Epidemiol. Infect. (2015), 143, 2604–2612.

© Cambridge University Press 2015

doi:10.1017/S0950268814003720

Potential coverage of circulating HPV types by current and

developing vaccines in a group of women in Bosnia and
Herzegovina with abnormal Pap smears

I. SALIMOVI C´ -BE Š I C´ * M. HUK I C´

1 2, 3
AND

1
University Clinical Centre – Sarajevo, Department of Clinical Microbiology, Bolnicˇka 25, Sarajevo, Bosnia and
Herzegovina
2
International Burch University, Department of Genetics and Bioengineering, Francuske revolucije bb, Ilidža,
Sarajevo, Bosnia and Herzegovina
3
Academy of Sciences and Arts of Bosnia and Herzegovina, Department of Medical Sciences, Bistrik 7, Sarajevo,
Bosnia and Herzegovina

Received 17 July 2014; Final revision 4 December 2014; Accepted 8 December 2014;
first published online 12 January 2015

SUMMAR Y
The objectives of this study were to identify human papillomavirus (HPV) genotypes in a group
of Bosnian-Herzegovinian women with abnormal cytology and to assess their potential coverage
by vaccines. HPVs were identified by multiplex real-time PCR test (HPV High Risk Typing
Real-TM; Sacace Biotechnologies, Italy) of 105 women with an abnormal cervical Pap smear
and positive high-risk (HR) HPV DNA screening test. The most common genotypes in the study
were HPV-16 (32·6%, 48/147), HPV-31 (14·3%, 21/147), HPV-51 (9·5%, 14/147) and HPV-18
(7·5%, 11/147). The overall frequency of HR HPV-16 and/or HPV-18, covered by currently
®
available vaccines [Gardasil® (Merck & Co., USA) and Cervarix ; (GlaxoSmithKline, UK)] was
lower than the overall frequency of other HPVs detected in the study (40·1%, 59/174, P = 0·017).
Group prevalence of HR HPVs targeted by a nine-valent vaccine in development (code-named
V503) was higher than total frequency of other HPVs detected (68·0%, 100/147, P < 0·001).
Development of cervical cytological abnormalities was independent of the presence of multiple
2
infections (χ = 0·598, P = 0·741). Compared to other HPVs, dependence of cervical diagnosis and
HPV-16, -18 (P = 0·008) and HPV-16, -18, -31 (P = 0·008) infections were observed. Vaccines
targeting HR HPV-16, -18 and -31 might be an important tool in the prevention of cervical
disease in Bosnia and Herzegovina.

Key words: Cervical cancer, high-risk HPV, HPV type, HPV vaccines, hybrid capture 2, V503.

IN T R OD UC T IO N of HPV genotypes distributed at the local level.

