MAJOR ARTICLE

Fall in Human Papillomavirus Prevalence

Following a National Vaccination Program
Sepehr N. Tabrizi,1,2,3,4 Julia M. L. Brotherton,5,8 John M. Kaldor,9 S. Rachel Skinner,8 Eleanor Cummins,4 Bette Liu,9
Deborah Bateson,10 Kathleen McNamee,6,7 Maria Garefalakis,11 and Suzanne M. Garland1,2,3,4
1
Regional World Health Organization Human Papillomavirus Laboratory Network, Department of Microbiology and Infectious Diseases, The Royal
Womens Hospital, Victoria, Australia; 2Department of Obstetrics and Gynecology, University of Melbourne, Australia; 3Department of Microbiology,
and 4Murdoch Childrens Research Institute, Royal Childrens Hospital, Parkville, Australia; 5Registries, Victorian Cytology Service, East Melbourne,
Australia; 6Family Planning Victoria, Box Hill, and 7Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia;
8
Sydney University Discipline of Pediatrics and Child Health, Childrens Hospital Westmead, Australia; 9The Kirby Institute, University of New South
Wales, Darlinghurst; 10Family Planning New South Wales, Asheld; and 11Family Planning Western Australia, Northbridge, Western Australia

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(See the Editorial Commentary by Hariri and Markowitz, on pages 16335.)

Background. In April 2007, Australia became the rst country to introduce a national government-funded
human papillomavirus (HPV) vaccination program. We evaluated the programs impact on genotype-specic
HPV infection prevalence through a repeat survey of women attending clinical services.
Methods. HPV genoprevalence in women aged 1824 years attending family planning clinics in the prevaccine period (20052007) was compared with prevalence among women of the same age group in the postvaccine
period (20102011). The same recruitment and testing strategies were utilized for both sets of samples, and comparisons were adjusted for potentially confounding variables.
Results. The prevalence of vaccine HPV genotypes (6, 11, 16, and 18) was signicantly lower in the postvaccine sample than in the prevaccine sample (6.7% vs 28.7%; P < .001), with lower prevalence observed in both
vaccinated and unvaccinated women compared with the prevaccine population (5.0% [adjusted odds ratio, 0.11;
95% condence interval, 0.060.21] and 15.8% [adjusted odds ratio, 0.42; 95% condence interval, 0.190.93],
respectively). A slightly lower prevalence of nonvaccine oncogenic HPV genotypes was also found in vaccinated
women (30.8% vs 37.6%; adjusted odds ratio, 0.68; 95% condence interval, 0.460.99).
Conclusions. Four years after the commencement of the Australian HPV vaccination program, a substantial
decrease in vaccine-targeted genotypes is evident and should, in time, translate into reductions in HPV-related lesions.

Australia was the rst country to implement a national

government-funded vaccination program to prevent
cervical cancer. From April 2007 through December
2008, a school-based delivery strategy was used to
offer free human papillomavirus (HPV) vaccination to
girls aged 1217 years, and from July 2007 through

Received 17 April 2012; accepted 15 June 2012; electronically published 19

October 2012.
A portion of this data was presented at Preventing Cervical Cancer: Integrating
Screening and Vaccination Conference, on 911 November 2011 in Melbourne,
Australia.
Correspondence: Sepehr N. Tabrizi, PhD, Department of Microbiology and Infectious Diseases, The Royal Womens Hospital, Locked Bag 300, Parkville, Victoria
3052, Australia (sepehr.tabrizi@thewomens.org.au).
The Journal of Infectious Diseases 2012;206:164551
The Author 2012. Published by Oxford University Press on behalf of the Infectious
Diseases Society of America. All rights reserved. For Permissions, please e-mail:
journals.permissions@oup.com.
DOI: 10.1093/infdis/jis590

