Direct, indirect and total effectiveness of bivalent HPV vaccine in women in Galicia, Spain
Direct, indirect and total effectiveness of bivalent HPV vaccine in women in Galicia, Spain
M. Jesus Purriños-Hermida 0 1
MarÂõa Isolina Santiago-PeÂ rez 0 1
Mercedes Treviño 1
Rafaela Dopazo 1
Angelina Cañizares 1
Isolina Bonacho 1
Matilde Trigo 1
M. Eva FernaÂ ndez 1
Ana Cid 1
David GoÂ mez 1 2
Patricia OrdoÂ ñez 1
Amparo Coira 1
M. J. Armada 1
Magdalena Porto 1
Sonia Perez 1
Alberto Malvar-Pintos 0 1
0 Servizo de EpidemioloxÂõa, DireccioÂn Xeral de SauÂde PuÂblica, ConsellerÂõa de Sanidade, Xunta de Galicia , Santiago de Compostela , Spain , 2 Microbiology Department, University Hospital of Santiago , Santiago de Compostela , Spain , 3 Gynecology Department, University Hospital of Santiago , Santiago de Compostela , Spain , 4 Microbiology Department, University Hospital of A Coruña , A Coruña , Spain , 5 Gynecology Department, University Hospital of A Coruña , A Coruña , Spain , 6 Microbiology Department, University Hospital of Pontevedra , Pontevedra , Spain , 7 Gynecology Department, University Hospital of Pontevedra , Pontevedra , Spain , 8 Microbiology Department, University Hospital of Ourense , Ourense , Spain
1 Editor: Magdalena Grce, Rudjer Boskovic Institute , CROATIA
2 Gynecology Department, University Hospital of Ourense , Ourense , Spain , 10 Microbiology Department, University Hospital of Ferrol , Ferrol , Spain , 11 Microbiology Department, University Hospital of Lugo , Lugo , Spain , 12 Fingoy Primary Care Department, Sanitary Area of Lugo , Lugo , Spain , 13 Gynecology Department, University Hospital of Vigo , Vigo , Spain , 14 Microbiology Department, University Hospital of Vigo , Vigo , Spain , 15 Galicia Sur Health Research Institute , Vigo, Vigo , Spain
3 Members of the HPV Vaccine Impact Surveillance Working Group of Galicia is provided in the Acknowledgments. SERGAS , Santiago de Compostela , Spain
Bivalent human papillomavirus (HPV) vaccine was incorporated into the childhood vaccination calendar in Galicia, Spain in 2008. The objectives of this study were to estimate direct, indirect and total effectiveness of HPV vaccine and to identify sexual habits changes in the post-vaccination period in Galicia, Spain.Endocervical scrapings of 745 women attending 7 Health Areas of the Galician Public Health Service were collected in the post-vaccination = 397) and women born in 1994 or later (n = 348). Twelve high-risk human papillomavirus (HR-HPV) genotypes were detected by Cobas® 4800 HPV test (Roche Diagnostics, Mannheim, Germany). The Linear Array® HPV Genotyping Test (Roche Diagnostics) was used for HR-HPV genotype detection other than HPV 16/18. Information about sexual habits was collected by a self-filled questionnaire. Post-vaccination data were compared to previously published pre-vaccination data obtained between 2008 and 2010 in Galicia from women of the same age (18±26 years old, n = 523). The Stata 14.2 software was employed for statistical analyses.Data from 392 unvaccinated and 353 vaccinated women were compared. For unvaccinated and vaccinated women, HPV 16/18 prevalence was 9.2% and 0.8%, respectively, and HPV 31/33/45 prevalence was 8.4% and 1.1%, respectively. Direct, indirect and total effectiveness of the HPV vaccine were (%, 95% CI): 94 (72−99), 30 (-11−56) and 95 (79 −99), respectively, for HPV 16/18 and 83 (46−94), -10 (-88−33) and 84 (54−94), respectively, for HPV 31/33/45. The number of women with first intercourse before 17 years old and 3 or
Data Availability Statement: All relevant data are
within the paper and its Supporting Information
Funding: Funded by CIF: S 15 11 00 1 H DireccioÂn
xeral de SauÂde PuÂblica Edificio Administrativo S.
