长期抗逆转录病毒治疗与肛门生殖器癌症风险
Long-term Antiretroviral Therapy and Anogenital Cancer Risk
HIV感染者肛门生殖器癌症风险显著升高，但长期抗逆转录病毒治疗能否降低这一风险尚不清楚。研究在博茨瓦纳30至65岁成人中开展目标试验模拟，纳入14312人，其中42%为HIV感染者，前瞻性发现1045例肛门生殖器癌症。与无HIV者相比，癌症相对风险随治疗时间延长而升高：未治疗为4.6，治疗不足5年为4.0，5至9年为4.6，10年及以上达7.4；治疗10年以上者各类癌症风险最高。既往晚期HIV病史也增加风险，但治疗后可减弱。结论是长期抗病毒治疗并未降低肛门生殖器癌症风险，需要加强预防策略。
为什么推荐给您：大型前瞻性队列挑战了长期抗病毒治疗降低癌症风险的假设，有临床意义。
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摘要Abstract
BACKGROUND: People with human immunodeficiency virus (HIV) (PWH) experience substantially increased risk of anogenital cancer. Whether long-term antiretroviral therapy (ART) reduces anogenital cancer risk is unknown.
METHODS: A target trial emulation using a case-cohort design among Botswana adults aged 30-65, sampled via a probability-based household survey across 30 communities. Cases of cervical, vulvar, anal, and penile cancer were prospectively ascertained at the country's principal treatment centers. We estimated the marginal relative risk (RR) of incident anogenital cancer by ART duration, compared with adults without HIV, using g-computation from weighted models that accounted for shared determinants of human papillomavirus, and HIV infection, access to cancer care, and ART duration.
RESULTS: 14 312 participants were enrolled (42% PWH), including 1045 (79% PWH) with incident anogenital cancer-792 cervical, 106 vulvar, 80 anal, and 67 penile cancers. Compared with people without HIV, the marginal RR (95% CI) of anogenital cancer increased with longer durations of ART (P = .001) (no ART: 4.6; 4.3-5.0; <5 years: 4.0; 3.7-4.3; 5-9 years: 4.6; 4.2-5.0; ≥10 years: 7.4; 6.8-8.1). Individuals receiving ART for ≥10 years had the highest RR for each cancer evaluated: cervix, 4.4 (4.0 to 4.8); vulva, 36 (22-57); anus, 15 (11-20); and penis, 102 (42-250). Prior advanced HIV disease was associated with increased risk but this effect diminished on ART and contributed relatively little to overall risk.
CONCLUSIONS: Long-term utilization of ART was not associated with a reduction in anogenital cancer risk. Improved prevention strategies are needed for PWH.