montis francesca via raffaello, 5 assemini 070

FORMATO EUROPEO
PER IL CURRICULUM
VITAE
INFORMAZIONI PERSONALI
Nome
MONTIS FRANCESCA
Indirizzo
VIA RAFFAELLO, 5 ASSEMINI
Telefono
070 94854245
Fax
070 94854242
E-mail
Nazionalità
Data di nascita
[email protected]
ITALIANA
18/08/1976
ESPERIENZA LAVORATIVA
• Date (da – a)
• Nome e indirizzo del datore di
lavoro
• Tipo di azienda o settore
• Tipo di impiego
• Principali mansioni e responsabilità
• Date (da – a)
• Nome e indirizzo del datore di
lavoro
• Tipo di azienda o settore
• Tipo di impiego
• Principali mansioni e responsabilità
ESPERIENZA LAVORATIVA
LUGLIO 2013 – IN CORSO
ASL 8
DISTRETTO SOCIOSANITARIO AREA OVEST - CURE DOMICILIARI DIRIGENTE MEDICO
GIUGNO 2013 –SETTEMBRE 2013
ISFORCOOP CAGLIARI
FORMAZIONE PROFESSIONALE
DOCENTE per N 3 CORSI (2 CORSI SUPEROSS, 1 CORSO OSS, 1 TUTORAGGIO (n 31 ore)
TECNICO PROFESSIONALE)
Insegnamento:Igiene ed educazione alla salute, elementi di igiene e principi di
epidemiologia. Lezioni frontali e con supporto informatico,verifiche in itinere,partecipazione
alle riunioni del corpo docente,valutazione dei corsisti.
• Date (da – a)
• Nome e indirizzo del datore di
lavoro
• Tipo di azienda o settore
• Tipo di impiego
• Principali mansioni e responsabilità
AA 2012-2013
UNIVERSITA’ DEGLI STUDI DI CAGLIARI – FACOLTA’ DI MEDICINA E CHIRURGIA -
• Date (da – a)
• Nome e indirizzo del datore di
lavoro
• Tipo di azienda o settore
AA 2012-2013
UNIVERSITA’ DEGLI STUDI DI CAGLIARI – FACOLTA’ DI MEDICINA E CHIRURGIA -
Pagina 1 - Curriculum vitae di
[ MONTIS FRANCESCA]
CORSO DI LAUREA IN ASSISTENZA SANITARIA
DOCENTE A CONTRATTO
INSEGNAMENTO IGIENE DELL’AMBIENTE (SSD MED 42),lezioni frontali e con supporto
informatico,verifica dell’apprendimento
CORSO DI LAUREA IN TECNICHE DELLA PREVENZIONE
• Tipo di impiego
• Principali mansioni e responsabilità
ESPERIENZA LAVORATIVA
DOCENTE A CONTRATTO
INSEGNAMENTO TECNICHE DI VALUTAZIONE DEL RISCHIO (SSD MED 42) lezioni frontali e
con supporto informatico,verifica dell’apprendimento
• Date (da – a)
• Nome e indirizzo del datore di
lavoro
• Tipo di azienda o settore
• Tipo di impiego
• Principali mansioni e responsabilità
MAGGIO 2010 – APRILE 2012 & GIUGNO 2012 – GIUGNO 2013
ASL 8
• Date (da – a)
• Nome e indirizzo del datore di
lavoro
• Tipo di azienda o settore
• Tipo di impiego
• Principali mansioni e responsabilità
AA ACCADEMICO 2011-2012
UNIVERSITA’ DEGLI STUDI DI CAGLIARI – FACOLTA’ DI MEDICINA E CHIRURGIA -
ESPERIENZA LAVORATIVA
CENTRO DI RIFERIMENTO REGIONALE PER LE MALATTIE RARE
INCARICO LIBERO PROFESSIONALE
Progetti attuativi del Piano Sanitario nazionale 2006-2008 in materia di Malattie Rare,
Responsabile Prof Renzo Galanello ; svolgimento del proprio incarico presso RAS –
Assessorato Igiene e Sanità e dell’Assistenza Sociale, Servizio dell’assistenza
ospedaliera, autorizzazioni e accreditamenti delle strutture sanitarie e socio-sanitarie
Riorganizzazione della rete dei presidi in ambito regionale (ridefinizione e
aggiornamento della rete malattie rare) al fine di garantire e migliorare la presa in
carico dei pazienti, la continuità assistenziale e una risposta multidisciplinare integrata
di diagnosi, cura, riabilitazione e supporto alla persona e alla famiglia;
individuazione di modelli assistenziali per garantire la presa in carico dei soggetti con
malattie rare attraverso un costante confronto tra le Regioni ed in collaborazione con
l’ISS mediante la promozione di protocolli diagnostico-terapeutici condivisi.
attività di raccolta dati sulle malattie rare al fine di attivare il registro regionale per la
prevenzione e sorveglianza delle stesse e garantire il flusso attivo dei dati
epidemiologici dalla regione all’ISS (Registro nazionale) .
