Performance of Different Follow-Up Strategies and Genotype-Based Recurrence Risk After Treatment of Cervical High-Grade Squamous Intraepithelial Lesion.

OBJECTIVE: Our aim was to evaluate the performance of different follow-up strategies after treatment for cervical intraepithelial neoplasia (CIN) 2 or 3, including human papillomavirus (HPV) detection, cytology, or colposcopy, as well as their combinations. Additionally, we compared the influence of the persistence of HPV 16/18 versus that of other high-risk HPV genotypes (HR-HPV) in the recurrence risk. METHODS: Retrospective register-based study, including women who had an excision of the transformation zone for CIN2 or CIN3 at our institution, between January 2011 and December 2022. The outcome assessed was histopathological recurrence/persistence of CIN2 or worse. RESULTS: Of the 721 women included, 6.8% (49/721) had recurrence/persistence. The sensitivity, specificity, and positive and negative predictive values of the HPV test were 97.4%, 80%, 22.3%, and 99.8%, respectively, whereas for cotesting (HR-HPV and cytology), 86.8%, 90.1%, 34.4%, and 99.1%, respectively. The referral rates for colposcopy were 24.3% and 14.2%, respectively. The sensitivity of colposcopy was low (40.0%).Women who were initially positive for non-16/18 genotypes at baseline who became HPV16/18 positive during follow-up, had a statistically significant increased risk of CIN2 or worse, compared with those who tested positive only for other HR-HPV genotypes during both stages (hazard ratio = 4.98; 95% CI = 1.66-14.91). CONCLUSIONS: Human papillomavirus testing is the best strategy for follow-up after treatment of cervical HSIL. The addition of cytology triage decreases by more than 40% the referrals for colposcopy, without significantly missing cases of recurrence/persistence. Human papillomavirus 16/18 in the follow-up, regardless of being previously positive, is associated with higher risk of recurrence/persistence of HSIL.

Is Vulvodynia Associated With an Altered Vaginal Microbiota?: A Systematic Review.

INTRODUCTION: Vulvodynia is defined as vulvar pain of at least 3 months' duration, without clear identifiable cause, which may have potential associated factors. It can have a significant impact on women's quality of life due to a combination of physical pain, emotional distress, and limited treatment options. Despite affecting a considerable number of women worldwide, the causes and underlying mechanisms of vulvodynia remain poorly understood. Given the recognized association of the vaginal microbiota with various gynecologic disorders, there has been growing interest in exploring the potential role of the vaginal microbiota in the etiology of vulvodynia. This systematic review aims to evaluate the current literature on the association between the vaginal microbiota and vulvodynia. MATERIAL AND METHODS: A systematic search of multiple databases, including PubMed, Scopus, Web of Science, Cochrane Library, and Ovid MEDLINE, was conducted to identify relevant peer-reviewed studies up to May 12, 2023. The following search terms were used across these databases: "vulvodynia," "vestibulodynia," "vulvar vestibulitis," "microbiome," "microbiota," and "flora." RESULTS: A total of 8 case-control studies were included, the quality of which was assessed using the Newcastle-Ottawa Scale. Data extraction and synthesis were performed using a standardized protocol. In most studies, no major differences were found between the vaginal bacterial composition of women with vulvodynia and that of controls. No specific bacterial taxa were consistently associated with vulvodynia. The relationship between vaginal microbiota diversity and vulvodynia remains to be fully understood. CONCLUSIONS: The role of vaginal microbiota in vulvodynia, if any, remains unclear. Because of the cross-sectional nature of the included studies, it is not possible to make any causal inferences. Further research, using larger and more diverse study populations and advanced sequencing techniques, is necessary to gain a better understanding of the potential relationship between the vaginal microbiota and vulvodynia.

The International Society for the Study of Vulvovaginal Disease (ISSVD) Vulvar Awareness Day Campaign: Knowledge of Vulvovaginal Diseases Among Italian Obstetrics and Gynecology Residents.