December 2009, general practitioners and other community providers offered free vaccination to women
aged 26 years. Since 2009, routine HPV vaccination
has continued for girls in the rst year of high school
(age, 1213 years) as part of the National Immunization Schedule. During 20072009, an estimated 83%
of girls aged 1217 received at least 1 dose of HPV
vaccine and 70% completed the 3-dose HPV vaccination course [1]. Among women aged 1826 years, recorded coverage in this period was 55% and 32% for
1-dose and 3-dose coverage, respectively [2]. This was
less than true coverage because notication in this age
group to the national vaccine register was not compulsory, although it did attract a small notication
payment per dose [2]. The Australian HPV
vaccination program has exclusively used the quadrivalent vaccine, which protects against HPV genotypes

Postvaccine HPV Prevalence Reduction

JID 2012:206 (1 December)

1645

METHODS
Study Design and Participants

We used a repeat cross-sectional design to compare HPV

prevalence in 2 samples of women recruited from sentinel
clinical sites. The rst or prevaccine implementation
sample was made up of women aged 1824 years (at the time
of recruitment) who were recruited from participating family
planning clinics (FPCs) for Papanicolaou screening during the
recruitment period of 20052007 and had participated in the
WHINURS study [13] in Sydney, Melbourne, and Perth, 3 of
Australias 4 largest cities and home to nearly one-half the
Australian population. All FPCs in Australia are government
funded and provide a wide range of reproductive and sexual
health services, including clinical screening, diagnosis and
treatment, professional education, and health promotion. Each
of Australias major cities has either 1 or 2 FPC sites that are
recognized as attracting a wide range of clients from across the
sociodemographic spectrum.
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Tabrizi et al

The second or postvaccine implementation sample comprised women aged 1824 years who had attended FPCs in
the same cities during the recruitment period 20102011 for
Papanicolaou screening. These women would have been aged
1420 years at the time they were vaccinated, if they participated in the school- or community-based components of the
HPV vaccination program between 2007 and 2009. Any
impact measured in this age group would most closely approximate the benet that might be expected for future cohorts of
adolescents. Based on vaccine registry data, the recorded HPV
vaccine coverage among women aged 1824 years in 2011 was
74% for 1 dose and 55% for 3 doses [1, 2]. Under Australian
guidelines, cervical screening begins at age 18 years or 2 years
after rst intercourse, whichever is later. Therefore, on the
basis of their age, the women in the second sample were in
both the vaccinated cohort and eligible for cervical screening
at the time of recruitment. The recruitment for the postvaccine sample is ongoing, and the current study is based on an
interim data analysis.
Of 2 FPCs in Melbourne, only 1 participated in the prevaccine phase, whereas both joined the postvaccine phase. Participants were recruited from both Perth FPCs in both phases.
The Sydney FPC that had participated in the prevaccine phase
moved premises soon afterward to a nearby site within the
city. Both this site and a second major Sydney FPC participated in the postvaccine phase. All the clinics participating in the
prevaccine and postvaccine phases were located within the
same metropolitan areas.
The procedures to recruit participants were identical for the
prevaccine and postvaccine samples. Clinic staff identied ageeligible women at the time of a consultation that included
routine Papanicolaou testing. Invitation to participate depended on judgment by the clinician that there was sufcient time
to raise the study in the context of the clinical visit. Written,
informed consent was obtained from those who agreed to participate. At the time of the Papanicolaou test, each woman
had a sample of exfoliated cervical cells collected in Preservcyt
(Thin Prep, Cytyc) for HPV DNA testing. Information on
age, current use of hormonal contraception, smoking status,
and postcode of residence was collected. Those enrolled in the
postvaccine group were also asked to provide information relating to HPV vaccination status, sexual and reproductive
history, and knowledge of risk factors for cervical cancer. Approval to conduct the study was obtained from research and
ethics committees at each of the sites that enrolled
participants.
Laboratory Testing

Identical laboratory methods for HPV genotype detection

were used for both the prevaccine and postvaccine groups
[13]. Briey, 1 mL of cervical cells in Preservcyt was pelleted
and resuspended in 200 L of phosphate-buffered saline for

