Aim:  To analyze the clinical features and colpohistology of women with vaginal intraepithelial neoplasia (VAIN).

Vaginal intraepithelial neoplasia (VaIN) is less common than intraepithelial neoplasia at other non-cervical sites and can be challenging to manage. This survey describes current clinical practice by colposcopists in the UK. An online questionnaire was emailed to all the lead colposcopists in U.K. A total of 86 (43%) responses were obtained. The median number of cases of VaIN seen in a year was five (range 0-100. Most clinics (95%) managed low grade VaIN conservatively. Local vaginal mucosal excision was the most common surgical procedure. Half of respondents adopted observation, although 64% of the units referred cases to a cancer centre. More than half used a combination of cytology and colposcopy for follow-up; only two reported using Human papilloma virus testing. Seventy-seven of eighty-six lead colposcopists did not have a local guideline and would support national guidance. Treatment differed across the UK with no agreed management guidelines.Impact statement Vaginal intraepithelial neoplasia (VaIN) is a pre-cancerous condition of lower genital tract and usually co-exists with cervical intraepithelial neoplasia (CIN) rather than in isolation. Unlike CIN, VaIN can be extremely challenging to manage in view of its anatomical proximity to bladder and bowel and also difficulty in accessing fornices. If diagnosed during the definitive management of CIN at the time of hysterectomy and confined to the upper vagina, it could be surgically treated at the same time. VaIN can be more challenging post-hysterectomy, especially following a failed medical and conservation option. Various treatment options are adopted for management of VaIN with no standardisation of care. A national survey was conducted to assess the management of VaIN amongst lead colposcopists. The national survey has added valuable results, despite a response rate of only 43%. The survey confirmed conservative approach to low grade VaIN but differing treatment for high grade VaIN. This clearly calls for the implementation of a national guideline in the UK to standardise management of VaIN, though it may be quite challenging. The survey could help inform implementation of HrHPV testing in recurrent or persistent VaIN.

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 aim of the study were to identify the risk factors for recurrent vaginal intraepithelial neoplasia (VaIN)1+ and to evaluate the efficacy of laser vaporization in patients who underwent hysterectomy for the treatment of cervical intraepithelial neoplasia (CIN).

The aim of the study was to analyze the clinical features of women found to have vaginal intraepithelial neoplasia (VaIN), the treatment modalities that they were offered, and clinical outcomes after treatment and follow-up.This is a retrospective review of all cases of biopsy-proven or treated VaIN occurring for a 15-year period at Southend University Hospital, United Kingdom.Eighty-eight cases of VaIN were identified. The age range was from 24 to 76 years, and 39% of cases were low grade (VaIN 1) and 60% high grade (VaIN 2 and 3). Sixty-five percent of patients had either already undergone or would go on to have treatment for cervical intraepithelial neoplasia. Of those with low-grade disease, 86% were managed conservatively with a 97% success rate. Similarly, with high-grade disease, 77% were managed with laser treatment with a success rate of 76% for primary treatment. Of the 6 cases of high-grade disease treated conservatively, 50% subsequently needed active treatment. There was 1 case of progression to vaginal cancer (1.3%).Vaginal intraepithelial neoplasia remains an uncommon premalignant condition. It can affect women of all ages and is commoner in those who are immunosuppressed. Observation of low-grade disease is safe and the abnormality often resolves spontaneously. For persistent disease or higher-grade abnormalities, there are many treatment options but laser vaporization is the most commonly used. However, because of the nature of VaIN, recurrence is common even after treatment and further management can be challenging. The overall rate of malignant progression is small but protracted follow-up may be necessary.

We aim to describe the history of iodine testing of the cervix and identify areas where further work is required.We conducted a search of PubMed and Google Scholar. Full article texts were reviewed. Reference lists were screened for additional articles and books. 37 basic articles in journals including ones written in German and three basic articles in books were identified.Glycogen staining of the ectocervical squamous epithelium with iodine goes back to Paul Ehrlich (1854-1915). Walter Schiller (1887-1960) examined nearly 200 different dyes and found that vital staining of the cervical squamous epithelium was best achieved with Lugol's iodine solution, which was indicated by Jean Guillaume Lugol (1786-1851) for disinfection of the vagina. In 1928 W. Lahm observed that the glycogen content of a squamous epithelium cell decreases as anaplasia increases. From the outset, H. Hinselmann included the iodine test in the minimum requirements for colposcopy. In 1946 H. J. Wespi first mentioned the finding of an "uncharacteristic iodine negative area." The first international colposcopic terminology from Graz in 1975 lists the "iodine light area" among the different colposcopy findings. The IFCPC nomenclatures from Rome 1990, Barcelona 2002, and Rio de Janeiro 2011 have evaluated the iodine test and classified their findings differently. A breakthrough to effective cervical cancer screening in resource-limited settings in Africa, India, and Latin America was achieved with R. Sankaranarayanan's publication on naked-eye visual inspection of the cervix after application of Lugol's iodine.This paper is a step toward a better understanding of what we think and do today with iodine testing and what problems and upcoming tasks will arise in future.Copyright © 2021. Published by Elsevier B.V.

