Search Results (24)

Background: Vaginal intraepithelial neoplasia (VaIN) is a rare but potentially precancerous condition strongly associated with human papillomavirus (HPV) infection. Despite increased detection rates due to HPV screening and colposcopy, diagnosis and management remain challenging. This study aimed to evaluate the epidemiological characteristics, risk factors, and outcomes of VaIN in patients referred to a tertiary academic center. Methods: We conducted a retrospective analysis of 48 patients who underwent colposcopy-directed vaginal biopsies between January 2019 and June 2024 at the Medical University of Warsaw. Data collected included patient demographics, HPV status, cytology, histopathology, and treatment outcomes. Patients were grouped based on the presence and grade of VaIN (VaIN 1 vs. VaIN 2/3). Statistical analyses were performed using SPSS software. Results: VaIN was diagnosed in 24 patients (50%), VaIN was confirmed in half of the cohort, VaIN 2 in 30%, and VaIN 3 in 18% of cases. HPV infection and prior cervical pathology were significantly associated with VaIN diagnosis (P = 0.03 and P = 0.05, respectively), and high-risk HPV infection correlated with higher-grade lesions (P = 0.04). Among VaIN 2+ cases, most patients required laser ablation or surgical excision, while VaIN 1 often regressed spontaneously. Regression occurred in 11 cases, and high-risk HPV infection was inversely associated with spontaneous regression (P = 0.04). Conclusions: This study confirms the central role of HPV, particularly high-risk subtypes, in VaIN pathogenesis. Conservative management may be appropriate for VaIN 1, while VaIN 2+ requires active intervention. HPV genotyping should be integrated into diagnostic workups, and long-term follow-up is essential due to the risks of persistence and recurrence. Full article

Cervical intraepithelial neoplasia (CIN) is a premalignant cervical condition closely linked to persistent high-risk HPV infection, a major risk factor for cervical cancer. This study aims to investigate the relationship between cervicovaginal infections, HPV infection, and CIN development in 94 Romanian women with cervical lesions. Comprehensive assessments included HPV genotyping, cytology, colposcopy, and histopathology. In 53.20% of cases, vaginal infections were identified, with Candida albicans most frequently associated with HPV. Histopathology revealed 48.94% low-grade CIN, 42.55% high-grade CIN, and 8.51% invasive carcinoma. There was a strong correlation between high-risk HPV types (especially HPV 16 and 18), colposcopic findings, histopathology, and age. This study emphasizes the mutual effect of cervicovaginal infections and HPV infection in increasing the risk of developing CIN and cervical cancer among Romanian women. Persistent infection with high-risk HPV types, particularly HPV 16 and 18, has been confirmed as a primary driver of CIN and cervical cancer progression. Full article

Background/Objectives: The study aimed to investigate the efficacy of medication treatment with glycyrrhizinic acid for cervical intraepithelial neoplasia (CIN) 1 lesions. Methods: Women with histologically confirmed CIN 1 in cervical biopsies were included in the prospective study. Participants of the study group used glycyrrhizinic acid spray (Epigen spray) topically 10 days (Epigen 10-day subgroup) or 20 days (Epigen 20-day subgroup) per month for 6 months. Women in the control group had no treatment. There were two follow-up visits 6 months apart. All patients were screened for human papillomavirus (HPV) before enrollment and during the first follow-up visit. Results: There were 50 patients in the Epigen group and 50 patients in the control group. At the first follow-up visit, in the histological findings, progression to CIN 2+ was 6.7% in the Epigen 20-day subgroup, 31.1% in the control group, and the persistence of CIN 1 was 86.7% in the Epigen 20-day subgroup and 62.2% in the control group, p = 0.03. Large loop excision of the transformation zone (LLETZ) was statistically significantly more frequent in the control group after the first follow-up visit (10% in the Epigen 20-day subgroup vs. 30% in the control group, p = 0.032). No such relationships were found during the second follow-up visit. Conclusions: The vaginal spray of the glycyrrhizinic acid used 20 days per month appears to decrease the risk of the progression of CIN 1 lesions, with the need to perform LLETZ. However, a similar effect is not observed after stopping usage. Full article