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16 and 18 [3], the main causes of high-grade cervical intraepithelial neoplasia (CIN grades 2 and 3) in Australian women,
and genotypes 6 and 11, which cause most genital warts [4, 5].
Denitive proof of the programs effectiveness in reducing
cervical cancer will not be evident for several decades.
However, there have already been early signs of success, manifested as substantially lower numbers of both new genital
warts presentations at sexual health clinics [6, 7] and histologically conrmed diagnoses of high-grade cervical lesions [8]
among young women in the vaccine cohort, compared with
their predecessors at the same age.
Another outcome measure that is increasingly being recognized as relevant for HPV vaccine evaluation is the prevalence
of infection with vaccine-targeted genotypes. With placebocontrolled trials no longer ethically feasible, genotype prevalence has been endorsed as an appropriate surrogate outcome
for comparative trials of new HPV vaccine constructs [9], as
well as providing an important basis for population monitoring of vaccine program effectiveness [1012].
We conducted Australias rst study of HPV genoprevalence, known as WHINURS (Women, Human papillomavirus
prevalence, Indigenous, Non-Indigenous, Urban, Rural Study),
just prior to the implementation of the national HPV vaccination program. This study involved recruitment of women at
34 sentinel clinical sites from around the country and provided estimates of the prevalence of specic genital HPV genotypes [13]. With 4 years having elapsed since implementation
of the vaccination program, we initiated a follow-up survey to
assess changes in the prevalence of HPV genotypes in young
Australian women. Here we report on the rst analysis of ndings in women aged 1824 years at participating clinics in 3 of
Australias major cities.

Statistical Analysis

The primary analyses compared women in the prevaccine and

postvaccine samples, with the latter being further stratied
into 2 groups based on whether or not participants reported
having received at least 1 dose of HPV vaccine. Comparisons
of sociodemographic characteristics and HPV prevalence were
then made across the 3 groups ( prevaccine, postvaccine unvaccinated, and postvaccine vaccinated). It was hypothesized
that if the groups had comparable sociodemographic proles,
we would see a lower prevalence of vaccine types in women
who had received the vaccine, compared with both the prevaccine women and the postvaccine women who had not received
the vaccine.
We analyzed HPV prevalence as (1) any HPV genotype; (2)
any HR-HPV genotype (16, 18, 31, 33, 35, 39, 45, 51, 52, 56,
58, 59, or 68); (3) any HR-HPV genotype excluding the
vaccine genotypes 16 and 18; (4) vaccine-preventable HPV genotypes (6, 11, 16, and 18); and (5) other prespecied groupings of nonvaccine genotypes. Vaccine effectiveness (VE) was
calculated by comparing the prevalence of HPV infection
between the vaccinated and unvaccinated group in the postvaccine sample using the standard formula VE = 1 RR,
where RR is the ratio of the prevalences in these 2 postvaccine
samples.
We also compared the groups of women according to sociodemographic variables including age, socioeconomic status
(upper or lower 50th percentile, based on the Socioeconomic
Indexes for Areas, a score that ranks Australian residential

postcodes according to information from the 2006 Census on

indicators including median income, education level, and
household numbers) [21], residential area (major city or other,
based on the Accessibility/Remoteness Index of Australia
[ARIA], classies residential postcodes into major cities) [22],
current use of hormonal contraceptives, and current smoking
status.
In addition, for postvaccine study participants, we also
compared vaccinated and unvaccinated women with regard to
their reported age at rst sexual intercourse (in years), education (higher or lower, based on completion of at least high
school or technical college), and whether they were Australian
born. To test for differences in proportions or means between
the groups of women, 2 tests or t tests and analysis of variance were used, respectively. We used logistic regression to
adjust comparisons of prevalence by sociodemographic characteristics that were found to vary between the groups of
women and report adjusted odds ratios (ORs). Statistical signicance was tested at the level of P < .05. All analyses were
conducted using Stata software (version 10.1).
RESULTS
During the prevaccine phase of recruitment, metropolitan
FPCs in Sydney, Melbourne, and Perth recruited 202 women
aged 1824 years. During the postvaccine phase, FPCs recruited 404 women aged 1824 years. In the postvaccine sample, 9
women reported that they did not know whether or not they
had received any doses of the HPV vaccine and were excluded
from analyses by vaccine status.
Women from the prevaccine sample were slightly older
than those from the postvaccine sample (mean age, 21.6 vs
21.2 years; P = .005) and less likely to be using hormonal contraceptives at the time of recruitment (60.9% vs 74.2%;
P = .001), but other characteristics were similar between
groups (Table 1). Of women recruited to the postvaccine
sample, 85.6% (n = 338) reported that they had been vaccinated with at least 1 dose, and of those who recalled the number
of doses, 279 (86.4%) of 323 women stated that they received
all 3, giving a self-reported 3-dose coverage rate of 70.6%.
Within the postvaccine sample, women who stated that they
had been vaccinated were slightly younger than unvaccinated
women (mean age, 21.1 vs 21.8 years; P = .009), had a higher
education status (95.0% vs 87.7% completed high school or
technical college; P = .03), and were more likely to be born in
Australia (88.5% vs 59.7%; P < .001). These 2 groups were
similar for other characteristics including their age at rst reported sexual intercourse (mean age, 16.5 vs 16.7 years;
P = .3), socioeconomic status, use of hormonal contraceptives,
and smoking status.
Across the 3 categories of women ( prevaccine, postvaccine
unvaccinated, and postvaccine vaccinated), the only

