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.

Evaluation of Host Gene Methylation as a Triage Test for HPV-Positive Women-A Cohort Study.

OBJECTIVES: This study was designed to evaluate the performance of a host gene methylation marker panel (ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671) in the triage of human papillomavirus (HPV)-positive women, its possible impact in a cervical cancer screening program, and the possible influence of the variation of the rate of HPV16/18 in its performance. MATERIALS AND METHODS: Cohort study in which consecutive women referred for colposcopy in an organized cervical cancer screening program had repeated HPV testing, colposcopy, and biopsies. The women that remained HPV positive at the time of colposcopy were tested with the panel of DNA methylation markers. The performance of the test was evaluated and compared to standard practice. RESULTS: The study test had a sensitivity and specificity for cervical intraepithelial neoplasia (CIN) 2+ of 60.8% (49.1-71.6%) and 88.4% (83.2-92.5%), respectively. For CIN3+, it was of 78.0% (64.0-88.5%) and 86.0% (80.8-90.2%), respectively.The rate and level of methylation positively correlated with the severity of disease. The use of methylation reduces the referral for colposcopy to 25.5%, while detecting 78.0% of the CIN3+ cases. Referral of all HPV16/18-positive cases and triage of the other high-risk HPV-positive cases with methylation, detects 90.0% of the cases of CIN3+, while reducing the number of referrals to 43.2%.The variation in the rate of HPV16/18 does not relevantly affect the performance of the methylation panel. CONCLUSIONS: The studied methylation panel has a high sensitivity and specificity for CIN3+ and reduces the rate of referrals for colposcopy, without relevant variation according to the rate of HPV16/18.

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.

Vulvar Inspection During Cervical Cancer Screening Procedures: The Ugly Reality.

ABSTRACT: Vulvar examination during procedures for cervical carcinoma screening (CCS) can be a valid chance for early diagnosis of vulvar diseases and precancerous lesions. With this aim an online questionnaire was sent to the members of the Italian Cervical Carcinoma Screening Group (GISCi) from either first level group (FLG, Pap/human papillomavirus test sampling) or second level group (SLG, colposcopy and treatments) to assess if and how vulvar examination was performed. 86% of FLG and 90.2% of SLG report performing vulvar examination prior to CCS procedures. 15% of SLG cannot manage basic vulvar diseases and they refer patients to specialized center. 54.3% underline lack of standardized protocol in case of vulvar disease detection. Despite most health care professionals report examining the vulva during CCS procedures, vulvar cancer early diagnosis is still challenging.

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.

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.

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.

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).

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.

Wet Mount Microscopy of the Vaginal Milieu Does Not Predict the Outcome of Fertility Treatments: A Cross-sectional Study.

OBJECTIVE: The aim of the study was to evaluate whether vaginal dysbiosis (bacterial vaginosis [BV] or moderate/severe aerobic vaginitis [AV]/desquamative inflammatory vaginitis) in women subjected to intrauterine insemination (IUI) or in vitro fertilization/intracytoplasmic sperm injection influences the rates of pregnancy. MATERIALS AND METHODS: This is a cross-sectional study involving 392 women who underwent IUI or in vitro fertilization/intracytoplasmic sperm injection at a fertility clinic. All had a slide collected for phase contrast wet mount microscopy (WMM), which was classified according to the International Society for the Study of Vulvovaginal Disease recommendations. Correlation between flora patterns and the rate of pregnancy were evaluated. RESULTS: There were no differences in any of the groups in terms of pregnancy rate (biochemical, clinical, at first trimester ultrasound, or live birth) after stratifying for the presence of BV, moderate or severe (ms) AV, BV and/or moderate or severe AV, cytolysis, or abnormal vaginal flora (lactobacillary grade ≥ IIb). The presence of Candida species, cocci, or bacilli morphotypes other than lactobacilli also showed no differences. CONCLUSIONS: The vaginal flora assessment by WMM at the time of IUI or oocyte retrieval was not predictive of the success of fertility treatments.The absence of differences may be due to intrinsic limitations of WMM (i.e., identifying only bacterial morphotypes), a positive impact of the treatments in the vaginal flora or because the sperm and embryo transfer is made directly into the uterine cavity, thus overcoming any cervical or vaginal dysbiosis disadvantage. Future studies should focus on the endometrial milieu, rather than in the vaginal and/or cervical one.

The Vaginal Microbiome: II. Vaginal Dysbiotic Conditions.

