Hildesheim Allan, Herrero Rolando, Wacholder Sholom, Rodriguez Ana C, Solomon Diane, Bratti M Concepcion, Schiller John T, Gonzalez Paula, Dubin Gary, Porras Carolina, Jimenez Silvia E, Lowy Douglas R
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
JAMA. 2007 Aug 15;298(7):743-53. doi: 10.1001/jama.298.7.743.
Viruslike particle human papillomavirus (HPV) vaccines were designed to prevent HPV infection and development of cervical precancers and cancer. Women with oncogenic HPV infections might consider vaccination as therapy.
To determine whether vaccination against HPV types 16 and 18 increases the rate of viral clearance in women already infected with HPV.
Phase 3, masked, community-based randomized trial conducted in 2 provinces of Costa Rica.
A total of 2189 women aged 18 to 25 years who were recruited between June 2004 and December 2005. Participants were positive for HPV DNA at enrollment, had at least 6 months of follow-up, and had follow-up HPV DNA results.
Participants were randomly assigned to receive 3 doses of a bivalent HPV-16/18 L1 protein viruslike particle AS04 candidate vaccine (n = 1088) or a control hepatitis A vaccine (n = 1101) over 6 months.
Presence of HPV DNA was determined in cervical specimins by a molecular hybridization assay using chemiluminescence with HPV RNA probes and by polymerase chain reaction using SPF10 primers and a line probe assay detection system before vaccination and by polymerase chain reaction after vaccination. We compared rates of type-specific viral clearance using generalized estimating equations methods at the 6-month visit (after 2 doses) and 12-month visit (after 3 doses) in the 2 study groups.
There was no evidence of increased viral clearance at 6 or 12 months in the group who received HPV vaccine compared with the control group. Clearance rates for HPV-16/18 infections at 6 months were 33.4% (82/248) in the HPV vaccine group and 31.6% (95/298) in the control group (vaccine efficacy for viral clearance, 2.5%; 95% confidence interval, -9.8% to 13.5%). Human papillomavirus 16/18 clearance rates at 12 months were 48.8% (86/177) in the HPV vaccine group and 49.8% (110/220) in the control group (vaccine efficacy for viral clearance, -2.0%; 95% confidence interval, -24.3% to 16.3%). There was no evidence of a therapeutic effect for other oncogenic or nononcogenic HPV categories, among women receiving all vaccine doses, among women with single infections, or among women stratified by the following entry variables: HPV-16/18 serology, cytologic results, HPV DNA viral load, time since sexual debut, Chlamydia trachomatis or Neisseria gonorrhoeae infection, hormonal contraceptive use, or smoking.
In women positive for HPV DNA, HPV-16/18 vaccination does not accelerate clearance of the virus and should not be used to treat prevalent infections.
clinicaltrials.gov Identifier: NCT00128661.
病毒样颗粒人乳头瘤病毒（HPV）疫苗旨在预防HPV感染以及宫颈癌前病变和癌症的发生。致癌性HPV感染的女性可能会考虑将接种疫苗作为一种治疗方法。
确定接种16型和18型HPV疫苗是否能提高已感染HPV女性的病毒清除率。
在哥斯达黎加的2个省份进行的3期、双盲、基于社区的随机试验。
2004年6月至2005年12月期间招募的2189名年龄在18至25岁之间的女性。参与者在入组时HPV DNA呈阳性，至少有6个月的随访时间，且有随访的HPV DNA检测结果。
参与者被随机分配在6个月内接受3剂二价HPV-16/18 L1蛋白病毒样颗粒AS04候选疫苗（n = 1088）或对照甲型肝炎疫苗（n = 1101）。
在接种疫苗前，通过使用HPV RNA探针的化学发光分子杂交试验以及使用SPF10引物和线性探针分析检测系统的聚合酶链反应来确定宫颈标本中HPV DNA的存在情况；接种疫苗后则通过聚合酶链反应来确定。我们使用广义估计方程方法在2个研究组的6个月随访（2剂疫苗接种后）和12个月随访（3剂疫苗接种后）时比较了型特异性病毒清除率。
与对照组相比，接种HPV疫苗组在6个月或12个月时没有证据表明病毒清除率增加。HPV疫苗组6个月时HPV-16/18感染的清除率为33.4%（82/248），对照组为31.6%（95/298）（病毒清除的疫苗效力为2.5%；95%置信区间为-9.8%至13.5%）。HPV疫苗组12个月时HPV 16/18的清除率为48.8%（86/177），对照组为49.8%（110/220）（病毒清除的疫苗效力为-2.0%；95%置信区间为-24.3%至16.3%）。在接受所有疫苗剂量的女性、单一感染的女性或按以下入组变量分层的女性中，没有证据表明对其他致癌或非致癌HPV类别有治疗效果：HPV-16/18血清学、细胞学结果、HPV DNA病毒载量、首次性行为后的时间、沙眼衣原体或淋病奈瑟菌感染、激素避孕药使用情况或吸烟情况。
对于HPV DNA呈阳性的女性，接种HPV-16/18疫苗不会加速病毒清除，不应将其用于治疗现有的感染。
clinicaltrials.gov标识符：NCT00128661。