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DNA extraction using the automated MagNA Pure LC isolation and purication system (Roche Molecular Systems) with
the DNA-I isolation kit [14]. Following nucleic acid isolation,
all samples were initially assessed for the presence of 13 highrisk HPV (HR-HPV) genotypes using the Amplicor HPV test
kit (Roche Molecular Systems). Any specimen shown to be
negative for HR-HPV types was tested for the presence of
mucosal HPV DNA using L1 consensus primer set PGMY09PGMY11 [15]. Polymerase chain reaction (PCR) products
were detected by enzyme-linked immunosorbent assay
(ELISA) using a generic biotin-labeled probe for detection of
the presence of mucosal HPV sequences in the sample [16].
Samples positive for HPV by either the Amplicor test or the
PGMY09-PGMY11 PCR-ELISA were subsequently genotyped
using the Linear Array HPV genotyping test (Roche) modied
by using an automated blot processor, BeeBlot (Bee Robotics),
for the hybridization and washing steps, as previously validated by our laboratory [1719]. HPV genotyping proles were
manually interpreted and veried using the HPV reference
guide provided with each test kit. Any sample positive for the
HPV 52/33/35/58 probe line on the Linear Array test was
further tested to conrm the presence or absence of HPV
type 52 [20].

Table 1.

Characteristics of Women According to Study and Vaccination Status

Characteristic

Prevaccine
Group
(n = 202)

Postvaccine
Group
(n = 404)

Age, mean years (SD)

21.6 (1.8)

21.2 (1.8)

Pa

Postvaccine
Unvaccinated
Group (n = 57)

Postvaccine
Vaccinated
Group (n = 338)

Pb

.005c

21.8 (1.9)

21.1 (1.8)

.001c
.1
.4

Residing in major city

Higher socioeconomic
group

192 (95.1)
159 (78.7)

362 (90.9)
312 (78.0)

.08
.8

49 (87.5)
40 (71.4)

304 (91.3)
266 (79.4)

Hormonal contraceptive use

Current smoker

123 (60.9)
60 (29.7)

299 (74.2)
109 (27.6)

.001c
.6

36 (63.2)
15 (26.8)

257 (76.3)
90 (27.3)

<.001c
.8

Data are no. (%) of women, unless otherwise indicated. Percentages do not include missing values.
a

P value for difference between prevaccine and postvaccine groups.

P value for difference across 3 groups: prevaccine, postvaccine unvaccinated, and postvaccine vaccinated.

