Anyplex II HPV test in detection and follow-up after surgical treatment of CIN2+ lesions.

Human papillomavirus (HPV) tests differ for technology, targets, and information on the genotype and viral load. In this study, we evaluated the performance of the Seegene Anyplex II HPV HR (Anyplex) assay in the detection of cervical intraepithelial lesions (CIN) and as a test-of-cure in the follow-up after surgical treatment. One hundred and sixty-seven women referred to the European Institute of Oncology, Milan, for surgical treatment of CIN2+ were enrolled. A cervical sample was taken before treatment and at the first follow-up visit: on these samples, Qiagen Hybrid Capture 2 (HC2), Roche Linear Array HPV Test (Linear Array), cytology and histology were performed at baseline, HC2, and cytology at follow-up. Anyplex genotyping HPV test was performed on a post aliquot from liquid-based cytology specimens when available. The concordance between Anyplex and HC2 was 93.6% at baseline and 76.7% at follow-up (3-9 months after treatment), respectively. The concordance between Anyplex and Linear Array was evaluable only at baseline (92.9%). No recurrence occurred in women without the persistence of the same genotype at follow-up. Seven women relapsed: six had persistence of the same genotypes (five HPV16, one HPV33, and one HPV39), while one tested negative not only with Anyplex but also with HC2 for the persistence of low-risk genotype infection (HPV73 only detected by Linear Array). Anyplex test represents a valid option for HPV detection and genotyping in order to stratify women at risk of high-grade lesions at baseline and to monitor patients treated for CIN2+ lesions during follow-up.

Onclarity Performance in Human Papillomavirus DNA Detection in Formalin-Fixed Paraffin-Embedded Cervical Samples.

OBJECTIVES: Diagnosis of HPV infection is usually performed from cervical liquid-based cytology specimens (LBC), but these often contain a large amount of human papillomavirus (HPV) genotypes, most of which might cause transient infections. The aim of the study was to evaluate the performance of BD Onclarity HPV test genotyping method on formalin-fixed, paraffin-embedded (FFPE) cervical specimens compared with genotyping results from LBC. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded specimens from women surgically treated for cervical intraepithelial lesions (CINs) at the European Institute of Oncology, Milan, from September 2012 to June 2013 were retrieved from the archives of the Department of Pathology of the European Institute of Oncology. The FFPE and LBC specimens were genotyped using the same extended genotyping Onclarity assay. RESULTS: We collected 99 samples (26 CIN 1, 30 CIN 2, and 43 CIN 3+), but 15 were excluded from the analysis: these 84 samples show an overall agreement of 89% for HPV status between FFPE Onclarity samples versus LBC samples. The FFPE and LBC samples showed identical genotype in 75% samples, compatible genotype (at least 1 of the genotypes detected in LBC sample was found in the tissue sample) in 14% specimens, and discrepant genotype in 11% samples. CONCLUSIONS: Our data demonstrate a very good concordance between HPV genotypes found in cytological and tissue samples, suggesting that the Onclarity method could also be used to detect HPV in tissue samples and that the HPV genotype detected in FFPE samples is one of the HPV detected in cytological samples, supporting the thesis that one lesion is caused by one HPV genotype.

Distribution of High-Risk Human Papillomavirus Genotypes and Multiple Infections in Preneoplastic and Neoplastic Cervical Lesions of Unvaccinated Women: A Cross-sectional Study.