In order to take appropriate measures in diagnostics,
prophylaxis and therapy of human papillomavirus
(HPV) infection in a specific geographical area, it is
necessary to determine the epidemiological pattern
* Author for correspondence: Dr I. Salimovic´-Bešic´, University
Clinical Centre – Sarajevo, Department of Clinical Microbiology,
Bolnicˇka 25, 71000 Sarajevo, Bosnia and Herzegovina.
(Email: irma.salimovic_besic@yahoo.com)
Bosnia and Herzegovina (B&H) is one of nine
Central and Eastern European (CEE) countries
(Albania, Bulgaria, Croatia, FYR of Macedonia,
Montenegro, Romania, Serbia, Slovakia) with an es-
tablished and opportunistic cytology-based cervical
cancer screening programme with complementary
high-risk (HR) HPV DNA testing [1, 2]. According to
the latest recommendations [3], this model of cervical
cancer prevention should be progressively modified
to an organized screening programme with the
HPV epidemiology in B&H and vaccines 45
 46 I. Salimovic´-Bešic´ and M.
immediate predict the potential squamous cells of unde- Care of Sarajevo Canton,
Hukic´
implementation of coverage of vaccination termined significance B&H) and some
universal HPV vacci- HR HPV types and to (37/105), low-grade gynaecolo- gists in
nation into the national better define choice of squamous intraepithelial private practice in
immunization schedule. secondary prevention of lesion (33/105) to high- Sarajevo (B&H), who
Nevertheless, HPV cervical cancer in B&H, grade squamous were re- ferred to
vaccination has already studies based on the intraepithelial lesion University Clinical
been inte- grated into distribution of individual (35/105), and HR HPV Centre – Sarajevo (B&H)
the national HPV types targeted by infection detected by or the Institute for
immunization vaccines are crucial. HPV DNA screening Biomedical Diagnostics
programme in three of The aim of this study test were included in the and Research
the CEE countries: was to determine the study. The average age ‘Nalaz’ in
Bulgaria (from 2012), distribution of HPV of the women was 36·6 Sarajevo
FYR Macedonia (from genotypes in a group of ± (B&H) for
2009) and Romania Bosnian-Herzegovinian 9·5 years (range 19–62 HPV testing.
(from women with proven HPV years). Women were Conventional Pap
2008), primarily infection and abnormal mainly recruited from smears were taken by
targeting females aged cervi- cal cytology, as outpatient clinics (the gynaecolo- gists and
12 years [3]. In B&H, well as to assess the Public In- stitution examined by
both prophylactic potential coverage of Centre for Women and experienced cytologists
vaccines have been identified HPV Maternity Health inde- pendently of HPV
®
genotypes by vaccines. testing.
regis- tered: Cervarix
(GlaxoSmithKline, UK,
since 2007) and Specimen
® M
Gardasil (Merck & E collection for
Co., USA, since 2008), T laboratory
and are commercially H analysis
available currently for O Cervical specimens
voluntary D were collected from
immunization. As those S
June 2010 to December
vaccines protect against 2012 with digene
the two main HR HPV This section presents a Cervical Sampler-STM
genotypes (HPV-16, brief overview of the (Qiagen, USA)
HPV-18), it is design and methods (88/105),
necessary to assess used in the study. More Abbott Cervi-Collect
whether these two detailed data have been Specimen Collection kit
HR HPVs are dominant described elsewhere [5]. (Abbott Molecular,
in the study population, Germany) (14/105) or
or if vac- cines directed ThinPrep Pap Test
against a broader S PreservCyt Solution
spectrum of HR HPVs t
(Cytic Corporation,
could be more effective u
d USA) (3/105). All
in this region. A nine- samples were stored for
y
valent next-generation up to 7 days at +4 °C,
HPV vaccine, code- or for longer at
s
named V503 (Merck & −20 °C/−70 °C until
u
Co., USA), is at the b testing. HPV testing
final stage of clinical j was per- formed at: (a)
trials (Phase III), e University Clinical
designed to protect c Centre – Sarajevo, B&H,
against an additional t
Department of Clinical
five HR HPVs (HPV- s
Microbiology – Division
31, -33, -35, -45, A group of women (n = of Virology, (b)
-52, -58), as an upgrade 105) with positive Institute for Biomedical
of Gardasil vaccine cervical cy- tology Diagnostics and
(Merck
ranging from atypical Research ‘Nalaz’ in
& Co.) [4]. In order to
 HPV epidemiology in B&H and vaccines 47
Sarajevo, B&H. p
i
n
D g
N
A a
- s
b s
a a
s y
e s
d
Clinical material
d included in the study
e was separated into
t appropriate aliquots
e required for extraction
c of total nucleic acids.
t Specimens were stored at
i a temperature of +4 °C
o
for up to 7 days, or for
n
longer at −20 °C/−70
a °C until genotyping
s assay was performed.
s Total nucleic acid
a extraction was
y performed by using
s NucliSENS
®