P < .05.

consistently had the lowest prevalences of HPV, and the differences were particularly striking for the HPV genotypes
covered by the vaccine, with only 5.0% of vaccinated women
in the postvaccine sample having 1 of these genotypes. We
also found signicant differences between the 3 groups in the
prevalence of HPV types 6, 16, and 18 (Table 2) and no signicant differences for selected other HR-HPV genotypes.
Vaccine effectiveness against vaccine-type HPV infection was
73% (95% condence interval [CI], 48%86%; P < .001).
After adjusting for age and use of hormonal contraceptives,
compared with women in the prevaccine sample, those in the
postvaccine sample who reported being vaccinated were significantly less likely to be positive for any HPV genotype (OR,
0.49; 95% CI, 0.340.71), HR-HPV genotypes (OR, 0.48; 95%

Figure 1. Differences in human papillomavirus (HPV) genoprevalence between prevaccine and postvaccine populations. *P < .05 for difference in
percentages between groups. Abbreviations: CI, condence interval; excl, excluding; HR-HPV, high-risk HPV.
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characteristics which differed signicantly were age and hormonal contraceptive use (Table 1); we therefore adjusted for
these when comparing HPV prevalence across these 3 groups.
There were highly signicant differences in crude HPV
prevalence between the prevaccine and postvaccine samples
(Figure 1). The prevalence of any HPV genotype was 59.9% vs
48.0% in the prevaccine and postvaccine groups, respectively
(P = .006). For the vaccine-targeted HPV genotypes, the difference was even greater at 28.7% vs 6.7%, respectively
(P < .001). When the postvaccine sample was stratied according to self-reported vaccination status, there were highly significant differences across the 3 groups in the proportions of
women positive for any type of HPV, HR-HPV types, and
HPV vaccine genotypes (Table 2). Vaccinated women

Table 2.

Prevalence of Human Papillomavirus (HPV) Genotypes According to Study and Vaccination Status

HPV Genotype

Prevaccine
Group
(n = 202)

Postvaccine
Group
(n = 404)

Any

121 (59.9)

194 (48.0)

95 (47.0)
76 (37.6)

138 (34.2)
126 (31.2)

High-risk
High-risk excluding 16 and 18
Vaccine types

Postvaccine
Unvaccinated
Group (n = 57)

Postvaccine
Vaccinated
Group (n = 338)

.006

33 (57.9)

157 (46.5)

.007

.002
.1

24 (42.1)
20 (35.1)

111 (32.8)
104 (30.8)

.004
.3

Pa

Pb

58 (28.7)

27 (6.7)

<.001

9 (15.8)

17 (5.0)

<.001

16
18

43 (21.3)
17 (8.4)

20 (4.9)
9 (2.2)

<.001
<.001

6 (10.5)
5 (8.8)

13 (3.9)
4 (1.2)

<.001
<.001

11 (5.5)

2 (0.5)

<.001

2 (3.5)

0 (0.0)

<.001

3 (1.5)
21 (10.4)

1 (0.3)
37 (9.2)

.08
.6

0 (0.0)
9 (15.8)

1 (0.3)
26 (7.7)

.2
.1

11
31, 33, 35, and 45
Data are no. (%) of women.
a

P value for difference between prevaccine and postvaccine groups.

P value for difference across 3 groups: prevaccine, postvaccine unvaccinated, and postvaccine vaccinated.

DISCUSSION

Table 3. Association Between Human Papillomavirus (HPV)

Prevalence, by Groups of HPV Genotypes, and Study Group and
Vaccination Status
Status, Group

OR (95% CI)b

1.00
0.54 (0.380.78)

1.00
0.56 (0.390.80)

0.92 (0.501.69)

0.97 (0.521.80)

0.49 (0.340.71)

0.50 (0.340.73)

1.00

1.00

HPV positive
Prevaccine
Postvaccine
Postvaccine, not
vaccinated
Postvaccine,
vaccinated
High-risk HPV types
Prevaccine

Using a repeat cross-sectional design involving sentinel clinical sites, we have shown that a substantial and statistically signicant decrease in the prevalence of vaccine-preventable
HPV genotype infections has occurred following implementation of Australias national HPV vaccination program. The decrease was almost entirely restricted to the HPV genotypes
that the quadrivalent vaccine is designed to prevent, occurred
primarily in women who said that they had received the
vaccine, and could not be explained by other differences in the
characteristics of the women in the samples being compared.
As far as we are aware, this nding is the rst genoprevalencebased evidence of the protective effect of HPV vaccination
outside the setting of a clinical trial.
Our observation follows recent Australian reports of postvaccination decreases in genital warts and high-grade cervical
lesions among young women [6, 8]. It is consistent with the
high levels of vaccine coverage achieved under the Australian
program, combined with the efcacy of the HPV vaccine
observed in the prelicensure trials.