OBJECTIVES: The objective of this study is to investigate vulvovaginal disease (VVD) awareness in Italian obstetrics and gynecology (Ob/Gyn) residents. MATERIALS AND METHODS: A 25-question survey on VVD basic knowledge (17 questions) and willingness to improve it (8 questions) was distributed through Ob/Gyn resident online group chats, from different Italian Universities in January 2023. A total number of 250 residents were invited to participate; 124 responses were obtained (response rate: 50%). Data were collected and analyzed using descriptive statistics through REDCap. RESULTS: Overall, 87 of the 124 respondents (70%) fully completed the questionnaire and represented the study group. Residents were distributed among years of residency: 15% first year, 31% second year, 23% third year, 11% fourth year, and 20% fifth year. Most (60%) never attended a VVD clinic during residency, with an increasing percentage of attendance in later residency years (15% at first year vs 65% at fifth).Participants reported low knowledge of vulvar precancerous lesions and vulvoscopy but better knowledge of vaginitis, vulvar self-examination, and lichen sclerosus. Of the respondents, 50% were not satisfied with the education provided during residency, and more than 60% lacked confidence in managing VVD.All participants expressed a strong desire to improve their knowledge and skills, with 100% agreeing that every gynecologist should know the "basics" and 98% wanting to improve their knowledge through webinars (45%), lessons (34%), newsletters, and videos (19%). CONCLUSION: Our findings indicate a significant need to improve VVD knowledge among Italian Ob/Gyn residents. Further efforts are necessary to provide information about VVD and comprehensive training programs in Italian Universities.

Genital tract microbiota composition profiles and use of prebiotics and probiotics in gynaecological cancer prevention: review of the current evidence, the European Society of Gynaecological Oncology prevention committee statement.

Female genital tract (FGT) microbiota has been associated with the development of gynaecological cancers. Thus, the possibility of whether manipulation of the FGT microbiota can help in the prevention of disease should be investigated. Various prebiotics, probiotics, and other non-clinician prescribed agents have been reported to have therapeutic effects in cervical disease. Numerous studies have reported an association between human papillomavirus infection and subsequent cervical dysplasia and a decrease in the abundance of Lactobacillus species. A continuum of microbiota composition is observed from the vagina to the upper parts of the FGT, but no evidence suggests that manipulation of the vaginal microbiota can help to modify the composition of other FGT compartments. Although prebiotics and probiotics have been reported to be beneficial, the studies are small and of varying design, and high-quality evidence to support their use is lacking. Currently, no studies have examined these therapeutics in other gynaecological malignancies. Thus, recommendation of probiotics, prebiotics, or other over-the-counter supplements for the prevention of gynaecological cancers warrants larger, well designed studies.

Chlamydial and Gonococcal Genital Infections: A Narrative Review.

Sexually transmitted infections (STIs) constitute one of the leading causes of disease burden worldwide, leading to considerable morbidity, mortality, health expenditures, and stigma. Of note are the most common bacterial STIs, chlamydial and gonococcal infections, whose etiological agents are Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), respectively. Despite being usually asymptomatic, in some cases these infections can be associated with long-term severe complications, such as pelvic inflammatory disease, chronic pelvic pain, infertility, ectopic pregnancy, and increased risk of other STIs acquisition. As the symptoms, when present, are usually similar in both infections, and in most of the cases these infections co-occur, the dual-test strategy, searching for both pathogens, should be preferred. In line with this, herein we focus on the main aspects of CT and NG infections, the clinical symptoms as well as the appropriate state-of-the-art diagnostic tests and treatment. Cost-effective strategies for controlling CT and NG infections worldwide are addressed. The treatment for both infections is based on antibiotics. However, the continuing global rise in the incidence of these infections, concomitantly with the increased risk of antibiotics resistance, leads to difficulties in their control, particularly in the case of NG infections. We also discuss the potential mechanism of tumorigenesis related to CT infections. The molecular bases of CT and NG infections are addressed, as they should provide clues for control or eradication, through the development of new drugs and/or effective vaccines against these pathogens.

Genital and extragenital oncological risk in women with vulvar lichen sclerosus: A multi-center Italian study.