Screening for HR HPV miniMAG™ Magnetic

infection was performed Extraction kit
by one of the two (bioMérieux, France)
clinical assays: Hybrid from sample aliquots
Capture 2 assay (HC2; separated before the
Qiagen Corporation, HPV DNA screening
USA ) done with a HR test was performed. The
HPV probe cocktail and 400 μl aliquots of
the Abbott RealTime samples collected with
High Risk HPV test the digene Cervical
(Abbott Molecular), in Sampler-STM (Qiagen)
accord- ance withthe and the 1 ml aliquots of
manufacturers’ samples collected with
protocol. the Abbott Cervi-Collect
Specimen Collection kit
(Abbott Molecular) were
D trans- ferred for
N extraction. Samples
A taken in ThinPrep Pap
-
Test PreservCyt
b
a Solution (Cytic
s Corporation) were
e
d

g
e
n
o
t
y
48 I. Salimovic´-Bešic´ and M.
Hukic´
 HPV epidemiology in B&H and vaccines 49
separated in 5 ml hybridization diagnostic Type-specific Clinical Centre –
aliquots, centrifuged kit INNO-LIPA HPV calculations were made Sarajevo and the
for 12 min at Genotyping Extra without tak- ing into Institute for
1125 g, then 4 ml of (Innogenetics, account multiple HPV Biomedical Diagnostics
supernatant were Belgium). The 10 μl of infections, but con- and Research ‘Nalaz’ in
discarded and the pellet total nucleic acid sidering each identified Sarajevo (B&H). In
was resuspended in the extracts were used for HPV infection as a single order to protect the
remainder of the 1 ml the analysis. The assay infection. identity of the patients,
supernatant. works with a short PCR all clinical samples
DNA/RNA was eluted frag- ment (SPF10-PCR) used in the study were
in 55 μl elution buf- fer E
designed to discriminate coded and tested
t
and stored for a week at a broad spectrum of anonymously.
h
+4 °C or a month at −20 HPV types by reverse i
°C prior to testing. line probe hybrid- c
HPV genotyping was ization, thus allowing a R
performed by the the detection of 54 HPV l E
following assays types and the S
according identification of 28 of s U
manufacturer’s them. t
instructions: HPV High a L
Risk Typing Real-TM n
S d T
test (Sacace
t a
Biotechnolo- gies, Italy)
a r S
was used for qualitative d
t
detection and s A
i
genotyping of 12 HR s n
This study was a
HPVs: HPV-16, -18, t conducted according to l
-31, -33, i
the principles expressed y
-35, -39, -45, -51, -52, c
a in the Declaration of s
-56, -58, and -59 in the
l Helsinki, and was ap- i
cervical swabs. The test s
proved by the ethical
is based on multiplex
a review boards of the
real-time PCR o
n University
amplification run in f
a
four tubes for each
l
sample. Each tube y H
contained primers s P
directed against regions i V
of three HPV types s
with the human b- g
DStatistical analysis was e
globin gene used as performed with SPSS n
internal control. The for Windows v. 15·0 o
20 μl of total nucleic (SPSS Inc., USA). t
acid extracts per sample escriptive statistics were y
were used in four PCR expressed by frequency, p
reac- tions (8 μl master arithmetic mean, e
mix and 5 μl eluate standard deviation (S.D.), s
made 13 μl of each of minimum and maximum In the studied population
four PCR mixes). values and per- centages. of women (n = 105), 16
Genotyping of five The relationship of differ- ent HPV types
samples with cytological diagnosis were detected. Fifteen
indeterminate results and HPV type was HPV types were
obtained by High 2
evaluated by χ test of identified by the methods
Risk Typing Real-TM independence of used, while one remained
(Sacace Biotechnologies) variables. Significance uni- dentified (HPV-X)
was performed by a was based on P < 0·05. (Table 1). On the basis of
reverse line probe
 50 I. Salimovic´-Bešic´ and M.
viral onco- genic the exception of two
Hukic´
potential, 12/15 low-risk (HPV-6 and
identified HPV types HPV-11) types (Merck
belonged to the HR & Co.) was 68·0%
HPV genotypes group, (100/147) and signifi-
2
2/15 were probable HR cantly higher (χ =
genotypes, and 1/15 19·109, P < 0·001) than
genotype was placed the total frequency of
into the low- risk HPV the other HPVs
genotype group (Table detected. In one case
1). The frequency ( f ) of (0·7%, 1/147), HPV
individual HPV genotype remained
genotypes was undetermined (HPV-X),
calculated so that each although the presence
detected genotype was of HPV was
considered as a separate confirmed by the two
in- fection. In fact, this methods [INNO-LIPA
part of the data analysis HPV Genotyping Extra
did not take into account (Innogenetics), and HC2
the presence of multiple using an HR HPV
HPV infections. The probe cocktail
prevalence of different (Qiagen)].
HPV genotypes was
calcu- lated according to
the cumulative number M
of infections caused by u
each individual HPV l
type detected in the t
i
study. The most
p
common genotype was l
HPV-16 detected in e
32·6% (48/147),
followed by HPV-31 in H
14·3% (21/147), and P
HPV-51 in 9·5% V
(14/147) of women.
HPV-18 was the fourth i
most common geno- n
type in 7·5% (11/147) of f
e
women (Table 1). The
c
overall frequency of
t
infections caused by HR i
HPV-16 and/or HPV-18, o
covered by vaccines n
(Gardasil and Cervarix) s
was 40·1% (59/174) and
2
Of the tested women,
significantly lower (χ = multiple infections
5·7, P = 0·017) than the (consisting of
overall frequency of 2–5 different HPVs)
all other HPVs detected were present in 26·7%
in the study. By contrast, (28/105).
the frequency of seven
HR HPV genotypes
(HPV-16, -18, -31, -33,
-45, -52, -58) targeted by
the vaccine V503, with
 HPV epidemiology in B&H and vaccines 51