OR (95% CI)a

Postvaccine
Postvaccine, not
vaccinated
Postvaccine,
vaccinated

0.53 (0.370.75)

0.55 (0.380.79)

0.82 (0.451.51)

0.88 (0.481.64)

0.48 (0.330.70)

0.50 (0.340.74)

High-risk HPV types excluding 16 and 18

Prevaccine
1.00
Postvaccine

1.00

0.70 (0.491.01)

0.74 (0.511.07)

0.92 (0.491.71)

0.97 (0.521.84)

Postvaccine,
0.68 (0.460.99)
vaccinated
Vaccine types (6, 11, 16, and 18)

0.71 (0.481.04)

Postvaccine, not
vaccinated

Prevaccine

1.00

1.00

Postvaccine
Postvaccine, not
vaccinated

0.16 (0.090.26)
0.42 (0.190.93)

0.16 (0.090.26)
0.40 (0.180.90)

Postvaccine,
vaccinated

0.11 (0.060.21)

0.11 (0.060.21)

Adjusted for age and hormonal contraceptive use.

Adjusted for age, hormonal contraceptive use, region, socioeconomic

group, and smoking status.

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CI, 0.330.70), and vaccine-preventable HPV genotypes (OR,

0.11; 95% CI, 0.060.21) (Table 3). There was also a reduction
of borderline signicance in the prevalence of HR-HPV types
excluding 16 and 18 (OR, 0.68; 95% CI, 0.460.99). The unvaccinated postvaccine women were also less likely than the
prevaccine women to be positive for the HPV genotypes 6, 11,
16, and 18 (OR, 0.42; 95% CI, 0.190.93). These differences in
HPV prevalence were not materially affected by additionally
adjusting for socioeconomic status, region of residence, and
smoking status (Table 3).

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Tabrizi et al

that the drop in HPV prevalence demonstrated in our data is

due to a reduction in sexual exposure to infection. In addition,
recent data from United States has found that HPV vaccination status does not inuence sexual risk behavior in
adolescents [25].
This early sign of a major reduction in HPV prevalence,
only 4 years after implementation of a national vaccination
program, provides further evidence in favor of Australias substantial national investment in the program. As highly vaccinated cohorts from the national HPV vaccination school
program move into adulthood, this reduction should continue.
A reduction in prevalence of HPV genotype infections responsible for 70% of cervical cancers and >50% of high-grade
lesions should translate over time in reductions in the rate of
cervical abnormalities, with subsequent decreases in treatment
episodes, and ultimately reduction in the burden of illness and
death due to cervical cancer, as well as other anogenital HPVrelated cancers [8].
Our analyses also suggest the possibility that there has
already been a reduction in vaccine-related HPV genotypes
among unvaccinated women living in the Australian community. We are continuing to recruit from participating FPCs, to
reach a sample size that will allow us to estimate vaccine effectiveness according to the number of validated vaccine doses
received, and examine the extent of any herd immunity with
more precision.
Notes
Acknowledgments. We thank the studys research nurses Jennifer
Jolly, Mandy Johnson, and Tracey Rose, who have assisted with recruitment at each of the FPCs in New South Wales, Victoria, and Western
Australia, respectively, as well as all of the staff involved in the baseline
WHINURS study.
Author contribution. S. N. T., J. M. L. B., and J. M. K. contributed to
study design, data analysis, data interpretation, and writing of the
manuscript. S. R. S. and S. M. G. contributed to study design, data interpretation, and writing of the manuscript. B. L. contributed to data analysis,
data interpretation, and writing of the manuscript. D. B., K. M., and
M. G. contributed to study design, site enrolment, and writing of the
manuscript. E. C. performed laboratory testing and contributed to data
analysis and writing of the manuscript.
Financial support. This work was supported by Australian National
Health and Medical Research Council Project Grant [APP1007685] and
Anti- Cancer Council for Victoria Grant in Aid [628754]. John Kaldor
and Bette Liu are supported by Fellowships from the National Health and
Medical Research Council.
Potential conicts of interest. S. N. T. was an investigator on a national HPV prevalence study that received partial, equal, and unrestricted
funding from CSL Biotherapies and GlaxoSmithKline (GSK). J. M. L. B. is
an investigator on an Australian Research Council Linkage Grant, for
which CSL Biotherapies is a partner organization. J. M. L. B. was also an
investigator on a national HPV prevalence study that received partial,
equal, and unrestricted funding from CSL Biotherapies and GSK. B. L.
owns shares in Commonwealth Serum Laboratories, supplier of HPV
vaccine in Australia. S. M. G. has received advisory board fees and grant
support from CSL and GSK, and lecture and consultancy fees from
Merck. S. M. G. also reports having previously owned stock in CSL. S. G.
has received grant support from Merck and GSK to carry out clinical trials

