with HIV and identified all primary anal squamous cell carcinoma. We reported temporal trends in incident anal cancer cases from Jan 1, 1996, to Dec 31, 2020, and all-cause and anal cancer-related mortality in individuals diagnosed with anal cancer. Multivariable Poisson regression was used to explore risk factors for incident anal cancer and multivariable Cox regression was used to explore risk factors for anal cancer-related mortality. Findings: Among 28 175 individuals in HIV care (59·7% MSM), 227 primary anal cancer cases were diagnosed. Despite the increasing average age of the cohort, crude incidence rates of anal cancer in MSM declined slowly over time, from 107·0 (95% CI 75·7–147·0) per 100 000 person-years in 1996–2005 to 93·7 (75·3–115·0) per 100 000 person-years in 2013–20 (p=0·49). Crude incidence rates in men who do not have sex with men (non-MSM) and women were generally lower than in MSM, but increased slightly over time, from 51·08 (95% CI 20·54–105·25) to 67·82 (40·83–105·91; p=0·52) per 100 000 person-years in non-MSM and from 8·09 (0·20–45·06) to 24·95 (10·03–51·40; p=0·29) per 100 000 person-years in women. The age-adjusted incidence rate in MSM in 2013–20 was significantly lower (rate ratio 0·62 [95% CI 0·41–0·92]) compared with in 1996–2005. Changes in risk factors (less smoking, cumulative exposure to CD4 count of <200 cells per μL, and plasma HIV-1 RNA of >1000 copies per mL) mostly explained the decrease in anal cancer risk over time in MSM. 3866 (23·0%) of 16 819 MSM participated in anal cancer screening at least once. TNM tumour staging was more favourable (Cochrane-Armitage test for trend p=0·033) in individuals diagnosed during screening. Crude anal cancer-associated 5-year mortality in people living with HIV decreased from 30·4% (1996–2005) to 18·3% (2013–20; odds ratio 0·48; p=0·070). Anal cancer-related mortality was 3·7% (95% CI 0·5–23·5) in all men who had been screened and 24·0% (95% CI 18·1–31·3) in men who had not been screened (p=0·023). In men, screening participation (hazard ratio [HR] 0·31, p=0·051) and cumulative exposure to CD4 counts of less than 200 cells per μL (HR 1·11 per year; p=0·0022) were independently associated with anal cancer-related mortality. Interpretation: As anal cancer incidence is slowly declining in MSM but not in non-MSM and women, health-care professionals should not focus only on MSM for anal cancer prevention. Men diagnosed with anal cancer during screening had improved survival, probably because they were diagnosed at an earlier disease stage. Next to preventing anal cancer, these data are an important justification to screen those most at risk of anal cancer. Funding: None.
UR - http://www.scopus.com/inward/record.url?scp=85147106120&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S2352-3018(22)00368-X
DO - https://doi.org/10.1016/S2352-3018(22)00368-X
M3 - Article
C2 - 36640800
SN - 0140-6736
VL - 10
SP - e97-e106
JO - The Lancet HIV
JF - The Lancet HIV
IS - 2
ER -