Table 1. Distribution of human papillomavirus (HPV) types in women grouped according to their cervical
cytological diagnosis
 52 I. Salimovic´-Bešic´ and M.
Atypical squamous
Hukic´
cells of undetermined Low-grade squamous High-grade squamous
significance intraepithelial lesion intraepithelial lesion Total
Viral
HPV Percentage (%) Percentage (%) Percentage (%) Percentage oncogenic
type Freq. within group Freq. within group Freq. within group Freq. (%) potential

HPV-16 11 20·8 15 30·6 22 48·9 48 32·6 High risk

HPV-31 7 13·2 7 14·3 7 15·6 21 14·3 High risk
HPV-51 5 9·4 4 8·2 5 11·1 14 9·5 High risk
HPV-18 3 5·7 5 10·2 3 6·7 11 7·5 High risk
HPV-39 5 9·4 5 10·2 1 2·2 11 7·5 High risk
HPV-56 6 11·3 2 4·1 1 2·2 9 6·1 High risk
HPV-33 1 1·9 4 8·2 2 4·4 7 4·7 High risk
HPV-52 4 7·5 2 4·1 1 2·2 7 4·7 High risk
HPV-59 5 9·4 2 4·1 0 0·0 7 4·7 High risk
HPV-58 3 5·7 0 0·0 1 2·2 4 2·8 High risk
HPV-45 2 3·8 0 0·0 0 0·0 2 1·4 High risk
HPV-70 1 1·9 1 2·0 0 0·0 2 1·4 Low risk
HPV-35 0 0·0 0 0·0 1 2·2 1 0·7 High risk
HPV-53 0 0·0 1 2·0 0 0·0 1 0·7 Probable high
risk
HPV-66 0 0·0 0 0·0 1 2·2 1 0·7 Probable high
risk
HPV-X 0 0·0 1 2·0 0 0·0 1 0·7
Total 53 100·0 49 100·0 45 100·0 147 100·0

HPV-53, HPV-66 and HPV-70 were identified by INNO-LiPA HPV Genotyping Extra (Innogenetics, Belgium). In the case of
HPV-X, although the high-risk HC2 (Qiagen, USA) screening test showed a positive result the HPV High Risk Typing
Real-TM (Sacace Biotechnologies, Italy) , genotyping assay failed to identify this HPV type. Likewise, within the
INNO-LiPA HPV Genotyping Extra (Innogenetics) assay, specific SPF10-PCR HPV product was obtained, but HPV type
was not ultimately identified.

