宫颈癌是全球最致命但也是最容易预防的女性癌症类型，人乳头瘤病毒（HPV）感染是罪魁祸首，导致了99%的宫颈癌病例，其中2种基因型（HPV-16/18）占到了70%。接种疫苗是预防宫颈癌的一种有效手段，当前宫颈癌疫苗的免疫程序通常为2针（0,6个月）或者3针（0,1,6个月）。然而令人担忧的现实情况是，有相当多的年轻女性并没有按规定及时地完成2针或3针注注射。这是否会降低疫苗预防HPV感染的效果呢？近日，来自美国路易斯维尔大学（UL）的研究人员，对宫颈癌疫苗Cervarix（HPV16/18 AS04）2个大规模随机双盲III期研究（NCT00128661，NCT001226810）的数据进行了汇总分析，比较了注射1针、2针、3针疫苗预防HPV感染的有效性。结果发现，接种Cervarix预防主要基因型HPV毒株（HPV-16/18）感染时，接种1针与2针或3针的免疫保护率一样好（85.7% vs 76.0% vs 77.0%）。该项激动人心的研究结果已于近日发表于国际期刊《柳叶刀·肿瘤学》(The Lancet Oncology)(IF=24.752)。

　　研究的共同作者、路易斯威尔大学医学院Diane Harper博士表示，这些激动人心的发现，有望解决宫颈癌疫苗接种方面存在的严重现实问题，即：有多达三分之二的年轻女性没有及时地完成免疫程序所要求的全部2针或3针接种。而对于卫生当局，这一发现则意味着，尽管大多数女性并没有完成接种程序，但也没有浪费钱。

　　该研究的数据具有重大的现实意义，相对于目前的2针（0,6个月）和3针（0,1,6个月）免疫程序，1针免疫程序不仅能够提高接种的完成率，还能够降低疫苗接种成本，这将促使更多的发展中国家将HPV疫苗纳入常规的疫苗接种。

　　人乳头瘤病毒（HPV）是引发宫颈癌的罪魁祸首，导致了99%的宫颈癌病例，其中2种基因型（HPV-16/18）占到了70%。这2种基因型HPV与其他基因型HPV导致了一种名为宫颈重度上皮内瘤样病变（CIN3）的宫颈癌癌前病变。Cervarix（HPV16/18AS04）是英国制药巨头葛兰素史克（GSK）研发的一款宫颈癌疫苗，其2针（0,6）和3针（0,1,6）免疫程序已获全球多个国家批准，并广泛用于年轻女性群体的免疫接种。尽管Cervarix只靶向HPV-16/18毒株，但根据已完成的全部临床数据，Cervarix预防全部基因型HPV毒株所致CIN3的有效率高达93%，与默沙东另一款HPV疫苗Gardasil（4价疫苗）不相上下，后者靶向4种基因型HPV毒株（HPV-6/11/16/18）。2014年12月，FDA批准了Gardasil（9价疫苗），这是Gardasil（4价疫苗）的升级版，涵盖9种基因型HPV毒株（HPV-6/11/16/18/31/33/45/52/58），具有预防大约90%子宫颈、外阴、阴道和肛门癌症的潜力。当然，这取决于疫苗接种率的提高。然而Gardasil 9在提高疫苗接种方面也面临着一些制约因素，包括男性儿童中疫苗接种报销政策的缺乏以及该疫苗的3针（0,1,6）免疫程序。

　　研究的完整数据：

　　为了评估疫苗接种少于3针时的有效性，研究人员将NCT00128661（CVT）研究和NCT001226810（PATRICIA）研究进行了汇总分析，这是调查Cervarix在年轻女性群体中预防HPV感染有效性的唯一2个大规模、随机、双盲III期研究。汇总后的结果，有22327人接种3针，1185人接种2针，543例接种1针）。针对HPV-16/18感染的保护率分别为：3针为77.0%（95% CI:74.7–79.1），2针为76.0%（95% CI:62.0–85.3），1针为85.7%（95% CI:70.7–93.7）；针对HPV-31/33/45感染的保护率分别为：3针为59.7%（95% CI:56.0–63.0），2针为37.7%（95% CI:12.4–55.9），1针为36.6%（95% CI:-5.4–62.2）。

