Cervical carcinoma in the European Union: an update on disease burden, screening program state of activation, and coverage as of March 2014.

OBJECTIVE: Cervical cancer (CC) is defined as a disease of disparity. This is due to marked differences in CC incidence and mortality between developed and developing countries. As a continent, Europe is no exception. This study examines the state of activation of CC screening in the European Union as of March 2014, reviews CC incidence and mortality data, and highlights the initiatives adopted to extend program coverage to nonresponders. METHODS: The present study is based on the most recent data available from PubMed-indexed journals, the Web sites of the health ministries of each member state, and the Web sites of national cancer observatories; failing these sources, information was sought in scientific journals published in the local language. RESULTS: In 2003, the European Council recommended that priority be given to organized screening program activation. Nonetheless, a number of European Union member states still lack population-based organized screening programs, and few have implemented programs directed at disadvantaged populations. CONCLUSIONS: Several investigations have demonstrated that the women at higher CC risk are unscreened and underscreened ones. Since then, several member states have made significant efforts to set up effective prevention programs by adopting international quality standards and centralizing screening organization and result evaluation. Several developed countries and some new central-eastern European member states have poorly organized prevention programs that result in poor women's health. Diagnosis of CC is emotionally traumatic, but it is highly preventable. When CC is found early, it is highly treatable and associated with long survival and good quality of life.

A cross-sectional study to estimate high-risk human papillomavirus prevalence and type distribution in Italian women aged 18-26 years.

BACKGROUND: Pre-vaccination information on HPV type-specific prevalence in target populations is essential for designing and monitoring immunization strategies for cervical cancer (CC) prevention. Data on HPV prevalence in Italy are available for women over the age of 24 years, target of the population-based CC screening programmes; while data of HPV prevalence in younger ages are very limited. The present study enrolled Italian women aged 18-26 years in order to assess the prevalence and distribution of high-risk (HR) HPV types. Risk-factors correlated with HR-HPV positivity were also described. METHODS: A sample of 2,289 women was randomly selected from the resident population lists of ten Local Health Units (LHUs) located in six Italian Regions scattered across the country; both rural and urban LHUs were involved. Women aged between 18 and 26 years and living in the selected LHUs were included in the study; pregnant women and women who did not speak Italian were excluded. A total of 1,102 women met the inclusion criteria and agreed to participate. Participants were offered pap test and Hybrid-Capture 2 (HC2) test for HR-HPV types and genotyping was performed on positive smears. RESULTS: Out of 1,094 valid samples, 205 (18.7%) were HR-HPV positive. Women with 2-4 (ORadj = 4.15, 95%CI: 2.56-6.72) and ≥5 lifetime partners (ORadj = 10.63, 95%CI: 6.16-18.36) and women who have used any contraceptive in the last six months (ORadj = 1.67, 95%CI: 1.09-2.54) had a higher risk to be infected; women living with their partner had a lower risk (ORadj = 0.56, 95%CI: 0.34-0.92) to acquire infection than women living with parents/friends/alone. Among HC2 positive women, HPV16 was the most prevalent type (30.9%), followed by 31 (19.6%), 66 (12.9%), 51 (11.3%), 18 (8.8%), 56 (8.8%). Co-infections of HR-HC2 targeted types were found in 20.4% of positive samples. The HR-HPV prevalence in women with abnormal cytology (52.4%) was significantly higher than in women with normal cytology (14.6%); however 33.0% of HR-HPV infected women had an abnormal cytology. CONCLUSION: HR-HPV prevalence in Italian women aged 18-26 years was 19%, higher than what detected for older women, by other studies using the same molecular method and laboratory network; this result supports the choice of electing girls before the sexual debut as the primary target of HPV vaccination. The HPV type distribution found in this study may represent a baseline picture; an accurate post-vaccine surveillance is necessary to early detect a possible genotype replacement. The high prevalence of viral types other than vaccine-HPV types supports the necessity to guarantee the progression of CC screening programmes in vaccinated women.

Comparison of the conventional cervical smear and liquid-based cytology: results of a controlled, prospective study in the Abruzzo Region of Italy.

