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Objective Approximately 25% of ovarian cancer (OC) cases are related to an inherited predisposition. Genetic mutations for the oncosuppressor genes BRCA1 and 2 have the best-known linkage to a higher incidence of OC and breast cancer, in approximately 70% to 80% of hereditary OC cases. To provide the first comprehensive clinical description of screen-detected (SD) OCs during a 6-years surveillance of a cohort of young BRCA carriers and carriers who refuse risk-reducing salpingo-oophorectomy. Methods A prospective cohort study in a university hospital describing 191 women with BRCA1 and 2 mutations adhering continuously to our surveillance between 2015 and 2020, including a 6-monthly evaluation of cancer antigen 125 (CA 125) with concomitant transvaginal ultrasound (TVUS) performed by a dedicated specialist. Main outcomes were tumor's laterality, CA 125 at diagnosis, TVUS and computed tomography (CT) findings. Results Risk-reducing salpingo-oophorectomy was performed in 58/191 (30.4%) of mutation carriers during the study period (one OC case identified). Nine SD-OCs and no interval OCs were found in the remaining 133 women. OCs (FIGO stage I or II: 88.9%) occur mainly in BRCA 1 (77.8%), being bilateral in 85.7% BRCA 1 and unilateral in 100% BRCA 2. No lesions involved only the tubes: left ovaries/tubes were more frequently involved. We have described three new possible scenarios regarding imaging: 1) Evident cases (33.3%, TVUS and CT obvious for OC, CA 125 sensitivity: 100%), 2) Possible cases (55.6%, TVUS and CT are in general accordance, documenting new TVUS signs: increased solid pattern of the ovary with peripheral cortical small cysts, hypoechoic circular mass near the ovary, intraparenchymal small hyperechoic foci), and 3) Hidden cases (11.1%, the smallest lesion but the highest stage (IIIA2), with CA 125 44.2 U/mL and concomitant endometrial hyperplasia). Conclusions Different diagnostic tools must integrate to ensure early diagnosis of OC in BRCA mutation carriers adhering to a follow-up program.

Objective To create a prediction model including clinical variables for the prediction of premalignant/malignant endometrial pathology in premenopausal women with abnormal uterine bleeding (AUB). Methods This is an observational retrospective study including 240 premenopausal women with AUB referred to diagnostic hysteroscopy. Based on the presence of endometrial hyperplasia (EH) or cancer (EC), the women were divided into cases (EH/EC) and controls (no EH/EC). Univariate, stepwise logistic regression and ROC curve analysis were performed. Results 12 women had EH/EC (5%). Stepwise logistic regression analysis showed that EH/EC associated significantly with BMI ≥ 30 (OR=7.70, 95% CI 1.90 to 31.17), diabetes (OR=9.71, 95% CI 1.63 to 57.81), and a thickened endometrium (OR=1.20, 95% CI 1.08 to 1.34, criterion > 11 mm). The AUC was 0.854 (95% confidence intervals 0.803 to 0.896, p 11 mm, the percentage of premalignant/malignant endometrial pathology increases by 25%. It is likely that the simultaneous presence of several risk factors is necessary to significantly increase the probability of endometrial pathology.

In Italy, the cohorts of women who were offered Human papillomavirus (HPV) vaccination in 2007/08 will reach the age (25years) for cervical cancer (CC) screening from 2017. The simultaneous shift from cytology-based screening to HPV test-based screening gives the opportunity for unprecedented reorganisation of CC prevention. The ONS (National Screening Monitoring Centre) Directive and the GISCi (Italian Group for Cervical Screening) identified the consensus conference as the most suitable method for addressing this topic. A summary of consensus recommendations is reported here. The main objective was to define the best screening methods in girls vaccinated against HPV and the knowledge required for defining evidence-based screening strategies. A Jury made recommendations about questions and proposals formulated by a panel of experts representative of Italian scientific societies involved in CC prevention and based on systematic reviews of literature and evidence. The Jury considered changing the screening protocols for girls vaccinated in their twelfth year as appropriate. Tailored screening protocols based on vaccination status could be replaced by "one size fits all" protocols only when a herd immunity effect has been reached. Vaccinated women should start screening at age 30, instead of 25, with HPV test. Furthermore, there is a strong rationale for applying longer intervals for re-screening HPV negative women than the currently recommended 5years, but research is needed to determine the optimal screening time points. For non-vaccinated women and for women vaccinated in their fifteenth year or later, the current protocol should be kept.