　　另一方面，对于接种2针的女性群体，针对HPV-16/18感染，在第1个月接受第2针的保护率为75.3%（95% CI:54.2–87.5），在第6个月接受第2针的保护率为82.6%（95% CI:42.3–96.1，仅来自CVT研究数据）。针对HPV-31/33/45感染，在第1个月接受第2针的保护率为10.2%（95% CI:-42.0–43.3），在第6个月接受第2针的保护率为68.1%（95% CI:27.0–87.0，仅来自CVT研究数据），与接种3针的女性群体中的保护率相似。

　　数据解读：15-25岁女性群体，接种宫颈癌疫苗Cervarix（HPV16/18 AS04）4年后，针对HPV-16/18感染，接种1针和2针的保护率与接种3针的保护率相当。在6个月间隔接种2针（0,6），额外提供了针对HPV-31/33/45感染的横向保护。这些数据主张对HPV-16/18疫苗的一针有效性进行直接评估。

　　信源：One dose of GlaxoSmithKline's Cervarix may suffice

　　文献原文：Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA trials

　　DOI: http://dx.doi.org/10.1016/S1470-2045(15)00047-9

　　Background

　　There is some evidence to suggest that one or two doses of the HPV vaccine provides similar protection to the three-dose regimen. The main aim of the study was to ascertain HPV-16/18 vaccine efficacy in both full and naive cohorts and to explore protection conferred against non-vaccine HPV types, by number of doses received.

　　Methods

　　Summary data from the Costa Rica Vaccine Trial (CVT; NCT00128661) and ~the PATRICIA trial (NCT001226810), two phase 3, double-blind, randomised controlled clinical trials of the HPV-16/18 AS04-adjuvanted vaccine in young women, were combined in a post-hoc analysis (GlaxoSmithKline [GSK] e-track number 202142) to investigate the efficacy of fewer than three doses of the HPV-16/18 vaccine after 4 years of follow-up. Women were randomly assigned to receive three doses of the HPV-16/18 vaccine or to a control vaccine; yet, some received fewer doses. After exclusion of women with less than 12 months of follow-up or those who were HPV-16/18 DNA-positive at enrolment (for the HPV-16/18 endpoint), we calculated vaccine efficacy against one-time detection of incident HPV infections after three, two, and one dose(s). The primary study endpoint was one-time detection of first incident HPV-16/18 infections accumulated during the follow-up phase.

　　Findings

　　We assessed vaccine efficacy against incident HPV-16/18 infection in the modified total vaccinated cohort (22 327 received three doses, 1185 two doses, 543 one dose). Vaccine efficacy against incident HPV-16/18 infections for three doses was 77·0% (95% CI 74·7–79·1), two doses was 76·0% (62·0–85·3), and one dose was 85·7% (70·7–93·7). Vaccine efficacy against incident HPV-31/33/45 infections for three doses was 59·7% (56·0–63·0), two doses was 37·7% (12·4–55·9), and one dose was 36·6% (–5·4 to 62·2). Vaccine efficacy against incident HPV-16/18 infection for two-dose women who received their second dose at 1 month was 75·3% (54·2–87·5) and 82·6% (42·3–96·1) for those who received the second dose at 6 months (CVT data only). Vaccine efficacy against HPV-31/33/45 for two-dose women who received their second dose at 6 months (68·1%, 27·0–87·0; CVT data only), but not those receiving it at one month (10·1%, −42·0 to 43·3), was similar to the three-dose group.

　　Interpretation

　　4 years after vaccination of women aged 15–25 years, one and two doses of the HPV-16/18 vaccine seem to protect against cervical HPV-16/18 infections, similar to the protection provided by the three-dose schedule. Two doses separated by 6 months additionally provided some cross-protection. These data argue for a direct assessment of one-dose efficacy of the HPV-16/18 vaccine.

　　Funding

　　US National Cancer Institute, National Institutes of Health Office of Research on Women's Health, and Ministry of Health of Costa Rica (CVT); GlaxoSmithKline Biologicals SA (PATRICIA).