Prevalence of cervical human papillomavirus infection and types among women immigrated to Sicily, Italy

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1 Acta Obstetricia et Gynecologica. 2009; 88: SHORT REPORT Prevalence of cervical human papillomavirus infection and types among women immigrated to Sicily, Italy LUCIA GIOVANNELLI 1, ROSITA VASSALLO 2, DOMENICA MATRANGA 3, MARIO AFFRONTI 4, MARIA PIA CALECA 1, CARMELINA BELLAVIA 1, ANTONIO PERINO 2 & PIETRO AMMATUNA 1 1 University of Palermo Dipartimento di Scienze per la Promozione della Salute, Palermo, Italy, 2 University of Palermo Dipartimento Materno Infantile, Palermo, Italy, 3 University of Palermo Dipartimento di Biotecnologie Mediche e Medicina Legale, Palermo, Italy, and 4 University of Palermo Dipartimento di Medicina Clinica e delle Patologie Emergenti, Palermo, Italy Abstract We determined the prevalence of human papillomavirus (HPV) cervical infection and HPV genotypes among 115 women immigrating to Sicily (Italy), with regard to abnormal cytology and socio-behavioral characteristics in a cross-sectional, observational study. Information was collected with the help of cultural mediators/translators. HPV-DNA was assayed by the INNOLiPA HPV assay and a nested PCR/sequencing method. Sixty (52.2%) women came from sub-saharan Africa and 55 (47.8%) from Eastern Europe. HPV infection was found in 55 (47.8%) women. The most frequent types were the oncogenic types HPV-16 (7.8%), HPV-18 and 51 (6.0% each), HPV-52 (5.2%), 31, 53, and 68 (4.3% each). Twenty-seven (23.5%) women had cytological abnormalities associated with HPV infection (p0.04). Being single (OR2.98; 95%CI: ) and parity (OR0.29; 95%CI: ) were consistent predictors of HPV infection. Only 21 (18.2%) women returned to collect the results of their Pap and HPV tests. The high prevalence of HPV infection and oncogenic types among immigrant women make them a priority group for cervical cancer screening. Linguistically and culturally appropriate prevention efforts are needed to sensitize immigrant women regarding HPV-related issues and to conduct vaccine strategies for cervical cancer prevention. Key words: Cervical HPV infection, HPV genotype distribution, immigrant women Introduction Human papillomaviruses (HPV) are small DNA viruses which infect squamous epithelia, determining asymptomatic infections as well as various benign or malignant lesions. More than 120 HPV types have been identified: some of them, termed high-risk HPV (HR-HPV), such as HPV-16 and 18, are etiologically linked to high-grade cervical lesions and cancer (1). Estimates of HPV infection range from 2% in Asia and Europe to 44% in sub-saharan Africa, which could be due to different HPV assay used, as well as behavioral and sexual practices and this variation is also evident in regional distribution of HPV types (2). Given this, immigration in a specific geographical area can represent one modifying determinant of the local HPV infection profile, similar to what has been reported for other sexually transmitted diseases (3). Adequate information regarding HPV infection and types in non-native population is, therefore, important, as the information on its prevalence, especially in countries with high immigration rates. This is also pertinent to preventing cervical cancer among segments of the population, which are at increased risk of the disease (4). In Italy, there are an estimated 3,690,000 documented immigrants, approximately 50% of whom are women. While the prevalence of HPV infection has been investigated in the resident population (5,6), corresponding data on immigrants are lacking, Correspondence: Pietro Ammatuna, University of Palermo Dipartimento di Scienze per la Promozione della Salute, Palermo, Italy. ammatuna@unipa.it (Received 16 January 2009; accepted 6 April 2009) ISSN print/issn online # 2009 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS) DOI: /