Vaginal intraepithelial neoplasia (VAIN), linked to HPV infection, is a condition that is often overlooked during colposcopy, especially in the vaginal vault area, as clinicians tend to focus more on cervical lesions. This oversight can lead to missed or delayed diagnosis and treatment for patients with VAIN. Timely and accurate classification of VAIN plays a crucial role in the evaluation of vaginal lesions and the formulation of effective diagnostic approaches. The challenge is the high similarity between different classes and the low variability in the same class in colposcopic images, which can affect the accuracy, precision, and recall rates, depending on the image quality and the clinician’s experience. In this study, a dual-branch lesion-aware residual network (DLRNet), designed for small medical sample sizes, is introduced, which classifies vaginal lesions by examining the relationship between cervical and vaginal lesions. The DLRNet model includes four main components: a lesion localization module, a dual-branch classification module, an attention-guidance module, and a pretrained network module. The dual-branch classification module combines the original images with segmentation maps obtained from the lesion localization module using a pretrained ResNet network to fine-tune parameters at different levels, explore lesion-specific features from both global and local perspectives, and facilitate layered interactions. The feature guidance module focuses the local branch network on vaginal-specific features by using spatial and channel attention mechanisms. The final integration involves a shared feature extraction module and independent fully connected layers, which represent and merge the dual-branch inputs. The weighted fusion method effectively integrates multiple inputs, enhancing the discriminative and generalization capabilities of the model. Classification experiments on 1142 collected colposcopic images demonstrate that this method raises the existing classification levels, achieving the classification of VAIN into three lesion grades, thus providing a valuable tool for the early screening of vaginal diseases. Full article

It is now established that patients with rheumatoid arthritis (RA) have an increased risk of developing cervical cancer (CC) or its precursor, cervical intraepithelial neoplasia (CIN). However, the underlying mechanisms of this association have not been elucidated. RA is characterized by unresolved chronic inflammation. It is suggested that human papillomavirus (HPV) infection in RA patients exacerbates inflammation, increasing the risk of CC. The tumor microenvironment in RA patients with CC is also marked by chronic inflammation, which aggravates the manifestations of both conditions. Gut and vaginal dysbiosis are also considered potential mechanisms that contribute to the chronic inflammation and aggravation of RA and CC manifestations. Numerous clinical and pre-clinical studies have demonstrated the beneficial effects of various nutritional approaches to attenuate chronic inflammation, including polyunsaturated fatty acids and their derivatives, specialized pro-resolving mediators (SPMs), probiotics, prebiotics, and certain diets. We believe that successful resolution of chronic inflammation and correction of dysbiosis, in combination with current anti-RA and anti-CC therapies, is a promising therapeutic approach for RA and CC. This approach could also reduce the risk of CC development in HPV-infected RA patients. Full article

The data from the literature show that women undergoing a LEEP due to CIN3 have a greater risk of having subsequent high-grade anogenital intraepithelial neoplasia or cancer, and the risk is greater for vaginal cancer than for anal and vulvar cancers. It is hypothesized that the laparoscopic hysterectomy procedure may cause a higher incidence of VaIN in hysterectomized women. There are few studies addressing this issue, and they show mixed results. This study aimed to investigate the incidence of high-grade or severe VaIN in the population of women undergoing hysterectomy for CIN3 or benign uterine disease and illustrate the treatment options and follow-up. Methods: This retrospective study was conducted on 170 women who underwent a laparoscopic hysterectomy due to high-grade cervical intraepithelial neoplasia (CIN3) or benign gynecological disease. The follow-up strategy included performing a cotest and colposcopy with biopsy if necessary. The median time between primary treatment and a diagnosis of high-grade VaIN was 18 months. Results: High-grade or severe VaIN was found in eight patients after hysterectomy (4.7%). All cases of high-grade VaIN occurred in women with persistent HPV infection. The most frequent genotype was 16. Women hysterectomized due to CIN3 showed an eight-fold greater risk than women hysterectomized due to benign disease of developing high-grade VaIN. The risk of VaIN is low in women hysterectomized due to benign disease. The risk of developing VaIN is greater in women with viral persistence. Conclusion: All these elements suggest that it is a history of HPV-related disease of the lower genital tract and viral persistence, rather than hysterectomy itself, that should be considered risk factors for the development of high-grade VaIN. After hysterectomy, patients with a history of CIN should undergo annual screening with vaginal dome cytology and HPV testing. Full article