Altre attività riguardanti l’assistenza ospedaliera: componente del gruppo di lavoro
per l’adozione delle Linee guida regionali per la codifica delle informazioni cliniche
delle SDO (Determinazione RAS( n 906 del 13/09/2011); - supporto agli Uffici nella
valutazione e implementazione dei pacchetti di Day Service di varie tipologie
specialistiche in ambito regionale, componente del gruppo di lavoro per la revisone
della Legge Regionale 23 luglio del 1991 n 26 prestazioni di assistenza extraregione.
CORSO DI LAUREA IN OSTETRICIA
DOCENTE A CONTRATTO
INSEGNAMENTO IGIENE GENERALE ED APPLICATA (SSD MED 42) organizzazione lezioni
frontali e con supporto informatico,verifica dell’apprendimento
• Date (da – a)
• Nome e indirizzo del datore di
lavoro
• Tipo di azienda o settore
• Tipo di impiego
• Principali mansioni e responsabilità
AA ACCADEMICO 2010-2011
UNIVERSITA’ DEGLI STUDI DI CAGLIARI – FACOLTA’ DI MEDICINA E CHIRURGIA -
• Date (da – a)
• Nome e indirizzo del datore di
lavoro
• Tipo di azienda o settore
• Tipo di impiego
• Principali mansioni e responsabilità
GIUGNO 2008 – SETTEMBRE 2008
Pagina 2 - Curriculum vitae di
[ MONTIS FRANCESCA]
CORSO DI LAUREA IN OSTETRICIA
DOCENTE A CONTRATTO
INSEGNAMENTO IGIENE GENERALE ED APPLICATA (SSD MED 42) organizzazione lezioni
frontali e con supporto informatico,verifica dell’apprendimento
3M ITALIA – S p A
Health Information Systems
CO.CO.CO
Progetto di revisione, standardizzazione e completamento dei termine chiave
dell’elenco dei descrittori DRG per finalizzare la corretta assegnazione dei DRG
tramite l’utilizzo del software CodeFinder v.24.
ISTRUZIONE E FORMAZIONE
NOVEMBRE 2007
LUGLIO 2003
LUGLIO 2002
• Nome e tipo di istituto di istruzione
o formazione
• Principali materie / abilità
professionali oggetto dello studio
• Qualifica conseguita
• Livello nella classificazione
nazionale (se pertinente)
SPECIALIZZAZIONE IN IGIENE E MEDICINA PREVENTIVA
ISCRIZIONE ALL’ALBO DEI MEDICI-CHIRURGHI DELLA PROVINCIA DI CA
LAUREA IN MEDICINA E CHIRURGIA
UNIVERSITA’ DEGLI STUDI DI CAGLIARI – FACOLTA’ DI MEDICINA E CHIRURGIA -
MEDICO SPECIALISTA
ISTRUZIONE E FORMAZIONE
LUGLIO 1995
• Nome e tipo di istituto di istruzione
o formazione
• Principali materie / abilità
professionali oggetto dello studio
• Qualifica conseguita
• Livello nella classificazione
nazionale (se pertinente)
DIPLOMA DI MATURITA’ CLASSICA
LICEO GINNASIO”G.M DETTORI”
CAPACITÀ E COMPETENZE
PERSONALI
Acquisite nel corso della vita e della
carriera ma non necessariamente
riconosciute da certificati e diplomi
ufficiali.
• Capacità di lettura
• Capacità di scrittura
• Capacità di espressione orale
CAPACITÀ E COMPETENZE
RELAZIONALI
Vivere e lavorare con altre persone, in
ambiente multiculturale, occupando posti
in cui la comunicazione è importante e in
situazioni in cui è essenziale lavorare in
squadra (ad es. cultura e sport), ecc.
CAPACITÀ E COMPETENZE
PRIMA LINGUA
[ ITALIANO]
ALTRE LINGUE
[ INGLESE]
[ INGLESE]
[ buono]
[ elementare]
[ elementare]
[BUONE CAPACITÀ DI LAVORO IN GRUPPO, TEAM MULTIDISCIPLINARE, RELAZIONE CON I
COLLEGHI, CON PUBBLICO IN PARTICOLARE, PAZIENTI-UTENTI,RAPPRESENTANTI DI
ASSOCIAZIONI NEL CORSO DEL PROGETTO MALATTIE RARE SIA PRESSO
L’ASSESSORATO, SIA PRESSO L’ OSPEDALE MICROCITEMICO.
[]
ORGANIZZATIVE
Ad es. coordinamento e amministrazione
di persone, progetti, bilanci; sul posto di
lavoro, in attività di volontariato (ad es.
cultura e sport), a casa, ecc.
CAPACITÀ E COMPETENZE
TECNICHE
Con computer, attrezzature specifiche,
macchinari, ecc.
