Giuseppina Masia

Sexual behaviour and risk factors for the acquisition of human papillomavirus infections in young people in Italy: suggestions for future vaccination policies

BackgroundHuman Papillomavirus (HPV) is the most common sexually transmitted infection. The main risk factors correlated with HPV infection are: early sexual debut, the number of partners, frequency and type of sexual contact and partner’s sexual histories.We surveyed sexual habits among young people in order to provide information that might orient decision-makers in adopting HPV multi-cohort vaccination policies.MethodsWe administered a questionnaire to students (14–24 years old) in five Italian cities.Results7298 questionnaires were analyzed (4962 females and 2336 males); 55.3% of females (95% CI 53.9–56.7) and 52.5% of males (95% CI 50.5–54.5) reported regular sexual activity. The mean age at sexual debut was 15.7 ± 1.6 and 15.6 ± 1.6 for females and males, respectively, and the median age was 16 for both sexes.With regard to contraceptive use during the last year, 63.6% of males and 62.8% of females responded affirmatively; 42.6% of males and 42.8% of females used condoms.ConclusionThe results reveal precocious sexual activity among respondents, with the mean age at first intercourse declining as age decreases. Condom use proved to be scant. Considering lifestyle-related risk factors, males appear to have a higher probability of acquiring HPV infection than females.These data support the importance of promoting multi-cohort HPV vaccination strategies for females up to 25 years of age. It is essential to improve vaccination coverage through different broad-spectrum strategies, including campaigns to increase awareness of sexually transmitted diseases and their prevention.

HCV transmission in family members of subjects with HCV related chronic liver disease

To investigate the risk of sexual and intrafamilial transmission of HCV, 220 family members of 76 patients (index cases) with chronic type C viral liver disease were tested for serological markers of HCV Of the family members, 129 were offspring, 64 sexual partners, 15 parents and 12 siblings of the index cases. Anti-HCV was tested in all the household contacts; HCV-RNA was tested in antibody positive samples. The serologic markers of HCV were tested in a control group of 168 family members of 81 patients with chronic hepatitis unrelated to HCV. The overall prevalence of anti-HCV was 8.2% compared to 0.6% in the control group (p < 0.001). Sexual partners were anti-HCV positive more frequently than the other contacts (20% vs 2.2%; p < 0.001), without any difference in males or females. No correlation was observed between the occurrence of HCV infection in contacts and age, severity of liver disease or risk factor for the acquisition of HCV in the index cases. Seven of the 18 (39%) anti-HCV positive family contacts had biochemical evidence of chronic liver disease, histologically confirmed in the 6 patients who underwent a liver biopsy. Liver chemistry was normal in all the HCV-negative contacts. Ten of the 18 anti-HCV positive contacts (55%) were HCV-RNA positive. Genotypes were the same (lb) in 4 of the 7 viremic couples of subjects: in 3 of the 6 couples of sexual partners and in the only mother/son couple. These data suggest the occurrence of intraspousal transmission of HCV, while intrafamiliar acquisition of HCV in non-sexual contacts seems to be rare.

HCV, HIV, HBV and HDV infections in intravenous drug addicts

Hepatitis viruses and the acquired immunodeficiency viruses often infect intravenous drug addicts (IVDAs). Our study includes 255 IVDAs (26 females and 229 males, aged 20–35 years) from Cagliari. Of 255 subjects examined, 207 (81.1%) were positive for anti-HCV and 84 (32.9%) for anti-HIV. Nineteen (7.4%) subjects were HBsAg carriers, and 12 of these (63%) had an HDV super-infection. Markers of previous HBV infections were tested in 223 cases and 137 (61.4%) were found positive; of these 14 (10.2%) also had HDV infection. Of the 223 drug addicts examined for all infection markers, 18 (8%) were negative to all markers, 46 (20.6%) were positive to only one, 89(39.9%) were positive to two, 64 (28.7%) to three and 6 (2.6%) were positive to all. Subjects with a single infection were significantly fewer than those with multiple infections. The correlations studied among the various markers did not point out any statistically significant associations. Even so, a previous HBV infection was more common while active HBV/HDV infections were less common among subjects with anti-HCV; HDV infection was more common among HIV-positive subjects. In HBsAg carriers neither HBV-DNA nor HCV-RNA was detected; HCV-RNA was found more frequently in anti-HIV positive subjects than in subjects with the anti-HCV isolate.

