Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trial

Background Human papillomavirus (HPV) vaccination protects against HPV, a necessary risk factor for cervical cancer. We now report results from population-based follow-up of randomised cohorts that vaccination provides HPV-type-specific protection against invasive cancer.Methods Individually and/or...

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Main Authors: Joakim Dillner, Camilla Lagheden, Eero Pukkala, Tiina Eriksson, Tapio Luostarinen, Dan Apter, Matti Lehtinen, Katja Harjula, Marjo Kuortti, Johanna Palmroth, Tiina Petäjä, Pekka Nieminen, J Paavonen, Anne Bly, Penelope Gray, Kaisa Heikkilä, Mari Hokkanen, Heidi Karttunen, Mervi Nummela, Anna Soderlund-Strand, Ulla Veivo
Format: Article
Language:English
Published: BMJ Publishing Group 2021-12-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/11/12/e050669.full
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author Joakim Dillner
Camilla Lagheden
Eero Pukkala
Tiina Eriksson
Tapio Luostarinen
Dan Apter
Matti Lehtinen
Katja Harjula
Marjo Kuortti
Johanna Palmroth
Tiina Petäjä
Pekka Nieminen
J Paavonen
Anne Bly
Penelope Gray
Kaisa Heikkilä
Mari Hokkanen
Heidi Karttunen
Mervi Nummela
Anna Soderlund-Strand
Ulla Veivo
author_facet Joakim Dillner
Camilla Lagheden
Eero Pukkala
Tiina Eriksson
Tapio Luostarinen
Dan Apter
Matti Lehtinen
Katja Harjula
Marjo Kuortti
Johanna Palmroth
Tiina Petäjä
Pekka Nieminen
J Paavonen
Anne Bly
Penelope Gray
Kaisa Heikkilä
Mari Hokkanen
Heidi Karttunen
Mervi Nummela
Anna Soderlund-Strand
Ulla Veivo
author_sort Joakim Dillner
collection DOAJ
description Background Human papillomavirus (HPV) vaccination protects against HPV, a necessary risk factor for cervical cancer. We now report results from population-based follow-up of randomised cohorts that vaccination provides HPV-type-specific protection against invasive cancer.Methods Individually and/or cluster randomised cohorts of HPV-vaccinated and non-vaccinated women were enrolled in 2002–2005. HPV vaccine cohorts comprised originally 16–17 year-old HPV 16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2465) and HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866). Altogether, 3341 vaccines were followed by the Finnish Cancer Registry in the same way as 16 526 non-HPV-vaccinated controls. The control cohort stemmed from 15 665 originally 18–19 years-old women enrolled in 2003 (6499) or 2005 (9166) and 861 placebo recipients of the FUTURE II trial. The follow-up started 6 months after the clinical trials in 2007 and 2009 and ended in 2019. It was age aligned for the cohorts.Findings During a follow-up time of up to 11 years, we identified 17 HPV-positive invasive cancer cases (14 cervical cancers, 1 vaginal cancer, 1 vulvar cancer and 1 tongue cancer) in the non-HPV-vaccinated cohorts and no cases in the HPV-vaccinated cohorts. HPV typing of diagnostic tumour blocks found HPV16 in nine cervical cancer cases, HPV18, HPV33 and HPV52 each in two cases and HPV45 in one cervical cancer case. The vaginal, vulvar and tongue cancer cases were, respectively, positive for HPV16, HPV52/66 and HPV213. Intention-to-treat vaccine efficacy against all HPV-positive cancers was 100% (95% CI 2 to 100, p<0.05).Interpretation Vaccination is effective against invasive HPV-positive cancer.Trial registration number NCT00122681, Post-results; NCT00169494, Post-results; NCT00092534, Post-results.
