Impact of Human Papillomavirus (HPV)-6/11/16/18 Vaccine on All HPV-Associated Genital Diseases in Young Women
Impact of Human Papillomavirus (HPV)-6/11/16/18 Vaccine on All HPV-Associated Genital Diseases in Young Women
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DOI：
10.1093/jnci/djp534
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发表时间：
2010-03-03
影响因子：
10.3
通讯作者：
Haupt, Richard M.
中科院分区：
文献类型：
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作者：
Munoz, Nubia;Kjaer, Susanne K.;Haupt, Richard M.
研究背景：针对人乳头瘤病毒（HPV） 6型、11型、16型和18型（HPV6/11/16/18）的预防性疫苗对所有HPV相关生殖器疾病的影响，研究对象为接近性幼稚女性的人群，即“14型HPV阴性”，以及HPV暴露和未暴露女性的混合人群（意向治疗组）。方法研究了17 622名年龄在15-26岁的女性，她们参加了两项随机、安慰剂对照的HPV6/11/16/18疫苗的疗效试验（第一位患者于2001年12月28日，研究于2007年7月31日完成）。在第1天、第2个月和第6个月接种疫苗或安慰剂。所有妇女在第1天和之后每6-12个月进行宫颈阴道取样和巴氏涂片（Pap）检查。结果为宫颈上皮内瘤变；任何外部肛门生殖器和阴道病变；巴氏试验异常；还有阴道镜检查和最终治疗。绝对比率表示为每100人年有危险终点的妇女。结果平均随访3.6年，最长4.9年。在14种HPV阴性的人群中，疫苗接种在降低hpv16 /18相关的高级别宫颈、外阴和阴道病变以及hpv6 /11相关生殖器疣的风险方面达到100%有效。在意向治疗组中，接种疫苗也具有统计学意义地降低了任何高级宫颈病变的风险（降低19.0%；疫苗率= 1.43，安慰剂率= 1.76，差异= 0.33,95%可信区间[CI] = 0.13 ~ 0.54），外阴和阴道病变（降低50.7%；疫苗率= 0.10，安慰剂率= 0.20，差异= 0.10,95% CI = 0.04 ~ 0.16），生殖器疣(降低62.0%；疫苗接种率= 0.44，安慰剂接种率= 1.17，差异= 0.72,95% CI = 0.58 ~ 0.87)，子宫颈异常（减少11.3%；疫苗接种率= 10.36，安慰剂接种率= 11.68，差异= 1.32,95% CI = 0.74 ~ 1.90）和宫颈决定性治疗（减少23.0%；疫苗接种率= 1.97，安慰剂接种率= 2.56，差异= 0.59,95% CI = 0.35 ~ 0.83），与HPV病因类型无关。结论：在青少年和年轻女性中实施高覆盖率的HPV疫苗接种计划可能会导致生殖器疣、宫颈细胞学异常以及诊断和治疗程序的快速减少。从长远来看，宫颈癌、外阴癌和阴道癌的发病率可能会大幅下降。
Background The impact of the prophylactic vaccine against human papillomavirus (HPV) types 6, 11, 16, and 18 (HPV6/11/16/18) on all HPV-associated genital disease was investigated in a population that approximates sexually naive women in that they were "negative to 14 HPV types" and in a mixed population of HPV-exposed and-unexposed women (intention-to-treat group).Methods This analysis studied 17 622 women aged 15-26 years who were enrolled in one of two randomized, placebo-controlled, efficacy trials for the HPV6/11/16/18 vaccine (first patient on December 28, 2001, and studies completed July 31, 2007). Vaccine or placebo was given at day 1, month 2, and month 6. All women underwent cervicovaginal sampling and Papanicolaou (Pap) testing at day 1 and every 6-12 months thereafter. Outcomes were any cervical intraepithelial neoplasia; any external anogenital and vaginal lesions; Pap test abnormalities; and procedures such as colposcopy and definitive therapy. Absolute rates are expressed as women with end-point per 100 person-years at risk.Results The average follow-up was 3.6 years (maximum of 4.9 years). In the population that was negative to 14 HPV types, vaccination was up to 100% effective in reducing the risk of HPV16/18-related high-grade cervical, vulvar, and vaginal lesions and of HPV6/11-related genital warts. In the intention-to-treat group, vaccination also statistically significantly reduced the risk of any high-grade cervical lesions (19.0% reduction; rate vaccine = 1.43, rate placebo = 1.76, difference = 0.33, 95% confidence interval [CI] = 0.13 to 0.54), vulvar and vaginal lesions (50.7% reduction; rate vaccine = 0.10, rate placebo = 0.20, difference = 0.10, 95% CI = 0.04 to 0.16), genital warts (62.0% reduction; rate vaccine = 0.44, rate placebo = 1.17, difference = 0.72, 95% CI = 0.58 to 0.87), Pap abnormalities (11.3% reduction; rate vaccine = 10.36, rate placebo = 11.68, difference = 1.32, 95% CI = 0.74 to 1.90), and cervical definitive therapy (23.0% reduction; rate vaccine = 1.97, rate placebo = 2.56, difference = 0.59, 95% CI = 0.35 to 0.83), irrespective of causal HPV type.Conclusions High-coverage HPV vaccination programs among adolescents and young women may result in a rapid reduction of genital warts, cervical cytological abnormalities, and diagnostic and therapeutic procedures. In the longer term, substantial reductions in the rates of cervical, vulvar, and vaginal cancers may follow.