CAPACITÀ E COMPETENZE
Pagina 3 - Curriculum vitae di
[ MONTIS FRANCESCA]
[ Buona conoscenza del sistema operativo Windows XP;
Buona conoscenza di Office XP (Word, Excel, PowerPoint, Outlook);
Esperienza di ricerca e navigazione nel Web; ]
[ Descrivere tali competenze e indicare dove sono state acquisite. ]
]
ARTISTICHE
Musica, scrittura, disegno ecc.
ALTRE CAPACITÀ E COMPETENZE
Competenze non precedentemente
indicate.
PATENTE O PATENTI
ULTERIORI INFORMAZIONI
ALLEGATI
PUBBLICAZIONE articolo sulla rivista “Vaccine 27 (2009) A11–A16” dal titolo “Epidemiology and
genotype distribution of human papillomavirus
(HPV) in women of Sardinia (Italy)”;
[N1 PUBBLICAZIONE ]
Autorizzo il trattamento dei miei dati personali ai sensi del D.lgs. 196 del 30 giugno 2003 e ss.mm.ii..
Data 24/06/2014
Pagina 4 - Curriculum vitae di
[ MONTIS FRANCESCA]
Firma
Vaccine 27 (2009) A11–A16
Contents lists available at ScienceDirect
Vaccine
journal homepage: www.elsevier.com/locate/vaccine
Epidemiology and genotype distribution of human papillomavirus
(HPV) in women of Sardinia (Italy)
Giuseppina Masia a , Anna Paola Mazzoleni a , Graziella Contu b , Sergio Laconi c ,
Luigi Minerba a , Stefania Montixi a , Francesca Montis a , Annamaria Onano d ,
Emanuela Porcedda a , Rosa Cristina Coppola a,∗
a
Department of Public Health, University of Cagliari, 09042 Cagliari Monserrato, Italy
Oncologic Prevention Service Asl n. 8, Cagliari, Italy
c
S. Marcellino Hospital Asl n. 8 Cagliari, Italy
d
Health Promotion Mother-Child Service Asl n. 8, Cagliari, Italy
b
a r t i c l e
i n f o
Article history:
Received 21 August 2008
Received in revised form 24 October 2008
Accepted 27 October 2008
Keywords:
HPV epidemiology
HPV-DNA
HPV genotypes
a b s t r a c t
The human papillomavirus (HPV) infection is necessary for the development of cervical cancer. Our study
aims to evaluate the rate of HPV circulation in our population, to identify the prevalent genotypes and
to establish correlation with cervical abnormalities. Furthermore, the awareness of women about HPV
issues was investigated.
This study included 864 women attending the Oncologic Prevention Service for their routine Pap test
screening or the Health Promotion Mother-Child Service for counselling about sexual activity, from July
2006 to September 2007. All the participants gave their informed consent to be enrolled in the study
and were invited to fill in a questionnaire about the socio-cultural state, sexual activity and awareness
about HPV. The women samples were tested for HPV-DNA and HPV genotypes: any type of HPV-DNA was
detected in 31.0% of the women; single or multiple infections sustained by HPV-16 or HPV-18 represented
43.5% of all HPV infections, accounting for infections in 11.8% of the recruited women. The HPV and highrisk HPV (HR-HPV) prevalence significantly declined in women older than 46 years. The Pap test result was
available in 490 women; 48.1% of the Pap test positive women had also an HPV infection and among these
22.7% were infected by HPV-16 and/or HPV-18 genotype, while 51.9% (94/181) were HPV negative. The
analysis by binary logistic regression showed that genotype 16 and/or 18 is a risk factor for the Pap positive
test with a odds ratio (OR) of 2.9 (95% C.I. 1.4–5.9) and 3.6 (95% C.I. 1.58–8.42) respectively, while age is a
protective factor (OR 0.97, C.I. 95% 0.96–0.99); furthermore, the mean age at the first sexual intercourse
and the mean number of partners since the beginning of sexual activity, were statistically associated with
the risk of HPV infection. More than half of women were aware about HPV, its sexual transmission and of
its correlation with cervix cancer.
Our findings evidenced that HPV infection is frequent in women aged 18–46 years in Sardinia and
particularly that 16 and 18 HPV genotypes are detectable in more than 40% of the infected women. The
proportion of women informed about HPV issues is sufficient to guarantee an aware approach to HPV
vaccination.
© 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Human papillomavirus (HPV), a non-enveloped, doublestranded DNA virus, belonging to the Papillomaviridae family, that
primarily infects the epithelium and induces benign and malignant
lesions of the genital mucosa, is necessary for the development of
cervical cancer; the association between HPV and cervical cancer
∗ Corresponding author. Tel.: +39 070 51096200; fax: +39 070 51096558.
E-mail address: [email protected] (R.C. Coppola).
0264-410X/$ – see front matter © 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.vaccine.2008.10.095
is unique as no other major human cancer is dependent on a single
factor for its development [1–3].