Table 2. Frequency and percentage of multiple human The composition of multiple infections, as well as
papillomavirus (HPV) infections the HPV DNA test used for viral identification, and
cervical cytology diagnosis for each case are listed in
No. of HPV types present in
Table 3.
infection F (%)

1 77
2 19
3 5
4 3
5 1
Total of multiple infections 28
(2–5 HPV types)
Total 105
F, Frequency of single and multiple HPV infections and
their prevalence (%) in 105 tested women.
The most prevalent of these were double infections
(18·1%, 19/105). Frequency of multiple infections
decreased with increasing numbers of HPVs simul-
taneously present in infection (Table 2).
73·3
18·1 Analysis of HPV genotypes according to
4·7 cervical cytology
2·9
1·0 In cytological groups of women with atypical squa-
26·7 mous cells of undetermined significance (ASCUS)
and low-grade squamous intraepithelial lesion
100·0 (LSIL), respectively, 12 different HPV genotypes
(fASCUS = 53 and fLSIL = 49) were found. Of these,
one undetermined genotype (HPV-X) was present in
a woman with a low-grade cervical lesion. Eleven
different HPVs (fHSIL = 45) were identified in the
group of women with high-grade squamous intrae-
pithelial lesion (HSIL). The most common genotype
in all three groups of women separated according to
cervical cytology was HPV-16, detected in the
Table 3. Multiple human papillomavirus (HPV) infections and HPV DNA tests used for their detection in women
listed by increasing severity of cervical cytology
 RealTime High Risk
High-risk HC2 test HPV (Abbott Molecular, HPV High Risk Typing Real-TM
(Qiagen, USA) Germany) (Sacace Biotechnologies, Italy) Cervical cytology
HR HPV n.a. HPV-31, HPV-56, HPV-58 ASCUS
n.a. Others HPV-31, HPV-45, HPV-51, ASCUS
HPV-58, HPV-59
n.a. Others HPV-51, HPV-52 ASCUS
HR HPV n.a. HPV-16, HPV-51, HPV-59 ASCUS
HR HPV n.a. HPV-16, HPV-51, HPV-56 ASCUS
HR HPV n.a. HPV-31, HPV-52 ASCUS
HR HPV n.a. HPV-33, HPV-58 ASCUS
HR HPV n.a. HPV-31, HPV-39 ASCUS
HR HPV n.a. HPV-51, HPV-52 ASCUS
HR HPV n.a. HPV-16, HPV-56 ASCUS
HR HPV n.a. HPV-18, HPV-33 LSIL
n.a. HPV-18 and others HPV-18, HPV-39 LSIL
HR HPV n.a. HPV-16, HPV-18, HPV-51, HPV-59 LSIL
HR HPV n.a. HPV-31, HPV-39 LSIL
HR HPV n.a. HPV-16, HPV-31, HPV-39 LSIL
HR HPV n.a. HPV-16, HPV-31 LSIL
HR HPV n.a. HPV-16, HPV-33, HPV-39 LSIL
HR HPV n.a. HPV-16, HPV-31, HPV-52, HPV-59 LSIL
HR HPV n.a. HPV-16, HPV-33 LSIL
HR HPV n.a. HPV-16, HPV-31 LSIL
HR HPV n.a. HPV-16, HPV-18 HSIL
n.a. HPV-16 and others HPV-16, HPV-51 HSIL
HR HPV n.a. HPV-16, HPV-31 HSIL
HR HPV n.a. HPV-16, HPV-33 HSIL
HR HPV n.a. HPV-51, HPV-52 HSIL
HR HPV n.a. HPV-16, HPV-51 HSIL
HR HPV n.a. HPV-16, HPV-35 HSIL
HR HPV n.a. HPV-16, HPV-18, HPV-39, HPV-51 HSIL

HR, High risk; n.a., not applied; others, any HPV type in the group of the ten HR HPV types (HPV-31, -33, -35, -39, -45, -51,
-52, -56, -58, -59) and two probable HR HPV types (HPV-66 and HPV-68) detectable by RealTime High Risk HPV test
(Abbott Molecular), ASCUS, atypical squamous cells of undetermined significance; LSIL, low-grade squamous intraepithe-
lial lesion; HSI, high-grade squamous intraepithelial lesion.

