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

BackgroundHuman 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.MethodsIndividually 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.FindingsDuring 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).InterpretationVaccination is effective against invasive HPV-positive cancer.Trial registration numberNCT00122681, Post-results; NCT00169494, Post-results; NCT00092534, Post-results.

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Ten-year follow-up of human papillomavirus vaccine efficacy against the most stringent cervical neoplasia end-point—registry-based follow-up ofthree cohorts from randomized trials

BMJ Open ◽

10.1136/bmjopen-2017-015867 ◽

2017 ◽

Vol 7 (8) ◽

pp. e015867 ◽

Cited By ~ 33

Author(s):

Matti Lehtinen ◽

Camilla Lagheden ◽

Tapio Luostarinen ◽

Tiina Eriksson ◽

Dan Apter ◽

...

Keyword(s):

Human Papillomavirus ◽

Cervical Intraepithelial Neoplasia ◽

Cancer Registry ◽

Vaccine Efficacy ◽

Invasive Cervical Cancer ◽

Intraepithelial Neoplasia ◽

Cervical Intraepithelial Neoplasia Grade ◽

Hpv 16 ◽

Link Type

ObjectiveDue to long lag time between infection/cancer diagnoses human papillomavirus (HPV) vaccination programs will deliver vaccine efficacy (VE) estimates against cancer end-points late. Cancer registry follow-up of population-based, randomised trial cohorts of vaccinated and unvaccinated women was undertaken for the estimation of VE against cervical intraepithelial neoplasia grade three and invasive cancer (CIN3+).MethodsWe report interim results with 98 561 person years of Finnish Cancer Registry -based follow-up of individually and/or cluster randomised cohorts of HPV-16/18 vaccinated and unvaccinated adolescent women enrolled in June 2003/2005, and between May 2004 and April 2005, respectively. The cohorts comprised 15 627 18- to 19-year-old unvaccinated women (NCT01393470), and 2 401 and 64 16- to 17-year-old HPV-16/18 vaccinated women participating the PATRICIA (NCT00122681) and HPV-012 (NCT00169494) trials, respectively. The age-aligned passive follow-up started 6 months after the clinical trials’ end.ResultsDuring the follow-up of 4.5 to 10 years post enrolment we identified 75 cases of cervical intraepithelial neoplasia grade 3 (CIN3) and 4 cases of invasive cervical cancer (ICC) in the unvaccinated cohort, and 4 CIN3 cases in the HPV-16/18 vaccinated women. Diagnostic blocks were available for HPV typing from 87% of the cases. CIN3+ lesions were detectable in 54 cases. HPV16 was found in 26 of 50 unvaccinated CIN3+ cases, and in 3 CIN3+ cases in the HPV-16/18 vaccinated women. The latter were all baseline positive for cervical HPV16 DNA. Baseline data was not available for the unvaccinated women. Intention-to-treat VE against any CIN3+ was 66% (95% CI 8, 88).ConclusionsTen years post vaccination the AS04-adjuvanted HPV-16/18 vaccine shows continued efficacy against CIN3+ irrespectively of HPV type. Vaccine efficacy was not observed in baseline HPV16 DNA positive subjects.Trial registration numberNCT01393470.

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Effect of self-collection of HPV DNA offered by community health workers at home visits on uptake of screening for cervical cancer (the EMA study): a population-based cluster-randomised trial

The Lancet Global Health ◽

10.1016/s2214-109x(14)70354-7 ◽

2015 ◽

Vol 3 (2) ◽

pp. e85-e94 ◽

Cited By ~ 105

Author(s):

Silvina Arrossi ◽

Laura Thouyaret ◽

Rolando Herrero ◽

Alicia Campanera ◽

Adriana Magdaleno ◽

...

