Comparison of HPV-positive triage strategies combining extended genotyping with cytology or p16/ki67 dual staining in the Italian NTCC2 study.

BACKGROUND: Each high-risk HPV genotype has different oncogenic potential, and the risk of CIN3+ varies according to genotype. We evaluated the performance of different strategies of HPV-positivity triage combining cytology, p16/ki67 dual staining (DS), and extended genotyping. METHODS: Samples from 3180 consecutive women from the NTCC2 study (NCT01837693) positive for HPV DNA at primary screening, were retrospectively analyzed by the BD Onclarity HPV Assay, which allows extended genotyping. Genotypes were divided into three groups based on the risk of CIN3+. HPV DNA-positive women were followed up for 24 months or to clearance. FINDINGS: Combining the three groups of genotypes with cytology or DS results we identify a group of women who need immediate colposcopy (PPV for CIN3+ from 7.8 to 20.1%), a group that can be referred to 1-year HPV retesting (PPV in those HPV-positive at retesting from 2.2 to 3.8), and a group with a very low 24-month CIN3+ risk, i.e. 0.4%, composed by women cytology or DS negative and positive for HPV 56/59/66 or 35/39/68 or negative with the Onclarity test, who can be referred to 3-year retesting. INTERPRETATION: Among the baseline HPV DNA positive/cytology or DS negative women, the extended genotyping allows to stratify for risk of CIN3+, and to identify a group of women with a risk of CIN3+ so low in the next 24 months that they could be referred to a new screening round after 3 years. FUNDING: Italian Ministry of Health (grant number RF-2009-1536040). Hologic-Genprobe, Roche Diagnostics, and Becton & Dickinson provided financial and non-financial support.

Testing behavioral economics messages to increase non-responders' participation in organized colorectal cancer-screening programs: A randomized controlled trial.

This study aimed to evaluate the impact of behavioral economic-inspired messages on participation in colorectal cancer (CRC) screening programs. We conducted a randomized-controlled trial involving 11,505 non-responders to the CRC screening programs in Florence, Rome, and Turin in 2020. Participants aged 54-70 years were randomly assigned to four conditions. Individuals in the control conditions received a standard invitation letter while the three intervention groups included an additional paragraph featuring either i. normative feedback [F] message (giving feedback that invited subjects did not participate); ii. Minority norm [MN] message (only a minority did not participate); iii. F+ MN message (combining both messages). The primary outcome was the screening participation rate 90 days after the invitation was completed. A multivariate analysis was conducted adjusting for gender, age and birthplace. Overall, screening participation rates were 5.3% in the control condition, 7.0% in the F, 8.2% in the MN, and 7.4% in the F + MN arms (p = 0.002). Invited subjects in the MN arm were more likely to participate (adjusted Odds Ratio[aOR] = 1.38; 95% Confidence Interval [95%CI,1.13-1.68]), particularly those aged 54-59 years (aOR = 1.52; 95%CI:1.16-1.98), and 60-64 (aOR = 1.57; 95%CI:1.62-; 95%CI: 1.06-2.48). Additionally, individuals aged 60-64 invited in F and F + MN arms demonstrated a higher likelihood of participation (aOR for F arm = 1.60; 95%CI: 1.06-2.41; aOR for F + MN arm = 1.99; 95%CI: 1.35-2.92). The inclusion of MN and/or F messages in the invitation letter increased participation among previous non-responders <65 years. Behavioral economics is a promising area of interest for enhancing CRC screening participation. TRIAL REGISTRATION: ISRCTN registration number: ISRCTN11841256.

The 5-year risk of recurrence of grade 2/3 cervical intraepithelial neoplasia after treatment in a population screening programme by human papillomavirus status: A cohort study in central Italy.

