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The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries - a trend virtually restricted to women aged50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy.Thirty-eight local cancer registries, currently covering 15,274,070 women, equivalent to 49.2% of the Italian national female population, participated. Invasive cancers registered between 1990 and 2015 with an International Classification of Diseases for Oncology, 3rd revision, topography code C51 and morphology codes compatible with vulvar squamous cell carcinoma (n = 6294) were eligible. Incidence trends were analysed using joinpoint regression models, with calculation of the estimated annual percent change (EAPC), and age-period-cohort models.Total incidence showed a regular and significant decreasing trend (EAPC, -0.96; 95% confidence interval (CI), -1.43 to -0.48). This was entirely accounted for by women aged ≥60 years (EAPC, -1.34; 95% CI, -1.86 to -0.81). For younger women, the EAPC between 1990 and 2012 was 1.20 (95% CI, 0.34 to 2.06) with a non-significant acceleration thereafter. This pattern did not vary substantially in a sensitivity analysis for the effect of geographic area and duration of the registry. The age-period-cohort analysis revealed a risk decrease in cohorts born between 1905 and 1940 and a new increase in cohorts born since 1945.The decreasing trend observed among older women and the resulting decrease in total rate are at variance with reports from most Western countries. Age-period-cohort analysis confirmed a decreasing trend for earliest birth cohorts and an opposite one for recent ones.

Background The European guidelines for quality assurance in colorectal cancer (CRC) screening recommend that interval cancer rate be expressed as a proportion of background incidence rate. Aim To determine the crude and adjusted proportional incidence of interval CRC in an Italian regional two-yearly faecal immunochemical test (FIT) screening programme. Methods The programme (year of implementation, 2005) is targeted at over 1,000,000 people aged 50–69 years. The test is a one-sample OC-Sensor (Eiken Chemical Co., Tokyo, Japan). The study covered one-third of the regional area. Excerpts of 434,295 eligible negative FIT records dated 2005–2012 from 193,193 subjects were retrieved from the regional CRC screening data warehouse. By 31 December 2013, the cohort accumulated 198,302 man-years and 235,370 woman-years. Interval CRCs were identified by record-linkage with the local population-based cancer registry. Their number was divided by the expected number, estimated with age-period-cohort models, to obtain the proportional incidence. Results The proportional incidence of interval CRC for men and women was, respectively, 0.06 (95% confidence interval (CI), 0.04–0.09) and 0.17 (95% CI, 0.13–0.23) in the first interval year, and 0.21 (95% CI, 0.16–0.26) and 0.28 (95% CI, 0.22–0.36) in the second year. Conclusions The results were acceptable and in line with previous studies.

Background An increased risk of death by suicide in cancer patients has been documented since decades. We evaluated the risk of death by suicide in an Italian population-based cancer case series and added the results to a systematic review and meta-analysis of the literature. Methods The Italian series, including 127,042 primary cancer patients diagnosed between 1996 and 2014, was obtained from the Romagna Cancer Registry (northern Italy). Standardised mortality ratios (SMRs) were calculated. Regarding the systematic review and meta-analysis, the PubMed database was searched for English language studies published up to 2017. Fifty-seven potentially eligible papers were reviewed in full, and 19 of them were selected for analysis. The SMR was the first outcome, replaced by rate ratio if the SMR was not available. Findings In the Italian case series, an increased suicide risk was found for both sexes combined (SMR = 1.5; 95% confidence interval [CI]: 1.3–1.8), for males (SMR = 1.6; 95% CI: 1.4–1.9) but not females (SMR = 1.1; 95% CI: 0.7–1.7), for patients aged ≥55 years, with poor prognosis and advanced-stage disease and during the first year after diagnosis. The absolute excess risk of suicide was 0.9 per 10,000 patient-years. Multivariate analysis confirmed the role of univariate factors except for poor prognosis. Meta-analysis showed a strong heterogeneity between studies. The risk was significantly elevated for both sexes combined (pooled SMR = 1.7; 95% CI: 1.5–1.9), men (pooled SMR = 1.8; 95% CI: 1.6–2.0) and women (pooled SMR = 1.4; 95% CI: 1.3–1.6). There was no evidence for small-study effects. Interpretation The Italian study confirmed the previous common finding that cancer patients are at increased risk for suicide. A clinical multidisciplinary approach to support them is needed.

