Vaccine Effectiveness of One Dose of the Nonavalent Human Papillomavirus (HPV) Vaccine Among Young-adult Women in Sweden Among Women Participating in a Clinical Trial of Concomitant HPV Vaccination and Screening
Phase: PHASE4
Conditions: Incident HPV16, 18, 31, 33, 45, 52 or 58 Infection
Sponsor: Karolinska Institutet

 
 
 
Vaccine EƯectiveness of One Dose of the Nonavalent Human Papillomavirus (HPV) Vaccine 
Among Young-adult Women in Sweden Among Women Participating in a Clinical Trial of 
Concomitant HPV Vaccination and Screening (FASTER1DOSE) 
 
9th September 2025 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study Plan: 
Vaccine eƯectiveness of one dose of the nonavalent Human Papillomavirus (HPV) vaccine 
among young-adult women in Sweden among women participating in a clinical trial of 
concomitant HPV vaccination and screening (ClinicalTrials.gov ID: NCT04910802)  
Short title:  
Study Aim: To evaluate the vaccine eƯectiveness of 1 dose the nonvalent vaccine against human 
papillomavirus (HPV) 16, 18, 31, 33, 45, 52, and 58 infection among young adult women in Sweden 
participating in a nationwide HPV elimination trial. 
Primary aim: 
- 
To estimate the vaccine eƯectiveness of 1 dose of the nonavalent vaccine against 
HPV16, 18, 31, 33, 45, 51, 52, and 58 incident HPV infection among women born from 
1994 to 1999 participating in a nationwide HPV elimination trial (ClinicalTrials.gov ID: 
NCT04910802). 
Secondary aim: 
- 
To estimate the vaccine eƯectiveness among the women participating in the piloting 
phase of the trial (ClinicalTrials.gov ID: NCT04910802) (Stockholm region, the capital 
region of Sweden, only). 
- 
To estimate the vaccine eƯectiveness in relation to previous history of having received 
the HPV vaccine outside of the trial. 
- 
To estimate the cross-protective vaccine eƯectiveness of 1 dose of the nonavalent 
vaccine against HPV51, HPV35/39/68, and HPV56/59/66. 
Background 
HPV vaccination is the 1st pillar in the World Health Organization’s (WHO) strategy to eliminate 
cervical cancer as public health problem, deﬁned as an incidence of under 4 per 100,000 women-
years globally (WHO, 2020). Licensed prophylactic HPV vaccines are highly eƯicacious in 
preventing HPV infection and associated cancers (Joura et al, 2015; Porras et al, 2020; FUTURE II 
Study Group, 2007). At the time of licensure, the ﬁrst-generation vaccines were licensed with a 3-
dose schedule, and subsequently with a 2-dose schedule for women aged 15 and under. However, 
based on promising ﬁndings from observational studies of high vaccine eƯectiveness after only 
one dose, and subsequent clinical trials, the Strategic Advisory Group of Experts on Immunization 
(SAGE) recommended an oƯ-label HPV vaccination regimen of one dose for girls and women from 
the age of 9 to 20 years-old (Kreimer et al, 2015; Basu et al, 2021; WHO, 2022). However, for 
women aged 21 or older a 2-dose schedule is still recommended by the WHO (WHO, 2022). 
This nationwide trial of concomitant HPV vaccination among women aged 22 to 30-years-old in 
Sweden is a unique opportunity to evaluate the vaccine eƯectiveness of one dose of HPV 
vaccination among women over the age of 20 years old (Arroyo Muhr et al, 2024). Studies on the 
eƯicacy and eƯectiveness of one dose among women over the age of 20 years old are scarce and 
of varying quality.  The ﬁndings of this study will be crucial to inform public health decision makers 
and in contributing to the evidence base for assessing if the 2-dose schedule recommendation 
among women over 20-years-old is still warranted.  
Methods 