OBJECTIVES: (a) To estimate the risk of recurrent cervical intraepithelial neoplasia, grade 2/3 or worse (CIN2+/CIN3+), lesions within 5 years of follow-up in human papillomavirus-negative/human papillomavirus-positive cohorts; (b) to assess whether certain risk factors can predict the recurrence of CIN2+/CIN3+ lesions; and (c) to provide recommendations for follow-up after treatment of cervical intraepithelial neoplasia, grade 2/3 to prevent cervical cancer. SETTING: Organized cervical cancer screening programme in Central Italy. METHODS: We included 1063 consecutive first excisional treatments performed between 2006 and 2014 for screening-detected cervical intraepithelial neoplasia, grade 2/3 lesions among women aged 25-65. The study population was divided into two groups according to the human papillomavirus test results performed 6 months after treatment: Human papillomavirus-negative and human papillomavirus-positive cohorts. The 5-year risk of developing cervical intraepithelial neoplasia, grade 2/3 or worse (CIN2+/CIN3+) was estimated using the Kaplan-Meier method and the Cox regression model. RESULTS: Among 829 human papillomavirus-negative and 234 human papillomavirus-positive women, six (0.72%; three cervical intraepithelial neoplasia, grade 2, three cervical intraepithelial neoplasia, grade 3) and 45 (19.2%; 15 cervical intraepithelial neoplasia, grade 2, 30 cervical intraepithelial neoplasia, grade 3), respectively, developed CIN2+ recurrence within 5 years of follow-up. The cumulative risks for CIN2+ and CIN3+ were 0.9% (95% confidence interval: 0.4%-2.0%) and 0.5% (95% confidence interval: 0.1%-1.4%), respectively, for the human papillomavirus-negative cohort, and 24.8% (95% confidence interval: 18.5%-32.7%) and 16.9% (95% confidence interval: 11.4%-24.5%), respectively, for the human papillomavirus-positive cohort. Risk factors associated with increased risk of recurrence were both margins positive for the human papillomavirus-negative cohort, and positive margins, cervical intraepithelial neoplasia, grade 3 lesions, high-grade cytology and high viral load for the human papillomavirus-positive cohort. CONCLUSIONS: Human papillomavirus testing can identify women at increased risk of recurrence and this supports a recommendation for its use in the post-treatment follow-up of cervical intraepithelial neoplasia, grade 2/3 lesions.

The Consensus Project: Participation in cervical cancer screening by the first cohorts of girls offered HPV vaccination at age 15-16 years in Italy.

OBJECTIVE: To evaluate the association between human papillomavirus vaccination status and participation in cervical cancer screening (at age 25) by the first cohorts of girls who were offered vaccination at the age of 15 to 16 years in Italy. METHODS: Women born in 1993, 1994 and 1995 were invited to participate in cervical cancer screening between 2018 and 2020. We report participation in screening by vaccination status in three large areas, Florence province, Piedmont region and Savona province, where the Consensus Project was carried out. The relative risk of participation among vaccinated (≥2 doses) and unvaccinated women was estimated. Odds ratios (OR) of participation by vaccination status were estimated by logistic regression, adjusted by birthplace and birth cohort. RESULTS: Overall, 34,993 women were invited for screening: 13,006 (37.2%) participated and 10,062 of these agreed to participate in the Consensus intervention study. Among the invited women and screening participants, vaccinated women were 51.0% and 60.6%, respectively. Comparing vaccinated and unvaccinated women, the adjusted OR of screening participation was 1.80 (95% confidence interval (CI): 1.72-1.89), 2.17 (95% CI: 1.94-2.42), 1.59 (95% CI: 1.50-1.68) and 1.15 (95% CI: 0.86-1.54) for overall, Florence, Piedmont and Savona, respectively. About 33% of the invited women were unvaccinated and did not participate in screening: 25.8%, 59.5% and 64.2% of women born in Italy, in high migration pressure countries and in advanced development countries, respectively. CONCLUSIONS: Screening participation was higher among vaccinated than unvaccinated women. Active policies are needed to reduce inequalities, targeting the unscreened and unvaccinated population, particularly non-native women, to accelerate cervical cancer elimination in Italy.

Performance of HPV E6/E7 mRNA assay as primary screening test: Results from the NTCC2 trial.

As the primary screening test, E6/E7 mRNA has shown similar sensitivity for CIN3+ and lower positivity rate than the HPV DNA test. Nevertheless, the overall mRNA positivity is too high for immediate colposcopy, making a triage test necessary. The aim was to estimate the mRNA performance as a primary test with different triage strategies. All HPV DNA-positives were tested for mRNA, cytology and p16/ki67. A sample of HPV DNA-negatives was also tested for mRNA to estimate test specificity. We included all CIN3+ histologically diagnosed within 24 months since recruitment. Of the 41 127 participants, 7.7% were HPV DNA-positive, of which 66.4% were mRNA-positive. Among the HPV DNA-negatives, 10/1108 (0.9%) were mRNA-positive. Overall, 97 CIN3+ were found. If mRNA was used as the primary test, it would miss about 3% of all CIN3+ with a 22% reduction of positivity compared with HPV DNA. The weighted specificity estimate for

Implementation of a centralized HPV-based cervical cancer screening programme in Tuscany: First round results and comparison with the foregoing Pap-based screening programme.