OBJECTIVE: To compare conventional cervical testing (CCT) and liquid-based cytology (LBC) within a randomized trial performed during 2001-2002 in the Abruzzo Region of Italy, including a cost-outcome comparative analysis. STUDY DESIGN: Study subjects were recruited in the framework of a controlled, randomized study organized in the Abruzzo Region. Women aged 2 6-64 years were randomized to an active arm (LBC) or control arm (CC1). The particip ating laboratories had no previous ex perience with LBC. RESULTS: The inadequacy rate was 4.3% in CCT and 1.3% in the LBC arm (D < 0.001). Atypical squamous cells of undetermined sign ifi cance and atypical glands of undetermined significance reports were more frequent at CCT vs. LBC. A small, insignificant excess of low grade squamous intraepithelial lesions or high grade squamous epithelial lesions+ reports was observed in the LBC arm. The cervical intraepithelial neoplasia 2+ (CIN2+) detection rate was not statistically different in the 2 arms (CCT=0.54%, LBC= 0.66%, p = 0.28). In the overall series positive predictive value was slightly but not significantly higher in the LBC arm. LBC increased costs by 4.2% per both screened women and CIN2+ detected. CONCLUSION: The study reflects the introductory phase of LBC in laboratories without prior LBC experience. In this setting LBC reduced the inadequacy rate and decreased reading and was at least as sensitive as and more specific than CCT. Utilization of LBC in organized screening programs will be based on local feasibility, considering that the high cost of LBC is only partially compensated for by other benefits, such as residual cellular material, available for molecular testing, including human papillomavirus testing.

A comparison between Pap and HPV screening tests and screening methods.

The present study assesses the results of cervical cancer (CC) screening over two 3-year periods (2008-2010 and 2011-2013) by comparing two screening tests [Papanicolaou (Pap) and human papillomavirus (HPV) tests] and two screening methods (organized and spontaneous). The study population includes women aged 25-64 years who underwent CC screening between 2008 and 2010 and/or 2011 and 2013, divided into those who responded to an invitation letter (organized screening) and those who spontaneously underwent testing at a public or private facility (non-programmed screening). Between 2008 and 2010, the response rates increased from 27.7% in 2008 to 44.5% in 2009 and 67.6% in 2010 (P<0.001). Women aged 25-34 years had the lowest response rate, whereas respondents were more frequent among women aged 35-44 and 45-54 years. Significant differences (P<0.001) were identified between organized and spontaneous screening test results with regard to diagnostic categories high-grade squamous intraepithelial lesion (50.5 vs. 49.5%), low-grade squamous intraepithelial lesion (42.8 vs. 57.2%) and undetermined lesion atypical glandular cells (AGC; 57.5 vs. 42.5%) or atypical squamous cells of undetermined significance (ASC-US; 54.2 vs. 45.8%). Compared with spontaneous screening, the organized programme resulted in a larger number of women screened for CC; it reduced the frequency of undetermined diagnoses (AGC, ASC-US), and identified a larger number of high-grade lesions.

HtrA1: Its future potential as a novel biomarker for cancer.

HtrA1 appears to be involved in several physiological processes as well as in the pathogenesis of conditions such as Alzheimer's disease and osteoarthritis. It has also been hypothesized to play a role as a tumor suppressor. This manuscript reviews the current cancer-related HtrA1 research from the methodological and clinical standpoints including studies regarding its potential role as a tumor marker and/or prognostic factor. PRISMA method was used for study selection. The articles thus collected were examined and selected by two independent reviewers; any disagreement was resolved by a methodologist. A laboratory researcher reviewed the methods and laboratory techniques. Fifteen studies met the inclusion criteria and concerned the following cancer sites: the nervous system, bladder, breast, esophagus, stomach, liver, endometrium, thyroid, ovaries, pleura, lung and skin. Most articles described in vivo studies using a morphological approach and immunohistochemistry, whereas protein expression was quantified as staining intensity scored by two raters. Often the results were not comparable due to the different rating scales and study design. Current research on HtrA1 does not conclusively support its role as a tumor suppressor.

A large cross-sectional survey investigating the knowledge of cervical cancer risk aetiology and the predictors of the adherence to cervical cancer screening related to mass media campaign.

OBJECTIVES: The aims of this study were to compare the characteristics of women who got a Pap-test during the mass media campaign, carried out in an Italian region by broadcasts advertising, and two years later and to identify the determinants of knowledge of cervical cancer etiology and of the adherence to the mass media campaign. METHODS: A cross-sectional survey was carried out through a self-administered questionnaire. RESULTS: A total of 8570 randomly selected women were surveyed, 823 of these had a Pap-test during the mass media campaign period and 7747 two years later. Higher educational level, being not married, and living in urban areas were the main independent characteristics associated with a higher level of knowledge of cervical cancer etiology, although a previous treatment following a Pap smear abnormality was the strongest predictor (OR=2.88; 95% CI: 2.43-3.41). During the campaign period women had the Pap-test more frequently as a consequence of the mass media campaign (OR=8.28; 95% CI; 5.51-12.45). CONCLUSIONS: Mass media campaign is a useful tool to foster cervical screening compliance; however, its short-term effect suggests repeating it regularly.

