Prophylactic vaccination against human papillomavirus infection and disease in women: a systematic review of randomized controlled trials
Prophylactic vaccination against human papillomavirus infection and disease in women: a systematic review of randomized controlled trials
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DOI：
10.1503/cmaj.070948
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发表时间：
2007-08-28
影响因子：
14.6
通讯作者：
Fergusson, Dean
中科院分区：
文献类型：
--
作者：
Rambout, Lisa;Hopkins, Laura;Fergusson, Dean
背景：人类乳头瘤病毒（HPV）现在被认为是宫颈癌的一个必要原因，预防HPV疫苗旨在预防生殖器疣，宫颈癌前病变和宫颈癌现在是可用的。为了评估对疾病负担的潜在影响，我们对随机对照试验的证据进行了系统回顾。方法：我们进行了系统的文献检索，以确定预防性HPV疫苗接种的所有随机对照试验。从1950年到2007年6月的5个电子数据库（MEDLINE, MEDLINE in process， EMBASE， Cochrane Central Registry of Controlled Trials和Cochrane Library）的报告，所有纳入研究的参考书目和叙述性综述（2006 - 2007），临床试验登记，谷歌Scholar，公共卫生公告，选定的会议论文集（2004 - 2007年）和制造商关于未发表数据或正在进行的试验的信息由2名独立审稿人根据预先确定的资格标准进行筛选。疫苗必须包含至少一种致癌HPV毒株的覆盖。研究的主要结果是高级别宫颈病变（高级别鳞状上皮内病变，或2级或3级宫颈上皮内瘤变）的频率。次要结局是持续性HPV感染、低级别宫颈病变（低级别鳞状上皮内病变或1级宫颈上皮内瘤变）、外生殖器病变、不良事件和死亡。对所有临床和方法学上存在充分同质性的病例进行数据荟萃分析。结果：在筛选的456份报告中，9份纳入本综述（6份为随机对照试验报告，3份为初始试验的随访报告）。荟萃分析的结果显示，与对照组相比，预防性HPV疫苗接种与疫苗型HPV毒株引起的高级别宫颈病变频率降低相关：综合方案分析的Peto优势比为0.14(95%可信区间[CI] 0.09 - 0.21)，修正意向治疗分析的Peto优势比为0.52（95%可信区间[CI] 0.43 - 0.63）。疫苗接种在预防其他HPV相关感染和疾病结局方面也非常有效，包括持续性HPV感染、低级别病变和生殖器疣。大多数不良事件是轻微的。严重不良事件和死亡的发生率在疫苗组和对照组之间是平衡的。解释：在以前未感染过疫苗型HPV株的15 - 25岁女性中，预防性HPV疫苗接种似乎在预防HPV感染和癌前宫颈疾病方面非常有效。需要进行长期随访，以证实宫颈癌发病率和死亡率的下降。
Background: Human papillomavirus (HPV) is now known to be a necessary cause of cervical cancer, and prophylactic HPV vaccines aimed at preventing genital warts, precancerous cervical lesions and cervical cancer are now available. To gauge the potential impact on disease burden, we performed a systematic review of the evidence from randomized controlled trials.Methods: We conducted a systematic search of the literature to identify all randomized controlled trials of prophylactic HPV vaccination. Reports in 5 electronic databases covering 1950 to June 2007 (MEDLINE, MEDLINE in process, EMBASE, the Cochrane Central Registry of Controlled Trials and the Cochrane Library), bibliographies of all included studies and of narrative reviews (2006 - 2007), clinical trial registries, Google Scholar, public health announcements, selected conference proceedings (2004 - 2007) and manufacturers' information on unpublished data or ongoing trials were screened against predefined eligibility criteria by 2 independent reviewers. Vaccines had to contain coverage against at least 1 oncogenic HPV strain. The primary outcome of interest was the frequency of high- grade cervical lesions (high-grade squamous intraepithelial lesion, or grade 2 or 3 cervical intraepithelial neoplasia). The secondary outcomes were persistent HPV infection, low- grade cervical lesions (low-grade squamous intraepithelial lesion or grade 1 cervical intraepithelial neoplasia), external genital lesions, adverse events and death. Meta- analysis of the data was done in all cases where adequate clinical and methodological homogeneity existed.Results: Of 456 screened reports, 9 were included in the review (6 were reports of randomized controlled trials and 3 were follow- up reports of initial trials). Findings from the meta-analysis showed that prophylactic HPV vaccination was associated with a reduction in the frequency of high-grade cervical lesions caused by vaccine-type HPV strains compared with control groups: Peto odds ratio 0.14 (95% confidence interval [CI] 0.09 - 0.21) from combined per-protocol analyses, and 0.52 ( 95% CI 0.43 - 0.63) from modified intention-to-treat analyses. Vaccination was also highly efficacious in preventing other HPV-related infection and disease outcomes, including persistent HPV infection, low-grade lesions and genital warts. The majority of adverse events were minor. The incidence of serious adverse events and death were balanced between the vaccine and control groups.Interpretation: Among women aged 15 - 25 years not previously infected with vaccine-type HPV strains, prophylactic HPV vaccination appears to be highly efficacious in preventing HPV infection and precancerous cervical disease. Longterm follow-up is needed to substantiate reductions in cervical cancer incidence and mortality.