Human papillomavirus genotyping in high-grade vaginal intraepithelial neoplasia: A multicentric Italian study.

This study aimed to analyze the human papillomavirus (HPV) genotype distribution in a large cohort of high-grade vaginal intraepithelial neoplasia (VaIN) (vaginal HSIL, VaIN2/3) patients from two Italian referral centers. We included all patients with histologically confirmed VaIN2/3 from the Department of Surgical Sciences, Sant'Anna Hospital, University of Torino, Torino, Italy, and Ospedale Maggiore della Carità, Novara, Italy, between 2003 and 2022. After the histological evaluation of formalin-fixed paraffin-embedded samples, we performed HPV genotyping with VisionArray HPV Chip 1.0. We detected HPV DNA in 94.4% of VaIN2/3 (168/178), with HPV 16 as the most prevalent genotype, accounting for 51.8% of all infections, 41.2% of VaIN2 and 77.6% of VaIN3 cases. Other frequent genotypes were HPV 58 (8.3%, 10.9% of VaIN2 and 2.0% of VaIN3), HPV 73 (5.4%, 5.0% of VaIN2 and 6.1% of VaIN3), and HPV 31 (5.4%, 6.7% of VaIN2 and 2.0% of VaIN3). 73.2% of VaIN2/3 had a single HPV genotype infection and 26.8% a multiple infection (20.8% a double infection, 4.8% a triple infection, and 1.2% a quadruple infection). Single infection was more frequently present in VaIN3 than VaIN2 (81.6% vs. 69.8%). 69.1% of single infections and 73.3% of multiple infections had one or more genotypes covered by nine-valent HPV vaccine. HPV vaccination is expected to have a large impact on reducing the incidence of vaginal intraepithelial neoplasia.

The effect of vulvovaginal atrophy on women's quality of life from an Italian cohort of the EVES study.

Vulvovaginal atrophy (VVA) has an impact on the quality of life (QoL) of women. This post hoc analysis of the EVES study provides an overview of the QoL in postmenopausal Italian women in relation with VVA severity. We included 1066 women attending menopause/gynaecologic centres. A face-to-face survey (including QoL and sexual life questionnaires), joining an objective gynaecological examination to confirm VVA, were performed. The 65.5% of the participants presented severe vaginal, vulvar and/or urinary symptoms; an 86.9% had an objective confirmed VVA. Women with severe symptoms presented with significantly worse QoL scores than the women without. We found there were moderately significant correlations between vaginal and vulvar symptoms' severity and lower overall DIVA QoL scores (p<.0005, in both cases). Women with a confirmed VVA presented worse QoL scores than women without confirmation. Our data suggest a clear relationship between VVA severity and a decrease in QoL in postmenopausal Italian women.IMPACT STATEMENTWhat is already known on this subject? Vulvovaginal atrophy (VVA) appears as a common chronic disorder in postmenopausal women that, as soon as the oestrogen levels decrease, becomes a severe condition affecting their quality of life (QoL).What do the results of this study add? We provide new insight about QoL related to VVA severity in Italian postmenopausal women. Our local data demonstrates that QoL in Italian women suffering from menopause is directly related to the severity of vaginal and vulvar symptoms. The same correlation exists for urinary symptoms. QoL is also reduced in patients with an objectively confirmed VVA diagnosis.What are the implications of these findings for clinical practice and/or further research? The implications of our findings involve the need for a better management, not only of the physical aspects of VVA, but also of the non-physical dimensions. Clinicians should ask for the impact of VVA on QoL aspects, making postmenopausal women aware about the possible affected spheres. Medical personnel should conduct future campaigns in the Italian general population, not only in those asking for medical help, to make all women conscious about this silent disorder affecting physical and non-physical dimensions and in order to treat it at early stages.

Role of HPV testing in the follow-up of women treated for cervical dysplasia.

PURPOSE: The aim of study was to investigate factors predicting persistence or relapse of disease after cervical conisation for high-grade squamous intraepithelial lesions (CIN 2 or 3). METHODS: The study involved 78 women with high-grade squamous intraepithelial lesions, conservatively treated with loop electroexcision procedure for cervical conisation and subsequent with CO(2) laser-vaporisation of the cervical bed. Histological specimens were totally included and examined by an experienced pathologist. To evaluate the efficacy of treatment, the patients were examined with colposcopy and Pap smear 4 months after surgery and with PCR to search for and genotyping of HPV, 10 months after treatment. RESULTS: During the post-treatment follow-up, the cytologic examination showed persistent/relapsing disease in six patients (7.6%). In only 1 case, the deep margin of the cone was considered positive for CIN (16%).Ten months after treatment, viral typing revealed the persistence of high-risk HPV in all of these patients. Conversely, the viral follow-up of the other 72 patients without persisting/relapsing disease after treatment disclosed low-risk HPV genotypes in 6 cases, high-risk HPV in 2 cases (2.7%), whereas 7 cases had positive margins for CIN (9.7%). The risk of persistence and relapse of CIN in the group with positive margins was not statistically significant (P = 0.87), whereas it was in the group with HR-HPV positive (P = 0.000048). CONCLUSION: HPV testing is the most sensitive mean of identifying persistence or relapse early and is therefore capable of optimising follow-up after the treatment of high-grade CIN.