OBJECTIVE: The aim of the study was to investigate the distribution of high-risk (HR) human papillomavirus (HPV) genotypes and the role of multiple infection in preneoplastic and neoplastic cervical lesions, according to histology, age, and the number of genotypes per infection. MATERIALS AND METHODS: Nine hundred eighty-eight women affected by known HPV-related cervical lesions and attending the European Institute of Oncology, Milan, Italy, from December 2006 to December 2014, were selected for a cross-sectional study. Prevalence of HPV genotypes was calculated by histology and the number of genotypes per infection. Univariate and multivariable cervical intraepithelial neoplasia (CIN) 2-3 versus CIN 1 risks were estimated by logistic regression models. RESULTS: Overall, HPV 16 (53.1%), HPV 31 (15.1%), and HPV 58 (6.4%) were the most frequent genotypes in precancerous lesions. At multivariable analysis, HPV 16 (p = .02), 18 (p = .013), and 56 (p = .01) were significantly associated to worsen histology, whereas HPV 39 (p = .03) and 45 (p = .03) were statistically correlated only to the increasing number of genotypes per infections. Human papillomavirus 33 was the only genotype significantly related to both the number of genotypes per infection (p = .005) and age (p = .03). Infections by HR-HPV (odds ratio [OR] = 9.48, 95% CI = 3.77-23.8, p < .001), HPV genotypes covered by current vaccines (OR = 6.28, 95% CI = 4.05-9.75, p < .001), single HPV genotype (OR = 8.13, 95% CI = 4.12-16.0, p < .001), as well as age (OR = 1.13, 95% CI = 1.07-1.19, p < .001) were significantly associated to higher risk of CIN 2-3. CONCLUSIONS: The most of CIN 2+ lesions are sustained by HR-HPV genotypes, especially the ones covered by 9-valent vaccine; therefore, the widespread use of prophylactic HPV vaccines could significantly reduce the incidence of preneoplastic and neoplastic cervical lesions.

Onclarity Human Papillomavirus Extended Genotyping in the Management of Cervical Intraepithelial Neoplasia 2+ Lesions.

OBJECTIVE: Many methods are available today for human papillomavirus (HPV) testing; they differ for technology, targets, and information on the genotypes detected. In this study, we evaluated the performance of the Onclarity HPV assay in detection and follow-up of cervical preneoplastic lesions. MATERIALS AND METHODS: One hundred sixty-seven women referred to the European Institute of Oncology, Milan, for treatment of cervical lesions were enrolled. We investigated the utility of Onclarity extended genotyping HPV test in the management of cervical intraepithelial neoplasia (CIN) 2+ preneoplastic lesion. RESULTS: At baseline, the concordance was 92% (150/163) between Onclarity and Hybrid Capture 2 (HC2) and 93% (142/152) between Onclarity and linear array, respectively. At follow-up, the concordance between Onclarity and HC2 was 80%. Seven women relapsed: 6 had persistence of the same genotypes and 1 patient tested negative not only with Onclarity but also with HC2 for the presence of a low-risk genotype in the sample. CONCLUSIONS: This study showed that the evaluation of the HPV genotype persistence may represent a valid option to monitor patients treated for CIN 2+ lesions, because relapses were detected only in patients with persistence of the same genotype detected at baseline.

What Is the Role of Barbed Suture in Laparoscopic Myomectomy? A Meta-Analysis and Pregnancy Outcome Evaluation.

BACKGROUND: This work analyzes the feasibility and effectiveness of barbed suture during laparoscopic myomectomy. METHODS: Eight works have been carefully examined for the meta-analysis from all papers published online until November 2017. RESULTS: Barbed suture proved to be superior to traditional suture technique in blood loss in laparoscopic myomectomy (Standardized Mean Difference [SMD] -0.650, 95% CI -1.420 to -0.119, p = 0.098, test for heterogenity p < 0.0001, I2 = 95.54%), Hb drop (SMD -1.452, 95% CI -3.590 to 0.687, p = 0.183, test for heterogenity p < 0.0001, I2 = 99.08%), suturing difficulty (SMD -0.638, 95% CI -0.935 to -0.342, p ≤ 0.001, test for heterogenity p = 0.25, I2 = 27.84%), suturing time (SMD -1.197, 95% CI -1.848 to -0.549, p ≤0.001, test for heterogenity p = 0.0001, I2 = 83.30%) and total operative time (SMD -0.687, 95% CI -0.804 to -0.569, p ≤ 0.001, test for heterogenity p = 0.292, I2 = 17.44%). Barbed suture demonstrated to be better in comparison with the control group even with regard to the length of hospitalization (SMD -0.278, 95% CI -0.543 to 0.012, p = 0.040, test for heterogenity p = 0.025, I2 = 61.85%), and to perioperative complications (SMD 0.708, 95% CI 0.503-0.996, p = 0.048, test for heterogenity p = 0.79, I2 = 0%). CONCLUSION: Barbed suture significantly facilitates laparoscopic myomectomy by reducing the total operative/suturing time, estimated blood loss/Hb drop, and reduction of perioperative complications.

