Cinzia Campari

Background: Under the current Italian HPV-based cervical screening protocol, women with persistent high-risk human papillomavirus (HR-HPV) positivity at the 12-month recall are referred to colposcopy regardless of cytology results. Although this strategy maximizes lesion detection, it may result in a high number of colposcopies, most of which do not identify CIN2+. We evaluated whether partial HPV genotyping combined with cytology can improve risk stratification in women with persistent HPV positivity at the 12-month recall. Methods: A multicenter retrospective analysis of cervical screening data collected from four Italian screening programs (Florence, Padua, Umbria and Emilia Romagna) was performed. Among the 270,714 women screened between 2015 and 2019 (2016–2018 in Florence), 4589 women with persistent HR-HPV positivity at 12-month recall after baseline HPV-positive/NILM (negative for intraepithelial lesion or malignancy) results were included. Four alternative triage strategies based on cytology and HPV 16/18 genotyping were retrospectively simulated and compared with the current protocol. Outcomes included CIN2 (cervical intraepithelial neoplasia grade 2) or worse (CIN2+) detection, relative sensitivity for CIN2+ and CIN3 (cervical intraepithelial neoplasia grade 3) or worse (CIN3+), positive predictive value (PPV) and reduction in colposcopy referrals. Results: Under the current protocol, 4589 colposcopies identified 327 CIN2+ lesions, including 113 CIN3+ lesions, yielding a PPV for CIN2+ of 7.1%. Overall, 36.7% of CIN2+ lesions were associated with NILM cytology at recall. HPV 16/18 genotyping identified 43.3% of these cytologically occult lesions. In this retrospective simulation, among the evaluated strategies, referral of HPV 16/18-positive women regardless of cytology and referral of women with low-grade or worse cytology regardless of genotype would have achieved the most favorable balance between sensitivity and efficiency. This approach would have reduced colposcopy referrals by 57.7% (95% CI, 56.3–59.2), nearly doubled the PPV for CIN2+ to 13.4% (95% CI, 11.9–14.9) and maintained relative sensitivities of 79.2% (95% CI, 74.5–83.3) for CIN2+ and 85.0% (95% CI, 77.2–90.4) for CIN3+. Performance varied across centers, with imprecise center-specific estimates (relative CIN3+ sensitivity of Strategy 2 from 62.5% in Emilia Romagna to 91.1% in Umbria), so generalizability should be assessed cautiously. Conclusions: Combining partial HPV genotyping with cytology would have substantially improved risk stratification in women with persistent HR-HPV positivity at 12-month recall. In this retrospective simulation, a risk-based approach would have substantially reduced immediate colposcopies while maintaining a relative sensitivity for CIN3+ of 85.0%. These findings are hypothesis-generating and support prospective evaluation of integrating molecular and cytological information into 12-month recall management.

Background: Under the current Italian HPV-based cervical screening protocol, women with persistent high-risk human papillomavirus (HR-HPV) positivity at the 12-month recall are referred to colposcopy regardless of cytology results. Although this strategy maximizes lesion detection, it may generate substantial over-referral. We evaluated whether partial HPV genotyping combined with cytology can improve risk stratification in women with persistent HPV positivity at the 12-month recall. Methods: A multicenter retrospective analysis of cervical screening data collected from four Italian screening programs (Florence, Padua, Umbria and Emilia-Romagna) was performed. Among the 270,714 women screened between 2015 and 2019, 4,589 women with persistent HR-HPV positivity at 12-month recall after baseline HPV-positive/NILM results were included. Four alternative triage strategies based on cytology and HPV 16/18 genotyping were retrospectively simulated and compared with the current protocol. Outcomes included CIN2+ detection, relative sensitivity for CIN2+ and CIN3+, positive predictive value (PPV) and reduction in colposcopy referrals. Results: Under the current protocol, 4,589 colposcopies identified 327 CIN2+ lesions, including 113 CIN3+ lesions, yielding a PPV for CIN2+ of 7.1%. Overall, 36.7% of CIN2+ lesions were associated with NILM cytology at recall. HPV 16/18 genotyping identified 43.3% of these cytologically occult lesions. Among the evaluated strategies, referral of HPV 16/18-positive women regardless of cytology and referral of women with low-grade or worse cytology regardless of genotype achieved the most favorable balance between sensitivity and efficiency. This approach reduced colposcopy referrals by 57.7%, nearly doubled the PPV for CIN2+ to 13.4% and maintained relative sensitivities of 79.2% for CIN2+ and 85.0% for CIN3+. Conclusions: Combining partial HPV genotyping with cytology substantially improves risk stratification in women with persistent HR-HPV positivity at 12-month recall. A risk-based approach may markedly reduce unnecessary colposcopies while maintaining acceptable sensitivity for high-grade cervical lesions. These findings support the integration of molecular and cytological information into 12-month recall management strategies within HPV-based cervical screening programs.