2 738 L. Giovannelli et al. except for one analysis which mainly focused on immigrant women with a history of prostitution (7). The objective of this study was to assess the prevalence of HPV infection and type distribution among women who had immigrated to Sicily (south Italy), with reference to abnormal cervical cytology and selected socio-behavioral characteristics. Material and methods We examined 120 immigrant women who consecutively attended the outpatient clinic of Dipartimento di Medicina Clinica e delle Patologie Emergenti at the Policlinico University of Palermo between December 2007 and June The main reasons for consultations were abdominal complaints (14.3%), musculoskeletal pain (13.5%), cardiology/ vascular disorders (13.5%), and gynecological/urinary problems (12.8%). The women were invited to participate in the study and its purpose was explained; all agreed to participate and gave written informed consent. The study was approved by the Ethics Committee of the Policlinico University of Palermo. Personal interviews were conducted in Italian or English and women with insufficient language skills were interviewed with the help of cultural mediators/translators. Information relating to country of origin, age, time spent in Italy, education level, marital status, age at sexual debut, method of contraception, number of children, termination of pregnancies, history of sexually transmitted diseases, number of sexual partners, partner at risk (i.e. a male partner with multiple female sexual partners), and smoking habits was collected. The patients were sent to the Obstetrics and Gynecology Ambulatory at the Mother and Child Department, where they had a gynecological examination and cervical sampling for HPV testing and a Pap smear. Abnormal cytological results were classified as atypical squamous cell of undetermined significance, low-grade and high-grade lesions. Any cervical abnormalities were dealt with in compliance with the guidelines of the Italian Association of Colposcopy and Cervical/Vaginal Pathology. Cells for a HPV test were placed into 10 ml of cold phosphate saline. Total DNA was extracted using the QIAmp Mini Kit (Qiagen, Valencia, California, USA). The samples were checked for DNA by amplification of the human b-globin in a Mastercycler (Eppendorf, Germany) and the PCR products analyzed in 8% polyacrylamide gel, as described before (8). Two systems were used for HPV detection and typing. Initially, all samples were tested using the INNO-LiPA HPV Genotyping system (Innogenetics N.V., Ghent, Belgium), which is based on the combined use of SPF 10 PCR amplification and LiPA hybridization assays. This identifies 24 different HPV types. Due to the higher number of HPV types detected by the wide-spectrum SPF 10 primers than the specific probes, some samples yielded SPF 10 - positive/hybridization-negative results. These HPV types were subsequently amplified by a highly sensitive, wide-spectrum nested PCR assay with MY09/11 and GP05/06 primers, and HPV genotyping was performed by direct cycle sequencing analysis, as described elsewhere (8). The HPV types detected were considered as low-risk HPV (LR-HPV) or HR- HPV according to two epidemiological classifications of HPV types (1,9). To examine the association between HPV infection and various selected socio-demographic variables, continuous variables were categorized by using quartiles as class limits. For the univariate analysis, the crude odds ratio (OR) with corresponding 95% confidence interval (CI) was computed. Multivariate analysis was performed by logistic regression with a stepwise approach, examining only the variables which proved to be significant (p-value 50.05) in the univariate analysis. Data were analyzed using the Intercooled STATA, v. 9.0 statistical package (Stata Corporation, College Station, Texas, USA). Results There were five women (4.1%) with a b-globin negative result who were excluded from further analysis. Of the remaining 115 women, 60 (52.2%) came from sub-saharan Africa and 55 (47.8%) from Eastern Europe. HPV infection was ascertained in 55 (47.8%) women and the HPV type distribution is shown in Table I. A total of 25 (45.4%) women harbored LR-HPV types and 40 (72.7%) had HR- HPV types. Single infections were present in 39 (70.9%) women and multiple type infections were identified in 21 (18.3%); of the latter, 13 (61.9%) harbored two types, five (23.8%) three types, and three (14.3%) five types. A total of 27 different HPV types were identified: the most frequent were HPV- 16 (7.8% of all women), HPV-18 and 51 (6.0% each), HPV-52 (5.2%), 31, 53 and 68 (4.3% each); other types occurred at a B4% rate. HPV-18 was most frequent (8.3%) in African migrants; HPV-56 was only detected in African migrants (3.3%) and HPV-39 only in those from Eastern Europe (7.3%). No other significant differences were identified in the distribution of the remaining HPV types, nor in the frequency of multiple infections (data not shown). Twenty-seven (23.5%) women had cytological abnormalities, of which 15 (55.6%) were atypical

3 HPV cervical infection among immigrant women 739 Table I. HPV type distribution and prevalence as single and multiple genital infections in 115 women immigrating to Sicily, Italy. HPV-positive women HPV infection HPV genotype N % Single Multiple LR a HPV types Any LR type HR b HPV types Any HR type LR a Low-risk HPV; HR b high-risk HPV. squamous cell of undetermined significance, 10 (37.0%) were low-grade lesions and two (7.4%) high-grade lesions. HPV infection was evident in 18/ 27 (66.7%) women with an abnormal cytology and 37/88 (42.0%; p 0.04) women with a normal cytological result. The majority of the infected women (37/55: 67.3%) had normal cytology. The characteristics of the patients, together with the HPV status, are listed in Table II. The median age was 31.2 years (range: 2255), the mean length of their stay in Italy was 34.4 months (range: 8120 months). More than half (64.3%) had received a formal education. Median age at first sexual intercourse was 19.1 years (range 1240 years). Seventyeight women (67.8%) had one or more children and 65 (56.5%) reported a history of at least one termination. Non-monogamous women represented 70.4% of the group, although only 19.1% women reported more than three lifetime sexual partners. The prevalence of HPV infection was higher in women originating from Europe than those from Africa, but the difference was not statistically significant. Characteristics with significant associations with HPV infection included age, marital status, number of children, number of sexual partners, and having a partner at risk. However, when all these variables were analyzed in a logit model, only being single (OR 2.98; 95%CI: ) and parity (OR 0.29; 95%CI: ) were consistent predictors of HPV infection. Only 21 (18.2%) of the women returned to collect their Pap and HPV tests. Discussion We have shown that cervical HPV infection is prevalent in almost half (47.8%) of a cohort of immigrant women in Sicily, southern Italy. Only two other studies have assessed the HPV prevalence among women immigrating to Europe, and they also revealed high rates of infection, i.e. 42.2% in central/south Italy (7) and 39% in Spain (10). These

4 740 L. Giovannelli et al. Table II. Univariate and multivariate association of HPV-DNA detection with demographic, Clinical, and biological risk factors among 115 women immigrating to Sicily, Italy. Univariate analysis Multivariate analysis Variable n HPV % OR 95%CI OR 95%CI Country of origin Africa Eastern Europe ; 2.81 Age ; ; ; 0.59 Time in Italy (years) B ] ; 1.47 Education level No formal education Middle school ; 1.85 High school or university ; 5.80 Status Married Single ; ; 6.84 Age at sexual debut ; 3.58 ] ; 2.55 Contraceptive method ncm a Hormonal contraception ; 2.98 Condom ; 7.21 Number of children ; 4.08 ] ; ; 0.65 Termination of pregnancy ; 3.52 ] ; 1.82 History of sexually transmitted disease No Yes b ; 2.40 Sexual partners ; 6.97 ] ; 9.44 Partner at risk No Yes ; 8.51 Smoking No Yes ; 2.24 Note: Significant OR values are in bold. a Natural contraceptive methods: abstinence during the fertile days. b As referred: Chlamydia (n6; 37.5%), Candida (n4; 25.0%), Herpes simplex (n1; 6.2%), Trichomonas (n5; 31.2%).

