The challenging screen detection of ovarian cancer in BRCA mutation carriers adhering to a 6-month follow-up program: results from a 6-years surveillance.

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.

Clinical Characteristics and Long-Term Follow-up of Patients Treated for High-Grade Vaginal Intraepithelial Neoplasia: Results From a 20-Year Survey in Italy.

OBJECTIVES: The aim of this survey was to evaluate the different surgical approaches for women with high-grade vaginal intraepithelial neoplasia (HG-VaIN) used in 8 hospitals in central and northern Italy in the last 20 years. In particular, the baseline characteristics of the patients and factors potentially leading to excisional treatment rather than ablation were considered. Moreover, the clinical outcome of patients treated for HG-VaIN (disease persistence or recurrence and progression toward invasive vaginal cancer) was analyzed. MATERIALS AND METHODS: The medical records of all women initially diagnosed with HG-VaIN and subsequently treated in 8 Italian hospitals from January 1996 to December 2016 were analyzed in a multicenter retrospective case series. RESULTS: Among the 226 women included, 116 (51.3%) underwent ablative procedures and 110 underwent excisional surgery (48.7%). An ablative procedure was preferred in cases where multiple lesions were found on colposcopic examinations. Physicians decided more frequently to perform excisional procedures in women with menopausal status, high-grade referral cervical cytology, previous hysterectomy for human papillomavirus-related disease, or VaIN 3 on colposcopic-guided biopsy. CONCLUSIONS: The surgical treatment of HG-VaIN should be tailored according to the clinical characteristics of each woman and each lesion. However, in potentially high-risk cases (VaIN 3, previous hysterectomy for human papillomavirus-related disease, and menopausal women) or in those cases in which an occult invasive disease cannot be ruled out, an excisional approach should be preferred.In any case, long-term follow-up is advisable in women treated for HG-VaIN.

Corrigendum to "Prediction of Endometrial Hyperplasia and Cancer among Premenopausal Women with Abnormal Uterine Bleeding".

[This corrects the article DOI: 10.1155/2019/8598152.].

Expert consensus from the Italian Society for Colposcopy and Cervico-Vaginal Pathology (SICPCV) for colposcopy and outpatient surgery of the lower genital tract during the COVID-19 pandemic.

In the context of the COVID-19 pandemic, patients need to be evaluated within 2-4 weeks in the following cases: cytology result of "squamous cell carcinoma," "atypical glandular cells, favor neoplastic," "endocervical adenocarcinoma in situ," or "adenocarcinoma"; histopathological diagnosis of suspected invasion from cervical/vaginal biopsy, or invasive disease after a cervical excision procedure, vaginal excision, or vulvar biopsy/excision; sudden onset of strongly suggestive symptoms for malignancy. Digital imaging technologies represent an important opportunity during the COVID-19 pandemic to share colposcopic images with reference centers, with the aim of avoiding any concentration of patients. All patients must undergo screening for COVID-19 exposure and should wear a surgical mask. A high-efficiency filter smoke evacuation system is mandatory to remove surgical smoke. Electrosurgical instruments should be set at the lowest possible power and not be used for long continuous periods to reduce the amount of surgical smoke. The following personal protective equipment should be used: sterile fluid-repellant surgical gloves, an underlying pair of gloves, eye protection, FFP3 mask, surgical cap, and gown. The colposcope should be protected by a disposable transparent cover. A protective lens that must be disinfected after each use should be applied. The use of a video colposcope should be preferred.

Prediction of Endometrial Hyperplasia and Cancer among Premenopausal Women with Abnormal Uterine Bleeding.

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<0.0001). Considering the pretest probability for EH/EC of 5%, the prediction model with a positive likelihood ratio of 8.14 showed a posttest probability of 30%. The simultaneous presence of two or three risk factors was significantly more common in women with EH/EC than controls (50% vs. 6.6 and 25% vs. 0%, respectively, p<0.0001). 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.

Colposcopic patterns of vaginal intraepithelial neoplasia: a study from the Italian Society of Colposcopy and Cervico-Vaginal Pathology.

The aim of this study was to evaluate the colposcopic patterns observed in women with a histopathological diagnosis of vaginal intraepithelial neoplasia (VaIN). The medical charts and the colposcopy records of women diagnosed with VaIN from January 1995 to December 2013 were analysed in a multicentre retrospective case series. The abnormal colposcopic patterns observed in women with VaIN1, VaIN2 and VaIN3 were compared. The vascular patterns and micropapillary pattern were considered separately. A grade II abnormal colposcopic pattern was more commonly observed in women with a biopsy diagnosis of VaIN3 rather than with VaIN1 or VaIN2 (P<0.001). Vascular patterns were also more common in women with VaIN3 rather than with VaIN1 or VaIN2 (P<0.001). Moreover, in women with grade I colposcopy, the rate of VaIN3 was significantly higher when a vascular pattern was observed (62.5 vs. 37.5%; P=0.04). The micropapillary pattern was more common in women with grade I colposcopy and it was more frequently observed in women with VaIN1 rather than in those with VaIN2 or VaIN3 (P<0.001). Grade II abnormal colposcopic pattern was more commonly observed in women with VaIN3. Moreover, the detection of vascular patterns appeared to be associated with more severe disease (VaIN3) even in women with grade I colposcopy, whereas the micropapillary pattern should be considered an expression of a less severe disease (VaIN1 and VaIN2).

