High-risk HPV-positive and -negative high-grade cervical dysplasia: Analysis of 5-year outcomes.

OBJECTIVE: To evaluate the outcomes of high-risk (HR) HPV-positive and -negative women affected by high-grade cervical dysplasia. METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with high-grade cervical dysplasia undergoing conization between 2010 and 2014 were retrieved. All patients included had at least 5 years of follow-up. A propensity-score matching was adopted in order to reduce the presence of confounding factors between groups. Kaplan-Meir and Cox hazard models were used to estimate 5-year outcomes. RESULTS: Overall, data of 2966 women, affected by high-grade cervical dysplasia were reviewed. The study population included 1478 (85%) and 260 (15%) women affected by HR-HPV-positive and HR-HPV-negative high-grade cervical dysplasia. The prevalence of CIN2 and CIN3 among the HR-HPV-positive and -negative cohort was similar (p = 0.315). Patients with HR-HPV-positive high-grade cervical dysplasia were at higher risk of 5-year recurrence (after primary conization) that HR-HPV-negative patients (p < 0.001, log-rank test). Via multivariate analysis, HR-HPV-negative women were at low risk of recurrence (HR: 1.69 (95%CI: 1.05, 4.80); p = 0.018, Cox Hazard model). A propensity-score matched comparison was carried out in order to reduce biases that are related to the retrospective study design. In comparison to HR-HPV-negative patients, thosewith HR-HPV-positive CIN3 was associate with a 8-fold increase in the risk of recurrence (p < 0.001, log-rank test). CONCLUSIONS: HR-HPV-negative high-grade cervical dysplasia is not uncommon, accounting for 15% of our study population. Those patients experience more favorable outcomes than patients with documented HR-HPV infection(s). Further prospective studies are needed to corroborate our data.

Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser Conization: A 5-year follow-up study.

OBJECTIVE: Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+). METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. RESULTS: Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%;p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with [5-]year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001). CONCLUSIONS: HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia.

Early invasive vulvar squamous cell carcinoma arising in a woman with vulvar pemphigus vulgaris and systemic lupus erythematosus.

BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucous membranes. Genital involvement occurs when most other common sites are concurrently affected or are in remission. Systemic lupus erythematosus (SLE) is an autoimmune disease that may affect many parts of the body and the skin with occasional bullous lesions. Pemphigus vulgaris and SLE may be associated, albeit rarely. Here, we report the first case of a woman affected with SLE presenting with early invasive squamous cell carcinoma (SCC) arising from Pemphigus Vulgaris of the vulva. CASE PRESENTATION: A 27-year-old Caucasian woman was admitted to our Gynaecology Unit for bleeding vegetant lesions of the vulva. Her history was characterized by systemic lupus erythematosus and PV. Biopsy showed concomitant PV and vulvar intraepithelial neoplasia (VIN) grade 3. One month later a new biopsy revealed progression from VIN 3 to early SCC. Despite chemotherapy, no remission of disease was observed. She died six months after diagnosis CONCLUSION: Our case underlines PV as another chronic inflammatory disease of the lower genital tract predisposing to VIN-SCC. It suggests the need for careful follow-up of patients with chronic inflammatory disease, especially when concomitant autoimmune disorders are present. Moreover, a biopsy should be always performed if there are PV lesions because of the possibility of neoplastic disease.

Assessing the Long-Term Role of Vaccination against HPV after Loop Electrosurgical Excision Procedure (LEEP): A Propensity-Score Matched Comparison.