This study will utilize the population level trial of strategies to increase the speed of HPV 
elimination (clinical trials.gov ID: NCT04910802). 
A population-based trial of the ‘Even faster’ strategy to increase the speed of cervical cancer 
elimination commenced in 2021 in the capital region of Sweden (Stockholm County) as a piloting 
phase and expanded to the other regions of Sweden in Autumn 2022 (Clinicaltrials.gov, 
NCT04910802) (Dillner et al, 2021; Arroyo Muhr et al, 2024). Women were invited by letter, push 
notiﬁcation (via their personal mobile telephones) to attend a vaccination site for concomitant 
HPV vaccination (with the nonavalent vaccine Gardasil 9) and HPV-based cervical screening 
(using a self-sample). After 3 years women who had received their ﬁrst vaccine dose were invited 
to receive a second dose of the nonavalent HPV vaccine and to give a second screening sample.  
The vaccine eƯectiveness will be estimated as the HPV incidence among HPV negative vaccinated 
women (for a speciﬁc HPV type) divided by the incidence among a comparison group of all 
unvaccinated women attending routine screening in Sweden (whole trial or Stockholm region in 
the piloting phase). 
Data collection 
HPV screening results from the women participating in the trial will be obtained from the trial 
database and results from routine cervical screening will be extracted from the Swedish national 
cervical screening registry (NKCx) (Dillner et al, 2024).  
Data on HPV vaccination history among the eligible women (vaccinations received within Sweden 
only) shall be collected by linkage to the Swedish national vaccination register via the Swedish 
personal identiﬁcation number. Vaccination data will contain the HPV vaccine, date of 
vaccination and the dose number. 
Statistical Analyses 
To expedite evidence production, the ﬁrst report will include only Stockholm region (the piloting 
phase), approximately 19,000 women, whereas the ﬁnal report will include all women 
participating also in the other regions of Sweden, approximately 240,000 women.  
We shall estimate the incidence rate of incident HPV16, 18, 31, 33, 45, 52 or 58 infection 3 years 
after receiving one dose of the nonavalent vaccine, among the 1994-1999 born women 
participating in the elimination trial at the time who were HPV negative at baseline (negative for 
the speciﬁc HPV type in the analysis). This will be compared to the incidence rate among the HPV 
unvaccinated women born from 1993-1999, attending at least 2 rounds of routine cervical 
screening who were naïve for the given HPV type in the ﬁrst screening test. The incidence rate ratio 
comparing the incidence rate among the HPV vaccinated to the HPV unvaccinated women will be 
estimated using a Poisson regression model. To take account of possible confounding due to age 
and birth cohort wise herd eƯects, age and birth cohort will be adjusted for in the statistical 
model. Vaccine eƯectiveness will be computed as one minus the incidence rate ratio. 
When classifying whether the women were naive at baseline or not a buƯer period of 6 weeks 
between vaccination and screening sample will be implemented as a sensitivity analysis to 
exclude prevalent infections at the time of vaccination, or before the vaccine has had time to 
become eƯective (Markowitz et al, 2022). During the buƯer period the individual will not 
contribute person time to either the intervention or comparison groups. 

Secondary analyses will be conducted stratifying the HPV incidence ratios (both of incident) by 
HPV vaccination status outside the trial at the time of enrollment into the study.  
Power calculations for this study were conducted using a Monte Carlo simulation approach, 
whereupon 1000 data sets were simulated with expected degrees of variation based on the 
following assumptions: i) The baseline HPV18 incidence was assumed to be 2.1 per 100 person-
years (the rarest HPV type out of all the vaccine preventable HPV types in these birth cohorts) 
based on the incidence estimated by the International Agency for Research on Cancer (IARC) 
dynamic HPV transmission model previously parameterized to the Swedish population setting 
(Arroyo Mühr et al, 2024); ii) among the women born from 1994-1999 who reside in Sweden as 
according to the population registry, 35.3% will not have participated in elimination trial by the 
end of the enrollment period on the 30th of June 2025 (N=130,485 women), a conservative 
estimate of 70% of these women will have participated in the routine cervical screening program 
(N=91,349 women), among which 36.5% will have no previous history of HPV vaccination based 
on reported HPV vaccination coverage estimates from the Swedish vaccination register 
(N=33,339 women), therefore, given the current screening interval of 5 years in the age group, we 
expect the unvaccinated women in the target birth cohorts who comprise the comparison group 
to contribute >166,000 person years during the study period; iii) among the intervention group it 
is assumed that 99% of women are naive for HPV18 at enrolment and that 20% of the enrolled 
women will be lost to follow up between the ﬁrst and the second dose, out of which 36.5% will 
have had no previous history of HPV vaccination recorded in the Swedish vaccination register at 
the time of enrollment in the trial. Using these assumptions, we found that the study was highly 
powered (power = 100% power, 95% conﬁdence intervals, 99.6-100% with an alpha level of 0.05) 
to detect HPV18 vaccine eƯectiveness of 95%. Power calculation analyses were conducted using 
R statistical software (version 4.4.0) and the ‘simr’ package (version 1.0.7) (Green and MacLeod, 
2015). 
Ethical considerations 
The population-based even FASTER trial was approved by the Swedish Ethical Review Authority 
and the Swedish Medicinal Products Agency (decision numbers [DNR], 2020-07145 and 5.1-2021-
8496 respectively). All women participating in the trial provided informed consent to participate 
in the study before receiving HPV vaccination. Women with protected identity were not personally 
invited to participate in the trial but were eligible to participate if they so requested. This study is 
funded by Region Stockholm.  
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