Outcome of Persistent Low-Grade Cervical Intraepithelial Neoplasia Treated With Loop Electrosurgical Excision Procedure.

OBJECTIVE: The aim of the study was to evaluate the outcome of persistent (≥2 years) low-grade cervical intraepithelial neoplasia (CIN 1) treated with loop electrosurgical excision procedure (LEEP). MATERIALS AND METHODS: A study of 252 subjects with persistent biopsy-confirmed CIN 1 diagnosed after low-grade squamous intraepithelial lesions or atypical squamous lesions of undetermined significance on Papanicolaou test and treated with LEEP. Post-LEEP follow-up cytological, colposcopic, and molecular diagnostic examinations were scheduled at 6 months, 1 year, and yearly thereafter. RESULTS: The 252 subjects enrolled had a total number of 1,008 visits per colposcopies (median = 3, range = 1-7) during a median post-LEEP follow-up of 25 months (range = 12-121). The cumulative incidence of CIN 2+ at 2 years and at 3 years of follow-up was 2.3% (4/176) and 5.5% (7/128), respectively, or 1.7 cases (95% CI = 1-2.8) per 100 woman-years. Low-grade cervical lesions during post-LEEP follow-up were diagnosed in 70 subjects (27.8%) or 10 cases (95% CI = 7.9-12.6) per 100 woman-years. Overall, persistent and multiple high-risk HPV infections during follow-up were associated with increased rates of CIN persistence or progression. CONCLUSIONS: Women with persistent CIN 1 after atypical squamous lesions of undetermined significance/low-grade squamous intraepithelial lesion treated with LEEP had a low rate of progression to CIN 2+ but remained at a high risk of low-grade cervical abnormalities during follow-up. This information should be taken into account when deciding on the treatment strategy and counseling women with persistent CIN 1.

Multiple Papillomavirus Infection and Size of Colposcopic Lesions Among Women With Cervical Intraepithelial Neoplasia.

OBJECTIVE: The aim of the study was to evaluate the association between the size of cervical lesions as detected by colposcopy and multiple human papillomavirus (HPV) infection in subjects with cervical intraepithelial neoplasia (CIN). METHODS: A case series of 898 subjects with CIN diagnosed by histopathology and infected by high-risk HPV. Human papillomavirus genotypes were identified using the INNO-LIPA genotyping system. RESULTS: The rates of CIN 1, CIN 2, and CIN 3+ lesions were 53.1% (477/898), 14.1% (127/898), and 32.7% (294/898), respectively. Among CIN lesions diagnosed by loop electrosurgical excision procedure or by cold-knife conization, the rates of multiple as compared with single HPV infections increased from 31.7% (59/186) in lesions covering 0% to 25% of the cervix to 39.2% (40/102), 41.9% (13/31), and 48.9% (45/92) in those covering 26% to 50%, 51% to 75%, and more than 75% of the cervix, respectively (χ for trend = 7.9; p = .005). In ordered logistic regression, after correction for confounders, odds ratios (ORs) of larger cervical lesions were higher in multiple as compared with single infections (OR = 1.82; 95% CI = 1.24-2.66; p = .002). This association was confirmed among subjects infected by HPV 16 (OR = 2.45; 95% CI = 1.14-5.26; p = .02) and in CIN 3+ lesions (OR = 2.43; 95% CI = 1.23-4.80; p = .01). CONCLUSIONS: Multiple high-risk HPV infection is associated with larger cervical lesions as detected by colposcopy. This association was confirmed among subjects infected by HPV 16 and in CIN 3+ lesions.