Age-related changes in pre- and post-conization HPV genotype distribution among women with high-grade cervical intraepithelial neoplasia.

OBJECTIVE: To assess the effect of age on pre- and post-conization HPV genotype distribution. METHODS: The present retrospective observational study included consecutive women with high-grade cervical intraepithelial neoplasia who underwent conization at the Cervical Cancer Screening Centre of Reggio Emilia, Italy, and University Hospital of Modena, Italy, between February 1, 2012, and October 31, 2014. Pre-conization and 6-month post-conization HPV genotyping results were compared between four age groups (<30, 30-39, 40-49, and ≥50 years) and age-related changes in the HPV genotypes present were evaluated. RESULTS: There were 162 patients included. The lowest occurrence of pre-conization high-risk and probable high-risk HPV genotypes was observed among patients aged at least 50 years when compared with younger patients (P=0.017). Conversely, women aged at least 50 years exhibited the highest level of post-conization high-risk and probable high-risk HPV genotypes (P=0.043). Additionally, an increasing incidence of recording identical pre- and post-conization HPV genotypes was associated with increasing age (P=0.024), as was increasing post-treatment recurrence of cervical intraepithelial neoplasia grade 2+ (P=0.030). CONCLUSION: The presence of high-risk and probable high-risk HPV genotypes was lowest among older patients before conization and was highest among these patients post-conization; post-treatment HPV clearance decreased with age and increasing age could be a risk factor for post-conization recurrence.

Surgical approach and long-term clinical outcome in women with microinvasive cervical cancer.

AIM: To assess the efficacy and safety of conservative surgical approach for microinvasive cervical cancer with regards to cone margins status and lymph vascular space invasion (LVSI). PATIENTS AND METHODS: This was a multicentre retrospective cohort study of 153 women diagnosed with microinvasive cervical cancer over a 10 years period (1993-2003). RESULTS: In conservatively-treated women (n=80), neither cancer mortality nor disease relapse after 184.5 ± 20.5 months of follow-up was detected. Residual disease in women who underwent secondary surgery was significantly related to positive margins on the primary cone excision (p=0.005) while no correlation with LVSI emerged. CONCLUSION: Conization can represent the definitive treatment for stage IA1, if surgical margins are cancer-free, independently of LVSI. A conservative surgical approach could also be considered in women with IA2 cervical cancer when preservation of fertility is strongly requested. A close long-term surveillance should be scheduled for conservatively-treated women.

A risk-scoring model for the prediction of endometrial cancer among symptomatic postmenopausal women with endometrial thickness > 4 mm.

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.

Cervical nitric oxide metabolite levels and clinical variables as predictive factors of high-grade cervical intraepithelial neoplasia.

PURPOSE: To create a prediction model of high-grade cervical intraepithelial neoplasia (CIN) based on clinical variables and the cervical nitric oxide metabolite (NOx) levels of study participants. METHODS: This comparative study included 694 women undergoing colposcopy due to abnormal pap smear results. On the basis of the cervical biopsy results, the women were divided into the ≤ CIN 1 or CIN 2-3 group. The two groups were compared in terms of cervical NOx levels and clinical variables. Univariate, multivariate, and receiver-operating characteristic curve analysis were performed. RESULTS: Multivariate analysis showed that CIN 2-3 associated with more than two cervical biopsies [odds ratio (OR) = 5.16], high-grade squamous intraepithelial lesion cytology (OR = 16.19), condom non-use (OR = 4.28), cervical NOx levels ≤ 99.9 µmol/L (OR = 16.62), more than four lifetime male sexual partners (OR = 10.56), and age at first coitus of ≤ 15 years old (OR = 3.54). This combined model had a sensitivity of 86.49 %, a specificity of 90.74 %, a positive predictive value of 64.0 %, and a negative predictive value of 97.2 %. CONCLUSIONS: In the present sample, high-grade CIN associated with decreased cervical NOx levels. Thus, along with some clinical variables, cervical NOx levels may be an additional marker of cervical dysplasia.

Knowledge of HPV infection and vaccination among vaccinated and unvaccinated teenaged girls.

