TY - JOUR
T1 - Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers
T2 - Population-based follow-up of a cluster-randomised trial
AU - Lehtinen, Matti
AU - Lagheden, Camilla
AU - Luostarinen, Tapio
AU - Eriksson, Tiina
AU - Apter, Dan
AU - Bly, Anne
AU - Gray, Penelope
AU - Harjula, Katja
AU - Heikkilä, Kaisa
AU - Hokkanen, Mari
AU - Karttunen, Heidi
AU - Kuortti, Marjo
AU - Nieminen, Pekka
AU - Nummela, Mervi
AU - Paavonen, J.
AU - Palmroth, Johanna
AU - Petäjä, Tiina
AU - Pukkala, Eero
AU - Soderlund-Strand, Anna
AU - Veivo, Ulla
AU - Dillner, Joakim
N1 - Funding Information:
Funding Finnish Cancer Society, Swedish Cancer Society, Nordic Cancer Union, and GlaxoSmithKline Biologicals SA (study identifier 115006) supported the study, which discloses in the publication all the data on invasive cancers collected. GlaxoSmithKline Biologicals SA was provided the opportunity to review a preliminary version of this manuscript for factual accuracy, but the authors are solely responsible for final content and interpretation. GSK Biologicals SA (HPV-027, 115006) and Finnish Cancer Foundation (MS790) supported the study financially, Competing interests We declare that ML, DA, JD and JPaa have received grants from Merck & Co. Inc. and/or from the GSK group of companies through their respective employers. GSK Biologicals SA was provided the opportunity to review this manuscript but the authors are solely responsible for final content and interpretation.
PY - 2021/12/30
Y1 - 2021/12/30
N2 - 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.
AB - 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.
KW - epidemiology
KW - gynaecological oncology
KW - preventive medicine
KW - public health
KW - sexual medicine
U2 - 10.1136/bmjopen-2021-050669
DO - 10.1136/bmjopen-2021-050669
M3 - Article
AN - SCOPUS:85122610730
SN - 2044-6055
VL - 11
JO - BMJ Open
JF - BMJ Open
IS - 12
M1 - e050669
ER -