Background: Primary prevention through vaccination is a prophylactic approach aiming to reduce the risk of developing human papillomavirus (HPV)-related lesions. No mature and long-term data supported the adoption of vaccination in women undergoing conization. Methods: This is a retrospective multi-institutional study. Charts of consecutive patients undergoing conization between 2010 and 2014 were collected. All patients included had at least 5 years of follow-up. We compared outcomes of patients undergoing conization plus vaccination and conization alone. A propensity-score matching algorithm was applied in order to reduce allocation biases. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. Results: Overall, charts of 1914 women were analyzed. The study group included 116 (6.1%) and 1798 (93.9%) women undergoing conization plus vaccination and conization alone, respectively. Five-year recurrence rate was 1.7% (n = 2) and 5.7% (n = 102) after conization plus vaccination and conization alone, respectively (p = 0.068). After the application of a propensity-score matching, we selected 100 patients undergoing conization plus vaccination and 200 patients undergoing conization alone. The crude number of recurrences was 2 (2%) and 11 (5.5%) for patients undergoing conization plus vaccination and conization alone, respectively (p = 0.231). Vaccination had no impact on persistent lesions (no negative examination between conization and new cervical dysplasia; p = 0.603), but reduced the risk of recurrent disease (patients who had at least one negative examination between conization and the diagnosis of recurrent cervical dysplasia; p = 0.031). Conclusions: Patients having vaccination experience a slightly lower risk of recurrence than women who had not, although not statistically significantly different. Further evidence is needed to assess the cost effectiveness of adopting vaccination in this setting.

Uterine Papillary Serous Carcinoma Arising in a Polyp: A Multicenter Retrospective Analysis on 75 Patients.

OBJECTIVES: The objectives of this study were to evaluate whether the international recommendations on the management of uterine papillary serous carcinoma arising in a polyp are uniformly followed in Italian Oncologic Centers and whether the strategy adopted is effective. MATERIALS AND METHODS: Patients with uterine papillary serous carcinoma arising in a polyp and who had undergone a hysterectomy were identified in the 2003-2013 database of 7 Italian Gynecologic Oncology Centers. Clinical and pathologic characteristics and outcomes were compared between staging procedure types. Survival curves of the women were plotted using the Kaplan-Meier method and analyzed using Cox regression hazard model and the log-rank test. Associations between clinical parameters and the incidence of recurrence were assessed by generalized linear models and the Fisher test. RESULTS: A total of 75 patients met the inclusion criteria. Recurrence-free survival was affected positively by type of surgical staging and negatively by preoperative diagnosis of hypertension. The association between surgical staging and recurrence-free survival resulted significant at univariate survival analysis (P=0.048 and 0.045) and maintained a trend of significance (P=0.070) in multivariate analysis, whereas hypertension was demonstrated to be the principal influencing factor. CONCLUSIONS: The international recommendations on the management of uterine papillary serous carcinoma are not uniformly followed in daily practice, although the extension of the surgery seems to be associated with lower recurrence rates also when uterine papillary serous carcinoma is confined to a polyp or endometrial surface.

Atypical squamous cells and low squamous intraepithelial lesions in postmenopausal women: implications for management.

OBJECTIVES: To determine whether the use of local Estrogen Replacement Therapy (ERT) affects the adequacy of colposcopic examination; to distinguish abnormal cervical smears secondary to hypoestrogenism from abnormal cervical smears due to true preneoplastic changes; and to suggest an effective management of atypical squamous cells of undeterminated significance (ASCUS) and low grade squamous intraepithelial lesion (L-SIL) in menopausal women. STUDY DESIGN: Two-hundred fifty-four postmenopausal women with abnormal pap smears (L-SIL or ASCUS) underwent colposcopy and HPV DNA testing. All patients with positive colposcopy underwent punch biopsy, and all patients with positive histological findings underwent surgical treatment. Patients with negative colposcopy, both satisfactory [visible Squamo-Columnar Junction (SCJ)] and unsatisfactory, were treated with local estrogenic replacement therapy (ERT) for 3 months, and repeated colposcopy and pap smears. Patients with negative colposcopy and negative pap smears after ERT were included in a 6 months cytological and colposcopic follow-up. Patients with positive colposcopy underwent punch biopsy, if colposcopy was negative and cytology was positive, patients underwent endocervical curettage. RESULTS: One-hundred ninety-five had a diagnosis of ASCUS and 59 a diagnosis of L-SIL. At the first colposcopy, 39 patients showed a lesion and had an appropriate treatment. One-hundred eighty-eight in the ASCUS group and 27 in the L-SIL group had a negative colposcopy and were treated with local ERT. At first colposcopic examination, 37 of the 215 negative colposcopies resulted satisfactory and 178 of the 215 resulted unsatisfactory. After local ERT, 130 of the 178 patients had a satisfactory follow-up colposcopy. After ERT, 25 patients of 215 with initial abnormal CVS and negative colposcopy, required appropriate treatment. After ERT, 190 patients of 215 showed negative colposcopy and at cytologic follow-up showed 23 ASCUS and 167 normal CVS. CONCLUSIONS: A correct diagnosis and an efficient treatment seem to be obtained with a short-time ERT followed by a short-time cytological and colposcopic follow-up. With a single course of local ERT it may be possible to distinguish between benign CVS mimicking atrophy and true preneoplastic changes. Estrogen therapy will often cause enough ectropion of the endocervical cells so that the entire SCJ can be visualized. Moreover, it may reduce the number of endocervical curettage or loop excision or cone procedure for women with inadequate colposcopic examination.