OBJECTIVE: To evaluate performance of the first round of HPV-based screening in Tuscany region and compare it with the prior round of Pap-based screening. SETTING: Tuscany region of Italy, where HPV-based cervical cancer screening started in 2013, with a strong level of centralization screening tests at the Regional Laboratory for Cancer Prevention (ISPRO). METHODS: The transition from Pap- to HPV-based screening was initiated for older women and at 3 out of 12 Tuscany Local Health Units (LHUs). Data from the Florence and Grosseto LHUs (about 300,000 women) were analysed and performance screening indicators estimated. RESULTS: HPV-based indicators recorded good performance, with increased compliance vs. the Pap-based programme. We registered a substantial decrease in waiting times from sampling to test reporting, probably related to the centralization strategy. Since the screening protocol was the same and conducted at a single laboratory, we could hypothesize that the difference in HPV positivity (6.8% in Florence vs. 8.4% in Grosseto) was due to a real difference in HPV prevalence among women of the two LHUs. The transition to HPV-based screening led to a significant increase both in colposcopy referral rate (4.3% vs. 1.2%) and CIN2+ detection rate (8.3‰ vs. 3.4‰). CONCLUSIONS: HPV-based is more effective in detecting high-grade precancerous and cancerous lesions than Pap-based screening and is characterized by an "anticipatory effect" in the detection of CIN2+ lesions. The transition from Pap-based to HPV-based screening programme should include increased resources dedicated to colposcopy services. Centralization in a laboratory with long experience in this field promotes efficiency of the screening process.

p16/ki67 and E6/E7 mRNA Accuracy and Prognostic Value in Triaging HPV DNA-Positive Women.

BACKGROUND: The study presents cross-sectional accuracy of E6 and E7 (E6/E7) mRNA detection and p16/ki67 dual staining, alone or in combination with cytology and human papillomavirus (HPV)16/18 genotyping, as a triage test in HPV DNA-positive women and their impact on cervical intraepithelial neoplasia (CIN2+) overdiagnosis. METHODS: Women aged 25-64 years were recruited. HPV DNA-positive women were triaged with cytology and tested for E6/E7 mRNA and p16/ki67. Cytology positive women were referred to colposcopy, and negatives were randomly assigned to immediate colposcopy or to 1-year HPV retesting. Lesions found within 24 months since recruitment were included. All P values were 2-sided. RESULTS: 40 509 women were recruited, and 3147 (7.8%) tested HPV DNA positive; 174 CIN2+ were found: sensitivity was 61.0% (95% confidence interval [CI] = 53.6 to 68.0), 94.4% (95% CI = 89.1 to 97.3), and 75.2% (95% CI = 68.1 to 81.6) for cytology, E6/E7 mRNA, and p16/ki67, respectively. Immediate referral was 25.6%, 66.8%, and 28.3%, respectively. Overall referral was 65.3%, 78.3%, and 63.3%, respectively. Cytology or p16/ki67, when combined with HPV16/18 typing, reached higher sensitivity with a small impact on referral. Among the 2306 HPV DNA-positive and cytology-negative women, relative CIN2+ detection in those randomly assigned at 1-year retesting vs immediate colposcopy suggests a -28% CIN2+ regression (95% CI = -57% to +20%); regression was higher in E6/E7 mRNA-negatives (Pinteraction = .29). HPV clearance at 1 year in E6/E7 mRNA and in p16/ki67 negative women was about 2 times higher than in positive women (Pinteraction < .001 for both). CONCLUSIONS: p16/ki67 showed good performance as a triage test. E6/E7 mRNA showed the highest sensitivity, at the price of too high a positivity rate to be efficient for triage. However, when negative, it showed a good prognostic value for clearance and CIN2+ regression.

Characterization of cervico-vaginal microbiota in women developing persistent high-risk Human Papillomavirus infection.