5 HPV cervical infection among immigrant women 741 frequencies are higher than those evident in the resident population in Italy (719.7%) and Spain (1.33%) (5,6,10). Similarly, the rates of HR-HPV (34.8%) and multiple HPV infections in migrants (18.3%) were higher than those seen in the native Italian (HR-HPV rate: %; multiple HPV infections: 1.1%) and Spanish population (2.4 and 1%, respectively) (5,6,10). These findings are consistent with an increased risk of sexually transmitted diseases (3). Various HR-HPV types were detected in the immigrants, HPV-16 being the most common (7.8%), which is more than double that (2.93.7%) was reported in Italian women, and the same was observed for HPV-31. Some differences were present in terms of the distribution of HPV types between the two ethnic groups studied here: mainly in HPV- 18 (8.3% among African migrants), HPV-56 (only detected among those migrants), and HPV-39 (only detected among East European migrants); however, the sample size was not large enough for reliable deductions on this. Despite the high rate of HPV infection, only few cervical abnormalities were detected; nearly all were low-grade and associated with HPV infection. This was unexpected, given the women s migrant status and because the women came from countries with a particularly high prevalence of cervical cancer (4). High sensitivity of the HPV methods used may have lead to detection of transient/low-productive HPV infections, not associated with cytological changes. This study would suggest no association of HPV infection with the country of origin, since similar infection rate was found in African and East European migrants, and they were consistent with those revealed by local observational studies in the country of origin of the women (11,12). However, this finding need to be carefully considered, since the small sample size may have biased the assessment of HPV infection rate in the two groups. Younger age, marital status, and parity were determinants of HPV infection, consistent with various epidemiological studies on resident population (1,2,6). Most immigrant women did not return to find out about their test results, which indicates the necessity of disseminating knowledge regarding HPV and its link to cervical cancer in this segment of the population. Lack of information about HPV and cervical cancer could also represent a barrier to the acceptability of preventive HPV vaccines, which could affect public health benefits of vaccination in geographical areas like Italy with high immigration rates. A limitation of this study is the small clinic-based sample and the women cannot be considered fully representative of the general immigrant female population in Italy. However, it is to the best of our knowledge, the first study on HPV infection in immigrant women in the Mediterranean area. These women should be considered as a priority group for cervical screening, but for this, linguistically and culturally appropriate preventative efforts are required. Acknowledgements This work was supported by the Ministry of Instruction and University Research (fund MIUR 60%, 2006). Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. References 1. Muñoz N, Bosch FX, de Sanjosé S, Herrero R, Castellsagué X, Shah KV, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;/348:/ Clifford GM, Gallus S, Herrero R, Muñoz N, Snijders PJ, Vaccarella S, et al. Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis. Lancet. 2005;/366:/ Giuliani M, Suligoi B. Differences between nonnational and indigenous patients with sexually transmitted infections in Italy and insight into the control of sexually transmitted infections. Sex Transm Dis. 2004;/31:/ Garner EI. Cervical cancer: disparities in screening, treatment, and survival. Cancer Epidemiol Biomarkers Prev. 2003;/ 12:/242s7s. 5. Ammatuna P, Giovannelli L, Matranga D, Ciriminna S, Perino A. Prevalence of genital human papilloma virus infection and genotypes among young women in Sicily, South Italy. Cancer Epidemiol Biomarkers Prev. 2008;/17:/ Ronco G, Ghisetti V, Segnan N, Snijders PJ, Gillio-Tos A, Meijer CJ, et al. Prevalence of human papillomavirus infection in women in Turin, Italy. Eur J Cancer. 2005;/41:/ Tornesello ML, Duraturo ML, Buonaguro L, Vallefuoco G, Piccoli R, Palmieri S, et al. Prevalence of human papillomavirus genotypes and their variants in high risk West Africa women immigrants in South Italy. Infect Agent Cancer. 2007;/ 2:/ Giovannelli L, Lama A, Capra G, Giordano V, Arico P, Ammatuna P. Detection of human papillomavirus DNA in cervical samples: analysis of the new PGMY-PCR compared

6 742 L. Giovannelli et al. to the hybrid capture II and MY-PCR assays and a two-step nested PCR assay. J Clin Microbiol. 2004;/42:/ de Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H. Classification of papillomaviruses. Virology. 2004;/ 324:/ del Amo J, González C, Losana J, Clavo P, Muñoz L, Ballesteros J, et al. Influence of age and geographical origin in the prevalence of high risk human papillomavirus in migrant female sex workers in Spain. Sex Transm Infect. 2005;/81:/ Kulmala SM, Shabalova IP, Petrovitchev N, Syrjänen KJ, Gyllensten UB, Syrjänen SM, et al. Prevalence of the most common high-risk HPV genotypes among women in three new independent states of the former Soviet Union. J Med Virol. 2007;/79:/ Didelot-Rousseau MN, Nagot N, Costes-Martineau V, Vallès X, Ouedraogo A, Konate I, et al. Human papillomavirus genotype distribution and cervical squamous intraepithelial lesions among high-risk women with and without HIV-1 infection in Burkina Faso. Br J Cancer. 2006;/95:/35562.