Bleeding patterns during continuous estradiol with different sequential progestogens therapy.

OBJECTIVE: : To evaluate the effects on monthly bleeding of four different progestogens administered in association with transdermal estradiol in a continuous sequential estrogen-progestin therapy (CS-EPT). DESIGN: : This prospective, open, randomized, clinical trial included 100 healthy postmenopausal women. Patients were randomized into four treatment groups, each consisting of 25 women. Treatment consisted of 50 mug/day transdermal 17beta-estradiol for all women combined to receive four different progestogens (group A: medroxyprogesterone acetate, 10 mg/day; group B: nomegestrol acetate, 5 mg/day; group C: dydrogesterone, 10 mg/day; group D: micronized progesterone, 200 mg/day) per os from the 14th to 25th day of each 28-day cycle. The duration of treatment was 12 cycles. Patients were asked to record in a daily diary the occurrence of any vaginal bleeding, the days of application of each patch, the days of assumption of the different progestogens, and the exact moment of bleeding onset. RESULTS: : A total of 937 cycles could be evaluated. In 690 cycles (73.6%), regular progestogen-related bleeding was reported. Among the other cycles, we observed 73 episodes of amenorrhea (7.8%, each one lasting one cycle), 78 episodes of irregular bleeding (8.3%), and 96 episodes of spotting (10.2%). Patients receiving nomegestrol acetate had a significantly higher incidence of regular progestogen-associated bleeding in comparison with those receiving medroxyprogesterone acetate or natural progesterone, and patients receiving dydrogesterone had a significantly higher incidence of regular progestogen-associated bleeding in comparison with those receiving natural progesterone. CONCLUSION: : Our data suggest that CS-EPT generally leads to regular withdrawal bleeding in women without uterine pathology. Micronized progesterone seems to induce more irregular bleeding episodes.

Postmenopausal hypoestrogenism increases vasoconstrictor neuropeptides and decreases vasodilator neuropeptides content in arterial-wall autonomic terminations.

OBJECTIVE: To investigate the effects of postmenopausal hypoestrogenism on the content of autonomic vasoconstrictor (neuropeptide Y) and vasodilator neuropeptides (vasoactive intestinal peptide and substance P) at the arterial level. DESIGN: Prospective, clinical study. SETTING: Department of Gynecology and Obstetrics and Pathophysiology of Human Reproduction, University of Naples "Federico II," Naples, Italy. PATIENT(S): Twenty premenopausal women and 20 postmenopausal women, matched for age and parity. INTERVENTION(S): All patients underwent abdominal hysterectomy with bilateral oophorectomy for benign conditions. During surgery, a sample of uterine artery was obtained. The presence of E2, estrogen receptor alpha (ER alpha), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), and S100 (a generic neuronal marker) was evaluated by means of immunohistochemistry and Western-blot analysis. MAIN OUTCOME MEASURE(S): Mean arterial content of E2, ER alpha, VIP, NPY, and SP. RESULT(S): Both immunohistochemical and Western-blot analysis showed that after menopause, the reduction in E2 and ER alpha in the uterine artery wall is associated with a decrease in vasodilator neuropeptides and an increase in vasoconstrictor NPY. A similar immunopositivity for S100 was observed in pre- and postmenopausal samples, which demonstrated similar total neuronal fiber contents. CONCLUSION(S): Postmenopausal hypoestrogenism seems to increase arterial vascular tone through a reduction of vasodilator neuropeptides and an increase in vasoconstrictor peptides in the arterial-wall termination of the autonomous system. These changes in neuropeptide content in the arterial walls might represent a new mechanism underlying the negative effects of menopause on the cardiovascular system.