Knowledge, attitude and practice in primary and secondary cervical cancer prevention among young adult Italian women.

In Italy since 2007 vaccination against human papillomavirus (HPV) is offered to 11-year-old females, whereas vaccination for older age groups is still a matter of debate. To assess Italian young women's knowledge, attitudes and practice regarding primary and secondary cervical cancer prevention a cross-sectional study among young women aged 18-26 years was conducted in 2008. The survey collected information on in-depth awareness and knowledge regarding Pap testing, HPV infection, HPV vaccine and cervical cancer. The response rate was 57.7% with a wide range of variability (34-84%) amongst local health units. Among 667 women who participated in the survey poor awareness and various misconceptions regarding HPV and cervical cancer prevention were detected. Overall women were found to be more knowledgeable about Pap smears and cervical cancer than about HPV infection and the HPV vaccine. Respondents pointed to their healthcare providers as their most trusted source for medical information. Understanding women's knowledge on cervical cancer prevention, as well as related factors is important in helping to achieve and maintain adherence to cervical cancer preventive strategies. Moreover in order to minimize cervical cancer risk by improving women's adherence to preventive strategies, appropriate and adequate information dissemination, and guidance from health professionals appear to be crucial elements.

Distribution of high and low risk HPV types by cytological status: a population based study from Italy.

BACKGROUND: HPV type distribution by cytological status represents useful information to predict the impact of mass vaccination on screening programs. METHODS: women aged from 25 to 64 who attended cervical cancer screening in five different Italian regions were tested for HPV infection with Hybrid Capture II (HCII) low and high risk probes. Women repeating Pap-test upon unsatisfactory or positive results, or as a post-treatment and post-colposcopy follow-up analysis, were excluded from our study. High risk (HR) HPV positive samples were typed using GP5+/GP6+ primed PCR, followed by Reverse Line Blot for 18 high/intermediate risk HPV types, while low risk (LR) HPV positive samples were tested with type specific primers for HPV6 and HPV11. RESULTS: 3410 women had a valid HCII and Pap-test. The prevalence of HR and LR infections was 7.0% and 3.6%, 29.1% and 13.7%, 68.1% and 31.9%, 60.0% and 0.0%, 65.0% and 12.0%, for negative, ASC-US, L-SIL, ASC-H and H-SIL cytology, respectively. The fraction of ASC-US+ cytology due to HPV 16 and 18 ranged from 11.2 (HPV 16/18 alone) to 15.4% (including HPV 16/18 in co-infection with other virus strains), and that due to HPV 6 and 11 ranged from 0.2% (HPV 6/11 alone) to 0.7% (including HPV 6/11 in co-infection with other LR virus strains). CONCLUSIONS: mass vaccination with bivalent or quadrivalent HPV vaccine would modestly impact on prevalence of abnormal Pap-test in screening.

Estimated acceptance of HPV vaccination among Italian women aged 18-26 years.

In Italy vaccination against human papillomavirus (HPV) was introduced in the national immunization programme in 2007; the primary target for this vaccination is 11-year-old females, whereas vaccination for older age groups is still a matter of debate. This project was carried out in the period 2007-2009 to estimate the acceptance rate among 18-26-year-old, to whom free-of-charge vaccination was actively offered. Socio-demographic factors associated with acceptance were also investigated. A sample of 1159 women was randomly selected from resident population lists of 10 Local Health Units in 6 of Italy's 21 Regions; 1032 women were deemed eligible for the study. Of the eligible women, 580 received at least one vaccine dose for an acceptance rate of 56.2% and 542 received all three vaccine doses (52.6%). The acceptance rate was significantly higher for: residents of northern and central Italy (OR(adj)=2.22, 95%CI 1.64-3.01 and OR(adj)=1.77, 95%CI, 1.20-2.61 respectively), compared to southern Italy; women with a high educational level (OR(adj)=1.41; 95%CI: 1.02-1.93); and students (OR(adj)=1.64; 95%CI: 1.13-2.37). The low immunization rate highlights the difficulties of reaching young adult women, although the current coverage rates observed in the primary target population of HPV vaccination campaign (64%) emphasize that achieving high coverage rates is challenging also in younger age groups. Our results suggest that it would be premature to extend the active free-of-charge offer of HPV vaccination to older women and that efforts should be focused on the priority target, considering that the objective of 95% coverage established for this age group is still far from being attained.