To examine the screening history of vaginal intraepithelial neoplasia (VaIN) and vaginal cancer.We included women with histologically confirmed VaIN or vaginal cancer by colposcopy-directed biopsy between 1 January 2019 and 31 December 2019. The results of cytology, hrHPV, colposcopic examination and history of hysterectomy were retrospectively analysed.A total of 26,432 colposcopies were performed during the study period, among which 2131 women (1835 [86.1%] with VaIN 1; 268 [12.6%] with VaIN 2/3; and 28 [1.3%] with vaginal cancer) were retrospectively studied. hrHPV test positivity was significantly higher than that of cytology for VaIN 1 (84.4% vs 67.3%; P < 0.001) and VaIN 2/3 (92.0% vs 79.9%; P < 0.001) but not for vaginal cancer (84.6% vs 78.6%; P = 0.73). Additionally, the concordance rates for colposcopic impression were 79.5%, 54.5%, and 92.8% for VaIN1, VaIN2/3, and vaginal cancer, respectively. All 372 patients had a history of hysterectomy, and 81.0% (282/348) of indications were related to cervical precancer and cancer. Although cytology test positivity was significantly higher in patients with hysterectomy than in patients without hysterectomy (76.2% vs 67.5%; P < 0.001), cytology combined with hrHPV can help to detect more than 95% of VaIN and vaginal cancer cases in both groups (96.2% for patients with hysterectomy and 96.5% for patients without hysterectomy).VaIN and vaginal cancer are not rare diseases. Although cytology was sensitive (67.5%-76.2%) for detecting vaginal lesions regardless of hysterectomy, cytology combined with hrHPV improves detection accuracy up to 95% in both groups.© 2021 Zhang et al.

The treatment strategy for vaginal intraepithelial neoplasia (VaIN) 2-3 has not been established. This study aimed to investigate the efficacy of imiquimod in VaIN 2-3.Electronic databases (PubMed, EMBASE, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials) were searched from their inception until October 2019 and articles reporting imiquimod treatment for VaIN 2-3 were extracted. Additionally, the clinical records of women with VaIN 2-3 who had been treated with imiquimod in Shizuoka General Hospital from January 2016 to May 2020 were investigated. The data from the systematic search and the data from our hospital were analyzed, and a pooled complete response (CR) rate and response rate of imiquimod treatment for VaIN 2-3 were estimated. As a subgroup analysis, the CR rates and response rates were compared between women with and without a history of hysterectomy, and the rate ratio was calculated.Five articles described 28 women with VaIN 2-3 who underwent imiquimod treatment, and nine women with VaIN 2-3 were treated with imiquimod in our hospital. The discontinuation of the treatment was required in only one patient of the reported cases. The pooled CR rate and response rate of imiquimod, regardless of a history of hysterectomy, was 0.76 (95% CI, 0.59-0.87) and 0.89 (95% CI, 0.71-0.97), respectively. In the subgroup analysis, the CR rate in patients with hysterectomy was 0.98 (95% CI, 0.11-1.0) and in those without hysterectomy was 0.60 (95% CI, 0.30-0.84), and the rate ratio was 0.83 (95% CI, 0.48-1.19). The pooled response rates with and without a history of hysterectomy were not estimated, and the rate ratio was 0.83 (95% CI, 0.54-1.09).Imiquimod can be an effective treatment for vaginal intraepithelial neoplasia 2-3.Copyright © 2020 Elsevier Inc. All rights reserved.

