Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
Unit of Statistics and Pharmacoepidemiology, Danish Cancer Society Research Center, Copenhagen, Denmark.
Int J Cancer. 2020 May 1;146(9):2413-2422. doi: 10.1002/ijc.32565. Epub 2019 Aug 2.
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.
在这项基于登记的队列研究中，我们估计与非移植对照组相比，肾移植受者（RTR）发生人乳头瘤病毒（HPV）相关肛门生殖器前恶性肿瘤和癌症的风险。我们在全国肾脏病登记处中确定了 1990-2015 年期间丹麦的所有首次 RTR。对于每个 RTR，我们从背景人群中随机选择了 50 名年龄和性别匹配的非 RTR。该研究人群接受了长达 27 年的宫颈、阴道、外阴、阴茎和肛门上皮内瘤变 2-3 级（IN2/3）和癌症的诊断。我们分别使用年龄作为潜在时间尺度，通过 Cox 回归估计 RTR 与非 RTR 中男性和女性肛门生殖器 IN2/3 和癌症的风险比（HR），调整收入、教育、HPV 疫苗接种和免疫抑制状况。我们纳入了 4261 名 RTR 和 213673 名非 RTR。RTR 发生宫颈（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 的风险增加。大多数部位的肛门生殖器癌症的 HR 也增加。女性 RTR 在移植物功能期间发生肛门生殖器 IN2/3 的 HR 高于透析期间。在移植时年龄<40 岁的女性 RTR 中，10-15%在移植后 20 年内发生宫颈 IN2/3，5-12%发生阴道/外阴/肛门 IN2/3，而非女性非 RTR 分别为 4-8%和 0.2-0.4%。总之，RTR 发生 HPV 相关肛门生殖器前恶性肿瘤和癌症的风险明显高于非 RTR。