Over 120 HPV types have been identified and approximately 40
types infect the mucosal epithelium of the genital tract. Of these, 16
types have been classified as “high-risk” (HR-HPV) as they are associated with the malignant progression of cervical tumors and with
other genital and head–neck malignancies [4–6]. HPV types 16 and
18 account for approximately 70% of cervical cancer cases worldwide with other high-risk types such as HPV-45, HPV-31, HPV-33
and HPV-52 accounting for the remaining cervical malignancies
[7]. HPV “low-risk” types (LR-HPV), mainly HPV-6 and HPV-11, are
A12
G. Masia et al. / Vaccine 27 (2009) A11–A16
Table 1
Age specific numbers and proportion with respect to the whole sample of 864
women.
Age classes (years)
No.
%
18–24
25–35
35–45
≥46
277 (271)
235 (229)
205 (203)
147 (146)
32.1
27.2
23.7
17.0
Values in parenthesis represent number of specimens whose HPV-DNA analysis was
performed.
rarely detected in high-grade cervical lesions but cause the majority
of anogenital warts [8,9].
Virtually all epidemiological studies provide evidence that genital HPV infection is very common in young sexually active women
with prevalences as high as 76–80% [10,11]. In most cases (70–90%)
HPV infection is a transient and self-limited infection and the virus
is cleared by the host innate immune response [2,12]. The clearance of high-risk HPV types may require up to 14 months, a period
longer than required by low-risk HPV types (5–6 months) [11,13,14].
However, in some cases the immune response fails to clear the
infection and a persistent infection is established. In subjects persistently infected by high-risk HPV types there is a risk of progression
to high-grade cervical intraepithelial neoplasia (CIN) and invasive
cancer [2,15–19].
The link between HPV and cervical cancer has given impetus to
the development of prophylactic vaccines against the most common HPV types; in parallel interest has raised to determine age
specific burden of the infection and to identify the major genotypes
supporting infection in different countries.
In recent Italian studies the prevalence of HR-HPV genotypes
among women has been as high as 7–26% with a decreasing trend
in older classes [20,21].
This study aims to evaluate the prevalence of HPV infection in
a population of South Sardinia, to identify the prevalent genotypes
and to establish correlation with cervical abnormalities. Furthermore, the awareness of women about HPV issues was investigated.
2. Materials and methods
2.1. Study population
This study included 864 women attending the Oncologic Prevention Service for their routine Pap test screening or the Health
Promotion Mother-Child Service for counselling about sexual activity from July 2006 to September 2007. Both services are part of the
n. 8 Cagliari Health Service District. The size of age classes among
the women enrolled in the study is reported in Table 1.
At the time of their visit all the participants were informed
about the study and its purpose and gave their informed consent.
They were then invited to fill in a self administered questionnaire including data items about education, employment, lifetime
number of male sexual partners, age at first sexual intercourse,
history of sexually transmitted diseases, contraceptives methods,
smoking; some questions were also addressed to assess knowledge of women about HPV and their attitudes about anti-HPV
vaccine.
2.2. Sample preparation
Cervical specimens were collected with Cervex-brush and suspended in a 20 ml preservation solution, called Liqui-Prep, made
by a mixture dilute of denaturated ethanol (20%). The tube was
vortexed to remove all the material from the cervex; 1–2 ml of
preservation solution was then centrifuged at 2500 rpm for 10 min,
the supernatant was removed and discarded, the pellet obtained
was stored at −80 ◦ C until DNA extraction.
The DNA extraction was performed by adding x ␮l (range
20–100 ␮l according to the pellet size) of digestion buffer with
proteinase K and by incubating at 55 ◦ C O/N. After denaturation
of proteinase at 95–100 ◦ C PCR started.
2.3. PCR
An aliquot of crude lysate was used for the PCR.
The following primers derived from region L1 of the
viral genome, forward 5 -CTTTCAGGGCAATAATGA-3 , reverse 5 TGGTAGCTGGATTGTAGC-3 were used for the amplification in the
following 25 ␮l reaction mixture: 10× PCR buffer, 0.2 ␮M of each
primer, 200 ␮M of each dNTP (dATP, dCTP, dGTP, and dTTP), 2.5 units
of Taq polymerase (PerkinElmer/Cetus), 3 ␮l of sample DNA, double
distilled water. The amplification was performed in a DNA Thermal
Cycler (PerkinElmer/Cetus Instruments), using the following program set: 95 ◦ C for 2 min, 5 cycles 94 ◦ C 30 s, 50 ◦ C for 1 min, 72 ◦ C
for 1 min and 40 cycles 94 ◦ C 30 s, 45 ◦ C for 1 min, 72 ◦ C for 30 s
plus an additional 5 min at 72 ◦ C. Separate rooms were used for:
preparation of DNA template, preparation and storage of reagents,
setting up the amplification reaction. All reagents used in PCR were
prepared, aliquoted and stored in an area free from PCR-amplified
products. Amplification of a single copy human gene (␤-globin),
as control of DNA suitability for amplification, was performed in
each reaction tube; we also used a positive and negative control in
each reaction. Crude lysates that did not yield a ␤-globin product
were extracted with phenol/chloroform and the extracted DNA reamplified with the same ␤-globin primers. Samples that remained
negative for ␤-globin were considered not amplifiable and excluded
from this study.