Sexual behaviour and multiple infections in drug abusers

We have studied the prevalence and the serological profile of HBV, HCV, HDV and HIV infections in 137 Italian subjects addicted to the intravenous use of heroine and correlated the virological findings with sexual behaviour. HBV and HCV viremia were also measured in 114 patients. Anti-HCV was detected in 81% of the addicts, and one or more markers of HBV infection were detected in 62.8% (4.4% were carriers of HBsAg, 58.4% had evidence of past HBV infection and 13.1% of the latter also had HDV markers). Anti-HIV was positive in 23.4%; 26% of those positive for anti-HCV and 4.6% of those positive for HBV markers had no other viral marker: none had only anti-HIV. HBV-DNA was negative in the carriers of HBsAg, and HCV-RNA was not detected in any of the HBsAg carriers who also had circulating anti-HCV Overall, 34% of the anti-HCV positive addicts had HCV-RNA in their blood. The prevalence of the virus infection correlated with the duration of drug addiction but not with sexual behaviour, and sexual behaviour did not influence the acquisition of any virus. HCV infection was most frequent and probably the first infection to occur, but exposure to HBV was also common despite a low rate of HBsAg carriage. The prevalence of HDV infection was high (50%) in the HBsAg carriers, while the overall prevalence of HIV was lower (23%) than expected. Lack of HBV-DNA and HCV-RNA in carriers of HBV with anti-HCV in serum may indicate that HBV and HCV mutually inhibit their own replication.

Changing Pattern of Hepatitis A Virus Epidemiology in an Area of High Endemicity

Background Continuous assessment of hepatitis A virus (HAV) seroepidemiology is a useful tool to control the risk of infection. Objectives This study aimed to evaluate the changing patterns of anti-HAV seroprevalence in a population,which isgenerally considered to be anarea ofhigh endemicity. Patients and Methods Overall, the results of 3349 sera collected during the period 2005-2008 from patients attending the University Hospital of Cagliari, Italy were studied; their mean age was 52.7 years, (s + 16.22). Patients with liver disease were excluded from the study. Age specific seroprevalence results were compared with those observed in similar previous studies carried out in the same area. Results The overall prevalence of anti-HAV was 74.6% with consistently lower values in subjects younger than 40 years (17.5%; P < 0.0001) particularly in those under 30 years of age (8.9%, CI 5.8-11.9). A significant declining trend in age specific seroprevalence has been foundin people under 30 years;61% in 1988, 33% in 1995 and 8.9% in 2005-2008. Conclusions Our findings show that a significant decline inherd immunity has occurred in the last 20 years as a consequence of lower HAV circulation due to improvementsin socio-economical and hygienic conditions. Adolescents and young adults are becoming increasingly susceptible to HAV infections, as recent outbreaks of acute HAV hepatitis have occurred. Persistent environmental monitoring and the implementation of prevention measures must be considered in order to contain the risk related to this epidemiological shift.

TT virus infection in Italy: prevalence and genotypes in healthy subjects, viral liver diseases and asymptomatic infections by parenterally transmitted viruses

This study was aimed to evaluate TT virus prevalence in subjects with hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections in patients affected by hepatitis of unknown origin (non‐A–non‐E hepatitis) and in healthy subjects who had not been exposed to HBV, HCV and HIV. A total of 317 subjects were tested; 40 were HBsAg asymptomatic carriers, 57 subjects were anti‐HCV positive (45 without chronic hepatitis and 12 with HCV‐related chronic hepatitis), and 27 had chronic non‐A–non‐E hepatitis. Fifty‐seven subjects were intravenous drug users (IVDUs) (52 with HCV or/and HIV infections), seven patients underwent a liver transplant for fulminant hepatitis and 137 were healthy subjects from the general population. Overall, TTV‐DNA was detected in 62 subjects (19.6%): in 17.9% of the HBsAg carriers, in 14% of the anti‐HCV‐positive patients (in 8.3% and in 15.5% of patients with and without chronic hepatitis, respectively), in 22.2% of non‐A–non‐E hepatitis patients, in 22.8% of IVDUs, in 57.1% of fulminant hepatitis patients. TTV‐DNA was also found in 20.4% healthy subjects. The prevalence in the different subgroups was not statistically different. The genotypes were identified in 40 of the 62 (64.5%) TTV‐DNA positive samples: genotype 1a in 17.5%, 1b in 27.5%, genotype 2 in 27.5%, genotype 3 in 15.0%, genotype 4 in 5.0% and genotype 5 in 7.5%; the genotype distribution in the subsets of patients was not significantly different. In conclusion, this study showed that TTV infection is common in Italy; it is widespread throughout the entire population and five genotypes are present in Sardinia. Our results further dismiss the role of TTV as cofactor in influencing the clinical course of infections with other hepatitis viruses as well as the role of HIV in enhancing TTV transmission and replication.

Detection and genotyping of human papillomavirus in urine samples from unvaccinated male and female adolescents in Italy.

