Francesca Mancioli

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

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.

Placental Expression of CD100, CD72 and CD45 Is Dysregulated in Human Miscarriage

Context and Objective The etiology of miscarriage is often multifactorial. One major cause, immunological rejection of the fetus, has not been clearly elucidated. Our aim was to establish whether the semaphorin CD100, its natural receptor CD72, and the glycoprotein CD45, implicated in immune mechanisms, are involved in pregnancy loss by examining their placental expression with real-time PCR, immunohistochemistry and western blotting techniques. Patients Placenta tissue from 72 Caucasian women undergoing surgical uterine evacuation due to early spontaneous pregnancy loss between the 8th and 12th week of gestation was divided into four groups based on miscarriage number. Gestational age-matched placentas from 18 healthy women without a history of miscarriage undergoing voluntary pregnancy termination were the control group. Placenta from 6 Caesarean deliveries performed at 38–40 weeks of gestation was also studied. Results CD100, CD72 and CD45 were expressed in placenta and exhibited different mRNA and protein levels in normal pregnancy and miscarriage. In particular, protein levels were highly dysregulated around 10 weeks of gestation in first and second miscarriage placentas. The CD100 soluble form was produced and immediately shed from placental tissue in all samples. Conclusions Fetal CD100, CD72 and CD45 seem to play a role in miscarriage. The present data support the involvement of the fetal immune system in pregnancy maintenance as well as failure.

Abnormal Pap Smear and Diagnosis of High-Grade Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study.

Abstract The aim of this study was to analyze the correlation between the first diagnosis of high-grade Vaginal Intraepithelial Neoplasia (HG-VaIN: VaIN 2–VaIN 3) and the cytological abnormalities on the referral pap smear. All the women with histological diagnosis of HG-VaIN consecutively referred to the Gynecological Oncology Unit of the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014 and with a pap smear performed in the 3 months before the diagnosis were considered, and an observational cohort study was performed. A total of 87 women with diagnosis of HG-VaIN were identified. Major cytological abnormalities (HSIL and ASC-H) on the referral pap smear were significantly more frequent than lesser abnormalities (ASC-US and LSIL) in postmenopausal women (64.9% vs 36.7%, P = 0.02) and in women with a previous diagnosis of HPV-related cervical preinvasive or invasive lesions (70.5% vs 39.5%, P = 0.01). Diagnosis of VaIN 3 was preceded by major cytological abnormalities in most of the cases (72.7% vs 27.3%, P < 0.001). The diagnosis of HG-VaIN can be preceded by different abnormalities on referral pap smear. Major abnormalities are usually reported in postmenopausal women and in women with previous cervical HPV-related disease. However, ASC-US or LSIL do not exclude HG-VaIN, especially VaIN2. An accurate examination of the whole vaginal walls (or vaginal vault) must be performed in all the women who underwent colposcopy for an abnormal pap smear, and a biopsy of all suspicious areas is mandatory.

The impact of loop electrosurgical excision procedure (LEEP) for CIN 2,3 on spontaneous preterm delivery in twin pregnancies by assisted reproductive technique: preliminary data

Abstract The objective of this study was to compare the frequency of spontaneous preterm delivery before 35 weeks in 7 dichorionic twin pregnancies obtained after loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 2,3 with respect to 21 twin pregnancies without previous cervical treatment. All the pregnancies were obtained after assisted reproduction techniques (ART). Same age at delivery was observed between two groups (p = 0.81) and none of our twin pregnancies after LEEP had a threatened preterm labor while four controls (19%) underwent a spontaneous preterm delivery (p = 0.35). These preliminary data seem to indicate that LEEP may not be responsible of spontaneous preterm delivery in twin pregnancies subsequent to ART.

Cervical intraepithelial neoplasia in pregnancy: Interference of pregnancy status with p16 and Ki-67 protein expression