Keyword(s):

Cervical Cancer ◽

Community Health ◽

Community Health Workers ◽

Health Workers ◽

Randomised Trial ◽

Home Visits ◽

Population Based ◽

Cluster Randomised Trial ◽

Hpv Dna ◽

Cluster Randomised

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Direct notification of cervical cytology results to women improves follow-up in cervical cancer screening - A cluster-randomised trial

Preventive Medicine Reports ◽

10.1016/j.pmedr.2018.11.015 ◽

2019 ◽

Vol 13 ◽

pp. 118-125

Author(s):

Bettina Kjær Kristiansen ◽

Berit Andersen ◽

Flemming Bro ◽

Hans Svanholm ◽

Peter Vedsted

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Randomised Trial ◽

Cervical Cytology ◽

Cluster Randomised Trial ◽

Cluster Randomised

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Population-Based Human Papillomavirus Serosurvey Reveals HPV16/18 Herd Effect But No Clear Type-Replacement in Unvaccinated Females 6 Years Post Gender-Neutral Vaccination in a Cluster Randomised Trial

SSRN Electronic Journal ◽

10.2139/ssrn.3346512 ◽

2019 ◽

Author(s):

Penelope Gray ◽

Hanna Artemchuk ◽

Ville N. Pimenoff ◽

Tiina Eriksson ◽

Tapio Luostarinen ◽

...

Keyword(s):

Human Papillomavirus ◽

Randomised Trial ◽

Population Based ◽

Cluster Randomised Trial ◽

Herd Effect ◽

Cluster Randomised ◽

Gender Neutral

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Population-based enrolment of adolescents in a long-term follow-up trial of human papillomavirus vaccine efficacy

International Journal of STD & AIDS ◽

10.1258/095646206776253453 ◽

2006 ◽

Vol 17 (4) ◽

pp. 237-246 ◽

Cited By ~ 29

Author(s):

M Lehtinen ◽

I Idänpään-Heikkilä ◽

T Lunnas ◽

J Palmroth ◽

E Barr ◽

...

Keyword(s):

Human Papillomavirus ◽

Vaccine Efficacy ◽

Population Based ◽

Human Papillomavirus Vaccine ◽

Long Term Follow Up ◽

Papillomavirus Vaccine

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Effect of introducing human papillomavirus genotyping into real-world screening on cervical cancer screening in China: a retrospective population-based cohort study

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211010939 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110109

Author(s):

Binhua Dong ◽

Huachun Zou ◽

Xiaodan Mao ◽

Yingying Su ◽

Hangjing Gao ◽

...

Keyword(s):

Cervical Cancer ◽

Cohort Study ◽

Human Papillomavirus ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Cox Regression ◽

Intraepithelial Neoplasia ◽

Population Based ◽

Hpv Genotyping ◽

Cytology Screening

Background: China’s Fujian Cervical Pilot Project (FCPP) transitioned cervical cancer screening from high-risk human papillomavirus (HR-HPV) nongenotyping to genotyping. We investigated the clinical impact of this introduction, comparing performance indicators between HR-HPV genotyping combined with cytology screening (HR-HPV genotyping period) and the previous HR-HPV nongenotyping combined with cytology screening (HR-HPV nongenotyping period). Methods: A retrospective population-based cohort study was performed using data from the FCPP for China. We obtained data for the HR-HPV nongenotyping period from 1 January 2012 to 31 December 2013, and for the HR-HPV genotyping period from 1 January 2014 to 31 December 2016. Propensity score matching was used to match women from the two periods. Multivariable Cox regression was used to assess factors associated with cervical intraepithelial neoplasia of grade 2 or worse (CIN2+). The primary outcome was the incidence of CIN2+ in women aged ⩾25 years. Performance was assessed and included consistency, reach, effectiveness, adoption, implementation and cost. Results: Compared with HR-HPV nongenotyping period, in the HR-HPV genotyping period, more CIN2+ cases were identified at the initial screening (3.06% versus 2.32%; p < 0.001); the rate of colposcopy referral was higher (10.87% versus 6.64%; p < 0.001); and the hazard ratio of CIN2+ diagnosis was 1.64 (95% confidence interval, 1.43–1.88; p < 0.001) after controlling for health insurance status and age. The total costs of the first round of screening (US$66,609 versus US$65,226; p = 0.293) were similar during the two periods. Higher screening coverage (25.95% versus 25.19%; p = 0.007), higher compliance with age recommendations (92.70% versus 91.69%; p = 0.001), lower over-screening (4.92% versus 10.15%; p < 0.001), and reduced unqualified samples (cytology: 1.48% versus 1.73%, p = 0.099; HR-HPV: 0.57% versus 1.34%, p < 0.001) were observed in the HR-HPV genotyping period. Conclusions: Introduction of an HR-HPV genotyping assay in China could detect more CIN2+ lesions at earlier stages and improve programmatic indicators. Evidence suggests that the introduction of HR-HPV genotyping is likely to accelerate the elimination of cervical cancer in China.

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