The Mucosal Innate Immune Response in Primary Human Papillomavirus Infection: A Pilot Study.

OBJECTIVES: The purpose of the study was to evaluate the mucosal immune response in women affected by primary human papillomavirus (HPV) infection, in comparison with HPV-negative women with no previous history of HPV. METHODS: A case-control study comparing the activity of myeloperoxidase (MPO) and lactoferrin (LF) between 19 HPV-positive and 19 HPV-negative women matched for age. Plasmatic and cervicovaginal levels of polymorphonuclear neutrophils (PMN) exhibiting MPO and LF receptors were measured using cytofluorimetric analysis and expressed as mean of percentages. RESULTS: Cervicovaginal levels of MPO-/LF- PMN were lower among HPV-negative women, with a mean rate of 18.81% (SD, 21.38), as opposed to a mean rate of 35.56% (SD, 21.02) (P = 0.020) in HPV-positive women. A similar significant difference was not proven in plasma. The mean rates of plasmatic levels of MPO-/LF- PMN were 36.21% (SD, 16.87) and 36.93% (SD, 10.54) (P = 0.875) in cases and controls, respectively. All patients were evaluated 1 year later, and only 6 cases became negative. CONCLUSIONS: The presence of MPO-/LF- PMN has been considered as a marker of lower rate of apoptosis of HPV-infected cells. This could explain why HPV-positive women are less capable to deal with a primary infection.

Obstetric risk factors and time trends of neurodevelopmental outcome at 2 years in very-low-birthweight infants: a single institution study.

AIM: To assess the time trends of neonatal survival and infant neurodevelopmental outcome in very-low-birthweight children at 24 months corrected age over a 20-year period. METHOD: The study cohort comprised 857 infants (439 males and 418 females) weighing less than 1500g at birth or delivered before 32 weeks gestational age in the period 1989 to 2008. Neurological examination and cognitive assessment of the infants (Bayley Scales of Infant Development and Griffiths Mental Developmental Scale) were performed at 24 months corrected age. RESULTS: The prevalence of neonatal survival with normal neurodevelopmental outcome increased from 55.3% (104/188) in 1989 to 1993, to 61.4% in 1994-1998 (116/189), 68.3% in 1999 to 2003 (138/202), and 84.5% in 2004 to 2008 (235/278) (annual increase=1%, 95% CI 2.1-4.1; p<0.001). In logistic models, the increase in the rate of normal neurodevelopmental outcome during the periods studied was consistent across the categories of birthweight (≤1000g as opposed to >1000g), gestational age (≤28wks as opposed to >28wks), and clinical characteristics (pre-eclampsia/growth restriction as opposed to spontaneous prematurity/rupture of membranes). INTERPRETATION: The increased rate of normal neurodevelopmental outcome at 2 years among very-low-birthweight infants is independent of obstetric risk factors.

Effect of local estrogen therapy (LET) on urinary and sexual symptoms in premenopausal women with interstitial cystitis/bladder pain syndrome (IC/BPS).

The association between vulvodynia and interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic, debilitating disease of unknown etiology, may involve sex hormone-dependent mechanisms regulating vulvo-vaginal health. We aimed to prospectively investigate the effects of 12 weeks of local estrogen therapy (LET) on urinary/bladder and sexual symptoms in premenopausal women with IC/BPS. Thirty-four women (mean age: 36.1 ± 8.4) diagnosed with IC/BPS were treated vulvo-vaginally three-times/week with estriol 0.5 mg cream and tested by validated questionnaires (ICSI/ICPI, pain urgency frequency [PUF], female sexual function index [FSFI]) and by cotton swab testing, vaginal health index (VHI) and maturation index (MI) before and after treatment. Vulvodynia was present in 94.1% of IC/BPS women. A significant positive effect of LET was evident on urinary and sexual function (p < 0.001, for both) following 12 weeks, as well as an improvement of the VHI (p < 0.001) and the MI (p < 0.04). The results of this open study indicate that 12 weeks of local estriol cream at vaginal and vestibular level may ameliorate urinary/bladder pain symptoms, as well as may improve domains of sexual function. The association between vulvar pain and bladder pain could, therefore, be related to a vaginal environment carrying signs of hypoestrogenism, but further studies are needed to clarify this issue.

