Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Gynecologic Oncology, Medical University Vienna, Vienna, Austria.
Vaccine. 2021 Apr 15;39(16):2224-2236. doi: 10.1016/j.vaccine.2020.11.076. Epub 2021 Mar 18.
The extent of cross-protection provided by currently licensed bivalent and quadrivalent HPV vaccines versus direct protection against HPV 31-, 33-, 45-, 52-, and 58-related disease is debated. A systematic literature review was conducted to establish the duration and magnitude of cross-protection in interventional and observational studies.
PubMed and Embase databases were searched to identify randomized controlled trials (RCT) and observational studies published between 2008 and 2019 reporting on efficacy and effectiveness of HPV vaccines in women against non-vaccine types 31, 33, 45, 52, 58, and 6 and 11 (non-bivalent types). Key outcomes of interest were vaccine efficacy against 6- and 12-month persistent infection or genital lesions, and type-specific genital HPV prevalence or incidence. RCT data were analyzed for the according-to-protocol (bivalent vaccine) or negative-for-14-HPV-types (quadrivalent vaccine) efficacy cohorts.
Data from 23 RCTs and 33 observational studies evaluating cross-protection were extracted. RCTs assessed cross-protection in post-hoc analyses of small size subgroups. Among fully vaccinated, baseline HPV-naïve women, the bivalent vaccine showed statistically significant cross-protective efficacy, although with wide confidence intervals, against 6-month and 12-month persistent cervical infections and CIN2+ only consistently for HPV 31 and 45, with the highest effect observed for HPV 31 (range 64.6% [95% CI: 27.6 to 83.9] to 79.1% [97.7% CI: 27.6 to 95.9] for 6-month persistent infection; maximal follow-up 4.7 years). No cross-protection was shown in extended follow-up. The quadrivalent vaccine efficacy reached statistical significance for HPV 31 (46.2% [15.3-66.4]; follow-up: 3.6 years). Similarly, observational studies found consistently significant effectiveness only against HPV 31 and 45 with both vaccines.
RCTs and observational studies show that cross-protection is inconsistent across non-vaccine HPV types and is largely driven by HPV 31 and 45. Furthermore, existing data suggest that it wanes over time; its long-term durability has not been established.
目前许可的二价和四价 HPV 疫苗对 HPV 31、33、45、52 和 58 相关疾病的直接保护与交叉保护的程度存在争议。进行了系统的文献回顾，以确定干预性和观察性研究中交叉保护的持续时间和程度。
检索了 PubMed 和 Embase 数据库，以确定 2008 年至 2019 年间发表的关于 HPV 疫苗在女性中针对非疫苗型 31、33、45、52、58 和 6 和 11（非二价型）的疗效和有效性的随机对照试验（RCT）和观察性研究。主要研究结果为疫苗对 6 个月和 12 个月持续性感染或生殖器病变的效力，以及特定类型的生殖器 HPV 流行率或发病率。对符合方案（二价疫苗）或 14 种 HPV 型阴性（四价疫苗）效力队列的 RCT 数据进行了分析。
提取了 23 项 RCT 和 33 项观察性研究的交叉保护数据。RCT 对小亚组的事后分析进行了交叉保护评估。在完全接种疫苗、基线 HPV 阴性的女性中，二价疫苗对 6 个月和 12 个月持续性宫颈感染和 CIN2+具有统计学显著的交叉保护效力，尽管置信区间较宽，仅对 HPV 31 和 45 持续一致，对 HPV 31 的影响最大（范围为 64.6%[95%CI：27.6 至 83.9]至 79.1%[97.7%CI：27.6 至 95.9]，6 个月持续性感染；最长随访时间为 4.7 年）。在延长随访中未显示出交叉保护。四价疫苗对 HPV 31 的效力达到统计学意义（46.2%[15.3-66.4]；随访时间：3.6 年）。同样，观察性研究发现，两种疫苗对 HPV 31 和 45 的有效性均一致显著。
RCT 和观察性研究表明，交叉保护在非疫苗型 HPV 之间不一致，主要由 HPV 31 和 45 驱动。此外，现有数据表明，它随时间推移而减弱；其长期耐久性尚未确定。
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