Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Stichting HIV Monitoring, Amsterdam, Netherlands.
Lancet HIV. 2023 Feb;10(2):e97-e106. doi: 10.1016/S2352-3018(22)00368-X. Epub 2023 Jan 11.
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.
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.
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.
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.
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艾滋病毒感染者的肛门癌发病率很高，尤其是男男性行为者（MSM）。筛查和治疗癌前病变可能会阻止艾滋病毒感染者进展为肛门癌。我们研究了荷兰艾滋病毒感染者肛门癌诊断后的发病率和死亡率趋势，包括自 2007 年以来筛查的影响。
在这项观察性队列研究中，我们分析了正在进行的荷兰艾滋病治疗评估全国性队列（ATHENA）中持续的开放性全国性荷兰艾滋病治疗评估数据。我们纳入了所有同意参与的艾滋病毒感染者，并确定了所有原发性肛门鳞状细胞癌。我们报告了从 1996 年 1 月 1 日至 2020 年 12 月 31 日期间新诊断肛门癌病例的时间趋势，以及诊断为肛门癌患者的全因死亡率和肛门癌相关死亡率。多变量泊松回归用于探索肛门癌发病的危险因素，多变量 Cox 回归用于探索肛门癌相关死亡率的危险因素。
在 28175 名接受艾滋病毒治疗的人群中（59.7%为 MSM），诊断出 227 例原发性肛门癌。尽管队列的平均年龄不断增加，但 MSM 中肛门癌的粗发病率缓慢下降，从 1996-2005 年的每 100000 人年 107.0（95%CI 75.7-147.0）降至 2013-20 年的每 100000 人年 93.7（75.3-115.0）（p=0.49）。非男男性行为者（异性恋）和女性的粗发病率通常低于 MSM，但随着时间的推移略有上升，从非 MSM 的每 100000 人年 51.08（95%CI 20.54-105.25）上升至每 100000 人年 67.82（40.83-105.91；p=0.52），女性从每 100000 人年 8.09（0.20-45.06）上升至每 100000 人年 24.95（10.03-51.40；p=0.29）。2013-20 年 MSM 的年龄调整发病率明显低于 1996-2005 年（发病率比 0.62[95%CI 0.41-0.92]）。危险因素的变化（吸烟减少、累积 CD4 计数<200 个/μL 和血浆 HIV-1 RNA>1000 拷贝/ml）主要解释了 MSM 中肛门癌风险随时间的降低。在 16819 名 MSM 中，有 3866 名（23.0%）至少接受过一次肛门癌筛查。在筛查中诊断的个体的 TNM 肿瘤分期更为有利（Cochrane-Armitage 趋势检验 p=0.033）。艾滋病毒感染者的肛门癌相关 5 年死亡率从 1996-2005 年的 30.4%下降至 2013-20 年的 18.3%（比值比 0.48；p=0.070）。所有接受筛查的男性肛门癌相关死亡率为 3.7%（95%CI 0.5-23.5），未接受筛查的男性为 24.0%（95%CI 18.1-31.3）（p=0.023）。在男性中，筛查参与（风险比[HR]0.31，p=0.051）和累积 CD4 计数<200 个/μL 的暴露（每年增加 1.11；p=0.0022）与肛门癌相关死亡率独立相关。
尽管 MSM 中肛门癌的发病率正在缓慢下降，但非 MSM 和女性的发病率并没有下降，因此医疗保健专业人员不应仅将男男性行为者作为预防肛门癌的重点。在筛查中诊断为肛门癌的男性患者的生存率有所提高，可能是因为他们在疾病早期就得到了诊断。除了预防肛门癌之外，这些数据是对那些最有患肛门癌风险的人群进行筛查的重要理由。
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