在这项基于注册的队列研究中,我们估计了与非移植比较队列相比,肾移植受者(RTRs)发生人乳头瘤病毒(HPV)相关的肛门生殖器癌前病变和癌症的风险.我们在1990-2015年期间在丹麦的全国肾脏病登记中确定了所有首次RTR。对于每个RTR,我们从背景人群中随机选择了50个年龄和性别匹配的非RTR.对研究人群进行宫颈诊断,阴道,外阴,阴茎和肛门上皮内瘤变2-3级(IN2/3)和癌症长达27年。我们估计了RTR中肛门生殖器IN2/3和癌症的风险比(HRs)与非RTR通过Cox回归分别对男性和女性使用年龄作为基本时间尺度,调整收入,教育,HPV疫苗接种和免疫受损条件。我们包括4,261个RTR和213,673个非RTR。RTR对宫颈的危害增加(HR=2.1,95%CI:1.7-2.8),阴道(HR=35.0,95%CI:13.9-87.7),外阴(HR=16.4,95%CI:10.4-25.8),阴茎(HR=21.9,95%CI:11.1-43.5)和肛门(女性:HR=51.1,95%CI:28.0-93.1;男性:HR=39.0,95%CI:16.7-91.1)IN2/3。肛门生殖器癌的HR在大多数部位也增加。女性RTR中肛门生殖器IN2/3的HR在移植物功能期间倾向于高于透析期间。在移植时年龄<40岁的女性RTR中,移植后20年内有10-15%的宫颈IN2/3和5-12%的阴道/外阴/肛门IN2/3,与4-8和0.2-0.4%相比,分别,女性非RTR。总之,RTR与非RTR相比,发生HPV相关的肛门生殖器前恶性肿瘤和癌症的风险更高。
In this registry-based cohort
study, we estimated the risk of human papillomavirus (HPV)-related
anogenital premalignancies and cancer in renal transplant recipients (RTRs) compared to a nontransplanted comparison cohort. We identified all first-time RTRs in Denmark during 1990-2015 in a nationwide nephrology register. For each RTR, we randomly selected 50 age- and sex-matched non-RTRs from the background population. The
study population was followed for diagnoses of cervical, vaginal, vulvar, penile and anal intraepithelial neoplasia grades 2-3 (IN2/3) and cancer for up to 27 years. We estimated hazard ratios (HRs) of
anogenital IN2/3 and cancer in RTRs vs. non-RTRs by Cox regression separately for men and women using age as underlying timescale, adjusting for income, education, HPV vaccination and immunocompromising conditions. We included 4,261 RTRs and 213,673 non-RTRs. RTRs had increased hazard of cervical (HR = 2.1, 95% CI: 1.7-2.8), vaginal (HR = 35.0, 95% CI: 13.9-87.7), vulvar (HR = 16.4, 95% CI: 10.4-25.8), penile (HR = 21.9, 95% CI: 11.1-43.5) and anal (women: HR = 51.1, 95% CI: 28.0-93.1; men: HR = 39.0, 95% CI: 16.7-91.1) IN2/3. The HRs of
anogenital cancers were also increased at most sites. The HR of anogenital IN2/3 in female RTRs tended to be higher during graft function than during dialysis. In female RTRs aged <40 years at transplantation, 10-15% had cervical IN2/3 and 5-12% had vaginal/vulvar/anal IN2/3 within 20 years after transplantation, compared to 4-8 and 0.2-0.4%, respectively, of female non-RTRs. In conclusion, RTRs had substantially higher risk of HPV-related
anogenital premalignancies and cancer than non-RTRs.