Department of Management Policy and Community Health, The University of Texas Health Science Center at Houston, School of Public Health, Houston.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
JAMA Netw Open. 2018 Sep 7;1(5):e181999. doi: 10.1001/jamanetworkopen.2018.1999.
In the last 4 decades, survival among patients with human papillomavirus (HPV)-associated cancers has improved, while the incidence of these cancers has increased among younger cohorts. Among survivors of HPV-associated cancers, persistent HPV infection may remain a risk factor for preventable HPV-associated second primary cancers (HPV-SPCs).
To investigate the risk of HPV-SPCs among survivors of HPV-associated index cancers and to test the hypothesis that the HPV-SPC risk among these persons has increased over the last 4 decades.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of 9 cancer registries of the Surveillance, Epidemiology, and End Results (SEER) database was conducted to identify patients with HPV-associated (cervical, vaginal, vulvar, oropharyngeal, anal, and penile) cancers diagnosed from January 1, 1973, through December 31, 2014. The dates of analysis were July 1, 2017, to January 31, 2018.
The HPV-SPC risk was quantified by calculating standard incidence ratios (SIRs) and excess absolute risks (EARs) per 10 000 person-years at risk (PYR). The HPV-SPC risk by time was estimated using Poisson regression.
From 113 272 (73 085 female and 40 187 male) survivors of HPV-associated cancers, 1397 women and 1098 men developed HPV-SPCs. The SIRs for HPV-SPCs were 6.2 (95% CI, 5.9-6.6) among women and 15.8 (95% CI, 14.9-16.8) among men. The EARs were 18.2 per 10 000 PYR for women and 53.5 per 10 000 PYR for men. Among both women and men, those who had index oropharyngeal cancers had the highest HPV-SPC risk (SIR, 19.8 [95% CI, 18.4-21.4] and EAR, 80.6 per 10 000 PYR among women; SIR, 18.0 [95% CI, 16.9-19.1] and EAR, 61.5 per 10 000 PYR among men). Women who had index cervical cancers and men who had index anal cancers had the lowest HPV-SPC risk (SIR, 2.4 [95% CI, 2.2-2.7] and EAR, 4.5 per 10 000 PYR among women; SIR, 6.5 [95% CI, 4.7-8.8] and EAR, 18.5 per 10 000 PYR among men). Both women and men who had index HPV-associated cancers of any kind had a significantly higher risk of oropharyngeal HPV-SPCs. Over the last 4 decades, the risk of developing most types of HPV-SPCs after index cervical, vaginal, and vulvar cancers increased.
According to this study, the HPV-SPC risk among survivors of HPV-associated cancers is significant, implying that persistent HPV infection at multiple sites may be associated with HPV-SPCs. These findings have the potential to inform surveillance recommendations for survivors of HPV-associated cancers.
在过去的 40 年中，HPV 相关癌症患者的生存率有所提高，而年轻人群中这些癌症的发病率也有所增加。在 HPV 相关癌症的幸存者中，持续性 HPV 感染可能仍然是可预防的 HPV 相关第二原发癌症（HPV-SPCs）的风险因素。
调查 HPV 相关指数癌症幸存者中 HPV-SPC 的风险，并检验这些人 HPV-SPC 风险在过去 40 年中增加的假设。
设计、地点和参与者：本研究对监测、流行病学和最终结果（SEER）数据库中的 9 个癌症登记处进行了回顾性队列研究，以确定从 1973 年 1 月 1 日至 2014 年 12 月 31 日诊断为 HPV 相关（宫颈、阴道、外阴、口咽、肛门和阴茎）癌症的患者。分析日期为 2017 年 7 月 1 日至 2018 年 1 月 31 日。
通过计算标准发病率比（SIRs）和每 10000 人年风险（PYR）的超额绝对风险（EARs）来量化 HPV-SPC 风险。使用泊松回归估计 HPV-SPC 随时间的风险。
在 113272 名（73085 名女性和 40187 名男性）HPV 相关癌症幸存者中，有 1397 名女性和 1098 名男性发生了 HPV-SPCs。女性 HPV-SPCs 的 SIR 为 6.2（95%CI，5.9-6.6），男性为 15.8（95%CI，14.9-16.8）。女性的 EARs 为每 10000 PYR 18.2，男性为每 10000 PYR 53.5。在女性和男性中，患有指数口咽癌的患者 HPV-SPC 风险最高（SIR，19.8 [95%CI，18.4-21.4]和 EAR，女性 80.6 每 10000 PYR；SIR，18.0 [95%CI，16.9-19.1]和 EAR，男性 61.5 每 10000 PYR）。患有指数宫颈癌的女性和患有指数肛门癌的男性 HPV-SPC 风险最低（SIR，2.4 [95%CI，2.2-2.7]和 EAR，女性 4.5 每 10000 PYR；SIR，6.5 [95%CI，4.7-8.8]和 EAR，男性 18.5 每 10000 PYR）。患有任何类型 HPV 相关癌症的女性和男性都有更高的患口咽 HPV-SPC 的风险。在过去的 40 年中，指数宫颈、阴道和外阴癌症后发生大多数类型 HPV-SPC 的风险增加。
根据这项研究，HPV 相关癌症幸存者的 HPV-SPC 风险显著，这表明多个部位的持续性 HPV 感染可能与 HPV-SPCs 相关。这些发现有可能为 HPV 相关癌症幸存者的监测建议提供信息。