Hereditary breast/ovarian cancer (HBOC) syndrome is caused by the inheritance of monoallelic germline BRCA1/2 gene mutations. If BRCA1/2 mutation carriers are identified before the disease develops, effective actions against HBOC can be taken, including intensive screening, risk-reducing mastectomy and salpingo-oophorectomy, and risk-reducing medications. The Italian National Prevention Plan mandates the creation of regional BRCA genetic testing programmes. So far, however, only informal data have been reported on their implementation. We have designed a study aimed at evaluating the results of a population-based programme for risk assessment and genetic counselling and testing for BRCA1/2-related HBOC that is underway in the Emilia-Romagna region (northern Italy). The programme—which is entirely free—includes basic screening with an estimate of the likelihood of carrying a BRCA1/2 mutation using a familial risk assessment tool, a closer examination of women with suspected risk increase, an assessment of the need for further genetic counselling and, if needed, genetic testing and risk-reducing interventions. In this paper, the design of the programme and the protocol of the study are presented. The study has an observational, historical cohort design. Eligible are the women found to be at an increased risk of HBOC (profile 3 women). The main objectives are (i) to determine the precision of the programme in measuring the level of risk of HBOC for profile 3 women; (ii) to determine the characteristics of profile 3 women and their association with the risk management strategy chosen; (iii) to compare the age at onset, histologic type, tumour stage, molecular subtype, and prognosis of breast/ovarian cancers observed in the cohort of profile 3 women with the features of sporadic cancers observed in the general female population; (iv) to determine the level and the determinants of adherence to recommendations; and (v) to determine the appropriateness and timing of risk-reducing surgery and medications. Investigating the quality and results of the programme is necessary because the best practices in risk assessment and genetic counselling and testing for BRCA1/2-related cancer and the challenges they encounter should be identified and shared. The study has the potential to provide sound empirical evidence for the factors affecting the effectiveness of this type of service.

The aim of this study is to evaluate the real impact of COVID-19 during the entire 2020 period, compared with 2019. The data comes from a Cancer Registry in Northern Italy and we compared clinical and treatment characteristics of breast cancer by age, stage, treatment, and status screening. In 2020 there was no decrease in invasive tumours nor in in situ (513 vs. 493 and 76 vs. 73, respectively), while there was a significant decrease in surgery and increase in neoadjuvant chemotherapy (p = 0.016). In the screening range (aged 45–74), no change in stage and grading was observed. In the four periods examined there was an increase in new diagnoses during pre-lockdown, a decrease in tumours especially at age 75+ [IRR 0.45; 95%CI 0.25–0.79] during lockdown, a recovery of new diagnoses in women 45+ in the low incidence period while in the last period there was a significant increase only for ages 45–74 [IRR 1.48; 95% CI 1.11–1.98]. Screening activities were suspended from March to May, but over the summer and autumn the backlog was addressed. This suggests that a prompt resumption of programmed screening may have limited the impact of the pandemic on the delay of breast cancer diagnoses.

In women younger than 50 years, benefits of early diagnosis with tomosynthesis plus mammography screening seemed appreciable and could increase diagnosis of slow-growing, invasive cancers for women... Background Adding digital breast tomosynthesis (DBT) to digital mammography (DM) improves breast cancer screening sensitivity, but how this impacts mortality and other end points is unknown. Purpos...

(1) Background: This population-based study aimed at identifying the factors associated with the likelihood of detection of stage IA cervical carcinoma—versus the detection of stage IB through IV cervical carcinoma—and the patterns of surgical treatment. (2) Methods: Between 1995–2016, 3750 patients living in the Emilia-Romagna Region (northern Italy) were registered with cervical carcinoma, including 2942 eligible patients (median age, 53). Multivariate analysis was performed using binary logistic regression models. (3) Results: The likelihood of stage IA cervical carcinoma (n = 876, 29.8%) did not change over time, decreased with increasing patient age, and was lower for patients with adenocarcinoma and grade 3–4 disease. Three hundred and fifty (40.0%) patients had a conservative treatment, 317 (36.2%) had hysterectomy, 197 (22.5%) had hysterectomy with lymph node dissection (LND), and 12 (1.4%) had a conservative treatment with LND. The proportion of hysterectomy decreased from 70.6% in 1995–1999 to 46.9% in 2011–2016. The likelihood of hysterectomy increased above the age of 40. Among screening-aged (25–64 years) patients, the likelihood of hysterectomy did not differ between screen-detected and non-screen-detected ones. Hysterectomy was increasingly combined with LND. High tumour grade was the strongest determinant of LND during hysterectomy. (4) Conclusions: This study provided a multifaceted overview of stage IA cervical carcinoma over the last decades.

Objectives In 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. Methods We 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. Results Vaccination 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, Conclusion Active invitation could increase overall HPV immunisation coverage and reduce socio-demographic inequalities and the association with mothers' screening participation.