LaÂzaro s/n Santiago de Compostela
Competing interests: The authors have declared
that no competing interests exist.
more sexual partners along life was higher in the post-vaccination period (p < 0.05). A
positive impact of bivalent HPV vaccine was observed, both on direct and cross protection.
Sexual habits could have changed in the post-vaccination period.
Persistent infection of high-risk human papilloma virus (HR-HPV) is thought to be
responsible for about 100% of cervical cancer cases [
]; this cancer ranks second among
malign neoplasia in women worldwide [
] and causes, according to WHO estimates,
274,000 deaths per year [
]. In addition, HR-HPV are included among the etiological
agents of 78% of vagina cancer and most of their precursor lesions in young women [
31% of oropharyngeal cancer, 15% of vulva cancer, 4.3% of oral cavity cancer and 4.6% of
laryngeal cancer [
To reduce the incidence of these pathologies, mainly of cervical cancer, several vaccines
against HPV have been developed. HPV 16 and 18 are responsible for approximately 70% of
world cervical cancer [
] and HPV 6 and 11 genotypes are responsible for 90% of genital
warts. This is the reason why the first commercial vaccines were developed against these
genotypes: a bivalent vaccine against HPV 16 and 18 (with some cross-protection against HPV 31,
33 and 45) and a quadrivalent vaccine against genotypes HPV 6, 11, 16 and 18. Subsequently,
in 2014, the FDA approved a new vaccine against 9 genotypes (HPV 6, 11, 16, 18, 31, 33, 45, 52
and 58), which is licensed in Europe and now commercially available in Spain. Bivalent and
quadrivalent vaccines are very effective and safe vaccines [6±9].
In Galicia, the bivalent vaccine was introduced in the official immunization schedule for
girls at the end of 2008. Three doses (0±1±6 months) were administered to girls born after
the 1st of January of 1994 when they were 14 years old. In March 2014, there was a change
to the two-dose schedule (0±6 months) authorized by the Spanish Agency of Medicines and
Medical Devices. In January of 2016, the vaccination of 12 years old girls was introduced.
In Galicia, the pre-vaccination prevalence of HR-HPV genotypes was estimated to be
around 10% in female general population, 19% in women 16±19 years old and 23% in women
20±24 years old. The most frequent genotype was HPV 16, with a prevalence of 3.5% [
In different countries, the introduction of HPV vaccination programs produced a decrease
in the prevalence of HPV genotypes targeted by the vaccine (HPV 16 and 18) [
achievement is considered an intermediate step to reduce the incidence of HPV related cancer.
The effect of vaccination programs depends on vaccine use recommendations,
implementation strategies (with or without catch up) and the achieved coverage.
Therefore, in order to evaluate the vaccine effectiveness and its impact on our population, it
is essential to compare pre and post vaccine HPV prevalence. As HPV transmission route is
sexual, this comparison should take into account any change in women's sexual behavior.
The objective of this paper was to estimate direct, indirect and total effectiveness of bivalent
HPV vaccine and to identify changes in sexual habits after the introduction of the vaccination
program in Galicia, Spain.
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Materials and methods
In the post-vaccination period, the study population comprised women of 18±26 years old,
born in 1989 or later, living in Galicia (Spain), attending a primary care center, gynecology
department or family counseling center belonging to the Galician Public Health Service from
2014 to 2017. The exclusion criteria considered were: no previous intercourse with
penetration, current consultation for a sexually transmitted infection (including HPV related lesion
follow-up), pregnancy, giving birth in the previous 40 days, hysterectomy, psychiatric
disorders or inability to fill in a self-filled questionnaire.
Twenty-three collaborators working throughout the seven Health Areas of Galicia (Spain)
were selected by convenience criteria in order to cover the entire territory. Women were
offered to participate following an established system based on appointment schedule and year
of birth. Two cohorts were established according to the HPV vaccine recommendation stated
by 2008 official immunization schedule in Galicia, Spain: women born between 1989 and 1993
(older cohort) and women born in 1994 or later (younger cohort). Collaborators were asked to
include the same number of women from both groups (S1 Appendix). This patient
recruitment continues today in an ongoing study (2014±2019).