Treatment of high-grade vaginal intraepithelial neoplasia (VAIN) is controversial and could include surgical excision, topical medication, brachytherapy, or other treatments. We report the results of low-dose-rate (LDR) vaginal brachytherapy for grade 3 VAIN (VAIN-3) over a 25-year period at Gustave Roussy Institute.We retrospectively reviewed the files of all patients treated at Gustave Roussy Institute for VAIN-3 since 1985. The treatment consisted of LDR brachytherapy using a personalized vaginal mold and delivered 60 Gy to 5 mm below the vaginal mucosa. All patients had at least an annual gynecological examination, including a vaginal smear.Twenty-eight patients were eligible. The median follow-up was 41 months. Seven patients had a follow-up <2 years, and the median follow-up for the remaining 21 patients was 79 months. The median age at brachytherapy was 63 years (range, 38-80 years). Twenty-six patients had a history of VAIN recurring after cervical intraepithelial neoplasia and 24 had a previous hysterectomy. The median brachytherapy duration was 4.5 days. Median doses to the International Commission of Radiation Units and Measurements rectum and bladder points were 68 Gy and 45 Gy, respectively. The median prescription volume (60 Gy) was 74 cm(3). Only one "in field" recurrence occurred, corresponding to a 5- and 10-year local control rate of 93% (95% confidence interval, 70%-99%). The treatment was well tolerated, with no grade 3 or 4 late toxicity and only one grade 2 digestive toxicity. No second cancers were reported.LDR brachytherapy is an effective and safe treatment for vaginal intraepithelial neoplasia.

To retrospectively evaluate the efficacy of high-dose-rate brachytherapy of vaginal intraepithelial neoplasia with a special focus on analysis of toxicity.Twenty consecutive patients were irradiated with brachytherapy of vaginal intraepithelial neoplasia with component ca in situ (N=3). Late complications of the vagina graded using the CTCAE v.3.0. General assessment three-step scale was introduced for simplicity of analysis.The median age was 57 years (range: 28-80 years). The median follow-up time was 39 months (range: 14-115 months). Vaginal intraepithelial neoplasia recurrence was observed in 1 patient. The 3-year disease free survival rate was 90% (95% confidence interval [CI]: 71-100%). Observed late side effects: libido grades 1-2 in 15 (75%), vaginal discharge grade 2 (pad use indicated) in 2 (10%), dryness grade 2 (dyspareunia) in 7 (35%), mucositis grades 2-3 in 6 (30%), stenosis grades 2-3 in 7 (35%) and vaginitis grades 2-3 in 4 (20%) cases. General assessment was good in 9 (45%), average in 2 (10%), and bad in 9 (45%) patients. Treatment dose affected the toxicity (p=0.05). In groups of patients irradiated with biologically equivalent dose (assuming α/β=3Gy) of 47.3-63Gy and ≥70Gy, the risk of poor or moderate toxicity amounted to 16.7% (95% CI: 0-47%) and 71.4% (95% CI: 48-95%), respectively.Brachytherapy revealed to be effective method of vaginal intraepithelial neoplasia treatment, but applying EQD2≥70Gy into vagina generates unacceptable toxicity.Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Vaginal intraepithelial neoplasia (VAIN) is an uncommon premalignant condition which can be difficult to eradicate. In view of the low incidence worldwide and lack of published work available there is no gold standard treatment. The aim of this study was to assess the outcome of VAIN 3 treated by brachytherapy at a single institution over a 20-year period.A retrospective review of medical records was performed 1985-2004 inclusive based on hospital admissions with an ICD-9/10 diagnosis of VAIN.22 patients with pathologically confirmed VAIN3 were treated with intracavitary brachytherapy over this time period. Median age at time of treatment was 56 years (range 37-70) and median follow up was 77 months. The majority of patients were post-menopausal smokers who presented asymptomatically following hysterectomy for cervical dysplasia/neoplasia. Medium dose rate Selectron was the method of choice, typically 48 Gy prescribed to point Z (located 0.5 cm lateral to ovoid surface) over two insertions 1 week apart. Acute toxicity was minimal. There were 5 cases of RTOG G3 toxicity, predominantly stenosis of the vagina, and 1 case of G4 toxicity resulting in vaginal ulceration. Recurrent/residual VAIN3 was documented in three patients; one of whom was successfully treated by laser ablation while the other two went on to develop invasive or micro-invasive vaginal carcinoma. The first remained disease free 17 years later following external beam radiotherapy but the second died of peri-operative complications as a consequence of radical surgery. Late progression was documented in one patient 14 years after initial treatment and was suspected in a further patient who succumbed to metastatic squamous cell carcinoma of uncertain origin 8 years later.Medium dose rate brachytherapy is a well tolerated form of treatment for VAIN3 but patients must be counseled regarding potential toxicity. Long-term follow up is advised due to risk of late recurrence and second malignancy.