Changes in cervico-vaginal microbiota with Lactobacillus depletion and increased microbial diversity facilitate human papillomavirus (HPV) infection and might be involved in viral persistence and cancer development. To define the microbial Community State Types (CSTs) associated with high-risk HPV-persistence, we analysed 55 cervico-vaginal samples from HPV positive (HPV+) women out of 1029 screened women and performed pyrosequencing of 16S rDNA. A total of 17 samples from age-matched HPV negative (HPV-) women were used as control. Clearance or Persistence groups were defined by recalling women after one year for HPV screening and genotyping. A CST IV subgroup, with bacterial genera such as Gardnerella, Prevotella, Megasphoera, Atopobium, frequently associated with anaerobic consortium in bacterial vaginosis (BV), was present at baseline sampling in 43% of women in Persistence group, and only in 7.4% of women in Clearance group. Atopobium genus was significantly enriched in Persistence group compared to the other groups. Sialidase-encoding gene from Gardnerella vaginalis, involved in biofilm formation, was significantly more represented in Persistence group compared to the other groups. Based on these data, we consider the CST IV-BV as a risk factor for HPV persistence and we propose Atopobium spp and sialidase gene from G. vaginalis as microbial markers of HPV-persistence.

Determinants of Viral Oncogene E6-E7 mRNA Overexpression in a Population-Based Large Sample of Women Infected by High-Risk Human Papillomavirus Types.

Cervical cancer screening by human papillomavirus (HPV) DNA testing with cytology triage is more effective than cytology testing. Compared to cytology, the HPV DNA test's higher sensitivity, which allows better protection with longer intervals, makes it necessary to triage the women with a positive result to compensate its lower specificity. We are conducting a large randomized clinical trial (New Technologies for Cervical Cancer 2 [NTCC2]) within organized population-based screening programs in Italy using HPV DNA as the primary screening test to evaluate, by the Aptima HPV assay (Hologic), the use of HPV E6-E7 mRNA in a triage test in comparison to cytology. By the end of June 2016, data were available for 35,877 of 38,535 enrolled women, 2,651 (7.4%) of whom were HPV DNA positive. Among the samples obtained, 2,453 samples were tested also by Aptima, and 1,649 (67.2%) gave a positive result. The proportion of mRNA positivity was slightly higher among samples tested for HPV DNA by the Cobas 4800 HPV assay (Roche) than by the Hybrid Capture 2 (HC2) assay (Qiagen). In our setting, the observed E6-E7 mRNA positivity rate, if used as a triage test, would bring a rate of immediate referral to colposcopy of about 4 to 5%. This value is higher than that observed with cytology triage for both immediate and delayed referrals to colposcopy. By showing only a very high sensitivity and thus allowing a longer interval for HPV DNA-positive/HPV mRNA-negative women, a triage by this test might be more efficient than by cytology.

Cervical cancer screening in immigrant women in Italy: a survey on participation, cytology and histology results.

Cervical cancer screening programmes in Italy actively invite all 25-64-year-old resident women for the Pap test every 3 years irrespective of their citizenship. Immigrant women come from countries where screening is absent or poorly implemented and the prevalence of human papillomavirus is often high. These women therefore have significant risk factors for cervical cancer. The Italian Group for Cervical Cancer Screening promoted a survey of all the screening programmes on the participation and the positivity and detection rates in Italian and foreign women in 2009-2011. Aggregated data for participation, cytology results, compliance with colposcopy and histology results were collected, distinguishing between women born in Italy and abroad. All comparisons were age adjusted. Forty-eight programmes out of 120 participated in the immigrant survey, with 3 147 428 invited and 1 427 412 screened Italian women and 516 291 invited and 205 948 screened foreign women. Foreign women had a slightly lower participation rate compared with Italians (39.9 vs. 45.4%), whereas compliance with colposcopy was similar (90%). Foreigners showed a higher risk of pathological findings than Italians: cytology positivity [relative risk (RR)=1.25, 95% confidence interval (CI) 1.24-1.27] and detection rate for cervical intraepithelial neoplasia grade 2 (CIN2) (RR=1.39, 95% CI 1.31-1.47), CIN3 (RR=2.07, 95% CI 1.96-2.18) and cancer (RR=2.68, 95% CI 2.24-3.22). The ratio between cancer and CIN was higher in immigrants (0.06 vs. 0.04, P<0.01). Foreign women had a higher risk of cervical precancer and cancer. Because of their high risk and because opportunistic screening does not cover this often disadvantaged group, achieving high participation in screening programmes for foreigners is critical to further reducing the cervical cancer burden in Italy.

hr-HPV testing in the management of women with ASC-US+ and in the follow-up of women with cytological abnormalities and negative colposcopy. Recommendations of the Italian group for cervical cancer screening (GISCi).