During this post-vaccination period, HPV detection cervical scrapings were collected in
ThinPrep PreservCyt Solution (Hologic, Marlborough, MA, USA) in 6 Health Areas and in
BD SurePath™ Collection Vial (Becton Dickinson, New Jersey, USA) in one Health Area.
Twelve HR-HPV genotypes were detected by Cobas1 4800 HPV test (Roche Diagnostics,
Mannheim, Germany): HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. The Linear
Array1 HPV Genotyping Test (Roche Diagnostics, Mannheim, Germany), which identifies
eighteen HR-HPV (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73 and 82), was
used in case of HR-HPV genotype detection other than HPV 16/18.
On the other hand, in the pre-vaccination period (2008±2010), the study population
comprised women of 18±26 years old, living in Galicia (Spain) and attending the Galician Public
Health Service at Pontevedra, which is one of the seven Health Areas of Galicia (Spain). The
exclusion criteria were the same as in the post-vaccination period. The HR-HPV prevalence
observed in these patients were previously published [
]. In this period, the HPV detection
was done using ThinPrep PreservCyt Solution (Hologic), Cobas1 Amplicor HPV test (Roche
Diagnostics), which detects eleven HR-HPV genotypes (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52,
56, 58, 59 and 68). The Linear Array1 HPV Genotyping Test (Roche Diagnostics) was utilized
in case of a positive result.
In both periods, sexual habits information was collected by a self-filled written
questionnaire (S2 and S3 Appendixes).
Vaccination status evaluation
The vaccination status was self-reported and also extracted from the electronic clinical history.
Women who received at least two HPV vaccine doses were considered as vaccinated. Women
who did not received any dose of HPV vaccine were considered unvaccinated. Women who
received a single dose of vaccine were also excluded from the analysis. All women from the
pre-vaccination period were unvaccinated. For data comparison between vaccinated and
unvaccinated women, the vaccination status was considered as stated in the electronic clinical
history. When this information was not registered, the vaccination status was considered as
stated in the questionnaire. When no information was available, the women was considered as
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Detection of HPV 16 and/or 18 was assigned to the HPV 16/18 group. Detection of at least one
of the three following genotypes HPV 31, 33, 45 was assigned to the HPV 31/33/45 group.
Detection of any HR-HPV genotype different than HPV 16/18/31/33/45 was assigned to the
other HR-HPV group. Detection of genotypes pertaining to more than one HPV group in the
same sample was considered as a positive result in the corresponding HPV groups.
The prevalence and the 95% confidence interval (95% CI) were calculated for each HPV
genotype group. In case of detection of any HR-HPV, other than HPV 16/18, that could not be
analyzed by the Linear Array test, the assignment to the HPV 31/33/45 group or to the other
HR-HPV group was performed using the system of chained equations (multiple imputation,
MICE) by logistic regression [
For each HPV genotype group, vaccine effectiveness was estimated as 1 ±prevalence ratio (1
±PR). PR was calculated using a Poisson regression model considering the HPV status
(positive or negative) as the dependent variable and the groups to be compared as independent
variable: (1) vaccinated vs. unvaccinated women from post-vaccination period (direct
effectiveness), (2) unvaccinated women from post-vaccination period vs. women from
prevaccination period (indirect effectiveness), (3) vaccinated women from post-vaccination
period vs. women from pre-vaccination period (total effectiveness), (4) women from
post-vaccination period vs. women from pre-vaccination (overall effectiveness). The model was
estimated unadjusted and adjusting by age group (18±20, 21±23, 24±26), by first intercourse > 16
years old, 3 or more partners along life, and 2 or more partners in the last year. In the
post-vaccination period, a comparison was also performed by inclusion year: first biennium (2014±15)
and second biennium (2016±17). The variance was estimated using the Huber and White
Epidemiological data were compared by vaccination status and time period. The qualitative
variables were compared using Fisher's exact test. The concordance between two methods of
vaccination status estimation was measured by Cohen's kappa coefficient.
To assess the statistical significance, a level of significance of 5% was considered (p < 0.05).
The Stata 14.2 software was used for statistical analysis.
