Division of Research and Public Health, National Institute of Cancer, Bogotá, Colombia .
J Natl Cancer Inst. 2010 Mar 3;102(5):325-39. doi: 10.1093/jnci/djp534. Epub 2010 Feb 5.
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).
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 endpoint per 100 person-years at risk.
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.
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.
在近似于性未成熟女性的人群中（即“对 14 种 HPV 类型均为阴性”）以及 HPV 暴露和未暴露的混合人群（意向治疗组）中，研究了预防性 HPV 疫苗（HPV6/11/16/18）对所有 HPV 相关生殖器疾病的影响。
本分析研究了 17622 名年龄在 15-26 岁的女性，她们参加了两种 HPV6/11/16/18 疫苗的随机、安慰剂对照、疗效试验之一（第一个患者于 2001 年 12 月 28 日入组，研究于 2007 年 7 月 31 日完成）。疫苗或安慰剂在第 1 天、第 2 个月和第 6 个月给予。所有女性在第 1 天和此后每 6-12 个月接受宫颈阴道采样和巴氏涂片（Pap）检测。结局是任何宫颈上皮内瘤变；任何外阴生殖器和阴道病变；巴氏涂片异常；以及阴道镜检查和明确治疗等程序。绝对发生率以每 100 人年风险的终点女性数表示。
平均随访时间为 3.6 年（最长 4.9 年）。在对 14 种 HPV 类型均为阴性的人群中，疫苗接种可使 HPV16/18 相关的高级别宫颈、外阴和阴道病变以及 HPV6/11 相关的生殖器疣的风险降低高达 100%。在意向治疗组中，疫苗接种也显著降低了任何高级别宫颈病变的风险（降低 19.0%；疫苗率=1.43，安慰剂率=1.76，差异=0.33，95%置信区间[CI]为 0.13 至 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 至 0.16）、生殖器疣（降低 62.0%；疫苗率=0.44，安慰剂率=1.17，差异=0.72，95%CI=0.58 至 0.87）、巴氏涂片异常（降低 11.3%；疫苗率=10.36，安慰剂率=11.68，差异=1.32，95%CI=0.74 至 1.90）和宫颈明确治疗（降低 23.0%；疫苗率=1.97，安慰剂率=2.56，差异=0.59，95%CI=0.35 至 0.83），与 HPV 类型无关。
青少年和年轻女性的高覆盖率 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迅速减少。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。