Compared to spontaneous screening, an organized screening programme is characterized by the presence of protocols and recommendations for all stages including follow-up. Despite the availability of well-functioning screening programmes throughout the country, the follow-up protocol after an abnormal Pap test and negative colposcopy is not clearly defined in Italy, and there is no uniformity of indications. HPV testing for oncogenic human papillomavirus (hr-HPV) has a high negative predictive value (NPV) and high positive predictive value (PPV) for CIN2+ and its employment can reduce follow-up assessments. In order to provide indications about the management of women with ASC-US+ and the follow-up of women with cytological abnormalities and negative colposcopy, a literature analysis was carried out, taking into consideration European and American guidelines and good practice recommendations from the most important scientific associations and regulatory agencies. GISCi (Italian Group for Cervical Screening) drafted recommendations for the management of women with ASC-US, L-SIL, ASC-H, AGC, and H-SIL until their return to the routine screening interval. This protocol can be applied not only in the management of abnormal Pap smears in cytology-based programmes, but also in the management of abnormal Pap test triage after HPV positive test when HPV is the primary screening test. The protocols approved within the screening programmes must have an extensive consensus among all involved professionals, including any that women might meet outside the programme.

Human papillomavirus prevalence in paired urine and cervical samples in women invited for cervical cancer screening.

With the introduction of Human papillomavirus (HPV) vaccination in young girls in 2007, it is important to monitor HPV infections and epidemiological changes in this target population. The present study has evaluated the detection of human papillomavirus DNA in paired cervical and urine samples to understand if HPV testing in urine could be used as non-invasive method to monitor HPV status in young women. The study enrolled 216 twenty five-year-old women, resident in Florence and invited for the first time to the cervical cancer Screening Program within a project evaluating the impact of HPV vaccination. HPV genotyping was performed on 216 paired urine and cervical samples. The overall concordance between cervix and urine samples, investigated by HPV genotyping (INNO-LiPA HPV Genotyping Extra), was: 85.6% (184/215), 84.6% (182/215), 80% (172/215) when the same HPV, at least the same HR HPV and all HR HPV, respectively, were detected. HPV type specific concordance in paired urine and cervical samples was observed in 85.8% (175/204) of women with normal cytology and in seven out of nine women with abnormal cytology. Urine seems to be a suitable and reliable biological material for HPV DNA detection as evidenced by the high concordance with HPV detected in cervical samples. These results suggest that urine could be a good noninvasive tool to monitor HPV infection in vaccinated women.

Participation and risk of high grade cytological lesions among immigrants and Italian-born women in an organized cervical cancer screening program in Central Italy.

Few studies analyzed the risk for high-grade squamous intraepithelial lesions or worse (HSIL+) among immigrants and natives attending organized cervical cancer (CC) screening programs (SP). We evaluated participation and diagnosis of HSIL+ by country of birth with logistic models. Overall 540,779 invitation letters were delivered to target women of Florence SP in three screening rounds (years 2000-2002, 2003-2005, 2006-2008). The probability of attending screening was lower for immigrants than natives, but the difference decreased from 35% (1st round) to 20% (2nd-3rd round) for women born in high migration pressure (HMP) countries. The risk of HSIL+ was double than natives for HMP-born women from countries with high prevalence of human papillomavirus, even adjusting for age and previous history of Pap test. This is an important public health problem due to an increasing proportion over time of immigrant women with a lower attendance and greater risk for CC.

The Pap smear screening as an occasion for smoking cessation and physical activity counselling: effectiveness of the SPRINT randomized controlled trial.