This study received approval from the Ethics Committee of Clinical Investigation of Galicia
(Santiago de Compostela, Spain). All study participants were informed about the purpose of
the survey and were asked to sign a consent form before taking part in the study.
Confidentiality was ensured during data collection and subsequent publication of the results.
Epidemiological characteristics of the population included in
A total of 745 women (average age 21.7 years ± 2.2 SD) from all Health Care Areas of Galicia
were included in the post-vaccination period: 447 (60%) in the first biennium (2014±2015) and
298 (40%) in the second biennium (2016±2017). The older cohort (53.3%) was born between
1989 and 1993. The younger cohort (46.7%) was born in 1994 or later. Eighty two percent was
born in Galicia. Fifty seven percent had their first sexual relationship before age 17 and 71%
declared to have had a sexual partner in the last year. The average age at the first intercourse
4 / 14
was 16.4 years ± 1.7 SD. The vaccination coverage information was available in the electronic
clinical history in 480 cases. It was only available in questionnaires in 209 cases and it was not
available in 56 cases. The global vaccination coverage was 47% (10% with two doses and 90%
with three doses). The vaccination coverage was 43% and 53% in the first and second biennium,
respectively. A 96% concordance (Kappa 0.90) was observed between women knowledge about
their vaccination status and the information registered in the clinical history.
Table 1 shows demographic characteristics and sexual habits of unvaccinated and
vaccinated women, belonging to the post-vaccination period. The average age was 22.9 years for
unvaccinated women vs. 20.4 for vaccinated women. The number of partners along life was 2
or more for 84.5% of unvaccinated women vs. 5 or less in 83.3% of vaccinated women
(p = 0.022). The proportion of women having their first sexual relationship before age 17 was
54% in unvaccinated women vs. 61% in vaccinated women (p = 0.022).
Epidemiological comparison with pre-vaccination period
pre-vaccination period. The proportion of women having 3 or more partners along life was
47.2% in pre-vaccination period vs. 57.8% of women studied in the post-vaccination period
(p < 0.001). The proportion of women having their first sexual relationship before age 17 was
36.9% in the pre-vaccination period vs. 57.5% in the post-vaccination women (p < 0.001).
Prevalence of HPV genotypes
HPV 16/18 was detected by the Cobas1 4800 HPV test (Roche Diagnostics) in 39 (5.2%)
samples and other HR-HPV different than 16/18 in 199 (26.7%). Among these 199 samples, 128
(64.3%) were genotyped by the Linear Array1 HPV genotyping test (Roche Diagnostics) and
the genotype was automatically assigned in the rest of samples as described in the statistical
analysis section. The calculated prevalence of three groups of HR-HPV in the studied
populations is reported in Fig 1.
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Fig 1. Global HR-HPV group prevalence by period of study. HR-HPV group prevalence in post-vaccination
period by vaccination status and post-vaccination biennium.
Vaccine effectiveness against HPV 16/18
In the post-vaccination period, 39 women had a positive result for HPV 16/18. The prevalence
of HPV 16/18 was 9.2% (95% CI: 6.5−12.5) in unvaccinated women vs. 0.8% (95% CI: 0.2−2.5)
in vaccinated women (Fig 1), giving rise to an adjusted direct effectiveness of 94% (95% CI: 72
−99) (Fig 2 and Table 3). The adjusted total effectiveness was 95% (95% CI: 79−99); and the
adjusted overall effectiveness was 61% (95% CI: 39−74). More detailed results are collected in
Vaccine effectiveness against HPV 31/33/45
The prevalence of HPV 31/33/45 was 8.4% (95% CI: 5.9−11.6) for unvaccinated women vs.
1.1% (95% CI: 0.3−2.9) for vaccinated women (Fig 1). The adjusted direct effectiveness
calculated in this case was 83% (95% CI: 46−94) (Fig 2 and Table 4). The adjusted total effectiveness
was 84% (95% CI: 54−94) and adjusted overall effectiveness was 36% (95% CI: -2−60). More
detailed results are given in S5±S8 Tables.