OBJECTIVE: This series of articles, titled The Vaginal Microbiome (VMB), written on behalf of the International Society for the Study of Vulvovaginal Disease, aims to summarize the recent findings and understanding of the vaginal bacterial microbiota, mainly regarding areas relevant to clinicians specializing in vulvovaginal disorders. MATERIALS AND METHODS: A search of PubMed database was performed, using the search terms "vaginal microbiome" with "dysbiosis," "bacterial vaginosis," "cytolytic vaginosis," "desquamative inflammatory vaginitis," and "aerobic vaginitis." Full article texts were reviewed. Reference lists were screened for additional articles. RESULTS: The second article in this series focuses on vaginal dysbiotic conditions. Dysbiosis is a term describing imbalances in bacterial communities. Given that lactobacillus-dominated microbiota are thought to be the most optimal, vaginal dysbiosis is usually considered as lactobacilli-depleted VMB. Bacterial vaginosis (BV), the most common vaginal dysbiotic condition, is a polymicrobial disorder, considered the leading cause for vaginal discharge in women worldwide. In addition, we review the VMB in other vaginal conditions associated with lactobacilli depletion: desquamative inflammatory vaginitis and aerobic vaginitis. We also discuss the controversial diagnosis of cytolytic vaginosis, related with lactobacilli overgrowth. CONCLUSIONS: Bacterial vaginosis displays complex microbiology. The heterogeneity and diversity within the genus Gardnerella may impact the progression of BV. Bacterial biofilms may contribute to the etiology and persistence of BV, and various bacteria may affect its clinical presentation and pathogenicity. Lack of lactobacilli is not always accompanied by an overgrowth of anaerobes.

The Vaginal Microbiome: I. Research Development, Lexicon, Defining "Normal" and the Dynamics Throughout Women's Lives.

OBJECTIVE: This series of articles, titled The Vaginal Microbiome, written on behalf of the International Society for the Study of Vulvovaginal Disease, aims to summarize the current findings and understanding of the vaginal bacterial microbiota, mainly regarding areas relevant to clinicians specializing in vulvovaginal disorders. MATERIALS AND METHODS: A database search of PubMed was performed, using the search terms "vaginal microbiome" (VMB) with "research," "normal," "neonate," "puberty," "adolescent," "menopause," and "ethnicities," as well as "human microbiome project." Full article texts were reviewed. Reference lists were screened for additional articles. RESULTS: In the last 2 decades, many studies applying molecular techniques were performed, intending to characterize the vaginal microbiota. These studies advanced our understanding of how vaginal health is defined. The first article in this series focuses on the advancement of VMB research, technical definitions, the definition of "normal" VMB, and the dynamics of VMB throughout women's lives. CONCLUSIONS: Understanding how microorganisms inhabiting the vagina interact with each other and with the host is important for a more complete understanding of vaginal health. The clinical application of microbial community sequencing is in its beginning, and its interpretation regarding practical clinical aspects is yet to be determined.

The Vaginal Microbiome: IV. The Role of Vaginal Microbiome in Reproduction and in Gynecologic Cancers.

OBJECTIVE: This series of articles, titled The Vaginal Microbiome (VMB), written on behalf of the International Society for the Study of Vulvovaginal Disease, aims to summarize the recent findings and understanding of the vaginal bacterial microbiota, mainly regarding areas relevant to clinicians specializing in vulvovaginal disorders. MATERIALS AND METHODS: A search of PubMed database was performed, using the search terms "vaginal microbiome" with "reproduction," "infertility," "fertility," "miscarriages," "pregnancy" "cervical cancer," "endometrial cancer," and "ovarian cancer." Full article texts were reviewed. Reference lists were screened for additional articles. RESULTS: The fourth article of this series focuses on 2 distinct areas: the role of VMB in various aspects of human reproduction and, in sharp contrast, the association between the VMB and gynecologic malignancies. Several of the negative pregnancy outcomes have been associated with an altered VMB. Dysbiosis is remarkably linked with poor pregnancy outcomes from preconception to delivery. The associations between the microbiome and gynecologic cancers are described. CONCLUSIONS: The development of the microbiome research, enabled by molecular-based techniques, has dramatically increased the detection of microorganisms and the understanding of bacterial communities that are relevant to maternal-fetal medicine in health and disease, as well as in gynecological malignancies. Proving causation in cancer is difficult because of the complex interactive nature of potential causative factors. Certain elements of the microbiota have been shown to provoke inflammatory reactions, whereas others produce anti-inflammatory reactions; this balance might be impaired with a change in microbial variety.

The Vaginal Microbiome: V. Therapeutic Modalities of Vaginal Microbiome Engineering and Research Challenges.