The European Commission Initiative on Breast Cancer recommendation for triennial screening of women aged 70–74 is based on very weak evidence. A cohort of Italian women who had their last biennial screening mammography at age 68–69 was followed up for 5 years, assumed to represent the interval to another hypothetical screening mammography, in order to determine the annual proportional incidence of interval breast cancer. The cohort included 118,370 women. They had their last mammography between 1997 and 2008. Incident breast cancers were identified by record-linking the cohort with the regional breast cancer registry. The expected incidence in the age range 65–74 was estimated with an age-period-cohort model. The number of interval cancers was divided by the expected number to obtain their proportional incidence. Overall, there were 298,658 woman-years at risk with 371 interval cancers versus 988.8 expected. In the first, second, third, fourth, and fifth interval year, the proportional incidence was 0.09 (95% confidence interval, 0.06–0.13), 0.32 (0.25–0.39), 0.60 (0.49–0.73), 0.75 (0.60–0.92), and 0.81 (0.60–1.07), respectively. Between the second and the fifth year, tumour stage and molecular subtype did not change significantly. Though not supported by these findings, the proposal of triennial screening for women aged 70–74 merits further research, because the 95% confidence interval of the third-year proportional incidence of interval cancer included 0.50—the maximum limit considered acceptable for women aged 50–69. • The third-year incidence of breast cancer relative to the expected one was 0.60 (95% confidence interval, 0.49–0.73). • Between the second and the fifth year, tumour stage and molecular subtype did not change significantly (p >0.10). • The proposal of a 3-year screening interval at age 70–74 merits further evaluation.

Objective To estimate the proportional incidence (PI) of first- and second-year interval breast cancer among women aged 45–49. Methods In the Emilia-Romagna Region (northern Italy), women aged 45–49 are invited to mammography screening annually, and women aged 50–74 biennially. For younger ones, the proportional incidence of interval cancer in the first and unique interval year was calculated using standard methods. For the second, hypothetical year, it was estimated using two different estimates of the ratio between the second- and the first-year proportional incidence observed among women aged 50–54. Overall, 567,151 negative mammography records were used. Results In the first interval year, the observed proportional incidence of interval cancer among women aged 45–49 was 0.27 (95% confidence interval (CI), 0.22–0.33), within the European limit considered desirable for women aged 50–69 (Conclusion The more up-to-date estimate of 0.48, slightly below the maximum limit considered acceptable for women aged 50–69 (

Objectives: Prognostic definition and treatment of breast cancer are supported by multigene testing. A recent trial (TAILORx) provided evidence against the use of adjuvant chemotherapy in early breast cancer (HR+ HER2−) with an intermediate result (11–25) in a multigene test (Oncotype DX). These results consequently fueled great discussion among oncologists. We aimed to estimate the burden of Italian incident breast cancer patients who, each year, may be involved in such decision-making. Methods: We used the data collected in the Romagna Cancer Registry to estimate the number of cases with the inclusion criteria of the TAILORx trial. Adjustments based on geographical variability in breast cancer incidence in Italy were applied to national estimates. Cases were estimated by Oncotype DX recurrence risk groups: ⩽10, 11–25, ⩾26. We also estimated the proportion of grade 1, 2, or 3 disease among breast cancer cases. Results: An overall 52,300 breast cancer cases were estimated to be diagnosed in Italy in 2018. Of these, 18,225 fit the TAILORx inclusion criteria: 3,025 were expected to have a low risk of recurrence (⩽10), 11,536 (63.3% of all cases) an intermediate risk (11–25), and 3,664 a high risk (⩾26). Among the group at intermediate risk, who may benefit from less aggressive therapy, 2,414 were estimated to have grade 1 disease, 7,618 grade 2, and 1,983 grade 3. Conclusions: This article provides reliable estimates on the burden of Italian women with breast cancer who, once tested with multigene testing, could potentially have their treatment changed to hormone therapy only.

Background & Aims We investigated the magnitude and temporal patterns of the decreasing trend in main performance measures of fecal immunochemical test (FIT) screening for colorectal cancer (CRC) observed in second and subsequent rounds. Methods We followed up 494,187 participants from the first round of a regional biennial FIT screening program in Italy (cut-off value for positivity, 20 μg hemoglobin/g feces) for 5 total rounds (2005–2016). At each round, only compliant participants were eligible. Performance measures from the first, third, fourth, and fifth rounds were compared with those from the second round (the first incidence round) using rate ratios from multivariate Poisson regression models and relative risk ratios from multinomial logistic regression models. Results Between the second and the third rounds, a significant 20% to 30% decrease was found in the proportion of men with a positive FIT result (from 5.2% to 4.3%) and in detection rates of advanced adenoma (from 13.4 to 10.2 per 1000), CRC (from 1.7 to 1.4 per 1000), and advanced neoplasia (from 15.1 to 11.6 per 1000). Positive predictive values (PPVs) decreased by 10% or less between the second and third rounds. Detection rates and PPVs for adenoma stabilized by the fourth and fifth rounds. The PPVs for advanced adenoma, CRC, and advanced neoplasia decreased slightly in men and women by the fourth and fifth rounds. The detection rate of proximal colon cancer stabilized after the second round, whereas the detection rate of distal colon cancer decreased until the fourth round in men (from 0.7 to 0.3 per 1000), and the fifth round in women. Conclusions These findings support the notion that FIT screening prevents progression of a subset of advanced adenomas. Screening intensity could be modulated based on results from previous rounds, with a risk-based strategy.

