人乳头瘤病毒疫苗针对最严格的宫颈肿瘤终点（基于登记处的随访）的十年随访
Ten-year follow-up of human papillomavirus vaccine efficacy against the most stringent cervical neoplasia end-point-registry-based follow-up of .
作者信息
Lehtinen Matti, Lagheden Camilla, Luostarinen Tapio, Eriksson Tiina, Apter Dan, Harjula Katja, Kuortti Marjo, Natunen Kari, Palmroth Johanna, Petäjä Tiina, Pukkala Eero, Siitari-Mattila Mari, Struyf Frank, Nieminen Pekka, Paavonen Jorma, Dubin Gary, Dillner Joakim
机构信息
University of Tampere, Tampere, Finland.
Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
出版信息
BMJ Open. 2017 Aug 18;7(8):e015867. doi: 10.1136/bmjopen-2017-015867.
OBJECTIVE
Due to long lag time between infection/cancer diagnoses human papillomavirus (HPV) vaccination programs will deliver vaccine efficacy (VE) estimates against cancer end-points late. Cancer registry follow-up of population-based, randomised trial cohorts of vaccinated and unvaccinated women was undertaken for the estimation of VE against cervical intraepithelial neoplasia grade three and invasive cancer (CIN3+).
METHODS
We report interim results with 98 561 person years of Finnish Cancer Registry -based follow-up of individually and/or cluster randomised cohorts of HPV-16/18 vaccinated and unvaccinated adolescent women enrolled in June 2003/2005, and between May 2004 and April 2005, respectively. The cohorts comprised 15 627 18- to 19-year-old unvaccinated women (NCT01393470), and 2 401 and 64 16- to 17-year-old HPV-16/18 vaccinated women participating the PATRICIA (NCT00122681) and HPV-012 (NCT00169494) trials, respectively. The age-aligned passive follow-up started 6 months after the clinical trials' end.
RESULTS
During the follow-up of 4.5 to 10 years post enrolment we identified 75 cases of cervical intraepithelial neoplasia grade 3 (CIN3) and 4 cases of invasive cervical cancer (ICC) in the unvaccinated cohort, and 4 CIN3 cases in the HPV-16/18 vaccinated women. Diagnostic blocks were available for HPV typing from 87% of the cases. CIN3+ lesions were detectable in 54 cases. HPV16 was found in 26 of 50 unvaccinated CIN3+ cases, and in 3 CIN3+ cases in the HPV-16/18 vaccinated women. The latter were all baseline positive for cervical HPV16 DNA. Baseline data was not available for the unvaccinated women. Intention-to-treat VE against any CIN3+ was 66% (95% CI 8, 88).
CONCLUSIONS
Ten years post vaccination the AS04-adjuvanted HPV-16/18 vaccine shows continued efficacy against CIN3+ irrespectively of HPV type. Vaccine efficacy was not observed in baseline HPV16 DNA positive subjects.
TRIAL REGISTRATION NUMBER
NCT01393470.
目的
由于人类乳头瘤病毒（HPV）疫苗接种计划与感染/癌症诊断之间存在较长的滞后时间，针对癌症终点的疫苗效力（VE）估计结果将较晚得出。我们对基于人群的已接种和未接种疫苗女性的随机试验队列进行癌症登记随访，以评估针对三级宫颈上皮内瘤变和浸润性癌（CIN3+）的疫苗效力。
方法
我们报告了中期结果，该结果来自芬兰癌症登记处对2003年6月/2005年分别单独和/或整群随机分组的HPV-16/18疫苗接种和未接种疫苗的青春期女性队列进行的98561人年的随访。这些队列包括15627名18至19岁未接种疫苗的女性（NCT01393470），以及分别参与PATRICIA试验（NCT00122681）和HPV-012试验（NCT00169494）的2401名和6416至17岁接种HPV-16/18疫苗的女性。年龄匹配的被动随访在临床试验结束6个月后开始。
结果
在入组后的4.5至10年随访期间，我们在未接种疫苗的队列中发现了75例三级宫颈上皮内瘤变（CIN3）和4例浸润性宫颈癌（ICC），在接种HPV-16/18疫苗的女性中发现了4例CIN3病例。87%的病例可获得用于HPV分型的诊断样本。在54例病例中检测到CIN3+病变。在50例未接种疫苗的CIN3+病例中有26例检测到HPV16，在接种HPV-16/18疫苗的女性中有3例CIN3+病例检测到HPV16。后者宫颈HPV16 DNA基线均为阳性。未接种疫苗的女性没有基线数据。针对任何CIN3+的意向性分析疫苗效力为66%（95%CI 8，88）。
结论
接种疫苗十年后，佐剂为AS04的HPV-16/18疫苗对CIN3+仍具有持续效力，与HPV类型无关。在基线HPV16 DNA阳性的受试者中未观察到疫苗效力。
试验注册号
NCT01393470。
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