2.4. Analysis of the amplification products
Mixture were analysed by electrophoresis in 2% agarose gel
stained by ethidium bromide and visualized by UV light. As molecular weight marker we used a ladder Phi-X 174 digested with Hae-III.
HPV genotyping was done by PCR-reverse hybridization. Briefly, a
segment of the L1 region was amplified with GP5+/GP6+ consensus
primers and labelled during PCR through the incorporation of Dig11-dUTP (Roche Applied Science, Mannheim, Germany). Labeled
amplicons were then hybridized to a panel of 24 type specific
probes (high-risk: HPV-16, 18, 26, 30, 31, 33, 34, 35, 45, 51, 52, 56,
58, 59, 68 and 73; low-risk: HPV-6, 11, 40, 42, 43, 44, 54 and 70),
previously immobilized to the surface of NucleoLink wells (NUNC,
Denmark) and detected with a POD-conjugated anti-digoxigenin
antibody (Roche Applied Science, Mannheim, Germany) and the
tetra methyl benzidine (TMB) substrate (Sigma–Aldrich, Milan).
2.5. Statistical analysis
The statistical analysis of the data was obtained by the SPSS
Statistical Software v. 15.0 (SPSS Inc., Chicago, IL). All data are
reported as the mean value, median or frequencies and odds ratios
(ORs) point estimates and their 95% confidence intervals (95% CI)
were computed by LRM procedure for binary data to estimate the
association between each covariate levels and HPV infection while
adjusting for the effect of other variables retained in the model.
Statistical significance was accepted if the p value was 0.05 or less.
3. Results
Among the 849 women eligible for the DNA analysis (15 samples were not amplified and then were excluded from the data
G. Masia et al. / Vaccine 27 (2009) A11–A16
A13
Fig. 1. Age specific prevalence of any type of HPV (HPV+) and of high-risk HPV (HR-HPV) in 849 women.
processing), any type of HPV-DNA was detected in 264 samples
(31.0%, 95% C.I. 27.8–34.0); particularly the age specific HPV-DNA
prevalence was 32.8% (95% C.I. 27.2–38.4) in women aged 18–24
years, 37.5% (95% C.I. 31.2–43.8) in those aged 25–35 years, 32.0%
(95% C.I. 25.6–38.4) in the 36–45 years group and 15.7% (95% C.I.
9.8–21.6) in women older than 46 years. Out of the 264 HPVDNA positive samples, 34 were not genotyped because they did
not match any of the specific probes used in the panel; thus
the overall population study to assess HPV genotypes prevalence was made up by 815 females: the prevalence of HR-HPV
was 20.3% (166/815; 95% C.I. 17.5–23.1) and the age specific HRHPV prevalence was 22.1% (95% C.I. 17.1–27.1) in 18–24 years
class, 24.0% (95% C.I. 18.5–29.5) in the 25–35 years, 17.7% (95%
C.I. 12.5–22.9) in the 36–45 years group and 10.3% (95% C.I.
5.3–15.2) in the oldest class (Fig. 1). Furthermore, the overall
prevalence of women infected by LR-HPV genotypes was 7.7%
(63/815).
DNA of genotypes 16 and/or 18 was detected in 100 (43.5%), out
of the 230 HPV-DNA positive samples (as reported above, 34 specimens were not genotyped), accounting for 11.8% of the recruited
women; particularly in 50.0% (95% C.I. 39.0–61.0) of the 80 genotyped samples in 18–24 years age class, 44.7% (95% C.I. 34.1–56.6) of
the 76 samples in the 25–35 years class, 53.7% (95% C.I. 40.4–67.0) of
the 54 samples in 36–45 years class and 45.0% (95% C.I. 23.2–66.8)
in 20 women older than 46 years. No difference emerged in proportions of 16 and/or 18 genotypes presence according to age classes
among HPV infected women.
The results of HPV genotyping in the 230 samples are reported in
Fig. 2: single or multiple infections sustained by HPV-16 or HPV-18
accounted for 43.5% of all HPV infections; furthermore 67 samples
(29.1%) were positive for other HR-HPV genotypes. Therefore, only
27% of infections in our study were supported by LR-HPV.
The Pap test result was available in 490 women (56.7%): 309
(63%) were negative, 105 (21%) had a cytological diagnosis of
atypical squamous cervical cells of undetermined significance
(ASCUS), 61 (12%) of low-squamous intraepithelial lesion (LSIL) and 15 (3.1%) high-squamous intraepithelial lesion (H-SIL).
Fig. 2. Distribution of high-risk HPV (HR-HPV), HPV-16 in single or multiple infections, HPV-18 in single or multiple infections and low-risk (LR-HPV) HPV genotypes
in 230 samples.
The prevalence of HPV-DNA was 17.8%, 35.2%, 63.9% and 73.3%
respectively (Table 2). No significant difference emerged in HPV
prevalence among women with normal cytology according to age
classes.