Objectives To report changes in incidence of cervical tumours by disease stage, following the introduction of an organized cytology-based screening programme. Methods An intention-to-screen study of a cytology-based screening programme targeting 1,219,000 women aged 25–64 in northern Italy was carried out. Based on the previously reported trend in total incidence of cervical cancer, the study period 1995–2014 was divided into 1995–1996 (pre-screening, or reference, years), 1997–1998 (screening implementation phase), 1999–2006 (transition phase, when incidence decreased), and 2007–2014 (steady-state phase, when incidence stabilized again). Tumour stage was categorized as preinvasive (cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ), early (pT1a), advanced (pT1b or greater, ypT), and unknown (pT1 not otherwise specified, pTx, missing information). Average annual incidence rates observed in each phase were compared with the expected (reference) rates, using the incidence rate ratio, calculated with a Poisson regression model. Results In the steady-state phase, incidence rate ratios were: CIN3, 1.55 (95% confidence interval, 1.41–1.70); early-stage squamous carcinoma, 0.49 (0.36–0.67); advanced-stage squamous carcinoma, 0.44 (0.33–0.57); unknown-stage squamous carcinoma, 0.69 (0.48–0.99); adenocarcinoma in situ, 1.44 (0.72–2.88); early-stage adenocarcinoma, 2.65 (0.82–8.53); advanced-stage adenocarcinoma, 1.03 (0.56–1.91); and unknown-stage adenocarcinoma, 0.46 (0.23–0.92). Conclusions After stabilization, changes in incidence by tumour stage included a 55% increase for CIN3 and a 50–55% decrease both for early- and advanced-stage squamous carcinoma, but no significant changes for glandular tumours. These data will serve to quantify the incremental impact of the implementation of human papillomavirus-based screening, introduced in 2015.

To compare the results of 5 years of annual mammography screening at age 45–49 with the results of 5 years of biennial screening at age 50–54 and 55–69. In an Italian screening programme, data from 1,465,335 mammograms were analysed. Recall rates, invasive assessment rates, surgical biopsy (including excisional biopsy and definitive surgical treatment) rates, and cancer detection rates were calculated for the first screen (first) and, cumulatively, for the second and subsequent screens (second+). The rate ratios between younger women and the two groups of older ones were (in parentheses, original figures per 1000 mammograms if not otherwise specified): recall rate: first 1.11 (103.6 vs. 93.5) and 1.11 (vs. 93.2), second+ 2.10 (208.9 vs. 99.7) and 2.77 (vs. 75.5); invasive assessment rate: first 0.94 (23.0 vs. 24.5) and 0.94 (vs. 24.6), second+ 1.63 (35.8 vs. 22.0) and 1.56 (vs. 23.0); surgical biopsy rate: first 0.68 (5.9 vs. 8.6) and 0.45 (vs. 13.2), second+ 1.35 (11.5 vs. 8.5) and 0.88 (vs. 13.0); total detection rate: first 0.63 (4.3 vs. 6.7) and 0.37 (vs. 11.7), second+ 1.30 (8.9 vs. 6.8) and 0.74 (vs. 12.0); total positive predictive value of surgical biopsy: first 0.93 (72.8% vs. 78.0%) and 0.82 (vs. 88.9%), second+ 0.96 (77.2% vs. 80.5%) and 0.83 (vs. 92.7%). Younger women experienced two to threefold higher cumulative recall rates at second+ screens and limited differences in surgical biopsy rate. Albeit encouraging, these results must be completed with further investigation, especially on interval cancer incidence. • At repeated screens, cumulative recall rate was two- to threefold higher for younger women. • Differences in cumulative surgical referral and surgical biopsy rates were moderate. • Differences in positive predictive value of surgical biopsy were particularly small.