Vaccine effectiveness against other HR-HPV genotypes
The prevalence of other HR-HPV is shown in Fig 1. The prevalence of other HR-HPV for
vaccinated women and unvaccinated women, was 24.6% (95% CI: 20.2−29.5) and 24.7% (95% CI:
20.6−29.3), respectively, yielding a PR of 1 (Table 5). No significant differences were found
between their prevalence ratios for the periods 2014±15 (1.09, 95% CI: 0.78−1.53) and 2016±17
(1.15, 95% CI: 0.66−1.99). More detailed results are shown in S9±S12 Tables.
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Fig 2. Adjusted effectiveness of HR-HPV 16/18 and 31/33/45, in vaccinated vs. unvaccinated women in the
postvaccination period (direct effectiveness), unvaccinated women in the post-vaccination period vs. women in the
pre-vaccination period (indirect effectiveness), vaccinated women vs. women in the pre-vaccination period (total
effectiveness), and vaccinated and unvaccinated women in the post-vaccination period vs. women in the
prevaccination period (overall effectiveness).
Regarding sexual habits changes in the Galician population, it was observed that women
included in the post-vaccination period started sexual activity earlier and had a higher number
of sexual partners along life than women included in the pre-vaccination period. In addition,
analyzing only women included in the post-vaccination period, the youngest women
(vaccinated group) were younger at first intercourse than the older women (unvaccinated group).
Despite of this, an important decrease in HPV 16/18 prevalence and a high direct
immunization effectiveness (94%) was observed in vaccinated women in comparison with unvaccinated
women in the same period of time (post-vaccination period).
On the other hand, the estimated unadjusted PR for HPV 16/18 between the
post-vaccination and the pre-vaccination period was 0.5 (50% decrease), reaching values previously
reported by Markowitz et al. [
] or Kavanagh et al. [
Although unvaccinated women at the post-vaccination period started sexual risk behaviors
earlier than women at the pre-vaccination period, the indirect vaccination effectiveness was
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Vaccinated vs. Unvaccinated
Unvaccinated vs. Pre-vaccination period
Vaccinated vs. Pre-vaccination period
Post vs. Pre-vaccination period
PR: Prevalence ratio. CI: Confidence interval.
p < 0.05, statistically significant.
29.7% (p = 0.145). This suggests a herd immunological effect of this vaccine already observed
in other studies by Cameron et al. [
] and Tabrizi et al. [
]. As expected, the total
effectiveness was estimated to be 95%, which we believe, it has not been previously reported. The
overall vaccine effectiveness was 61%, as obtained from an adjusted prevalence ratio of 0.39, which
is in line with that published by Mesher et al. [
We also looked for cross-protection in this vaccinated population. The estimated direct and
total vaccination effectiveness were 83% and 84%, respectively, for the HPV 31/33/45 group of
genotypes. These results agree with the trend already observed by Kavanagh et al. [
women receiving three vaccine doses and by Cameron et al. [
] in those receiving two doses.
The cross-protection findings could have clinical consequences in the prevention of
precancerous and cancerous lesions related to HPV 31/33/45 [
]. Although these genotypes are not
targeted by the vaccine, certain cross-protection was already published [
] and explained by
their genetic relationship with HPV 16/18. Likewise, the results of this study are consistent
with those observed by Drolet et al. [
] as well as with the results of Mesher et al. [
obtained for the 16±18 year-old group with an estimated HPV vaccine coverage of 65%; in
these studies, there was no direct information about the vaccination status of women included
in the target group for vaccination.
On the other hand, the overall vaccine effectiveness was 36%, which seems to indicate that
there is a population effect, although the CIs show that is not statistically significant probably
due to small sample size. It is remarkable that in other studies [
], analyzing the
introduction of quadrivalent vaccine, there were not statistically significant differences in the
prevalence of genotypes 31/33/45 between pre-vaccination and post-vaccination periods. Unlike the
large direct and total effectiveness, indirect effectiveness was not observed for HPV 31/33/45.