Table 2
Frequency of HPV-DNA according to the Pap test result in 490 women.
Pap test result
HPV+ no. (%)
95% C.I.
Negative
309
55 (17.7)
13.5–22.0
ASCUS
105
37 (35.2)
26.1–44.3
L-SIL
61
39 (63.9)
51.8–75.9
H-SIL
15
11 (73.3)
50.9–95.7
Total
490
142(29)
24.9–32.9
A14
G. Masia et al. / Vaccine 27 (2009) A11–A16
Fig. 3. Distribution of Pap test results (negative; atypical squamous cervical cells of undetermined significance, ASCUS; low-squamous intraepithelial lesion, L-SIL; highsquamous intraepithelial lesion, H-SIL) according to age groups.
The distribution of the Pap test results in the different age classes
is reported in Fig. 3: the prevalence of normal cytology was lower
in women younger than 24 years than in the older classes (p < 0.05).
Overall, 48.1% of the Pap test positive women had also an HPV
infection and among these 22.7% were infected by HPV-16 and/or
HPV-18 genotype, while 51.9% (94/181) (95% C.I. 44.6–59.2) was
HPV-DNA negative; 82.2% (254/309) (95% C.I. 77.9–86.4) of women
with a normal Pap test were HPV-DNA negative, while 17.8% had
HPV-DNA and among these 8.4% had 16 and/or 18 HPV genotype.
Among HPV-DNA positive women 61.3% (95% C.I. 53.2–69.3) had an
abnormal Pap test result, vs. 27% (95% C.I. 23.3–31.6) in HPV negative
women; these differences were statistically significant (p < 0.05)
(Fig. 4).
The analysis by binary logistic regression was performed to
assess whether the positive Pap test was influenced by the contemporary presence of several factors such as age of the subject and the
HPV genotype. The analysis showed that genotype 16 and/or 18 is a
risk factor for the Pap positive test with a OR of 2.9 (95% C.I. 1.4–5.9)
and 3.6 (95% C.I. 1.58–8.42) respectively, while age is a protective
factor (OR 0.97, C.I. 95% 0.96–0.99).
Pieces of information emerged by the questionnaire are reported
in Table 3.
The age at the first sexual intercourse and the number of
partners since the beginning of sexual activity, were statistically
associated with positivity to HPV (p < 0.01).
No significant association were found among women tested HPV
positive and negative as regards to the educational qualifications,
working condition, the habit of smoking, the use of oral contraceptives and recurrent genital infections.
The answers to the questionnaire about awareness on HPV,
its mode of transmission and its association with cervix cancer,
showed that 61.9% of women knew about HPV (32.5% of positive
and 25.1% of negative women, p > 0.05), 57.6% were also aware about
its sexual transmission (36.0% among positive and 21.9% among
negative women, p < 0.05) and that 61.8% of women knew of its correlation with cervix cancer (32.5% of positive vs. 25.8% of negative
women, p > 0.05).
Overall, compliance to the HPV vaccine was expressed in 90.3%
of women.
4. Discussion
Fig. 4. Association with Pap test results in HPV-DNA positive and negative women
(n = 490).
Our findings document that HPV infection is frequent in women
aged from 18 to 46 years in Sardinia; in our population the overall 31% prevalence of infections with any HPV type correlates with
the 20% prevalence of high-risk HPV. These results are consonant to
findings on HPV and HR-HPV prevalence reported in Apulia, another
area of South Italy [20]. The steady decrease of HPV and HR-HPV
prevalence across increasing age is consistent with worldwide data;
it could be argued that HPV and particularly HR-HPV infection,
without lesion, in older women do not represent new infections
but are the tail of long lasting infections which may deserve more
attention and require a closer follow up because of the increased
risk of cancerogenicity related to the length of infection.
The high frequency of single or multiple HPV-18 infection
observed in our study is a peculiar finding compared to HPV
epidemiology described in Italy [23–29]; HPV prevalence among
women with normal cytology (17.8%) is also consistently higher
G. Masia et al. / Vaccine 27 (2009) A11–A16
A15
Table 3
Information collected by the questionnaire drawn up by the women enrolled into the study.
Features
Missing data
Education
No. (% of 604 responses)
Middle school
8 (1.3)
Secondary school
124 (20.5)
University
472 (78.1)
260
Working condition
No. (% of 709 responses)
Worker
309 (43.6)
Unemployed
39 (5.5)
Never working
361 (50.9)
155
Knowledge about HPV
Did you ever heard of HPV?
No. (% of 805 responses)
Do you know about HPV sexual transmission?
No. (% of 805 responses)
Do you know about the link between HPV and cervical cancer?