Vulvar lichen sclerosus is a chronic inflammatory disease involving vulvar skin. The risk of developing invasive vulvar cancer for women with LS is reported in the literature, but the risk of extra-vulvar tumors has been under-investigated. This multicentric study aims to estimate the risk of developing cancers in a cohort of women with a diagnosis of vulvar lichen sclerosus. METHODS: A cohort of women diagnosed with and treated for vulvar lichen sclerosus in three Italian gynecological and dermatological clinics (Turin, Florence, and Ferrara) was retrospectively reviewed. Patient data were linked to cancer registries of the respective regions. The risk of subsequent cancer was estimated by dividing the number of observed and expected cases by the standardized incidence ratio. RESULTS: Among 3414 women with a diagnosis of vulvar lichen sclerosus corresponding to 38,210 person-years of follow-up (mean 11.2 years) we identified 229 cancers (excluding skin cancers and tumors present at the time of diagnosis). We found an increased risk of vulvar cancer (standardized incidence ratio = 17.4; 95 % CL 13.4-22.7), vaginal cancer (standardized incidence ratio = 2.7; 95 % CL 0.32-9.771), and oropharyngeal cancer (standardized incidence ratio = 2.5; 95 % CL 1.1-5.0), and a reduced risk of other gynecological tumors (cervical, endometrial, ovarian) and breast cancer. CONCLUSIONS: Patients with vulvar lichen sclerosus should undergo annual gynecological check-up with careful evaluation of the vulva and vagina. The increased risk of oropharyngeal cancer also suggests the need to investigate oropharyngeal cavity symptoms and lesions in patients with vulvar lichen sclerosus.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) consensus statement on the management of vaginal intraepithelial neoplasia.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vaginal intraepithelial neoplasia (VaIN). The management of VaIN varies according to the grade of the lesion: VaIN 1 (low grade vaginal squamous intraepithelial lesions (SIL)) can be subjected to follow-up, while VaIN 2-3 (high-grade vaginal SIL) should be treated. Treatment needs individualization according to the patient's characteristics, disease extension and previous therapeutic procedures. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Total vaginectomy is used only in highly selected cases of extensive and persistent disease. Carbon dioxide (CO2) laser may be used as both an ablation method and an excisional one. Reported cure rates after laser excision and laser ablation are similar. Topical agents are useful for persistent, multifocal lesions or for patients who cannot undergo surgical treatment. Imiquimod was associated with the lowest recurrence rate, highest human papillomavirus (HPV) clearance, and can be considered the best topical approach. Trichloroacetic acid and 5-fluorouracil are historical options and should be discouraged. For VaIN after hysterectomy for cervical intraepithelial neoplasia (CIN) 3, laser vaporization and topical agents are not the best options, since they cannot reach epithelium buried in the vaginal scar. In these cases surgical options are preferable. Brachytherapy has a high overall success rate but due to late side effects should be reserved for poor surgical candidates, having multifocal disease, and with failed prior treatments. VaIN tends to recur and ensuring patient adherence to close follow-up visits is of the utmost importance. The first evaluation should be performed at 6 months with cytology and an HPV test during 2 years and annually thereafter. The implementation of vaccination against HPV infection is expected to contribute to the prevention of VaIN and thus cancer of the vagina. The effects of treatment can have an impact on quality of life and result in psychological and psychosexual issues which should be addressed. Patients with VaIN need clear and up-to-date information on a range of treatment options including risks and benefits, as well as the need for follow-up and the risk of recurrence.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) Consensus Statement on the Management of Vaginal Intraepithelial Neoplasia.