Persistent HPV infections may cause cervical and vaginal intraepithelial neoplasia (CIN and VaIN). Traditional methods might destroy the structure and function of the cervix. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive targeted therapy. This study aims to evaluate the efficacy and safety of ALA-PDT for CIN and VaIN and the clearance of HPV. A retrospective study of 303 patients who confirmed CIN or VaIN and received ALA-PDT was conducted. All the patients were followed up at six and twelve months after treatment and then annually thereafter. The effect was evaluated through HPV genotyping, a cytology test, and colposcopy-directed biopsy if necessary. After ALA-PDT, the remission rates for CIN 2, CIN 3, VaIN 2, and VaIN 3 were 90.6%, 88.5%, 87.3%, and 77.8%. For CIN 1, the remission rate at the six-month follow-up was 93.1%. The total HPV clearance rates were 72.5% at the six-month follow-up and 85.7% at the 12-month follow-up. The most common adverse event was vaginal discharge. No severe adverse effect was observed. ALA-PDT is an effective and safe treatment for all grades of CIN and VaIN and is helpful in clearing HPV with minimal side effects. This treatment may not influence fertility and delivery. Full article

(1) Background: Cervical intraepithelial neoplasia (CIN) is a precancerous condition linked to human papillomavirus (HPV) infection, often necessitating surgical interventions carrying the risk of subsequent preterm births. This study explores the potential of imiquimod (IMQ), as a non-invasive alternative treatment. The focus is on understanding IMQ impact on immune checkpoint molecules, particularly PD-1, PD-L1, and sHLA-G, which play pivotal roles in shaping immune responses and cancer progression. (2) Methods: Forty-three patients diagnosed with a high-risk squamous intraepithelial lesion (HSIL, p16-positive) self-applied 5% IMQ encapsulated in sachets containing 250 g of cream into the vaginal cavity three times a week for 16 weeks. The impact of IMQ therapy on cervical lesion regression was assessed through immunohistochemistry (IHC), examining changes in sHLA-G, PD-L1, and PD-1 levels. The antiviral activity of IMQ was evaluated through HPV-E7 immunofluorescence. Ethical considerations were adhered to, and the research methods were based on a previously approved clinical trial (clinicaltrials.gov Identifier: NCT04859361). (3) Results: IMQ treatment demonstrated efficacy, leading to lesion regression. sHLA-G levels in CIN before starting IMQ application were associated with unsuccessful treatment (p = 0.0036). IMQ did not significantly alter the expression of PD-1. We observed a decrease in PD-L1 levels in those who were successfully treated (p = 0.0509) and a reduction in HPV burden. (4) Conclusions: IMQ exhibits promise as a non-invasive treatment for CIN, emphasising its potential to modulate the immune microenvironment. Baseline sHLA-G levels emerge as potential predictors of treatment response. Understanding the nuanced dynamics of immune checkpoints sheds light on IMQ mechanism of action. Further exploration is warranted to decipher the intricate mechanisms underlying IMQ treatment in the context of cervical lesions. Full article

This comprehensive review encompasses studies examining changes in the cervical and cervico-vaginal microbiota (CM and CVM) in relation to human papillomavirus (HPV) using next-generation sequencing (NGS) technology. HPV infection remains a prominent global health concern, with a spectrum of manifestations, from benign lesions to life-threatening cervical cancers. The CM and CVM, a unique collection of microorganisms inhabiting the cervix/vagina, has emerged as a critical player in cervical health. Recent research has indicated that disruptions in the CM and CVM, characterized by a decrease in Lactobacillus and the overgrowth of other bacteria, might increase the risk of HPV persistence and the progression of cervical abnormalities. This alteration in the CM or CVM has been linked to a higher likelihood of HPV infection and cervical dysplasia. NGS technology has revolutionized the study of the cervical microbiome, providing insights into microbial diversity, dynamics, and taxonomic classifications. Bacterial 16S rRNA gene sequencing, has proven invaluable in characterizing the cervical microbiome, shedding light on its role in HPV infections and paving the way for more tailored strategies to combat cervical diseases. NGS-based studies offer personalized insights into an individual’s cervical microbiome. This knowledge holds promise for the development of novel diagnostic tools, targeted therapies, and preventive interventions for cervix-related conditions, including cervical cancer. Full article

