Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study.
Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study.
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DOI：
10.1016/s1470-2045(21)00453-8
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发表时间：
2021-11
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通讯作者：
Sankaranarayanan R
中科院分区：
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作者：
Basu P;Malvi SG;Joshi S;Bhatla N;Muwonge R;Lucas E;Verma Y;Esmy PO;Poli URR;Shah A;Zomawia E;Pimple S;Jayant K;Hingmire S;Chiwate A;Divate U;Vashist S;Mishra G;Jadhav R;Siddiqi M;Sankaran S;Prabhu PR;Kannan TPRA;Varghese R;Shastri SS;Anantharaman D;Gheit T;Tommasino M;Sauvaget C;Pillai MR;Sankaranarayanan R
一项旨在比较印度青少年女孩中三剂和两剂四价人乳头瘤病毒（HPV）疫苗的随机试验在印度政府试验中暂停HPV疫苗接种后转换为队列研究。在这篇文章中，修订后的队列研究的目的是比较单次接种与三次和两次接种在预防接种后10年持续性HPV 16和18感染方面的疫苗有效性。在随机试验中，从印度的9个中心招募了10-18岁的未婚女孩，并随机分配到两剂或三剂四价HPV疫苗（Gardasil [Merck Sharp & Dohme，怀特豪斯站，新泽西州，美国];肌内注射0.5 mL）。在暂停招募和疫苗接种后，该研究默认为纵向前瞻性队列研究，根据方案接受的疫苗剂量将参与者分配至4个队列：两次给药队列（在第1天和第180天或之后接种疫苗），三剂队列（第1、60和180天或更晚）、两次剂量默认队列（第1和60天或更晚）和单次剂量默认队列。每年对参与者进行随访。从结婚后18个月或第一次分娩后6个月（以较早者为准）的参与者中收集宫颈标本，以评估HPV感染事件和持续性。已婚参与者在25岁时接受宫颈癌筛查。未接种疫苗的妇女年龄匹配的已婚接种疫苗的参与者被招募作为对照。分析了单剂接种者对持续性HPV 16和18感染（主要终点）的疫苗有效性，并在调整未接种疫苗和接种疫苗队列之间潜在混杂因素分布的不平衡后，与两剂和三剂接种者进行了比较。本试验已在ISRCTN（ISRCTN 98283094）和ClinicalTrials.gov（NCT 00923702）注册。在2009年9月1日至2010年4月8日（疫苗接种暂停日期）期间招募了接种疫苗的参与者，并随访了中位持续时间9.0年（IQR 8.2 - 9.6）。4348名参与者接受了三次剂量，4980名参与者接受了两次剂量（0和6个月），4949名参与者接受了单次剂量。在可评价终点的参与者中，针对持续性HPV 16和18感染的疫苗有效性为95.4%。（95% CI 85·0-99·9）（评估了2135名女性），两次剂量队列（评估了1452名女性）为93.1%（77.3 - 99.8），三次剂量接受者（评估了1460名女性）为93.3%（77.5 - 99.7）。单剂量HPV疫苗提供了类似的保护，防止HPV 16和18的持续感染，近70%的宫颈癌的基因型，由两个或三个剂量提供。比尔和梅林达·盖茨基金会。
A randomised trial designed to compare three and two doses of quadrivalent human papillomavirus (HPV) vaccine in adolescent girls in India was converted to a cohort study after suspension of HPV vaccination in trials by the Indian Government. In this Article, the revised aim of the cohort study was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years post vaccination. In the randomised trial, unmarried girls aged 10–18 years were recruited from nine centres across India and randomly assigned to either two doses or three doses of the quadrivalent HPV vaccine (Gardasil [Merck Sharp & Dohme, Whitehouse Station, NJ, USA]; 0·5 mL administered intramuscularly). After suspension of recruitment and vaccination, the study became a longitudinal, prospective cohort study by default, and participants were allocated to four cohorts on the basis of the number vaccine doses received per protocol: the two-dose cohort (received vaccine on days 1 and 180 or later), three-dose cohort (days 1, 60, and 180 or later), two-dose default cohort (days 1 and 60 or later), and the single-dose default cohort. Participants were followed up yearly. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Married participants were screened for cervical cancer as they reached 25 years of age. Unvaccinated women age-matched to the married vaccinated participants were recruited to serve as controls. Vaccine efficacy against persistent HPV 16 and 18 infections (the primary endpoint) was analysed for single-dose recipients and compared with that in two-dose and three-dose recipients after adjusting for imbalance in the distribution of potential confounders between the unvaccinated and vaccinated cohorts. This trial is registered with ISRCTN, ISRCTN98283094, and ClinicalTrials.gov, NCT00923702. Vaccinated participants were recruited between Sept 1, 2009, and April 8, 2010 (date of vaccination suspension), and followed up over a median duration of 9·0 years (IQR 8·2–9·6). 4348 participants had three doses, 4980 had two doses (0 and 6 months), and 4949 had a single dose. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95·4% (95% CI 85·0–99·9) in the single-dose default cohort (2135 women assessed), 93·1% (77·3–99·8) in the two-dose cohort (1452 women assessed), and 93·3% (77·5–99·7) in three-dose recipients (1460 women assessed). A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and 18, the genotypes responsible for nearly 70% of cervical cancers, to that provided by two or three doses. Bill & Melinda Gates Foundation.