ABSTRACT: The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vaginal intraepithelial neoplasia (VaIN). The management of VaIN varies according to the grade of the lesion: VaIN 1 (low grade vaginal squamous intraepithelial lesions (SIL)) can be subjected to follow-up, while VaIN 2-3 (high-grade vaginal SIL) should be treated. Treatment needs individualization according to the patient's characteristics, disease extension and previous therapeutic procedures. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Total vaginectomy is used only in highly selected cases of extensive and persistent disease. Carbon dioxide (CO2) laser may be used as both an ablation method and an excisional one. Reported cure rates after laser excision and laser ablation are similar. Topical agents are useful for persistent, multifocal lesions or for patients who cannot undergo surgical treatment. Imiquimod was associated with the lowest recurrence rate, highest human papillomavirus (HPV) clearance, and can be considered the best topical approach. Trichloroacetic acid and 5-fluorouracil are historical options and should be discouraged. For VaIN after hysterectomy for cervical intraepithelial neoplasia (CIN) 3, laser vaporization and topical agents are not the best options, since they cannot reach epithelium buried in the vaginal scar. In these cases surgical options are preferable. Brachytherapy has a high overall success rate but due to late side effects should be reserved for poor surgical candidates, having multifocal disease, and with failed prior treatments. VaIN tends to recur and ensuring patient adherence to close follow-up visits is of the utmost importance. The first evaluation should be performed at 6 months with cytology and an HPV test during 2 years and annually thereafter. The implementation of vaccination against HPV infection is expected to contribute to the prevention of VaIN and thus cancer of the vagina. The effects of treatment can have an impact on quality of life and result in psychological and psychosexual issues which should be addressed. Patients with VaIN need clear and up-to-date information on a range of treatment options including risks and benefits, as well as the need for follow-up and the risk of recurrence.

Vulvar High-Grade Squamous Intraepithelial Lesion and the Risk of Recurrence and Progression to Cancer.

OBJECTIVE: This study aimed to analyze which clinical characteristics are associated with recurrence and progression of vulvar high-grade squamous intraepithelial lesion (vHSIL). MATERIALS AND METHODS: This was a retrospective cohort study, including all women with vHSIL followed in 1 center between 2009 and 2021. Women with a concomitant diagnosis of invasive vulvar cancer were excluded. Medical records were reviewed for demographic factors, clinical data, treatment type, histopathologic results, and follow-up information. RESULTS: A total of 30 women were diagnosed with vHSIL. The median follow-up time was 4 years (range = 1-12 years). More than half of the women (56.7% [17/30]) underwent excisional treatment, whereas 26.7% (8/30) underwent combined (excisional plus medical) treatment, and 16.7% (5/30) only had medical treatment (imiquimod). Six women had recurrence of vHSIL (20% [6/30]), with a mean time to recurrence of 4.7 ± 2.88 years. The progression rate to invasive vulvar cancer was 13.3% (4/30), with a mean time to progression of 1.8 ± 0.96 years. Multifocal disease was associated with progression to vulvar cancer ( p = .035). We did not identify other variables associated with progression; no differences were found between women with and without recurrences. CONCLUSIONS: Multifocality of the lesions was the only variable associated with progression to vulvar cancer. This reinforces the idea that these lesions are a challenge in both treatment and surveillance, involving a more difficult therapeutic decision with greater associated morbidity.

Scoping review of cytolytic vaginosis literature.

BACKGROUND: Cytolytic vaginosis (CV) is a little-known, controversial condition that is typically not considered for women presenting with vulvovaginitis symptoms. Objective: The objective of this scoping review was to identify and compile the global evidence on CV. METHODS: A medical librarian searched Prospero, Wiley Cochrane Library, Ovid Embase, Ovid Medline, EBSCO CINAHL, ProQuest Dissertations and Theses Global, and Scopus, from inception to April 4, 2019 and updated to October 17, 2021. Studies were eligible if they discussed CV. Two independent reviewers conducted study selection and data extraction. RESULTS: Sixty-four studies were identified, with 67% of studies (n = 43) published since 2007. Studies were from around the world, including the United States (28%, n = 18), Brazil (11%, n = 7), Portugal (11%, n = 7), and China (11%, n = 7). Fifty percent of studies (n = 32) were reviews; the remainder were observational; and of these, 78% (n = 25) were cross-sectional. The most frequent topics included: diagnosis (19%, n = 12), prevalence (17%, n = 11), and overview of CV (50%, n = 32). Evidence for prevalence in symptomatic women (median prevalence of 5%, interquartile range 3%-8%) was based only on 16% of studies (n = 10) with minimal evidence on prevalence in asymptomatic women and across different geographic regions. Microbiological findings, including abundant lactobacilli and fragmented epithelial cells, were found useful to distinguish between CV and vulvovaginal candidiasis, and Lactobacillus crispatus was noted to dominate the vaginal flora in women with CV. Most studies used subjective criteria to diagnose CV as the condition lacks gold-standard microscopic criteria. The suggested primary treatment (baking soda irrigations) was largely based on expert opinion, and there was minimal evidence on associations between CV and other conditions. CONCLUSION: Knowledge gaps currently exist in all realms of CV research. Additional research is needed to confirm the validity of CV and ensure that women are diagnosed and treated effectively.