Obstetric outcomes in patients who have undergone excisional treatment for high-grade cervical squamous intra-epithelial neoplasia.

OBJECTIVE: To evaluate the relationships between excisional treatment for high-grade cervical intra-epithelial neoplasia (CIN2+) and obstetric outcomes in terms of preterm delivery risk, premature rupture of membrane (PROM) and type of delivery, and between pre-term delivery and the type of excisional technique (radio frequency excision, laser conization). METHODS: This was a retrospective study of the obstetric outcomes of 2316 women aged 25-45 years who underwent excisional treatment for CIN2+ at the Obstetric and Gynecological Clinic of Ospedale Maggiore della Carità in Novara and at the Obstetric and Gynecological Department of Ospedale Sant'Anna in Torino in the period 2005-2014 and were evaluated until April 2016, and 57,937 untreated women of the same age, from the same centers. RESULTS: After treatment, 320 women had at least one pregnancy leading to delivery after a mean of 3.35 years. Treatment significantly increased the risk of preterm delivery. Compared with no treatment, the risk of preterm birth was higher in women who had undergone treatment (33.13% vs. 6.60%). Techniques removing or ablating more tissue, such as large loop excision of the transformation zone, were associated with worse outcomes (OR 2.96, 95% IC 1.72-5.10). Smoking habits significantly increase the risk of preterm delivery in the treated women (OR 2.82, 95% IC 1.61-4.9). The risk of premature rupture of the membranes (PROM) (40% vs. 23.22%), the risk of preterm PROM (pPROM) (13.13% vs. 2.71%) and dystocic births (18.75% vs 4.48%) were also significantly increased after treatment. Caesarean sections were less frequent among the treated women (15.94% vs. 32.41%). CONCLUSIONS: Our findings reveal a relationship between cervical excisional treatment and pre-term delivery, PROM, and the method of delivery. In order to minimise risk and guarantee the best obstetric outcome, patient treatment and follow-up should be personalised.

Latent human polyomavirus infection in pregnancy: investigation of possible transplacental transmission.

AIMS: The purpose of the study was to investigate the transplacental transmission of the human polyomaviruses JCV and BKV. METHODS: Urine and blood samples from 300 pregnant women underwent cytological analysis to search for 'decoy cells', nested PCR to identify presence and genotype of isolated polyomaviruses, and sequence analysis of the transcription control region. Nested PCR was also used to study the umbilical cord blood of all their newborns. RESULTS: Decoy cells were identified in only one urine sample (1/300; 0.33%); polyomavirus DNA was detected in 80 urine samples (26.6%) corresponding to BKV alone in 28 samples (9.3%), JCV alone in 49 samples (16.3%) and both JCV-BKV in three samples (1%). Blood samples were positive in 17 cases (5.6%), corresponding to BKV alone in 10 (3.3%), and JCV alone in 7 (2.3%). Rearrangements of the transcription control region were found in only one urinary JCV strain, consisting of the insertion of 13 bp at D block, whereas point mutations were identified in 11 BKV and 11 JCV strains detected from urine. Sequence analysis of the BKV strains detected in blood samples revealed a 20 bp insertion of P block (P42-61) in human chromosomes 20 (five cases) and 14 (three cases); two JCV strains had single bp point mutations. The search for polyomavirus DNA in umbilical cord blood samples was always negative. CONCLUSIONS: Polyomavirus DNA was frequently detected in pregnancy, whereas genomic rearrangements were rare, and no evidence of transplacental transmission of polyomavirus was obtained.

Fatal splenic rupture in a pregnant woman with hemoglobin C/beta-thalassemia and myeloid metaplasia.

Splenic rupture with intraperitoneal hemorrhage is a fatal condition that is rarely encountered during the third trimester of pregnancy; its pathogenetic mechanisms and causes are largely unknown. We report a case of splenic rupture in a pregnant woman that caused the death of the mother and child. The patient was a carrier of double heterozygosis for hemoglobin C/beta-thalassemia. Spleen and liver enlargement due to extramedullary hematopoiesis was found at autopsy. Our data suggest that rare and hidden hematologic disorders should be considered as possible causes of splenic enlargement and rupture during pregnancy.

Interobserver variability of colposcopic interpretations and consistency with final histologic results.

OBJECTIVE: To evaluate the interobserver reliability of colposcopy and the prediction of final histologic results. MATERIALS AND METHODS: Visibility of the squamocolumnar junction, presence and grading of atypical transformation zone (ATZ), and presence and grading of cervical intraepithelial neoplasia (CIN) were assessed by nine expert colposcopists in 100 cervigrams. Pairwise kappa, group kappa, and class-specific kappa values were computed. Frequency and degree of interobserver disagreement on CIN and ATZ grading and correlation with histologic results were studied. RESULTS: The median pairwise kappa and the group kappa values were excellent for ATZ detection, acceptable for the squamocolumnar junction, and poor for the other variables; the presence of ATZ had a sensitivity for CIN of 90.2% and a specificity of 48.6%; the colposcopic impression of high-grade CIN had a sensitivity of 54.4% and a specificity of 88%. CONCLUSIONS: Some colposcopic predictions are reproducible between observers, predictive of the histologic results, and can be integrated in the algorithm for the management of patients with abnormal Pap smear results.