People with HIV have a substantially higher risk of anal cancer than the general population. We aimed to identify risk factors associated with the development of anal cancer among people with HIV to implement more effective and targeted screening strategies. We conducted a multicentre retrospective cohort study in 16 hospitals across Catalonia and the Balearic Islands, Spain, between Jan 1, 1998, and Dec 31, 2022. Treatment-naive people with HIV nested in the PISCIS cohort aged 16 years and older with biopsy-proven squamous cell carcinoma of the anus or anal canal were eligible for inclusion. Data were retrieved from every hospital registry and were centrally validated in the PISCIS cohort and the Public Data Analysis for Health Research and Innovation Program. The primary outcome was the incidence rate (IR) of histologically confirmed anal cancer. We used Poisson regression to examine the association between the following risk factors and incidence of anal cancer: age, mode of HIV transmission, nadir CD4 cell count, and time period of HIV diagnosis. Among 14 238 people with HIV, 107 (0·8%) developed anal cancer, with an overall IR of 72·5 cases per 100 000 person-years (95% CI 59·4–87·6) and median follow-up of 9·5 years (IQR 4·4–15·7). Of these patients with anal cancer, 37 (34·6%) died, of which 24 (64·9%) deaths were related to anal cancer. Incidence was highest among people with HIV with historical nadir CD4 counts of less than 200 cells per μL (IR 105·0 person-years, 95% CI 82·0–132·5) and lowest among those with counts of more than 350 cells per μL (2·9 person-years, 0·1–16·0). Among men who have sex with men (MSM), the IR was 211·5 person-years (95% CI 151·1–211·7) among those with a CD4 count of less than 200 cells per μL, 37·6 person-years (16·2–74·1) among those with a count of 200–350 cells per μL, and 4·8 person-years (0·1–26·9) among those with a count of more than 350 cells per μL. Among people with HIV younger than 30 years, there were no cases of anal cancer among women or men who do not have sex with men, and one case among MSM with a nadir CD4 count of more than 350 cells per μL (IR 4·8 person-years, 95% CI 0·1–26·9). In the multivariable analysis, people with HIV with nadir CD4 counts of more than 350 cells per μL had the lowest risk of developing anal cancer, compared with people with HIV with counts of less than 200 cells per μL (adjusted IR ratio 0·03, 95% CI 0·00–0·25; p=0·0010) or 200–350 cells per μL (0·30, 0·17–0·55; p<0·0001). Compared with people with HIV younger than 30 years, people with HIV aged 60 years and older had an adjusted IR ratio of 27·6 (3·7–206·9; p=0·0010) and people with HIV aged 45–59 years of 21·6 (3·0–156·4; p=0·0020). Compared with individuals diagnosed after 2015, a diagnosis of HIV before 1998 had an adjusted IR ratio of 33·0 (7·9–137·5; p<0·0001). A nadir CD4 count threshold below 350 cells per μL, particularly less than 200 cells per μL, has the potential to identify people with HIV at heightened risk of developing anal cancer. Customised screening strategies that prioritise screening for individuals at high risk with this surrogate marker could maximise available resources. External validation of these data with other cohorts is required before screening recommendations can be updated. Catalan Health Department, Generalitat de Catalunya.

中文翻译：

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确定西班牙 HIV 感染者肛门癌的危险因素：PISCIS 队列中的一项多中心回顾性队列研究


艾滋病毒感染者患肛门癌的风险比一般人群高得多。我们的目的是确定与艾滋病毒感染者患肛门癌相关的危险因素，以实施更有效、更有针对性的筛查策略。我们于 1998 年 1 月 1 日至 2022 年 12 月 31 日期间在西班牙加泰罗尼亚和巴利阿里群岛的 16 家医院进行了一项多中心回顾性队列研究。PISCIS 队列中年龄 16 岁及以上且接受活检的初治 HIV 感染者经证实的肛门或肛管鳞状细胞癌符合纳入条件。从每个医院登记处检索数据，并在 PISCIS 队列和健康研究与创新计划公共数据分析中进行集中验证。主要结局是组织学证实的肛门癌的发病率（IR）。我们使用泊松回归来检查以下危险因素与肛门癌发病率之间的关联：年龄、HIV 传播方式、最低 CD4 细胞计数和 HIV 诊断时间段。在 14 238 名 HIV 感染者中，107 名 (0·8%) 患上肛门癌，总体 IR 为每 10 万人年 72·5 例（95% CI 59·4–87·6），中位随访时间9·5 年（IQR 4·4–15·7）。这些肛门癌患者中，死亡37例（34·6%），其中24例（64·9%）死亡与肛门癌相关。在历史最低 CD4 计数低于 200 个细胞/μL 的 HIV 感染者中，发病率最高（IR 105·0 人年，95% CI 82·0–132·5），在细胞计数超过 350 个的 HIV 感染者中发病率最低每μL（2·9 人年，0·1–16·0）。 在男男性行为者 (MSM) 中，CD4 计数低于 200 个细胞/μL 的人中，IR 为 211·5 人年 (95% CI 151·1–211·7)，37·6 人每μL细胞计数为200-350个的人为-年（16·2-74·1），每μL细胞计数超过350个的人为4·8人年（0·1-26·9）每微升。在 30 岁以下的 HIV 感染者中，未与男性发生性关系的女性或男性中没有肛门癌病例，MSM 中 1 例最低 CD4 计数超过 350 个细胞/μL (IR 4·8人年，95% CI 0·1–26·9）。在多变量分析中，与 CD4 计数低于 200 个细胞/μL 的 HIV 感染者相比，最低 CD4 计数超过 350 个细胞/μL 的 HIV 感染者患肛门癌的风险最低（调整后的 IR 比率 0·03， 95% CI 0·00–0·25；p=0·0010) 或 200–350 个细胞/μL (0·30、0·17–0·55；p<0·0001)。与 30 岁以下的 HIV 感染者相比，60 岁及以上的 HIV 感染者的调整后 IR 比率为 27·6（3·7–206·9；p=0·0010），而 45–59 岁的 HIV 感染者的调整后 IR 比率为 27·6（3·7–206·9；p=0·0010） 21·6 年（3·0–156·4；p=0·0020）。与 2015 年之后诊断的个体相比，1998 年之前诊断出 HIV 的调整后 IR 比率为 33·0 (7·9–137·5；p<0·0001)。 CD4 计数阈值最低值低于 350 个细胞/μL，特别是低于 200 个细胞/μL，有可能识别出罹患肛门癌风险较高的 HIV 感染者。使用这种替代标记优先筛查高风险个体的定制筛查策略可以最大限度地利用可用资源。在更新筛查建议之前，需要与其他队列对这些数据进行外部验证。加泰罗尼亚卫生部，加泰罗尼亚自治区。