Therapeutic Options for Chlamydia trachomatis Infection: Present and Future.

Sexually transmitted infections (STIs), such as Chlamydia trachomatis (Ct) infection, have serious consequences for sexual and reproductive health worldwide. Ct is one of the most common sexually transmitted bacterial infections in the world, with approximately 129 million new cases per year. C. trachomatis is an obligate intracellular Gram-negative bacterium. The infection is usually asymptomatic, notwithstanding, it could also be associated with severe sequels and complications, such as chronic pain, infertility, and gynecologic cancers, and thus there is an urgent need to adequately treat these cases in a timely manner. Consequently, beyond its individual effects, the infection also impacts the economy of the countries where it is prevalent, generating a need to consider the hypothesis of implementing Chlamydia Screening Programs, a decision that, although it is expensive to execute, is a necessary investment that unequivocally will bring financial and social long-term advantages worldwide. To detect Ct infection, there are different methodologies available. Nucleic acid amplification tests, with their high sensitivity and specificity, are currently the first-line tests for the detection of Ct. When replaced by other detection methods, there are more false negative tests, leading to underreported cases and a subsequent underestimation of Ct infection's prevalence. Ct treatment is based on antibiotic prescription, which is highly associated with drug resistance. Therefore, currently, there have been efforts in line with the development of alternative strategies to effectively treat this infection, using a drug repurposing method, as well as a natural treatment approach. In addition, researchers have also made some progress in the Ct vaccine development over the years, despite the fact that it also necessitates more studies in order to finally establish a vaccination plan. In this review, we have focused on the therapeutic options for treating Ct infection, expert recommendations, and major difficulties, while also exploring the possible avenues through which to face this issue, with novel approaches beyond those proposed by the guidelines of Health Organizations.

Reply to De Giorgi et al. Comment on "Kesic et al. Early Diagnostics of Vulvar Intraepithelial Neoplasia. Cancers 2022, 14, 1822".

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Changes in the Vaginal Microbiota of Women With Secondary Localized Provoked Vulvodynia.

OBJECTIVE: The etiology of localized provoked vulvodynia (LPV) remains unknown, but observations suggest the involvement of the vaginal microbiota. We examined the vaginal microbiota of women with LPV and healthy controls, upon after a low-oxalate diet (LOD). MATERIALS AND METHODS: A total of 9 women diagnosed with secondary LPV and 21 healthy controls were recruited from the Galilee Medical Center in Israel and subjected to prospective evaluations of their vaginal microbiota. Total DNA was extracted from vaginal discharge samples provided before and after following LOD for 3 weeks and was then subjected to 16S sequencing. Data obtained were then used to evaluate α and ß diversity, identify differentially abundant bacterial taxa in LPV, and determine their impact on the metabolism. RESULTS: These evaluations revealed decreased diversity in the vaginal microbiota of women with LPV and identified the Ochrobactrum genus and Pseudomonadaceae family as indicators for LPV. In addition, we identified 23 differentially expressed bacterial metabolic pathways between the LPV and control samples and revealed that LOD could induce changes in the ß diversity of LPV vaginal microbiomes, which was further supported by some degree of pain reduction in patients. CONCLUSIONS: Localized provoked vulvodynia and LOD were associated with shifts in the vaginal microbiota. However, the impact of these changes on the development of LPV requires additional studies with a larger cohort.