ASCUS group in 20·8% (11/53), in the LSIL group in
30·6% (15/49) and in the HSIL group in 48·9%
(22/45). In the group of women with ASCUS cytology
index, HPV-16 was followed by HPV-31 (13·2%, 7/53)
and HPV-56 (11·3%, 6/53), while genotype HPV-18
equal to HPV-58 was the sixth the most common
HPV-51 in 11·1% (5/45) and HPV-18 in 6·7% (3/45)
(Table 1).
The dependence of cytological diagnosis (ASCUS,
LSIL or HSIL) and infections caused by HPV-16
and -18, or HPV-16, -18, and -31, respectively,
compared to other HPVs was observed (χ = 9·7,
2

HPV genotype in the group (5·7%, 3/53). After 2

HPV-16, in the group of women with LSIL cytology
index, HPV-31 was present in 14·3% (7/49), and
then each of HPV-18 and HPV-39 genotypes
were identified in 10·2% (5/49). In women with
high-grade cervical lesions, as in the previous
two groups of women, HPV-31 was the second
most prevalent genotype (15·6%, 7/45), followed by
P = 0·008 and χ = 9·59, P = 0·008). Global percentage
of infections caused by HPV-16 and -18, or HPV-16,
-18 and -31, respectively, increased with severity of
cervical cytology, while global proportion of infec-
tions caused by other HPVs declined (Fig. 1).
However, development of cervical cytological ab-
normalities was independent of the presence of mul-
2
tiple infections (χ = 0·598, P = 0·741) (Fig. 2).
Fig. 1. Infections caused by HPV-16, -18 and HPV-16, -18, -31, respectively, vs. other HPV types in women with atypical
squamous cells of undetermined significance, low-grade squamous intraepithelial lesion or high-grade squamous intraepithelial
lesion of the cervix.