No. (% of 801 responses)
Yes
498 (61.9)
Yes
463 (57.6)
Yes
495 (61.8)
No
307 (38.1)
No
342 (42.4)
No
306 (38.2)
Recurrent genital infections
No. (% of 781 responses)
Yes
353 (45.2)
No
428 (54.8)
Smoking habit
No. (% of 746 responses)
Smoker
442 (59.2)
Non-smoker
304 (40.8)
Oral contraceptive use
No. (% of 770 responses)
Yes
610 (79.2)
No
160 (20.8)
Number of partners in the last year
No. (% of 762 responses)
None
36 (4.7)
1
568 (74.5)
Age at first sexual intercourse
784 responses
Mean (years)
16.1
Median (years)
17
80
No. of partners since beginning of sexual activity
765 responses
Mean (no.)
5.4
Median (no.)
3
99
Compliance to HPV vaccine
No. (% of 683 responses)
Yes
617 (90.3)
No
66 (9.7)
than reported in women of southern Europe by a meta-analysis
study [22].
Our study confirms the association of HPV infection and cytological abnormalities and underlines the crucial role of genotypes
16 and 18 in determining abnormalities in the Pap test. About half
of the women with a positive Pap test (including ASCUS) were also
infected by HPV and over 20% of them were infected by an HR-HPV
type. This finding emphasizes the need of a follow up in women who
are HPV-DNA positive. However, HPV test is not sufficient in surveillance for cervical cancer: as a matter of fact the test was negative in
about one-third (34.2%) of the 76 women with squamous intraepithelial lesions of low or high grade and therefore HPV surveillance
would have missed about one-third of the negative HPV women
with an abnormal Pap test result requiring a cytological follow up.
The low rate of HPV infection in women with overall cytological
abnormalities, ASCUS included, is an unexpected finding as there
is no clear explanation to it; one can argue about the possibility of
inadequate way in cervical sample collection or low sensitivity of
HPV test; these questions need further investigation.
Therefore, our data suggest the opportunity to integrate both
diagnostic items, HPV-DNA and Pap test, considering the complementary use aimed to identify the virological or cytological risk. The
availability of new and standardized diagnostic markers to identify
persistent infections could provide an useful tool to plan out specific
follow up in screened women.
The age of the first sexual intercourse and the number of sexual
partners since the debut of sexual activity were confirmed as risk
factors in HPV infection. This finding indicates the most suitable
age for HPV vaccination is the period preceding sexual activity. The
educational and working condition, as well as smoking or the use
of oral contraceptives, did not seem to increase the risk of HPV
infection.
The evaluation of the knowledge of women about the HPV issues
evidenced that more than half of women was aware about the
problem of HPV and of its association with cervical cancer. This
59
59
63
83
118
94
>1
158 (20.7)
102
181
awareness represents a crucial assumption to achieve high compliance to the new vaccines. Of note, in our study emerged that the
use of vaccines containing 16 and 18 HPV genotypes, would prevent
15% of infections in the girls younger than 24 years.
The implementation on a large scale of vaccination in adolescents will probably modify the future epidemiological scenario of
HPV. The contemporary vaccination of other target adolescents
would allow to accomplish substantial changing in HPV spread in
the short term; therefore, strategies of vaccination including new
cohorts of vaccines should be considered.
Acknowledgements
We are grateful to Valeria Caredda and the team of the Oncologic Prevention Service of the health district of Cagliari (Carmela
Atzori, Liliana Cardia, Irene Casu, Fedela Corda, Rossana Deplano,
Gina Lai, Alberto Orani, Gabriella Pillosu, Mario Porcu, Andreana
Raffatellu) and to Antonella Boi, Maria Rosaria Lai, Margherita Porcu
and Silvana Sanna of the Health Promotion Mother-Child Service of
Cagliari, for their decisive cooperation in the recruitment of women.
References
[1] Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al.
Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189(1):12–9.
[2] Ho GY, Bierman R, Beardesley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998;
338(7):423–8.
[3] Bosch FX, Lorincz A, Munoz N, Mejer XJ, Shah KV. The causal relation between
human papillomavirus and cervical cancer. J Clin Pathol 2002;55:244–65.
[4] Heard I. Ano-genital lesions due to human papilloma virus infection in women.
Med Mal Infect 2005;35(May (5)):302–5.
[5] Reithmuller D. Ano-genital papillomaviruses infections in women. Rev Prat
2006;56(November (17)):1893–900.
[6] Psyrri A, Dimaio D. Human papillomaviruses in cervical and head-and-neck
cancer. Nat Clin Pract Oncol 2008;5(January (1)):25–31.
A16
G. Masia et al. / Vaccine 27 (2009) A11–A16
[7] Munoz N, Bosch FX, Castellagué X, Dìaz M, de Sanjosé S, Hammouda D, et al.
Against which human papillomavirus types shall we vaccinate and screen? The
international perspective. Int J Cancer 2004;111(2):278–85.
[8] Von Krog G. Management of anogenital warts (condylomata acuminata). Eur J
Dermatol 2001;11:598–604.
[9] Wiley DJ, Douglas J, Beutner K, et al. External genital warts: diagnosis, treatment
and prevention. Clin Infect Dis 2002;35(Suppl. 2):S210–24.