Objective. To create a prediction model including clinical variables for the prediction of premalignant/malignant endometrial pathology in premenopausal women with abnormal uterine bleeding (AUB). Methods. This is an observational retrospective study including 240 premenopausal women with AUB referred to diagnostic hysteroscopy. Based on the presence of endometrial hyperplasia (EH) or cancer (EC), the women were divided into cases (EH/EC) and controls (no EH/EC). Univariate, stepwise logistic regression and ROC curve analysis were performed. Results. 12 women had EH/EC (5%). Stepwise logistic regression analysis showed that EH/EC associated significantly with BMI ≥ 30 (OR=7.70, 95% CI 1.90 to 31.17), diabetes (OR=9.71, 95% CI 1.63 to 57.81), and a thickened endometrium (OR=1.20, 95% CI 1.08 to 1.34, criterion > 11 mm). The AUC was 0.854 (95% confidence intervals 0.803 to 0.896, p p Conclusion. When premenopausal vaginal bleeding occurs in diabetic obese women with ET > 11 mm, the percentage of premalignant/malignant endometrial pathology increases by 25%. It is likely that the simultaneous presence of several risk factors is necessary to significantly increase the probability of endometrial pathology.

Objective: Cervical cancer prevention shows a variability across Italian Regions unjustified by available evidence, increasing the health, economic and organizational burden. Evidence-based recommendations on topics not covered by international guidelines are needed to tackle existing inequalities. This article describes the rationale, methods, and process for development of the Multisociety Italian Guidelines for cervical cancer prevention. Methods: The Italian legislative framework requires guidelines to be consistent with methodological standards set by the National System for Guidelines (SNLG) of the National Institute of Health. Results: The nine scientific societies involved in cervical cancer prevention participated to the project, including clinicians, policy makers, methodologists, and researchers. Patients were involved as full voting panel members. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was adopted to assess the certainty of evidence collected by systematic reviews. The GRADE Evidenceto- Decision framework (EtD) was used to structure the appraisal of evidence and to formulate final recommendations. The EtD and a conflict-of-interests management policy were adopted to minimize the influence of competing interests. Discussion: Full transparency guided the reporting of each step of the process, to support the implementation of recommendations in each context and the future updating process. Considerations for subgroups, monitoring and evaluation of the implementation of recommendations and research priorities were also provided. A two-step review process by external experts and SNLG reviewers, prior to online publication, ensured the methodological robustness underlying final recommendations. Finally, to increase publication timeliness, guidelines are organised in chapters that group sets of related recommendations to be published independently.

Objective. To develop and test a risk-scoring model for the prediction of endometrial cancer among symptomatic postmenopausal women at risk of intrauterine malignancy.Methods. We prospectively studied 624 postmenopausal women with vaginal bleeding and endometrial thickness > 4 mm undergoing diagnostic hysteroscopy. Patient characteristics and endometrial assessment of women with or without endometrial cancer were compared. Then, a risk-scoring model, including the best predictors of endometrial cancer, was tested. Univariate, multivariate, and ROC curve analysis were performed. Finally, a split-sampling internal validation was also performed.Results. The best predictors of endometrial cancer were recurrent vaginal bleeding (odds ratio(OR)=2.96), the presence of hypertension(OR=2.01)endometrial thickness > 8 mm(OR=1.31), and age > 65 years(OR=1.11). These variables were used to create a risk-scoring model (RHEA risk-model) for the prediction of intrauterine malignancy, with an area under the curve of 0.878 (95% CI 0.842 to 0.908;P<0.0001). At the best cut-off value (score ≥ 4), sensitivity and specificity were 87.5% and 80.1%, respectively.Conclusion. Among symptomatic postmenopausal women with endometrial thickness > 4 mm, a risk-scoring model including patient characteristics and endometrial thickness showed a moderate diagnostic accuracy in discriminating women with or without endometrial cancer. Based on this model, a decision algorithm was developed for the management of such a population.