Background: Miscarriages are an important indicator of reproductive health but only few studies have analyzed their association with exposure to emissions from municipal solid waste incinerators.This study analyzed the occurrence of miscarriages in women aged 15–49 years residing near seven incinerators of the Emilia-Romagna Region (Northern Italy) in the period 2002–2006. Methods: We considered all pregnancies occurring in women residing during the first trimester of pregnancy within a 4 km radius of each incinerator. Addresses were geocoded and exposures were characterized by a dispersion model (ADMS Urban model) producing pollution maps for incinerators based on PM10 stack measurements and for other pollution sources based on NOx ground measurements. Information on pregnancies and their outcomes was obtained from the Hospital Discharge Database. Simplified True Abortion Risks (STAR) × 100 estimated pregnancies were calculated. We ran logistic regressions adjusting for maternal characteristics, exposure to other sources of pollution, and sites, considering the whole population and stratifying by miscarriage history. Results: The study analyzed 11,875 pregnancies with 1375 miscarriages. After adjusting for confounders, an increase of PM10 due to incinerator emissions was associated with an increased risk of miscarriage (test for trend, p = 0.042). The odds ratio for the highest quartile of exposed versus not exposed women was 1.29, 95% CI 0.97–1.72. The effect was present only for women without previous miscarriages (highest quartile of exposed versus not exposed women 1.44, 95% CI 1.06–1.96; test for trend, p = 0.009). Conclusion: Exposure to incinerator emissions is associated with an increased risk of miscarriage. This result should be interpreted with those of a previous study on reproductive health conducted in the same area that observed an association between incinerator exposure and preterm births. Keywords: Miscarriage, Spontaneous abortion, Incinerator exposure, Abortion risk factors

ObjectivesIn Emilia-Romagna, the Human Papillomavirus (HPV) vaccination campaign started in 2008 offering free vaccines for 1996 and 1997 cohorts. Systematic active invitation was implemented for the 1997 cohort. Our study aimed at measuring the impact of the active invitation campaign on HPV vaccine coverage and on coverage inequalities in 11-year-old girls. Second, we evaluated the effect of the HPV vaccination campaign on participation in cervical cancer screening by mothers of target girls.MethodsWe collected information on vaccination status for girls residing in Reggio Emilia in 2008 and mothers’ screening history, before and after the 2008 vaccination campaign. Log-binomial regression models were performed to estimate Relative Risk (RR) and 95% confidence intervals (CIs) of being vaccinated as regarded citizenship, siblings, mothers’ education, marital status and screening history, stratified by birth cohort. We also calculated RR of receiving a Pap test after the vaccination campaign as regarded education, daughter’s cohort and mothers' decision to have their daughter vaccinated. Interaction between education and cohort in mothers overdue for Pap testing was calculated.ResultsVaccination coverage was 46.3% for the uninvited cohort (1046/2260) and 77.9% for the invited cohort (1798/2307). In the uninvited cohort, daughters’ vaccination showed association with mothers’ education (8 to 11 years of education vs. graduated mothers, RR 1.61 95% CI 1.14–2.28), citizenship (foreigners vs. Italians, RR 0.45 95% CI 0.37–0.56) and screening history (regular vs. non-participant; RR 1.72 95% CI 1.26–2.36). In the invited cohort, only a slight association with screening history persisted (regular vs. non-participant; RR 1.20 95% CI 1.04–1.40). Highly educated under-screened mothers of the invited cohort showed a higher probability of receiving a Pap test after the vaccination campaign period (RR 1.27 95% CI 1.04–1.56) compared with those not invited,ConclusionActive invitation could increase overall HPV immunisation coverage and reduce socio-demographic inequalities and the association with mothers' screening participation.

Background HPV-test is more effective than Pap test in preventing cervical cancer. HPV-based screening will imply longer intervals and a triage test for HPV positive women. It will also permit the use of self-sampling devices. These innovations may affect population coverage, participation, and compliance to protocols, and likely in a different way for less educated, poorer, and disadvantaged women. Aim To describe the impact on inequalities, actual or presumed, of the introduction of HPV-based screening. Methods The putative HPV-based screening algorithm has been analysed to identify critical points for inequalities. A systematic review of the literature has been conducted searching PubMed on HPV screening coverage, participation, and compliance. Results were summarised in a narrative synthesis. Results Knowledge about HPV and cervical cancer was lower in women with low Socio-economic status and in disadvantaged groups. A correct communication can reduce differences. Longer intervals will make it easier to achieve high-population coverage, but higher cost of the test in private providers could reduce the use of opportunistic screening by disadvantaged women. There are some evidences that inviting for HPV test instead of Pap increases participation, but there are no data on social differences. Self-sampling devices are effective in increasing participation and coverage. Some studies showed that the acceptability of self-sampling is higher in more educated women, but there is also an effect on hard-to-reach women. Communication of HPV positivity may increase anxiety and impact on sexual behaviours, the effect is stronger in low educated and disadvantaged women. Many studies found indirect evidence that unvaccinated women are or will be more probably under-screened. Conclusions The introduction of HPV test may increase population coverage, but non-compliance to protocols and interaction with opportunistic screening can increase existing inequalities.