Fig. 2. Prevalence of single and multiple infections in women with atypical squamous cells of undetermined significance,
low-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion of the cervix. Independence of
cervical cytological diagnosis and infections caused either by a single HPV type or 2–5 HPV types simultaneously present.
Numbers in the chart represent frequencies and percentages of given HPV infection according to cytology.
D
I Despite the relatively
S small number of subjects
C involved in the study,
reliable statistical
U analysis of the data was
S made. Thus, the most
common genotype in
S the study was HPV-16,
I followed by HPV-31
O and
N
-51, similar to the
distribution pattern
Determination of published from Turkey
circulating HPV types [6]. Infections caused
in a popu- lation can by HPV-18 and -39
provide an early occupied fourth place.
measure of vaccine
impact. In particular,
it is important in
countries where
organized screening
programmes for the
pre- vention of
cervical cancer have
not yet been
established.
 According to these Merck’s application for well as groups of women normal cervical
results and data from V503, thus setting the with histologically cytology, ASCUS,
previous studies of stage for a near- term confirmed diagnoses of LSIL or CIN1 were not
B&H, regional studies approval. CIN1, CIN2, CIN3 and observed. However,
and meta-analysis [5, HPV-16 and HPV-31 invasive cervical cancer HPV-16 positivity
7–12], HR HPV-31, as were also the most was conducted. Data increased gradually, in
well as HPV-16, plays common genotypes in all were obtained from 423 the following order:
a key role in the three categories of PCR-based studies normal cy-
prevalence of HPV cervical cytological worldwide. Large tology/ASCUS/LSIL/CI
infection. The new changes and differences in the N1 (20·0–28·0%), over
generation of HPV individually have shown distribution of HPV CIN2/ HSIL
vaccines directed rising percent- age with genotypes in women (40·0/47·0%) to
against this genotype the severity of with CIN3/invasive carcinoma
may have a greater cytological changes of the cervix
public health contri- (from ASCUS to (58·0/63·0%). We
bution to protection of HSIL). The prevalence concluded in view of this
the development of of HR HPV-18, and results of the
cervical abnormalities -33 and -39 increased previous meta-analysis
than ones without it. from ASCUS to LSIL, [12], that the HPV-16
Currently avail- able and then declined from genotype, in particular,
vaccines targeted against LSIL to HSIL. HR as well as HPV-18 and
two high-risk genotypes genotypes HPV-45, -52, HPV-45, deserve special
(HPV-16 and -18) would -56 and -59 decreased attention in the
cover 40·1% of cases of from ASCUS to HSIL screening of HPV
HPV infection in women gradually. HPV-18 was infection.
involved in this study. not among the domi- Presence and
The combi- nation of nant genotypes, but in consequences of multiple
HR HPV-16, -18, -31, a previous study from HPV infec- tions are still
-33, -45, -52 and -58, B&H, this genotype unclear. Although the
contained in the nine- showed the highest accumulation of HPVs
valent vaccine oncogenic activity is often observed [14–
designated V503, would (100%) in the same 17], follow-up studies of
cover 68·0% of population of women infected women suggest
infections, which is [5]. that the presence of
significantly higher With the growing multiple HPV genotypes
coverage compared to cervical cytology index has no effect on the
the prevalence of other of LSIL to HSIL, as course of infec- tion
HPVs. The latest study seen in a study from [18].
on the potential impact Croatia [9], an in- There werre 26·7% of
of V503 vaccine [13], creasing prevalence of multiple infections
has shown that almost genotypes HPV-16, -18, detected in the study,
90·0% of cases of -31 and -33 was with dual infections
invasive cervical cancer recorded, while the prevailing. However, the
worldwide could be percentage of geno- development of
prevented. If this types HPV-45, -52 and cytological
vaccine reaches the -58 decreased. abnormalities in the
same level of efficiency Recently, a meta- categories of ASCUS,
as the previous two analysis of cross- LSIL and HSIL was
vaccines (Gardasil and sectional HR HPV-type not stat- istically
Cervarix), the global distribution in 115 dependent on such
incidence of cancer 789 HPV-positive infections.
would be significantly women [10] with The emergence of
reduced. In February normal cervical mixed infections is
2014, the Food and cytology or ASCUS, generally explained by
Drug Administration LSIL and HSIL way of transmission of
(FDA) accepted cytological changes, as HPV types and as-
sociation with risk In conclusion,
factors [16, 17], such as vaccines targeted
the number of lifetime against HR HPV-16,
sexual partners [19], -18 and -31 will be of
sexual behaviour of part- great importance for the
ners [20, 21], and recent prevention of cervical
sexual partners [22], or disease in B&H. Due
that it arises as a result to the limited number
of immunological of such studies
tolerance [23]. originating
Range of genotypes
identified in the study
depends on the
capability of the test
used for viral typing. In
the study, the main
typing test (HPV High
Risk Typing Real-TM,
Sacace Biotechnologies)
was chosen to identify
the majority of HPV
genotypes detected by
HPV DNA screening
tests [92·3% (12/13) for
the HC2 test (Qiagen)
and 85·7% (12/14) for
RealTime High Risk
HPV (Abbott
Molecular)]. By this
method, the number of
unspecified HPV
genotypes was relatively
low (3·4%, 5/147).
A single HPV-X
suggests that typing
tests used in the study
were capable of
identifying at least one
viral genotype in 99·3%
(146/147) of cases.
As in other studies
[24–26], false positivity
of the presence of HR
HPV infection was
obtained at a screening
test (HC2; Qiagen).
Cross-reactivity with
genotypes HPV-53
(probably a HR
genotype) and HPV-70
(low-risk genotype in
two cases) was found
due to hybridization
with complete viral
genomic probes supplied
in the kit.
from this area, it is C genotyping of cervical 10. Guan P, et al. Human
HPV with simultaneous papillomavirus types in
necessary to monitor
cervical cytology in 115,789
the circu- lation of the E
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