Reasons explaining this fact may be the sample size and/or the time elapsed since the vaccine
We have also analyzed the possibility of replacement between HR-HPV genotypes in the
post-vaccination period. The same prevalence for other HR-HPV was observed for vaccinated
and unvaccinated women, independently of the prevalence of HPV 16/18 and HPV 31/33/45,
discarding any replacement between genotypes. In the case that replacement had occurred,
one would expect a higher prevalence for vaccinated than for unvaccinated women, but the
adjusted prevalence ratio was 1.02. The observed increase in the prevalence of other HR-VPH
in the post-vaccination period versus the pre-vaccination period could be explained by the
greater presence of risk factors in the post-vaccination period.
Kavanagh et al. [
] did not find evidence of clinically significant high-risk
type-replacement, although they observed a trend over time for prevalence of any HR-HPV excluding 16/
18/31/33/45. This trend depended on birth cohort (more likely to infect the younger cohort)
and on the number of administered doses (less likely in case of complete vaccination with
three doses). This last finding of Kavanagh was not found in a study published by Cameron
et al. [
Different methods showed good concordance to estimate vaccination coverage,
demonstrating good knowledge about the HPV vaccine among the young population. In this study
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74% of the women of the cohort from 1994 onwards were vaccinated with three doses. This
proportion is very close to the 72% of global vaccination coverage in Galicia (data provided by
the Communicable Diseases Department of the Public Health General Direction from
ConsellerÂõa de Sanidade, Galicia, Spain, for birth cohorts from 1994 to 1999). This supports that
results of this study are representative of the Galician population. Although 90% of vaccinated
women included in this study received three doses, those receiving two doses were also
considered as vaccinated. This criterion allowed us to increase the sample size relying on data on two
doses vaccination effectiveness observed in other studies [
This study has several strengths. As stated by Cameron et al. [
], there are few studies in
which the vaccination status can be directly linked to HPV detection in cervical samples. In
addition, microbiological data are accompanied by sexual habits information and the
vaccination status was verified by the electronic clinical history. More than 98% of the population
have access to free health care. This supports that this study is a good representation of the
Galician female population. In our community, given the characteristics of the Public Health
System, there is nothing to presume that only a specific subgroup of women had been invited
Four limitations of this study could be listed: (i) the small sample size; (ii) the impossibility
of verifying the external validity of the sample; (iii) the imputation of data on 71 samples; and
(iv) the fact that two different methods were used for HPV detection in pre-vaccination and
post-vaccination periods, although these two tests have previously shown a very high
agreement for the detection of HR-HPV genotypes [
In conclusion, this study highlights the achievements of the vaccination program followed
in our community. A high direct effectiveness previously described for HPV 16/18 was also
supported by this study. A possibly relevant result is the high direct cross effectiveness (83%)
shown for some other genotypes (HPV 31/33/45) not targeted by the bivalent vaccine. An
indirect effectiveness of 30% was observed for genotypes 16/18; although statistical significance
was not achieved with our sample size, the information could be of interest, as it supports an
expected result not yet demonstrated. Our results seem to indicate that there was no common
HPV replacement by other types. Continuous surveillance importance lies not only in the
evaluation of vaccine effectiveness but also in the future assessment of genotype replacement or
cross protection persistence along time.
S1 Appendix. Sample size calculation.
S2 Appendix. Pre-vaccination questionnaire.
S3 Appendix. Post-vaccination questionnaire.
S1 Table. Prevalence ratio (PR) for HR-HPV 16/18 and 95% CI in vaccinated vs.
unvaccinated women in the post-vaccination period.
S2 Table. Prevalence ratio (PR) for HR-HPV 16/18 and 95% CI in unvaccinated women in
the post-vaccination period vs. women in the pre-vaccination period.
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S3 Table. Prevalence ratio (PR) for HR-HPV 16/18 and 95% CI in vaccinated women in the
post-vaccination period vs. women in the pre-vaccination period.
S4 Table. Prevalence ratio (PR) for HR-HPV 16/18 and 95% CI in vaccinated and
unvaccinated women in the post-vaccination period vs. women in the pre-vaccination period.
S5 Table. Prevalence ratio (PR) for HR-HPV 31/33/45 and 95% CI in vaccinated vs.
unvaccinated women in the post-vaccination period.
S6 Table. Prevalence ratio (PR) for HR-HPV 31/33/45 and 95% CI in unvaccinated women
in the post-vaccination period vs. women in the pre-vaccination period.