To date, there are evidence-based guidelines available for cervical dysplasia diagnosed in pregnancy. Certain functional biomarkers have proven useful in the prediction of regressing and non-regressing cervical intraepithelial neoplasia (CIN) lesions in non-pregnant women. In the present study, Ki-67 and p16 immunostaining were evaluated in different grades of CIN lesions diagnosed in pregnant or non-pregnant women with the aim to identify any differences in order to better understand the behavior of CIN in pregnancy. The current retrospective case-control study included 17 pregnant patients that conceived naturally with first-time onset of CIN occurring at no later than 16 gestational weeks. The control group included 17 non-pregnant patients matched for age, parity and number of previous sexual partners. Exclusion criteria included previous cervical treatment, immunocompromised status, chronic hepatitis B and/or C and cigarette smoking. p16 and Ki-67 protein expression were respectively detected using the CINtec Histology kit and monoclonal antibodies against Ki-67. p16 and Ki-67 staining were analyzed using a classification system based on the distribution of positivity on a semi-quantitative three point-scale. p16 and Ki-67 immune reactivity correlated positively with the grade of epithelial dysplasia in the total cohort of pregnant and non-pregnant patients; expression increased linearly from CIN1 to CIN3. Furthermore, the association between p16 immunostaining and CIN grade was significant in non-pregnant patients but not in pregnant patients. In pregnant patients, positivity for Ki-67 was less intense than in non-pregnant patients. These results appear to suggest that pregnancy status interferes with the expression of cellular proteins involved in cell-cycle regulation and the carcinogenic process induced by high-risk human papilloma virus, exhibiting increased variability in their staining.

Vaginal Intraepithelial Neoplasia: Histopathological Upgrading of Lesions and Evidence of Occult Vaginal Cancer.

Objective The aim of this study was to analyze women treated with excisional procedures for vaginal high-grade squamous intraepithelial lesions (HSILs). The histopathological upgrading of the lesions previously detected on vaginal biopsy and the presence of occult invasive vaginal cancer in the specimens excised were investigated, to identify a higher risk subset of women. Materials and Methods A retrospective analysis of the medical records of 86 women with a biopsy histopathologic diagnosis of vaginal HSIL (vaginal intraepithelial neoplasias [VaINs]: VaIN2 and VaIN3) and subsequent excisional therapy, consecutively referred to the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014, was performed. Results Of the 86 patients, 4 cases (4.6%) of occult vaginal cancer were detected, all of them in women previously diagnosed with VaIN3 on biopsy (4/39 cases, 10.3%). Women with diagnosis of VaIN2 on biopsy showed an upgrading of lesions, with diagnosis of VaIN3 on the final specimen in 5 (10.6%) of 47 cases, with no cases of VAIN2 upgraded to invasive cancer. In 33.3% of the women initially diagnosed with VaIN2 and with previous hysterectomy for human papillomavirus–related disease, a final histopathological upgrading of lesions emerged. Furthermore, tobacco use was significantly related to the histopathological upgrading of lesions previously detected on vaginal biopsy. Conclusions Women diagnosed with VaIN3 should be treated with excisional procedures as first-line surgical approach, given the risk of occult invasive disease in 10% of the cases. Women diagnosed with VaIN2 and with previous hysterectomy for human papillomavirus–related cervical diseases should always be carefully evaluated and possibly excised, given the higher risk of histopathological upgrading of lesions and thus the potential risk of occult vaginal cancer. Tobacco users should be considered as high-risk group.

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).

Possible role of placental CD100, CD72 and CD45 molecules in human miscarriage

The precise mechanism for recurrent miscarriage is unclear. A lot of metabolic alterations are involved in the missed intercommunication between mother and its foetus, causing their reciprocal intolerance. The identification of new molecules involved in pregnancy loss represents the main objective of our study. We analysed the semaphorin CD100, its natural receptor CD72 and the glycoprotein CD45, physically and functionally associated to CD100 in the placental tissues from recurrent miscarriages by real-time PCR, western blotting and immunohistochemistry. Placental tissue was obtained during surgical uterine evacuation in 72 caucasian women with early spontaneous pregnancy loss between 8th and 12th week of gestation and classified in four groups defined as first, second, third and fourth miscarriages. Other two normal placental groups were recruited: a) first trimester placentas (n = 18), matched for gestational age with placentas from spontaneous pregnancy loss; b) third trimester placentas (n = 6) at 38-40 weeks of gestation. We demonstrated that CD72, CD45 and CD100 mRNA were detectable in placental tissues with different expression in normal and pathological conditions. In addition, we demonstrated that CD72 and CD45 molecules were expressed in foetal macrophages and that their protein levels were especially deregulated in first and second miscarriages at about 10 weeks of gestation. On the contrary, CD100 cleaved protein appeared to be absent in placenta. In conclusion, our findings underline a possible role for CD100, CD72 and CD45 molecules in recurrent miscarriages, showing an important foetal involvement in the occurring of pregnancy loss.