[10] Weinstock H, Berman S, Caces Jr W. Sexually transmitted diseases among American youth: incidence and prevalence estimates, 2000. Perspect Sex Reprod
Health 2004;36:6–10.
[11] Brown DR, Shew ML, Qadadri B, Neptune N, Vargas M, Tu W, et al. A longitudinal
study of genital human papillomavirus infection in a cohort of closely followed
adolescent women. J Infect Dis 2005;191:182–92.
[12] Stanley M. Immune responses to human papillomavirus. Vaccine 2006;24
(Suppl. 1):S16–22.
[13] Franco EL, Villa LL, Sobrinho JP, Prado JM, Rousseau MC, Désy M, et al. Epidemiology of acquisition and clearance of cervical human papillomavirus infection
in women from high-risk area for cervical cancer. J Infect Dis 1999;180:1415–23.
[14] Giuliano AR, Harris R, Sedjo RL, Baldwin S, Roe D, Papenfuss MR, et al. Incidence,
prevalence, and clearance of type-specific human papillomavirus infections:
the Young Women’s Health Study. J Infect Dis 2002;186:462–9.
[15] Remmink AJ, Walboomers JMM, Helmerhorst TJM, Voorhorst FJ, Rozendaal L,
Risse EKJ, et al. The presence of persistent high-risk HPV genotypes in dysplastic
cervical lesions is associated with progressive disease: natural history up to 36
months. Int J Cancer 1995;61:306–11.
[16] Londesborough P, Ho L, Terry G, Cuzick J, Wheeler C, Singer A. Human
papillomavirus genotype as a predictor of persistence and development of
high-grade lesions in women with minor cervical abnormalities. Int J Cancer
1996;69:364–8.
[17] Liaw KL, Glass AG, Manod MM, Greer CE, Scott DR, Sherman M, et al. Detection
of human papillomavirus DNA in cytologically normal women and subsequent
cervical squamous intraepithelial lesions. J Natl Cancer Inst 1999;91:954–60.
[18] Schlecht NF, Kulaga S, Robitaille J, Ferreira S, Santos M, Miyamura RA, et al. Persistent human papillomavirus infection as a predictor of cervical intraepithelial
neoplasia. J Am Med Assoc 2001;286:3106–14.
[19] Snijders PJ, Steenberg RD, Heideman DA, Meijer CJ. HPV-mediated cervical carcinogenesis: concepts and clinical implications. J Pathol 2006;208(2):152–64.
[20] Martinelli D, Chironna M, Tafuri S, Neve A, Caputi G, Prato R, et al. Epidemiology
of HPV infections and cervical cancer in Apulia: a survey study and current data
analysis. Ann Ig 2007;19(6):499–508.
[21] Ronco G, Ghisetti V, Segnan N, et al. Prevalence of human papillomavirus infection in women in Turin, Italy. Eur J Cancer 2005;41:297–305.
[22] De Sanjosé S, Diaz M, Castellsagué X, Clifford G, Bruni L, Munoz N, et al.
Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect
Dis 2007;7:453–9.
[23] De Francesco MA, Gargiulo F, Schreiber C, Ciravolo G, Salinaro F, Manca N. Detection and genotyping of human papillomavirus in cervical samples from Italian
patients. J Med Virol 2005;75(April (4)):588–92.
[24] Centurioni MG, Puppo A, Merlo DF, Pasciucco G, Cusimano ER, Sirito R, et al.
Prevalence of human papillomavirus cervical infection in an Italian asymptomatic population. BMC Infect Dis 2005;5(September):77.
[25] Verteramo R, Pierangeli A, Calzolari E, Patella A, Recine N, Mancini E, et al. Masciangelo direct sequencing of HPV DNA detected in gynaecologic outpatients
in Rome, Italy. Microbes Infect 2006;8(August (9–10)):2517–21.
[26] Zerbini M, Venturoli S, Cricca M, Gallinella G, De Simone P, Costa S, et al. Distribution and viral load of type specific HPVs in different cervical lesions as
detected by PCR-ELISA. J Clin Pathol 2001;54(May (5)):377–80.
[27] Carozzi FM, Confortini M, Cecchini S, Bisanzi S, Cariaggi MP, Pontenani G, et al.
Triage with human papillomavirus testing of women with cytologic abnormalities prompting referral for colposcopy assessment. Cancer 2005;105(February
(1)):2–7.
[28] Tornesello ML, Duraturo ML, Botti G, Greggi S, Piccoli R, De Palo G, et al. Prevalence of alpha-papillomavirus genotypes in cervical squamous intraepithelial
lesions and invasive cervical carcinoma in the Italian population. J Med Virol
2006;78(December (12)):1663–72.
[29] Gargiulo F, De Francesco MA, Schreiber C, Ciravolo G, Salinaro F, Valloncini B, et
al. Prevalence and distribution of single and multiple HPV infections in cytologically abnormal cervical samples from Italian women. Virus Res 2007;125(May
(2)):176–82.