Objective: This study aimed to validate the use of liquid phenol-based chemical peeling therapy for cervical and vaginal intraepithelial neoplasia (CIN and VaIN, respectively), with the goal of circumventing obstetric complications associated with surgical treatment and to determine the factors associated with treatment resistance. Methods: A total of 483 eligible women diagnosed with CIN, VaIN, or both, participated in this study. Participants underwent phenol-based chemical peeling therapy every 4 weeks until disease clearance. Disease clearance was determined by negative Pap tests for four consecutive weeks or by colposcopy. HPV genotyping was conducted at the onset of the study and after disease clearance in select cases. Our preliminary analysis compared the recurrence and persistence rates between 294 individuals who received phenol-based chemical peeling therapy and 189 untreated patients. Results: At 2 years following diagnosis, persistent disease was observed in 18%, 60%, and 88% of untreated patients with CIN1–3, respectively, and <2% of patients with CIN who received phenol-based chemical peeling therapy. Among 483 participants, 10 immune-suppressed patients required multiple treatments to achieve disease clearance, and 7 were diagnosed with cervical cancer. Of the 466 participants, except those with cancer or immune suppression, the number of treatment sessions until CIN/VaIN clearance ranged from 2 to 42 (average: 9.2 sessions). In total, 43 participants (9.2%) underwent surgical treatment. Six patients (1.3%) experienced recurrence of CIN2 or worse, suggesting that treatment failed in 46 patients (9.9%). No obstetrical complications were noted among the 98 pregnancies following this therapy. Factors associated with resistance to this therapy include immune suppression, ages 35–39 years, higher-grade lesions, and multiple HPV-type infections. Conclusions: Phenol-based therapy is safe and effective for CINs and VaINs. Women aged < 35 years and with persistent CIN1 or CIN2 with a single HPV-type infection are suitable candidates for phenol-based chemical peeling therapy. However, this therapy requires multiple lengthy sessions. Full article

(1) Background: Vaginal intraepithelial neoplasia (VaIN) is a rare premalignant disease caused by persistent human papillomavirus (HPV) infection. Diagnosing VaIN is challenging; abnormal cytology and positive HPV tests are usually the first signs, but published data on their accuracy for detecting it are rare and contradictory. The aim of this study is to compare the results of hrHPV and cytology co-testing with the histological findings of the vagina. (2) Methods: In the certified Dysplasia Unit at Erlangen University Hospital, cytology and HPV samples from the uterine cervix or vaginal wall after hysterectomy were obtained between 2015 and 2023 and correlated with histological findings in biopsies from the vaginal wall. Women without vaginal biopsy findings or concomitant cervical disease were excluded. (3) Results: In all, 279 colposcopies in 209 women were included. The histological results were: benign (n = 86), VaIN I/vLSIL (n = 116), VaIN II/vHSIL (n = 41), VaIN III/vHSIL (n = 33), and carcinoma (n = 3). Accuracy for detecting VaIN was higher in women with previous hysterectomies. Positive HPV testing during colposcopy increased the likelihood for VaIN II/III/vHSIL threefold. The detection rate for VaIN III/vHSIL was 50% after hysterectomy and 36.4% without hysterectomy. (4) Conclusions: Women with risk factors for VaIN, including HPV-16 infection or prior HPV-related disease, need careful work-up of the entire vaginal wall. Hysterectomy for HPV-related disease and a history of cervical intraepithelial neoplasia (CIN) also increased the risk for VaIN II/III/vHSIL. Full article