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The main question arising from our nding is whether the

large reduction in the prevalence of HPV vaccine genotypes,
observed in samples of women recruited from FPCs in 3
major cities in 3 Australian states, is indicative of an effect in
the population of young Australian women as a whole. We
have condence that the nding can be generalized, for several
reasons. First, we recruited the prevaccine and postvaccine
samples from the same geographic locations and category of
service provider, to minimize changes in HPV risk-related
characteristics between the 2 periods. Although strict comparability of samples between the 2 periods is a general weakness
of nonrandomized comparative studies, we have adjusted
for all the available variables in comparing the 2 groups.
Clinicians at participating sites were encouraged to recruit
age-eligible women having Papanicolaou tests, and we have no
evidence that participation was related to any factor that
might be associated with HPV prevalence, or that it may have
differed between the 2 sample periods. We also found that the
decrease in HPV prevalence was maintained after adjusting
for differences between the samples in demographic and other
characteristics.
Finally, although the proportion of women in the postvaccine group who self-reported that they had been vaccinated
was higher than national coverage estimates, there is evidence
of underreporting to the national registry that provides these
estimates. An ongoing study validating self-reported vaccination status among women in the same age group against notications held on the register and, where details were available,
through follow-up with providers has found 91% of selfreported doses were recorded on the register, 6% were conrmed on follow-up with providers, and 3% were not able to
be conrmed on follow-up (Brotherton and Liu, unpublished
data). It is likely, therefore, that the self-reported coverage in
our sample is slightly higher than the true coverage, but also
that women attending for screening may be more regular
healthcare attendees and hence more likely to be vaccinated
than the general population of women. Overreporting of vaccination status among the vaccinees would tend to minimize the
true effect of vaccination on HPV infection, but HPV status
among unvaccinated women in the sample will still reect
HPV exposure within the community in which they reside.
The prevaccine survey [13] did not collect a sexual history
from participants, so we could not formally adjust for sexual
behavior. However, all participants are highly likely to have
been sexually active for at least 2 years, as they were attending
clinics for Papanicolaou screening. If there are differences in
sexual behavior between the 2 survey periods, they would be
expected to be in the direction of increasing levels of sexual
activity over time, based on the serial surveys of Australian
adolescent females between 2002 and 2008 demonstrating a
continuing trend of earlier age of rst sexual intercourse and
higher numbers of sexual partners [23, 24]. Thus it is unlikely

for HPV/cervical cancer vaccines, and she is a member of the Merck

global advisory and scientic advisory boards. S. R. S. is or has been an
investigator on several clinical trials evaluating GSKs HPV vaccine, and
her institution has received funding to collect data for these studies. S. R.
S.s institution has also received honoraria for Advisory Board membership, and reimbursement for attendance at conferences to present clinical
trials data from GSK Biologicals; and has received unrestricted research
funds from GSK Australia and CSL. All other authors report no potential
conicts.
All authors have submitted the ICMJE Form for Disclosure of Potential
Conicts of Interest. Conicts that the editors consider relevant to the
content of the manuscript have been disclosed.

References

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