Evidence map›Paper›PMID 26071347›Full record

Trial reportThe Lancet. Oncology2015

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.

Aimée R Kreimer, Frank Struyf, Maria Rowena Del Rosario-Raymundo, Allan Hildesheim, S Rachel Skinner, Sholom Wacholder, Suzanne M Garland, Rolando Herrero, Marie-Pierre David, Cosette M Wheeler and 35 more

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00128661 (A Double-Blind, Controlled, Randomized, Phase III Study of the Efficacy of an HPV16/18 VLP Vaccine in the Prevention of Advanced Cervical Intraepithelial Neoplasia), which is not on this map. Cited by 146 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed, 5 pooled it
31.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00128661 phase3completednot on this map

A Double-Blind, Controlled, Randomized, Phase III Study of the Efficacy of an HPV16/18 VLP Vaccine in the Prevention of Advanced Cervical Intraepithelial Neoplasia (CIN2, CIN3, Adenocarcinoma In Situ [AIS] and Invasive Cervical Cancer) Associated With HPV 16 or HPV 18 Cervical Infection in Healthy Young Adult Women in Costa Rica.

TypeinterventionalSponsorGlaxoSmithKlineRan2004 to 2010Enrolled7,466ConditionsCervical Cancer, Precancerous ConditionArmshuman papillomavirus 16/18 L1 virus-like particle/AS04 vaccine, hepatitis A inactivated virus vaccine
3 · Its place in the literature

Who cites it

146 citing papers in PubMed, 5 syntheses or guidelines pooled it, 299 citations in OpenAlex.

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86 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

45 authors at 7 institutions in 4 countries.

Aimée R KreimerDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: kreimera@mail.nih.gov.
Frank StruyfGSK Vaccines, Wavre, Belgium.
Maria Rowena Del Rosario-RaymundoDepartment of Obstetrics and Gynecology, San Pablo Colleges Medical Center, San Pablo City, Philippines.
Allan HildesheimDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
S Rachel SkinnerVaccine Trials Group, Telethon Institute for Child Health Research, Perth, WA, Australia; Sydney University Discipline of Paediatrics and Child Health, Children's Hospital at Westmead, Sydney, NSW, Australia.
Sholom WacholderDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Suzanne M GarlandMicrobiology and Infectious Diseases Department, Royal Women's Hospital and Department of Obstetrics and Gynaecology, University of Melbourne, Murdoch Childrens Research Institute Melbourne, VIC, Australia.
Rolando HerreroProyecto Epidemiologico Guanacaste, San José, Costa Rica; Section of Early Detection and Prevention, International Agency for Research on Cancer, Lyon, France.
Marie-Pierre DavidGSK Vaccines, Wavre, Belgium.
Cosette M WheelerDepartments of Pathology and Obstetrics and Gynecology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. Electronic address: cwheeler@salud.unm.edu.
Costa Rica Vaccine Trial Study Group Authors
Paula González
Silvia Jiménez
Douglas R Lowy
Ligia A Pinto
Caroline Porras
Ana Cecilia Rodriguez
Mahboobeh Safaeian
Mark Schiffman
John T Schiller
John Schussler
Mark E Sherman
PATRICIA Study Group Authors
F Xavier Bosch
Xavier Castellsague
Archana Chatterjee
Song-Nan Chow
Dominique Descamps
Francisco Diaz-Mitoma
Gary Dubin
Maria Julieta Germar
Diane M Harper
David J M Lewis
Genara Limson
Paulo Naud
Klaus Peters
Willy A J Poppe
Brian Ramjattan
Barbara Romanowski
Jorge Salmeron
Tino F Schwarz
Julio C Teixeira
Wiebren A A Tjalma
HPV PATRICIA Principal Investigators/Co-Principal Investigator Collaborators
GSK Vaccines Clinical Study Support Group
GlaxoSmithKline (Belgium) · BENational Institutes of Health · USCentre International de Recherche sur le Cancer · FRNational Cancer Institute · USRoyal Women's Hospital · AUThe Kids Research Institute Australia · AUUniversity of New Mexico · US

Funding

WOMEN'S CANCERS RESEARCH PROGRAMP30CA118100 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Yolanda Sanchez · 2005 to 2026
$57.1M
HPV and cancer at multiple anatomic sitesZIACP010209 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI KREIMER, AIMEE · 2010 to 2025
$7.9M
HPV Vaccine TrialsZIACP010177 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI HILDESHEIM, ALLAN · 2009 to 2009
$3.2M
Intramural NIH HHS ZIA CP010177NCI NIH HHS N01-CP-11005NCI NIH HHS P30 CA118100World Health Organization 001
6 · The paper itself

Abstract

backgroundThere 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.

methodsSummary 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.

findingsWe 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.

interpretation4 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.

fundingUS 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).

Indexed as

Adjuvants, ImmunologicAdolescentAdultAge FactorsCosta RicaDose-Response Relationship, DrugDouble-Blind MethodDrug Administration ScheduleFemaleFollow-Up StudiesHuman papillomavirus 16Human papillomavirus 18HumansPapillomavirus InfectionsPapillomavirus VaccinesRisk AssessmentAdjuvants, ImmunologicPapillomavirus Vaccines

Identifiers

PMID26071347
PMCPMC4498478
OpenAlexW2109016129

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.