Advancing Tailored Treatments: A Predictive Nomogram, Based on Ultrasound and Laboratory Data, for Assessing Nodal Involvement in Endometrial Cancer Patients.

Assessing lymph node metastasis is crucial in determining the optimal therapeutic approach for endometrial cancer (EC). Considering the impact of lymphadenectomy, there is an urgent need for a cost-effective and easily applicable method to evaluate the risk of lymph node metastasis in cases of sentinel lymph node (SLN) biopsy failure. This retrospective monocentric study enrolled EC patients, who underwent surgical staging with nodal assessment. Data concerning demographic, clinicopathological, ultrasound, and surgical characteristics were collected from medical records. Ultrasound examinations were conducted in accordance with the IETA statement. We identified 425 patients, and, after applying exclusion criteria, the analysis included 313 women. Parameters incorporated into the nomogram were selected via univariate and multivariable analyses, including platelet count, myometrial infiltration, minimal tumor-free margin, and CA 125. The nomogram exhibited good accuracy in predicting lymph node involvement, with an AUC of 0.88. Using a cutoff of 10% likelihood of nodal involvement, the nomogram displayed a low false-negative rate of 0.04 (95% CI 0.00-0.19) in the training set. The adaptability of this straightforward model renders it suitable for implementation across diverse clinical settings, aiding gynecological oncologists in preoperative patient evaluations and facilitating the design of personalized treatments. However, external validation is mandatory for confirming diagnostic accuracy.

The Editorial of the Special Issue "Diagnosis of Lower Genital Tract Disease".

A range of conditions involving the vulvovaginal and anal area, and those associated with human papillomavirus (HPV) infection, which can manifest as benign, pre-neoplastic, or neoplastic lesions, can be grouped into lower genital tract diseases [...].

Human Papillomavirus Genotype Richness and the Biodiversity of Squamous and Glandular Cervical Dysplasias: A Cross-Sectional Study.

The impact of multiple infections on the risk of cervical lesions is a subject of ongoing debate. This study aims to explore whether the richness of HPV genotype infections and the biodiversity of squamous and glandular cervical dysplasias could influence the progression of precancerous lesions. We conducted a cross-sectional analysis involving 469 women who attended the Colposcopy Unit at the European Institute of Oncology in Milan, Italy, from December 2006 to December 2014. HPV type richness was measured as the number of different genotypes per patient. We calculated the associations between richness and age, as well as histologic grade, along with Simpson's biodiversity index for cervical dysplasias. We observed significant inverse relationships between the richness of high-risk (HR) genotypes and both age (p = 0.007) and histologic grade (p < 0.001). Furthermore, as the histologic grade increased, the mean biodiversity index of cervical dysplasias decreased, with exceptions noted in cases of normal histology and adenocarcinoma in situ. Different histologic grades formed five clusters with distinct mean ages and mean biodiversity indices. These findings suggest that HPV genotype richness and the biodiversity of cervical dysplasias may play a crucial role in predicting the risk of high-grade cervical lesions, enabling personalized management of precancers.

Sparing Is Caring: Hormonal Retreatment in Women with Recurrent Endometrial Cancer after Fertility Preservation Management-A Single Centre Retrospective Study.