Objectives The main objective of the study was to evaluate if speculoscopy, a magnified chemiluminescent examination, combined with a Pap smear, could improve the detection of early cervical lesions compared with the Pap smear alone. Setting Pap tests and speculoscopies were performed in two family planning centres located in the surrounding areas of Modena. Colposcopic investigations and biopsies of the uterine cervix were performed in a second level centre (Gynaecological Prevention Centre of Modena Policlinico). Histological specimens were analysed at the Section of Pathological Anatomy of Modena Policlinico. Subjects The study population comprised 1000 women aged 25–64 years, invited to undergo a Pap smear every three years in accordance with the screening programme for cervical cancer started in Modena in 1997. Methods Midwives performed the Pap smear and speculoscopy in succession. Women with a positive Pap test and/or positive speculoscopy underwent colposcopy and, if colposcopic findings were positive, targeted punch biopsies were performed. Results A total of 1000 patients were subjected to cytology and speculoscopy examinations. Among these women, 10 had abnormal Pap smear findings whereas 144 had an abnormal speculoscopic pattern. Only three of 59 patients with a histological diagnosis of cervical intraepithelial neoplasia grade I (CIN I)/human papillomavirus and only three of seven patients with CIN II/CIN III had a positive Pap test. Conclusions Speculoscopy combined with a Pap test can significantly increase the detection of cervical lesions when included in a screening programme.

The occurrence of hemangioma in the female genital tract, particularly in uterine cervix, is rare. The majority of them show asymptomatic behavior. Surgical excision remains curative in most of the cases. Conservative therapies such as sclerosing agents, cryotherapy, and CO(2) laser excision may be alternatively applied. We present three cases of hemangiomas of the cervix in asymptomatic women, diagnosed as cavernous hemangioma in two cases and capillary hemangioma in one. All tumors were immunoreactive for CD31, CD34, factor-VIII-related antigen. Focal expression of estrogen receptors was detected. No positivity was obtained with progesterone receptor antibodies. The presence of estrogen receptor in the endothelial cells of the hemangioma of the cervix suggests a direct role of this hormone in the hemangioma development. A possible target therapy is discussed.

We investigated the prevalences of human papillomavirus (HPV) of type 6, 11, 16, 18, 31, 33, 35 and 42 in 276 cervical tissue samples biopsied from a group of North-Italian women in which a HPV infection of the cervix had been suspected. The specimens were evaluated by conventional histological examination and by HPV typing, using Southern blot hybridization on the extracted DNA. We related different degrees of squamous cervical dysplasia, showing or not viral cytopathic effects, with the HPV types harboured in the lesions. Significant rising of HPV 16 prevalences was observed proceeding from mild to moderate and to severe dysplasias both in presence (r = 0.9623, P less than 0.01) and in absence (r = 0.879, P less than 0.05) of koilocytosis, while an opposite trend was detected for HPV 6 and 11. In our sampling we did not find HPV 35 DNA sequences; in all occasions HPV 31 was associated with mild dysplasias. The absolute prevalences of types 18, 33 and 42 were generally low (from 2 to 3%); they did not show any association with specific histological damage of the cervix or with significant patterns related with the progression of cervical dysplasia.

BACKGROUND To increase the accessibility of qualified and anonymous information on sexually transmitted diseases (STDs) in Italy, a national telephone hotline was initiated in February 1997. GOAL The goal was to determine the profile of callers to the national STD hotline, assess their concerns, identify their sources for the hotline telephone number, and to compare callers' disease interests with diagnoses made at STD clinics. STUDY DESIGN The survey analyzed 3577 calls received from February 1997 to December 1999. Hotline operators addressed callers' questions, asked 6 short-answer questions, and recorded the data collected. RESULTS The survey showed callers' sex distribution (49.8% women, 50.2% men), average age (women's mean+/-standard deviation [SD], 34.3 +/- 11.8 y; men's mean +/- SD, 36.2 +/- 12.2 y), level of education (66.4% had a secondary school degree), residence (47.9% northern part of Italy), risk category (44% reported being definitely infected by a STD), specific disease interest (30% were concerned about HIV), and source of hotline telephone number (67.3% learned the hotline telephone number from magazines or newspapers). Hotline callers' specific disease interests were compared with diagnoses made at STD clinics; the top 4 disease concerns of hotline callers were HIV, genital herpes, human papillomavirus/genital warts, and mycosis, whereas the top 4 diagnoses made at STD clinics were genital warts, nonspecific vaginitis, nonspecific urethritis, and genital herpes. CONCLUSION The hotline seems to be an effective way to deliver information and to allay fears about STDs, although it needs to be promoted more widely, especially in central and southern Italy.