The introduction of vaccination against Human Papillomavirus (HPV) in adolescent girls in 2006 has focused virological surveillance on this age group. As few studies have evaluated HPV infections in young populations, further data are needed in order to improve and extend prophylactic policy and to monitor epidemiological changes. The present study aimed at evaluating overall and type-specific HPV prevalence in both female and male adolescents in Italy. HPV DNA detection and genotyping was performed on urine samples collected from 870 unvaccinated adolescents (369 females, 501 males, 11-18 years of age) in five cities in Italy. Following DNA extraction by means of a commercial kit (NucliSENS®-miniMAG®, bioMérieux), the L1 gene fragment was PCR amplified and genotyped by restriction fragment length polymorphism analysis. HPV DNA was detected in 1.5% of all samples, and in 3% and 0.4% of samples from females and males, respectively. In approximately 70% of HPV DNA positive adolescents, the infection was due to a single genotype, with 88.9% of genotypes belonging to the HR-clade. The only two HPV-positive boys (14 and 18 years old) had HPV-70 genotype. Only one of the 11 HPV-infected girls was in the 11-14 age-group. HPV prevalence was 4.2% in girls aged 15-18 years and 60% of infections were due to vaccine types HPV-16 or HPV-6/-11. This is one of the few studies, the first conducted in Italy, on HPV infection in adolescents. Urine testing is the easier way of detecting HPV infection in younger populations. Our data revealed a very low HPV prevalence, and no infections were observed in the 12-year-old vaccine target population. The majority of infections were seen in females aged 15-18 years. Overall, more than 50% and 30% of the potentially persistent HPV infections detected in this group could have been prevented by the quadrivalent and the bivalent vaccines, respectively.

Epidemiology and genotype distribution of human papillomavirus (HPV) in women of Sardinia (Italy).

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 high-risk 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.

Epidemiological impact of mandatory vaccination against hepatitis B in Italian young adults.

Background Viral hepatitis caused by hepatitis B virus (HBV) is a leading cause of acute and chronic liver diseases worldwide. Objectives In Italy, a mandatory vaccination policy was introduced in 1991 and was established for all newborns and 12-year-old individuals. In 2004, vaccination of 12-yearold adolescents was discontinued, and that of infants was maintained. Patients and Methods We evaluated the seroprevalence of HBV markers in 806 individuals, who were vaccinated at birth or at 12 years of age, to assess the effectiveness of the national policy against HBV. Results The overall prevalence of anti-HBs antibodies was 90.32% (95% confidence interval [CI]: 88.28–92.36%); 2.23% (95% CI: 1.21–3.25%) of the subjects were positive for both antibodies to HBsAg (anti-HBs) and antibodies to hepatitis B core antigen (anti-HBc), whereas 5.83% (95% CI 4.21–7.45) of the subjects were negative for all markers tested. Further, 1.61% (95% CI: 0.74–2.48%) of the subjects were positive for hepatitis B surface antigen (HBsAg). Conclusions Our data provide additional evidence that HBV vaccination can confer long-term immunity when performed at birth and when performed for healthy adolescents; moreover, the results show the effectiveness of the application of a national vaccination strategy.

Prevalence and molecular epidemiology of human papillomavirus infection in Italian women with cervical cytological abnormalities.

Background Human papillomavirus (HPV) infection is the most common sexually transmitted infection and high-risk HPV types are a necessary cause for the development of cervical cancer. The present study investigated the HPV-type specific prevalence in 650 women, aged 15-76 years, with cytological abnormalities and the association between HPV infection and cervical disease in a subset of 160 women for whom cytological results for Pap-Test were available, during the period 2008-2011 in Cagliari (Southern Italy). Design and Methods HPV-DNA extraction was performed by lysis and digestion with proteinase K and it was typed by using the INNOLiPA HPV Genotyping Assay. Results Overall the HPV prevalence was 52.6%; high-risk genotypes were found in 68.9% of women and multiple-type infection in 36.1% of HPV-positive women. The commonest types were HPV-52 (23.4%), HPV-53 (15.7%), HPV-16 (15.4%) and HPV-6 (12.4%). Among the women with cytological diagnosis, any-type of HPV DNA was found in 49.4% of the samples and out of these 93.7% were high-risk genotypes. Genotype HPV 53 was the commonest type among women affected by ASCUS lesions (21.4%), genotype 52 in positive L-SIL cases (22.5%), genotype 16 H-SIL (27.3%). Conclusions This study confirmed the high prevalence of HPV infection and high-risk genotypes among women with cervical abnormalities while, unlike previously published data, genotype HPV-52 was the most common type in our series. These data may contribute to increase the knowledge of HPV epidemiology and designing adequate vaccination strategies. Significance for public health Human papillomavirus (HPV) is the most common sexually-transmitted agent, which can cause cervical lesions and cancer in females. Efforts to reduce the burden of cervical cancer with cytology screening in the last years have had limited success. HPV infection and disease imposes a substantial burden of direct costs on the Italian National Health Service that have never been fully quantified. Monitoring HPV prevalence could represent a tool to follow the evolution of the infection in the vaccination and post-vaccination era, to understand the impact of HPV types in cervical diseases in Italy. Our survey shows an high frequency of infections sustained by HPV 52. Given the recent implementation of a widespread immunization program with vaccines not containing HPV 52, it has been relevant to prove the high prevalence of this HPV genotype from the beginning of the vaccination campaign, to avoid ascribing to the vaccination program a possible selection effect and the importance of non-vaccine HPV types in the burden of cervical disease, in order to assess the opportunity to realize new vaccine including other types.