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spelling doaj-art-692ac1b6817e4f91abaa5fdfa89f9c442024-12-08T15:25:08ZengBMJ Publishing GroupBMJ Open2044-60552021-12-01111210.1136/bmjopen-2021-050669Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trialJoakim Dillner0Camilla Lagheden1Eero Pukkala2Tiina Eriksson3Tapio Luostarinen4Dan Apter5Matti Lehtinen6Katja Harjula7Marjo Kuortti8Johanna Palmroth9Tiina Petäjä10Pekka Nieminen11J Paavonen12Anne Bly13Penelope Gray14Kaisa Heikkilä15Mari Hokkanen16Heidi Karttunen17Mervi Nummela18Anna Soderlund-Strand19Ulla Veivo20Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, SwedenDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenCancer Society of Finland, Helsinki, FinlandFICAN-Mid, Tampere, FinlandFinnish Cancer Registry, Helsinki, FinlandVL Medi, Helsinki, FinlandDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenTampere University Hospital, Tampere, FinlandFaculty of Social Sciences, Tampereen Yliopisto, Tampere, FinlandUniversity of Eastern Finland School of Medicine, Kuopio, Pohjois-Savo, FinlandObstetrics & Gynecology, Tampereen Yliopisto, Seinäjoki, FinlandDepartment of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandDepartment of Gynecology and Obstetrics, University of Helsinki, Helsinki, FinlandTampere University Hospital, Tampere, FinlandDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenTampere University Hospital, Tampere, FinlandTampere University Hospital, Tampere, FinlandTampere University Hospital, Tampere, FinlandTampere University Hospital, Tampere, FinlandClinical Microbiology, Lund University, Lund, SwedenTampere University Hospital, Tampere, FinlandBackground Human papillomavirus (HPV) vaccination protects against HPV, a necessary risk factor for cervical cancer. We now report results from population-based follow-up of randomised cohorts that vaccination provides HPV-type-specific protection against invasive cancer.Methods Individually and/or cluster randomised cohorts of HPV-vaccinated and non-vaccinated women were enrolled in 2002–2005. HPV vaccine cohorts comprised originally 16–17 year-old HPV 16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2465) and HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866). Altogether, 3341 vaccines were followed by the Finnish Cancer Registry in the same way as 16 526 non-HPV-vaccinated controls. The control cohort stemmed from 15 665 originally 18–19 years-old women enrolled in 2003 (6499) or 2005 (9166) and 861 placebo recipients of the FUTURE II trial. The follow-up started 6 months after the clinical trials in 2007 and 2009 and ended in 2019. It was age aligned for the cohorts.Findings During a follow-up time of up to 11 years, we identified 17 HPV-positive invasive cancer cases (14 cervical cancers, 1 vaginal cancer, 1 vulvar cancer and 1 tongue cancer) in the non-HPV-vaccinated cohorts and no cases in the HPV-vaccinated cohorts. HPV typing of diagnostic tumour blocks found HPV16 in nine cervical cancer cases, HPV18, HPV33 and HPV52 each in two cases and HPV45 in one cervical cancer case. The vaginal, vulvar and tongue cancer cases were, respectively, positive for HPV16, HPV52/66 and HPV213. Intention-to-treat vaccine efficacy against all HPV-positive cancers was 100% (95% CI 2 to 100, p<0.05).Interpretation Vaccination is effective against invasive HPV-positive cancer.Trial registration number NCT00122681, Post-results; NCT00169494, Post-results; NCT00092534, Post-results.https://bmjopen.bmj.com/content/11/12/e050669.full
spellingShingle Joakim Dillner
Camilla Lagheden
Eero Pukkala
Tiina Eriksson
Tapio Luostarinen
Dan Apter
Matti Lehtinen
Katja Harjula
Marjo Kuortti
Johanna Palmroth
Tiina Petäjä
Pekka Nieminen
J Paavonen
Anne Bly
Penelope Gray
Kaisa Heikkilä
Mari Hokkanen
Heidi Karttunen
Mervi Nummela
Anna Soderlund-Strand
Ulla Veivo
Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trial
BMJ Open
title Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trial
title_full Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trial
title_fullStr Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trial
title_full_unstemmed Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trial
title_short Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trial
title_sort human papillomavirus vaccine efficacy against invasive hpv positive cancers population based follow up of a cluster randomised trial
url https://bmjopen.bmj.com/content/11/12/e050669.full
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