BACKGROUND: The organized Cervical Cancer Screening Programme (CCSP) in Italy might represent an occasion to deliver smoking cessation (SC) counselling to women attending the Pap test examination. Evidence of effectiveness of physical activity (PA) promotion and intervention in adjunct to SC counselling is not strong.Objective of the SPRINT trial was to evaluate the effectiveness of a standard SC counselling intervention delivered by trained midwives in the CCSP, and whether the adjunct of a PA counselling to the SC counselling might increase quit rates. METHODS/DESIGN: We undertook a randomized controlled trial of 1,100 women undergoing the Pap examination in the three study centres Florence, Turin, and Mantua: 363 were randomly assigned to the SC counselling arm, 366 to the SC + PA counselling arm, and 371 to the control group. The intervention was a standard brief SC counselling combined with a brief counselling on increasing PA, and was tailored according to the Di Clemente-Prochaska motivational stages of change for SC and/or PA. Primary outcomes were quit rates, improvement in the motivational stages of change for SC, and reduced daily cigarette consumption. Analysis was by intention to treat. RESULTS: Participants randomized in both intervention arms and in the preparation stage of change for SC doubled their likelihood of quitting at 6-month follow-up in comparison to controls (odds ratio [OR]=2.1, 95% confidence interval [95% CI]:1.0-4.6). Moreover, participants in the intervention arms and in the contemplation stage were more likely to reduce their daily cigarette consumption after the intervention (OR=1.8, 95% CI:1.1-3.0). Our study did not show any effect of PA counselling on various outcomes. CONCLUSIONS: Smoking cessation counselling delivered by midwives to smokers in preparation and contemplation stages of change during the Pap-smear screening was effective and should be recommended, given the high number of women attending the cervical cancer screening programme in Italy. Moreover, the daily number of women invited for the Pap-smear examination should be slightly lowered, in order to let midwives deliver SC counselling to smokers. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52660565.

Cervical cancer screening visit as an occasion for counseling female smokers to quit.

AIMS AND BACKGROUND: In the last decades in Italy, a smaller decrease in smoking among women than in men has been observed and a younger age at start in young women. Nevertheless, gender-specific strategies for smoking cessation have rarely been developed, except those for pregnant women. A study was conducted to evaluate the feasibility of carrying out an intervention of primary prevention by counseling for smoking cessation the female smokers attending cervical cancer screening programs in Florence, Italy. METHODS: All female smokers attending the services for cervical cancer prevention at the Cancer Prevention and Research Institute in Florence, Italy, between March 2004 and January 2005, who volunteered to participate in the study, received a brief motivational stage-matched counseling for smoking cessation and a face to face interview at enrollment and after 6 and 12 months. The counseling was evaluated by comparing quit rates, changes in smoking intensity, and motivation to quit at the first and second follow-up periods to the same data collected at enrollment. Multivariate logistic regression analysis was performed to estimate the influence on smoking cessation of demographic characteristics, smoking habit and attitude to quit. RESULTS: 177 women participated in the study. After 1 year, a quit rate of 12.4% (95% CI, 7.5-17.3) was observed. Among those who never quit, there was a 39.3% reduction in the average daily cigarette consumption and a 51.9% reduction in smoking the first cigarette of the day immediately on awaking or just after breakfast. CONCLUSIONS: The results and the opportunity to contact a large number of female smokers on the occasion of cervical cancer screening suggest the importance to evaluate the efficacy of the intervention of primary prevention in this health setting.

[Methods to increase participation in cancer screening programmes]. / Metodi per aumentare la partecipazione ai programmi di screening oncologici.

OBJECTIVE: to synthesize scientific evidences about methods to increase cervical, breast and colorectal cancer screening participation. METHODS: a multidisciplinary working group has been set up to define the scope of the report and to conduct the evaluation. The scope and the final evaluation have been submitted to a stakeholder committee, including the Ministry of Health, the National Screening Observatory, regional screening program coordinators, scientific societies, and Lega Italiana Lotta ai Tumori, for comments and integrations. A systematic review of the principal biomedical and social literature databases was conducted to identify experimental and observational studies, updating the existing review by Jepson and coll. (Health Technol Assess. 2000;4(14):i-vii, 1-133). RESULTS: 5900 have been identified, 900 relevant for the topic.Among those, 148 reported quantitative information on intervention efficacy, other 90 came from the previous review. Organised screening programmes, based on invitation letter or on GP involvement,were consistently effective in increasing participation compared to spontaneous screening. Interventions are classified according to their target: individual, community, test simplification, health operators, health service organization. The report presents meta-analyses on efficacy, analyses of cost-effectiveness, impact on organisation and social inequality, and ethical and legal issues, of all the intervention reported in the literature. CONCLUSIONS: there are several interventions consistently effective in any context, some of them have minimal impact on costs and health service resources.