OBJECTIVE: To assess the knowledge of teenaged girls on human papillomavirus (HPV) infection and vaccination 12 months after the start of a vaccine administration and information campaign. METHODS: Between May 15 and June 15, 2009, an anonymous questionnaire was given to 629 girls attending a secondary school in a northeastern Italian city (286 were vaccinated against HPV, 343 were unvaccinated) to investigate their knowledge on HPV infection, transmission, prevention, vaccination, and post-vaccination behaviors. The responses were evaluated with respect to the vaccination status of the participants. RESULTS: Vaccinated teenaged girls had no more knowledge than unvaccinated ones about the route of HPV transmission, and the relationship between HPV and AIDS. Vaccinated girls had less knowledge than unvaccinated girls about preventing transmission by condom (P=0.003) and about the correlation between HPV and penile cancer (P=0.034) and warts (P=0.001). Furthermore, compared with unvaccinated girls, more vaccinated girls believed that contraceptive pills might prevent HPV-related disease (P=0.001). Vaccinated girls better understood the importance of performing regular Pap smears after vaccination (P=0.021). CONCLUSION: Knowledge on HPV infection and vaccination remains suboptimal, especially among vaccinated teenaged girls, despite a broad information campaign. Misconceptions about the utility of secondary prevention may increase risky sexual behaviors.

Loop electrosurgical excision procedure as a life event that impacts on postmenopausal women.

AIM: The aim of this study was to compare the psychological impact of loop electrosurgical excision procedure (LEEP) in pre- and postmenopausal women. MATERIAL AND METHODS: This was an observational comparative study including 231 pre- and 108 post-menopausal women undergoing LEEP who were subjected to an interview inquiring specific psychological domains concerning the impact of this surgical procedure. The associations between women's answers and their hormonal status were tested by logistic regression analysis. RESULTS: Multivariate analysis showed that after LEEP, postmenopausal women were associated with answers that indicated significant psychological changes concerning the impact of cervix disease (Odds Ratio [OR] = 2.38, 95% Confidence Interval [CI] 1.22-4.66), their body image (OR = 6.80, 95% CI 2.30-20.08), interpersonal relationship with their partner (OR = 8.32, 95% CI 1.77-38.99) and sexual health quality (OR = 2.25, 95% CI 1.15-4.39). CONCLUSION: Limited to our sample, the psychological impact of LEEP seems to be greater in postmenopausal than in premenopausal women. We speculate that LEEP could cause failure of psychological domains already weakened by menopause.

Pedunculated angiomyofibroblastoma of the vulva: case report and review of the literature.

Angiomyofibroblastoma (AMFB) is a rare benign mesenchymal tumour that occurs almost exclusively in the vulvovaginal region of women but can also occur occasionally in the inguinoscrotal region of men. It is a well-circumscribed lesion that clinically is often thought to represent a Bartholin's gland cyst and usually does not form a pedunculated mass. To our knowledge, only five cases of vulvar AMFB with pedunculated mass have been reported in the English literature and all cases involving the labia majora and middle-aged women. We report the first case of pedunculated AMFB of the vulva occurring in a young woman of 21 years old and involving the left labia minora. After excluding the most common diseases, pedunculated AMFB should be part of differential diagnosis in the workup of any pedunculated vulvar mass even in young women with a lesion involving the labia minora. We reviewed the literature and summarized all reported cases.

Prevalence and determinants of genital shedding of herpes simplex virus among women attending Italian colposcopy clinics.

OBJECTIVES: To determine the prevalence of herpes simplex virus (HSV) shedding among women attending Italian colposcopy clinics and describe their lifestyle, demographic characteristics, genital symptoms and signs. STUDY DESIGN: A cross-sectional study was performed to assess shedding of HSV among 4565 women requiring a gynecological consultation. An amplified enzyme immunoassay that detects an HSV type-common glycoprotein D was used to reveal HSV shedding in cervical specimens. Statistical analysis was performed using Chi-square test and Student's t test. RESULTS: A prevalence of 7.8% was found among colposcopy clinic patients. No significant differences regarding patients' average age, age at first sexual intercourse, contraceptive method used, and number of sexual partners in the previous year were found between subjects with and without viral shedding (P > 0.05). The detection of a concomitant genital infection with Trichomonas vaginalis as well as the report of previous episodes of genital herpes (GH) were significantly higher in the positive group (P < 0.01). Only 2.8% of the patients shedding HSV presented with vesicles and ulcers, with the majority of them being asymptomatic. CONCLUSION: This is the first Italian survey on genital herpes conducted among colposcopy clinic patients. Our data show that the prevalence of HSV shedding in this study population is high and confirms that the disease is often asymptomatic. The demographics and behavioural variables of women shedding HSV seem to differ from the ones assessed in high risk patients.

The Italian STD 'Hot-Line'. Making people aware.

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.