Background: Cervical intraepithelial neoplasia, the predisposing factor for cervical cancer (CC), is caused by human papillomavirus (HPV) infection and can be treated with imiquimod (IMQ). However, poor water solubility and side effects such as local inflammation can render IMQ ineffective. The aim of this study is to design a prolonged release nano system in combination with mucoadhesive–thermosensitive properties for an effective vaginal drug delivery. Methods: Polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), poly lactide-co-caprolactone (PLA-PCL), and poly L-lactide-co-caprolactone-co-glycolide (PLGA-PCL) were used to create IMQ nanoparticles. Chitosan (CS) was then added to the surfaces of the IMQ NPs for its mucoadhesive properties. The NPs were then incorporated into poloxamer hydrogels. The NPs’ size and morphology, encapsulation efficiency (EE), in vitro drug release, gel characterization, ex vivo drug permeation, and in vitro safety and efficacy were characterized. Results: Two batches of NPs were prepared, IMQ NPs and CS-coated NPs (CS-IMQ NPs). In general, both types of NPs were uniformly spherical in shape with average particle sizes of 237.3 ± 4.7 and 278.2 ± 5.4 nm and EE% of 61.48 ± 5.19% and 37.73 ± 2.88 for IMQ NPs and CS-IMQ NPs, respectively. Both systems showed prolonged drug release of about 80 and 70% for IMQ NPs and CS-IMQ NPs, respectively, within 48 h. The gelation temperatures for the IMQ NPs and CS-IMQ NPs were 30 and 32 °C, respectively; thus, suitable for vaginal application. Although ex vivo permeability showed that CS-IMQ NPs showed superior penetration compared to IMQ NPs, both systems enhanced drug penetration (283 and 462 µg/cm² for IMQ NPs and CS-IMQ NPs, respectively) relative to the control (60 µg/cm²). Both systems reduced the viability of cervical cancer cells, with a minimal effect of the normal vaginal epithelium. However, IMQ NPs exhibited a more pronounced cytotoxic effect. Both systems were able to reduce the production of inflammatory cytokines by at least 25% in comparison to free IMQ. Conclusion: IMQ and CS-IMQ NP in situ gels enhanced stability and drug release, and improved IMQ penetration through the vaginal tissues. Additionally, the new systems were able to increase the cytotoxic effect of IMQ against CC cells with a reduction in inflammatory responses. Thus, we believe that these systems could be a good alternative to commercial IMQ systems for the management of CC. Full article

Objective: This study aimed to investigate the preventive effect of a vaginal gel on p16/Ki-67-positive abnormal cytological cervical findings (ASC-US, LSIL) and hr-HPV in women. Methods: The study included 134 women with p16/Ki-67-positive ASC-US or LSIL. Participants were selected from a randomized controlled trial that focused on women with histological diagnoses of p16-positive CIN1 lesions or CIN2. In the treatment group (TG), 57 patients applied the vaginal gel daily for three months, while 77 patients in the “watchful wait” control group (CG) received no treatment. The study’s endpoints were cytological development, p16/Ki-67 and hr-HPV clearances. Results: At three months, cytopathological results improved in 74% (42/57) of patients in the TG, compared with 18% (14/77) in the CG. Progression occurred in 7% (4/57) of TG patients compared with 18% (14/77) of CG patients. The p16/Ki-67 status changed statistically significantly in favor of the TG (p < 0.001), with 83% (47/57) becoming negative, compared with 18% (14/77) in the CG. The prevalence of hr-HPV decreased significantly in the TG by 51%, and by 9% in the CG (p < 0.001). Conclusions: Topical application of the gel resulted in statistically significant clearance of hr-HPV and p16/Ki-67 concomitant with amelioration of cytological findings, thus providing effective prevention and protection against oncogenic development. Trial registration: ISRCTN11009040, on 10 December 2019. Full article

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. Full article

Background: in recent years, many studies were carried out to explore the role of vaginal microbiota in HPV infections and cervical intraepithelial neoplasia (CIN) progression. The aim of this study was to conduct a review of the literature to analyze the interaction between the vaginal microbiota, the CIN, and the immunological response. Methods: we performed a literature search, considering papers published between November 2015 and September 2021. Results: despite significant evidence suggesting a role of vaginal microbiota in the pathogenesis of HPV-related lesions, some studies still struggle to demonstrate this correlation. However, the vaginal microbiota of HPV-positive women shows an increased diversity, combined with a reduced relative abundance of Lactobacillus spp. and a higher pH. In cervical dysplasia progression, a strong association is found with new bacteria, and with the deregulation of pathways and hyperexpression of cytokines leading to chronic inflammation. Conclusions: in HPV progression, there is a strong correlation between potential biomarkers, such as Sneathia and Delftia found in community state types IV and II, and chronic inflammation with cytokine overexpression. Better analysis of these factors could be of use in the prevention of the progression of the disease and, eventually, in new therapeutic strategies. Full article