[Extension of organised cervical cancer screening programmes in Italy and their process indicators, 2010 activity]. / Estensione dei programmi organizzati di screening del cancro cervicale in Italia e loro indicatori di processo, attività 2010.

Italian national guidelines recommend to regions the implementation of organised screening programmes for cervical cancer. As in previous years since 1998 we collected aggregated tables of data from Italian organised cervical screening programmes in order to centrally compute process indicators. Data on women invited during 2010 and screened up to April 2011 were considered. In 2010, the target population of Italian organised screening programmes included 13,538,080 women, corresponding to 80.1% of Italian women aged 25-64 years. Compliance to invitation was 39.8%, with a strong North-South decreasing trend. However, it should be considered that many women are screened outside organised programmes. Among screened women, 4.7% were referred for repeat cytology and 62.7% of them complied; 2.5% of screened women were referred to colposcopy. Compliance with colposcopy referral was 85.9% among women referred because of ASC-US or more severe cytology and 88.7% among those referred because of HSIL or more severe cytology. The positive predictive value (PPV) of referral because of ASC-US or more severe cytology for CIN2 or more severe histology was 16.0%. The unadjusted detection rate of CIN2 or more severe histology was 3.2 per 1,000 screened women (3.5 standardised on the Italian population, truncated 25-64).

The Pap smear screening as an occasion for smoking cessation and physical activity counselling: baseline characteristics of women involved in the SPRINT randomized controlled trial.

BACKGROUND: Gender-specific smoking cessation strategies have rarely been developed. Evidence of effectiveness of physical activity (PA) promotion and intervention in adjunct to smoking cessation programs is not strong. SPRINT study is a randomized controlled trial (RCT) designed to evaluate a counselling intervention on smoking cessation and PA delivered to women attending the Italian National Health System Cervical Cancer Screening Program. This paper presents study design and baseline characteristics of the study population. METHODS/DESIGN: Among women undergoing the Pap examination in three study centres (Florence, Turin, Mantua), participants were randomized to the smoking cessation counselling [S], the smoking cessation + PA counselling [S + PA], or the control [C] groups. The program under evaluation is a standard brief counselling on smoking cessation combined with a brief counselling on increasing PA, and was delivered in 2010. A questionnaire, administered before, after 6 months and 1 year from the intervention, was used to track behavioural changes in tobacco use and PA, and to record cessation rates in participants. DISCUSSION: Out of the 5,657 women undergoing the Pap examination, 1,100 participants (55% of smokers) were randomized in 1 of the 3 study groups (363 in the S, 366 in the S + PA and 371 in the C groups). The three arms did not differ on any demographic, PA, or tobacco-use characteristics. Recruited smokers were older, less educated than non-participant women, more motivated to quit (33% vs.9% in the Preparation stage, p < 0.001), smoked more cigarettes per day (12 vs.9, p < 0.001), and were more likely to have already done 1 or more quit attempts (64% vs.50%, p < 0.001). The approach of SPRINT study appeared suitable to enrol less educated women who usually smoke more and have more difficulties to quit. TRIAL REGISTRATION NUMBER: ISRCTN: ISRCTN52660565.

Extension of organised cervical cancer screening programmes in Italy and their process indicators, 2009 activity.

Italian national guidelines recommend to regions the implementation of organised screening programmes for cervical cancer. As in previous years since 1998, we collected from Italian organised cervical screening programmes aggregated tables of data in order to centrally compute process indicators. Data on women invited during 2009 and screened up to April 2010 were considered. In 2009, the target population of Italian organised screening programmes included 13,120,269 women, corresponding to 78.0%of Italian women aged 25-64 years. Compliance to invitation was 39.3%, with a strong North-South decreasing trend. However, it should be considered that many women are screened outside the organised programmes. Of the women screened, 4.7%were referred for repeat cytology and 60.8% of them complied; 2.4% of screened women were referred to colposcopy. Compliance with colposcopy referral was 85.1% among women referred because of ASC-US or more severe cytology and 89.3% among those referred because of HSIL or more severe cytology. The positive predictive value (PPV) of referral because of ASC-US or more severe cytology for CIN2 or more severe histology was 16.2%. The unadjusted detection rate of CIN2 or more severe histology was 3.2 per 1,000 screened women (3.2 standardised on the Italian population, truncated 25-64).