Management options for vaginal intraepithelial neoplasia.

BACKGROUND: Vaginal intraepithelial neoplasia (VaIN) is a rare disease of the lower genital tract, strongly associated with HPV infection, which may progress to vaginal carcinoma. PURPOSE: The aim of this review is to summarise current treatment options, evaluate their efficacy and make provide recommendations on the optimal management of the disease. MATERIALS AND METHODS: A comprehensive search of the literature was performed using the PubMed database for articles referring to the treatment of VaIN. We restricted our search only in articles written in English with publication dates within the last 10 years. RESULTS: Surgical approach included local excision, CO2 laser ablation, CO2 laser skinning colpectomy and laparoscopic upper vaginectomy. Medical management was based on intravaginally administered topical agents such as 5% imiquimod cream, 5-fluorouracil cream and topical oestrogens. Intracavitary radiation therapy was reported in two forms: Low-dose rate (LDR) brachytherapy and high-dose rate (HDR) brachytherapy. All treatment options were well tolerated, with satisfactory cure rates and acceptable recurrence rates. CONCLUSION: The choice of treatment depends upon many factors. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Topical agents are useful for persistent, multifocal lesions or for women that cannot undergo surgical treatment. Brachytherapy is associated with high morbidity rates and should be reserved for women who have multifocal disease, are poor surgical candidates and/or have failed other treatments. CO2 laser ablation achieves minimal scarring and sexual dysfunction; however, invasive disease should be ruled out with biopsies before the initiation of the treatment.

A Narrative Review on the Clinical Utility of Electrical Impedance Spectroscopy for Diagnosing High-Grade Cervical Intraepithelial Neoplasia.

Colposcopy constitutes a pivotal step in the diagnosis and management of cervical intraepithelial neoplasia; nevertheless, the method has several inherent and external limitations. Electrical impedance spectroscopic (EIS) has been among the adjuncts that have been developed to increase the diagnostic accuracy of colposcopy. EIS is based on the principle that the trajectory of electrical current alters depending on the consistency of the tissues. In the present study, we investigate the diagnostic accuracy and clinical utility of EIS by means of searching the available evidence. Our search yielded 17 articles during the period 2005-2023. Subsequently, we focused on the performance metrics of the included studies. The general concept is that EIS, in combination with colposcopy, is a method with increased sensitivity and specificity in detecting high-grade cervical intraepithelial neoplasia as compared to colposcopy alone. However, we documented a heterogeneous distribution of these and other metrics, including the positive predictive value, the negative predictive value, and the area under the receiver operating characteristic curve (AUC). Additionally, we located potential confounders that might hamper the measurements of EIS and, as such, warrant further investigation in future research. We conclude that future studies should be directed towards randomized multicentric trials, whereas the advent of artificial intelligence might improve the diagnostic accuracy of the method by helping incorporate a large amount of data.

Detection of High-Grade Cervical Intraepithelial Neoplasia by Electrical Impedance Spectroscopy in Women Diagnosed with Low-Grade Cervical Intraepithelial Neoplasia in Cytology.

The authors attempt to address the importance of timely detection and management of cervical intraepithelial neoplasia (CIN) to prevent cervical cancer. The study focused on the potential of electrical impedance spectroscopy (EIS) as an adjunct to colposcopy, aiming to enhance the accuracy of identifying high-grade cervical lesions. Colposcopy, a widely used technique, exhibited variable sensitivity in detecting high-grade lesions, which relies on the expertise of the operator. The study's primary objective is to evaluate the effectiveness of combining colposcopy with EIS in detecting high-grade cervical lesions among patients initially diagnosed with low-grade CIN based on cytology. We employed a cross-sectional observational design, recruiting 101 women with abnormal cervical cytology results. The participants underwent colposcopy with acetic acid and subsequent EIS using the ZedScan device. The ZedScan results are categorized into color-coded probability levels, with red indicating the highest likelihood of high-grade squamous intraepithelial lesions (HSIL) occurrence. Results revealed that ZedScan exhibits a sensitivity rate of 89.5% and a specificity rate of 84% for detecting high-grade lesions. Colposcopy, on the other hand, recorded a sensitivity rate of 85.5% and a specificity rate of 92%. The agreement rate between ZedScan and biopsy is 79.2%, as indicated by a kappa coefficient of 0.71, while the agreement rate between colposcopy and biopsy is 74.3%, with a kappa coefficient of 0.71.

mTOR downstream effectors, 4EBP1 and eIF4E, are overexpressed and associated with HPV status in precancerous lesions and carcinomas of the uterine cervix.

The present study aims to investigate the expression levels of two critical mammalian target of rapamycin (mTOR) downstream effectors, 4E binding protein 1 (4EBP1) and eukaryotic initiation factor 4E (eIF4E) proteins, in precancerous squamous intraepithelial lesions and cancer of the uterine cervix, and their association with human papilloma virus (HPV) infection status. Uterine cervical biopsies from 73 patients were obtained, including 40 fresh-frozen samples and 42 archival formalin-fixed, paraffin-embedded tissue specimens. Whole protein extracts were analyzed for the expression of 4EBP1 and eIF4E proteins using western blotting. In addition, distribution of 4EBP1 and eIF4E protein expression and 4EBP1 phosphorylation (P-4EBP1) were analyzed by immunohistochemistry in archival tissues and correlated with the degree of dysplasia. The presence of high-risk HPV (HR-HPV) types was assessed by polymerase chain reaction. Using western blot analysis, high expression levels of 4EBP1 and eIF4E were observed in all uterine cervical carcinomas, which significantly correlated with the degree of dysplasia. By immunohistochemistry, overexpression of 4EBP1 and eIF4E was detected in 20 of 21 (95%) and 17 of 21 (81%) samples, respectively, in patients with high-grade dysplasia and carcinomas, compared with 1 of 20 (5%) and 2 of 20 (10%) samples, respectively, in patients with low-grade lesions or normal histology. All 4EBP1-positive cases tested were also positive for P-4EBP1. Furthermore, overexpression of 4EBP1 and eIF4E significantly correlated with the presence of HR-HPV oncogenic types. The present study demonstrated that critical effectors of mTOR signaling, which control protein synthesis initiation, are overexpressed in cervical high-grade dysplasia and cancer, and their levels correlate with oncogenic HPV types. These findings may provide novel targets for investigational therapeutic approaches in patients with cancer of the uterine cervix.