Vaginal Leptothrix: An Innocent Bystander?

Leptothrix are long bacteria of rare occurrence; although these bacteria have been implicated in causing vaginal symptoms identical to candidiasis, studies on prevalence and effect on overall vaginal health are lacking. In this study, we evaluated data of women referred to a private clinic for treating vulvovaginal symptoms (n = 1847) and reassessed data of our previous and ongoing studies (n = 1773). The overall rate of leptothrix was 2.8% (102/3620), and the mean age of affected women was 38.8 ± 10.65 years (range 18-76). The majority of the women with leptothrix had normal vaginal flora (63.7% [65/102]). Leptothrix was associated with a higher risk of candidiasis (relative risk (RR) 1.90, 95% confidence interval (CI) 1.1600-3.1013; p = 0.010) and a lower risk of bacterial vaginosis (RR 0.55, 95% CI, 0.3221-0.9398; p = 0.029) and cytolytic vaginosis (RR 0.11, 95% CI, 0.0294-0.4643; p = 0.002). No cases of trichomoniasis were observed. Human immunodeficiency virus infection increased the risk of leptothrix (RR 3.0, 95% CI, 1.6335-5.7245; p = 0.000). Among the women evaluated for vulvovaginal symptoms, 2.4% (45/1847) had leptothrix, and in 26.7% (12/45), leptothrix was considered the causative entity. This study suggests that leptothrix occurrence is rare; it remains unresolved if it can be a cause of vulvar symptoms.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) consensus statements on pre-invasive vulvar lesions.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).

Vulvar Paget's disease: outcomes of 51 patients treated with imiquimod cream.

BACKGROUND: Vulvar Paget's disease (VPD) is a rare neoplasm with high recurrence rates even after surgical treatment. Imiquimod topical cream is a promising therapy; however, experience with it is limited to small series or case reports. This study aims to analyze the effectiveness and safety of topical imiquimod in a large cohort of patients with VPD. METHODS: Fifty-five cases of histologically proven- VPD treated with topical imiquimod at the Gynecologic and Obstetric Division 1 U, S. Anna Hospital, University of Turin were retrospectively reviewed. We investigated the potential factors related to clinico-pathological response to imiquimod using univariate and multivariate logistic regression to estimate odds ratios (ORs). RESULTS: Four women discontinued the treatment due to side-effects. Of the remaining 51 (42 in situ tumors, and 9 micro-invasive tumors) who completed treatment, 22 (43%) achieved a complete clinico-pathological response. Among the women who had a complete response, there were no cases of recurrence (mean follow-up: 66 months). Symptomatic lesions (burning: OR 0.15, CI 0.03-0.67; itching: OR 0.07, CI 0.008-0.64), smaller tumors <60 mm (OR 0.15, CI 0.006-0.43), non-recurrent VPD (OR 0.19, CI 0.04-0.43) and treatment frequency of three application per week (OR 0.13, CI 0.04-0.50) were associated with a lower risk of persistence. Perianal involvement was associated with treatment failure (OR 7.79, CI 1.88-32.2). Multivariate analysis confirmed a predictive role for smaller tumors, non-recurrent VPD, and a treatment frequency of three applications per week. CONCLUSION: Imiquimod can be safely used for the treatment of VPD, even for micro-invasive tumors. Furthermore, we report some potential predictors of treatment response.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) Consensus Statements on Pre-invasive Vulvar Lesions.

ABSTRACT: The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).

Early Diagnostics of Vulvar Intraepithelial Neoplasia.