S7 Table. Prevalence ratio (PR) for HR-HPV 31/33/45 and 95% CI in vaccinated women in
the post-vaccination period vs. women in the pre-vaccination period.
S8 Table. Prevalence ratio (PR) for HR-HPV 31/33/45 and 95% CI in vaccinated and
unvaccinated women in the post-vaccination period vs. women in the pre-vaccination
S9 Table. Prevalence ratio (PR) for HR-HPV excluding 16/18/31/33/45 and 95% CI in
vaccinated vs. unvaccinated women in the post-vaccination period.
S10 Table. Prevalence ratio (PR) for HR-HPV excluding 16/18/31/33/45 and 95% CI in
unvaccinated women in the post-vaccination period vs. women in the pre-vaccination
S11 Table. Prevalence ratio (PR) for HR-HPV excluding 16/18/31/33/45 and 95% CI in
vaccinated women in the post-vaccination period vs. women in the pre-vaccination period.
S12 Table. Prevalence ratio (PR) for HR-HPV excluding 16/18/31/33/45 and 95% CI in
vaccinated and unvaccinated women in the post-vaccination period vs. women in the
We are very grateful to members/collaborators of the HPV Vaccine Impact Surveillance
Working Group of Galicia: University Hospital of Santiago (Estructura de GestioÂn Integrada
de Santiago de Compostela): Eva Rozas, Cristina SaÂnchez, Berta Novegil; University Hospital
of A Coruña (Estructura de GestioÂn Integrada de a Coruña): XoseÂ Anxo Vidal, Pilar Barral,
Amelia Mosquera, LucÂõa DuraÂn; University Hospital of Pontevedra (Estructura de GestioÂn
Integrada de PontevedraÐO SalneÂs): Genoveva Guinarte, AÂ ngeles Area, M Carmen Santos;
University Hospital of Ourense (Estructura de GestioÂn Integrada de Ourense, VerÂõnÐO Barco
de Valdeorras): Josefa JardoÂn, M Isabel de la Torre, BeleÂn Novoa, MarÂõa Villanueva, Carlos
MeneÂndez; University Hospital of Ferrol (Estructura de GestioÂn Integrada de Ferrol: Lorena
12 / 14
DomÂõnguez, Isaura GonzaÂlez; University Hospital of Lugo and Fingoy Primary Care
Department (Estructura de GestioÂn Integrada de Lugo, CervoÐMonforte de Lemos): M JesuÂs
MeÂndez, Zita MeÂndez; University Hospital of Vigo and Primary Care Departments of Health Area
of Vigo (Estructura de GestioÂn Integrada de Vigo): Paula Cibes, Luz Troitiño, Pilar Zamuz,
MarÂõa Alvarez-LarraÂn, Inmaculada Arena, Ana Isabel Costalago, Paula Ulloa, Dolores Fraile.
Lead author for this group: MarÂõa JesuÂs Purriños-Hermida.
Conceptualization: M. Jesus Purriños-Hermida, Alberto Malvar-Pintos.
Investigation: MarÂõa Isolina Santiago-PeÂrez, Mercedes Treviño, Rafaela Dopazo, Angelina
Cañizares, Isolina Bonacho, Matilde Trigo, M. Eva FernaÂndez, Ana Cid, David GoÂmez,
Patricia OrdoÂñez, Amparo Coira, M. J. Armada, Magdalena Porto, Sonia Perez, Alberto
Methodology: M. Jesus Purriños-Hermida, Alberto Malvar-Pintos.
Software: MarÂõa Isolina Santiago-PeÂrez.
Supervision: M. Jesus Purriños-Hermida, Alberto Malvar-Pintos.
Writing ± original draft: M. Jesus Purriños-Hermida, Sonia Perez.
Writing ± review & editing: M. Jesus Purriños-Hermida, MarÂõa Isolina Santiago-PeÂrez,
Mercedes Treviño, Angelina Cañizares, Matilde Trigo, Ana Cid, Patricia OrdoÂñez, Amparo
Coira, Sonia Perez, Alberto Malvar-Pintos.
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a randomised, double-blind trial. The Lancet. 2017; 390: 2143±2159.
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