Fertility-sparing treatment (FTS) of endometrial cancer (EC) has a high rate of remission but also a high rate of relapse (10-88%). Many women still wish to conceive at the time of relapse, but results regarding retreatment are still lacking. This study aims to evaluate the safety, oncological and pregnancy outcomes of repeated FST in women with recurrent EC. This is a retrospective single-center study that recruited patients who had uterine recurrence after achieving a complete response (CR) with FST for FIGO stage IA, well-differentiated (G1), endometrioid EC. All eligible women underwent a second FST. Among 26 patients with recurrence, 6 decided to receive a hysterectomy and 20 received fertility-sparing retreatment. In total, 17 out of 20 women (85%) achieved a CR in a median time of 6 months. A total of 2/20 women showed a stable disease and continued the treatment for a further 6 months and finally achieved a CR. In total, 1/20 women showed disease progression and underwent demolitive surgery. After relapse and a CR, 14 patients attempted to become pregnant, among whom 7 became pregnant (pregnancy rate 50%-life birth rate 29%). Secondary FST is a safe and effective option for women who desire to preserve fertility after the recurrence of early-stage EC.

Tips and Tricks for Early Diagnosis of Cervico-Vaginal Involvement from Extramammary Paget's Disease of the Vulva: A Referral Center Experience.

Cervico-vaginal (CV) localization of extra-mammary Paget's disease (EMPD) of the vulva is extremely rare. In order to investigate the incidence risk and the pathognomonic clinical and pathological features of this condition, a retrospective analysis was conducted including 94 women treated for vulvar EMPD at the European Institute of Oncology, Milan, Italy, from October 1997 to May 2020. Overall nine patients developed CV involvement from EMPD, with a cumulative incidence of 2.5% (95% CI: 0.5-8.0%) at 5 years, 6.5% (95% CI: 1.9-15.1%) at 10 years and 14.0% (95% CI: 4.8-27.8%) at 15 years, respectively. All cases except one were firstly detected by abnormal glandular cytology. None reported vaginal bleeding or other suspicious symptoms. The colposcopic findings were heterogeneous and could sometimes be misdiagnosed. Cervical and/or vaginal biopsies were always performed for histopathological diagnosis by identification of Paget cells in the epithelium or stroma. Most patients developed invasive EMPD (5/9) of the cervix and/or vagina and underwent hysterectomy with partial or total colpectomy. CV involvement from EMPD should not be underestimated in women with a long-standing history of vulvar Paget's disease. Liquid-based cytology with immunocytochemistry represents a valuable tool for early diagnosis and should be routinely performed during the required lifelong follow-up.

Which Risk Factors and Colposcopic Patterns Are Predictive for High-Grade VAIN? A Retrospective Analysis.

Colposcopic patterns of Vaginal Intraepithelial Neoplasia (VAIN) are not definitively related to histological grade. The aim of the present study was to investigate any correlation between clinical and colposcopic features and the development of high-grade VAIN. Two hundred and fifty-five women diagnosed with VAIN (52 VAIN1, 55 VAIN2 and 148 VAIN3) at the European Institute of Oncology, Milan, Italy, from January 2000 to June 2022, were selected for a retrospective analysis. Multivariate logistic regression was performed to estimate the association of risk factors and colposcopic patterns with VAIN grade. Smoking was associated with the development of VAIN (34.1%, p = 0.01). Most women diagnosed with VAIN3 (45.3%, p = 0.02) had a previous history of hysterectomy for CIN2+. At multivariate analysis, colposcopic grade G2 (OR = 20.4, 95%CI: 6.67−61.4, p < 0.001), papillary lesion (OR = 4.33, 95%CI: 1.79−10.5, p = 0.001) and vascularity (OR = 14.4, 95%CI: 1.86−112, p = 0.01) were significantly associated with a greater risk of VAIN3. The risk of high-grade VAIN should not be underestimated in women with a history of smoking and previous hysterectomy for CIN2+, especially when colposcopic findings reveal vaginal lesions characterized by grade 2, papillary and vascular patterns. Accurate diagnosis is crucial for an optimal personalized management, based on risk factors, colposcopic patterns and histologic grade of VAIN.