The spectrum of vulvar lesions ranges from infective and benign dermatologic conditions to vulvar precancer and invasive cancer. Distinction based on the characteristics of vulvar lesions is often not indicative of histology. Vulvoscopy is a useful tool in the examination of vulvar pathology. It is more complex than just colposcopic examination and presumes naked eye examination accompanied by magnification, when needed. Magnification can be achieved using a magnifying glass or a colposcope and may aid the evaluation when a premalignant or malignant lesion is suspected. It is a useful tool to establish the best location for biopsies, to plan excision, and to evaluate the entire lower genital system. Combining features of vulvar lesions can help prediction of its histological nature. Clinically, there are two distinct premalignant types of vulvar intraepithelial neoplasia: HPV-related VIN, more common in young women, multifocal and multicentric; VIN associated with vulvar dermatoses, more common in older women and usually unicentric. For definite diagnosis, a biopsy is required. In practice, the decision to perform a biopsy is often delayed due to a lack of symptoms at the early stages of the neoplastic disease. Clinical evaluation of all VIN lesions should be conducted very carefully, because an underlying early invasive squamous cancer may be present.

Risk Factors for Positive Margins in High-Grade Cervical Intraepithelial Neoplasia After Transformation Zone Excision.

OBJECTIVE: The aim of the study was to evaluate risk factors for positive margins on surgical specimens of patients submitted to transformation zone excision (TZE). MATERIALS AND METHODS: We conducted a retrospective study evaluating women submitted to TZE in our center, between 2012 and 2020. Our study population included only women with the diagnosis of high-grade intraepithelial lesion (HSIL) in the pathologic examination of the TZE surgical specimen. Positive margins were defined as the presence of HSIL in the endocervical and/or ectocervical margin of the specimen. Factors evaluated included demographic characteristics, pretreatment Pap smear and human papillomavirus test, colposcopic findings, TZE indication, and pathologic features of the surgical specimen. We performed univariate analysis and logistic regression modeling including variables associated with the outcome of positive margins in the univariate analysis. RESULTS: Our sample included 264 women, with a 15.2% positive margins rate (40 patients). In the univariate analysis, patients with immunocompromised status, HSIL Pap smear, and higher number of quadrants involved in colposcopic examination were more likely to have positive margins. After multivariate analysis, only immunocompromised status was found to be an independent risk factor (odds ratio = 4.94; 95% CI = 1.43-17.15; p < .05). CONCLUSIONS: Immunocompromised status was the sole significant predictor for positive margins in TZE surgical specimens. To our knowledge, this is the first report of immunodepression as a risk factor for positive margins in cervical excisional procedures.

Risk of Development of Vulvar Cancer in Women With Lichen Sclerosus or Lichen Planus: A Systematic Review.

OBJECTIVE: Vulvar lichen sclerosus (VLS) and possibly vulvar lichen planus (VLP) are associated with an increased vulvar cancer (VC) risk. We analyzed the risk of VC and its precursors after a diagnosis of VLS or VLP. MATERIALS AND METHODS: A search was performed to identify articles describing the development of vulvar neoplasia in women with VLS or VLP. This systematic review was registered with the PROSPERO database. RESULTS: Fourteen studies on VLS included 14,030 women without a history of vulvar neoplasia. Vulvar cancer, differentiated vulvar intraepithelial neoplasia (dVIN), and vulvar high-grade squamous intraepithelial lesion occurred in 2.2% (314/14,030), 1.2% (50/4,175), and 0.4% (2/460), respectively. Considering women with previous or current VC, the rate was 4.0% (580/14,372). In one study, dVIN preceded VC in 52.0% of the cases. Progression of dVIN to VC was 18.1% (2/11).The risk was significantly higher in the first 1-3 years after a biopsy of VLS and with advancing age; it significantly decreased with ultrapotent topical steroid use.For the 14,268 women with VLP (8 studies), the rates of VC, dVIN, and vulvar high-grade squamous intraepithelial lesion were 0.3% (38/14,268), 2.5% (17/689), and 1.4% (10/711), respectively. CONCLUSIONS: Vulvar lichen sclerosus is associated with an increased risk of VC, especially in the presence of dVIN and with advancing age. Ultrapotent topical steroids seem to reduce this risk. An increased risk of developing VC has been suggested for VLP. Hence, treatment and regular life-long follow-up should be offered to women with VLS or VLP.