OBJECTIVE: This series of articles, titled The Vaginal Microbiome (VMB), written on behalf of the International Society for the Study of Vulvovaginal Disease, aims to summarize the recent findings and understanding of the vaginal bacterial microbiota, mainly regarding areas relevant to clinicians specializing in vulvovaginal disorders. MATERIALS AND METHODS: A search of PubMed database was performed, using the search terms "vaginal microbiome" with "treatment," "diagnosis," and "research." Full article texts were reviewed. Reference lists were screened for additional articles. RESULTS: The currently available approaches for treating vaginitis or attempting to modulate the VMB are often insufficient. It has traditionally relied on the use of antibiotics, antiseptics, and antifungals. The fifth and last article of this series discusses the new and/or alternative therapeutic modalities. It addresses the role of probiotics, prebiotics and symbiotics, activated charcoal, biofilm disrupting agents, acidifying agents, phage therapy, and the concept of vaginal microbiome transplant. The challenges facing the research of VMB, including the clinical impact of microbiome manipulation, classification, and new diagnostic approaches are discussed. CONCLUSIONS: Microbiome research has grown dramatically in recent years, motivated by innovations in technology and decrease in analysis costs. This research has yielded huge insight into the nature of microbial communities, their interactions, and effects with their hosts and other microbes. Further understanding of the bacterial, fungal, phage, and viral microbiomes in combination with host genetics, immunologic status, and environmental factors is needed to better understand and provide personalized medical diagnostics and interventions to improve women's health.

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.

The Vaginal Microbiome: III. The Vaginal Microbiome in Various Urogenital Disorders.

OBJECTIVE: This series of articles, titled The Vaginal Microbiome (VMB), written on behalf of the International Society for the Study of Vulvovaginal Disease, aims to summarize the recent findings and understanding of the vaginal bacterial microbiota, mainly regarding areas relevant to clinicians specializing in vulvovaginal disorders. MATERIALS AND METHODS: A search of PubMed database was performed, using the search terms "vaginal microbiome" with "Candida," "vaginitis," "urinary microbiome," "recurrent urinary tract infections," "sexually transmitted infections," "human immunodeficiency virus," "human papillomavirus," "nonspecific vaginitis," "vulvodynia," and "vulvovaginal symptoms." Full article texts were reviewed. Reference lists were screened for additional articles. The third article in this series describes VMB in various urogenital disorders. RESULTS: Variable patterns of the VMB are found in patients with vulvovaginal candidiasis, challenging the idea of a protective role of lactobacilli. Highly similar strains of health-associated commensal bacteria are shared in both the bladder and vagina of the same individual and may provide protection against urinary tract infections. Dysbiotic VMB increases the risk of urinary tract infection. Loss of vaginal lactic acid-producing bacteria combined with elevated pH, increase the risk for sexually transmitted infections, although the exact protective mechanisms of the VMB against sexually transmitted infections are still unknown. CONCLUSIONS: The VMB may constitute a biological barrier to pathogenic microorganisms. When the predominance of lactobacilli community is disrupted, there is an increased risk for the acquisition of various vaginal pathogents. Longitudinal studies are needed to describe the association between the host, bacterial, and fungal components of the VMB.

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.

Vulvar High-Grade Squamous Intraepithelial Lesions and Cancer as a Risk Factor for Anal Cancer: A Review.

OBJECTIVES: Anal squamous cell carcinoma (ASCC) has a higher incidence described in certain groups, namely, in women with vulvar high-grade squamous intraepithelial lesions (vHSILs) and/or human papillomavirus squamous cell carcinoma (VSCC). This review describes terminology, vHSIL, and VSCC in their association with ASCC and the published recommendations for early detection of this cancer in these women. MATERIALS AND METHODS: A narrative review was conducted by the authors on vHSIL and VSCC as risk factors for ASCC. RESULTS: The ASCC and VSCC incidence are increasing. Women with vHSIL and/or VSCC can present with ASCC at diagnosis, being one of the highest-risk groups. Suspicious symptoms include rectal bleeding, pain, and a sensation of an anal mass. Digital anorectal examination can help detect early ASCC. Sensitivity of anal cytology in women with vHSIL and VSCC seems low, with the exception of immunosuppressed women with genital neoplasia (cervix, vagina, and vulva). There are still insufficient data on high-resolution anoscopy in women with vHSIL and/or VSCC as a screening method. CONCLUSIONS: Clinicians need be aware that women with vHSIL and VSCC comprise one of the highest-risk groups for ASCC. Inquiring suggestive symptoms of ASCC and a digital anorectal examination can help in the early detection of this type of cancer.

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).