Vulvar high-grade squamous intraepithelial lesion; the lesion shows full thickness abnormality of maturation, and acanthosis (hematoxylin and eosin, x 10 magnification).

Vulvar high-grade squamous intraepithelial lesion; the lesion shows full thickness abnormality of maturation, and acanthosis (hematoxylin and eosin, x 10 magnification).

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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 pati...

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... shows abnormal maturation and dysplastic features up to the lower third of the epithelium, while in VHSIL these abnormal features extend above the lower third of the epithelium ( Figure 5). Immunohistochemistry with p16 can be of help to distinguish VLSIL from VHSIL, or atrophy from VHSIL, as VHSIL shows block positivity compared with mimics. ...

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... It is also possible to perform cystoscopy or proctoscopy when deemed necessary. The standard treatment for VC generally includes wide excision or radical vulvectomy, based on size and location, with lymph node staging performed through a minimally invasive surgical technique, such as sentinel lymph node biopsy or inguinofemoral lymphadenectomy [6][7][8]. ...
... Although all included studies involved cases of different vulvar tumor types, including melanoma or extramammary Paget's disease [8], we specifically focused on cases of VSCC, except for vulvar Low-Grade Squamous Intraepithelial Lesion (vLSIL) and vulvar High-Grade Squamous Intraepithelial Lesion (vHSIL) evaluated in vulvoscopy. According to the latest 2015 guidelines from the International Society for the Study of Vulvovaginal Disease (ISSVD), Vulvar Squamous Intraepithelial Lesions are categorized into three types, including the previously mentioned vLSIL and vHSIL, as well as differentiated Vulvar Intraepithelial Neoplasia (dVIN), which is a non-Human-Papilloma-Virus (HPV)-associated intraepithelial neoplasia [7,9] representing a preinvasive lesion of high risk, with a substantial cancer risk of 43.2% [10]. Indeed, patients affected by dVIN are high-risk, where even clinically healthy tissues may exhibit molecular alterations. ...
... Indeed, patients affected by dVIN are high-risk, where even clinically healthy tissues may exhibit molecular alterations. Despite the complete surgical removal of dVIN lesions, the risk of cancer remains [7,10]. ...
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Simple Summary Vulvar cancer is a rare gynecological malignant neoplasm that makes necessary accurate preoperative management in order to stage the patient as best as possible, both locally and at the inguinofemoral lymph node level. The aim of this review is to perform a wide evaluation of all the tools that the clinician has at their disposal for a proper diagnosis, such as vulvoscopy, MRI, PET and ultrasound. Vulvoscopy remains essential to carrying out histological diagnosis. Furthermore, for the evaluation of the local extension of the disease and inguinofemoral and/or pelvic lymph nodes, MRI, PET and, more recently, ultrasound are fundamental. Abstract Vulvar carcinoma is a rare cancer affecting the genital tract, constituting 4% of gynecological tumors. Vulvar squamous cell carcinoma (VSCC) is the most common type. Diagnosis relies on biopsy during vulvoscopy, plus imaging such as ultrasonography (USG), magnetic resonance imaging (MRI) and positron emission tomography (PET). This review aims to lay out a thorough overview as to the current preoperative management of VSCC, both in case of vulvar and lymph node involvement. The data research was conducted using the following databases: MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library from 2010 to 2024. The selection criteria included only original articles. Seventeen studies were assessed for eligibility. A concordance rate of 62.3% for vHSIL and 65.2% for carcinoma at vulvoscopy, with a sensitivity of 98%, specificity of 40%, PPV (Positive Predictive Value) of 37% and NPV (Negative Predictive Value) of 98% in identifying malignant lesions was found. Regarding the reliability of PET for staging and assessing lymph node involvement, a mean SUV (Standardized Uptake Value) for malignant vulvar lesions of 8.4 (range 2.5–14.7) was reported. In the case of MRI, useful for the evaluation of loco-regional infiltration and lymph node involvement, the ratio of the short-to-long-axis diameter and the reader’s diagnostic confidence for the presence of lymph node metastasis yielded accuracy of 84.8% and 86.9%, sensitivity of 86.7% and 87.5%, specificity of 81.3% and 86.2%, PPV of 89.7% and 87.5% and NPV of 76.5% and 86.2%, respectively. A long lymph node axis >10 mm and a short diameter >5.8 mm were found to be predictors of malignancy. At USG, instead, the two main characteristics of potentially malignant lymph nodes are cortical thickness and short axis length; the combination of these ultrasound parameters yielded the highest accuracy in distinguishing between negative and positive lymph nodes. Despite the heterogeneity of the included studies and the lack of randomized clinical trials, this review provides a broad overview of the three imaging tools used for the presurgical management of VSCC. Nowadays, although MRI and PET represent the gold standard, ultrasound evaluation is taking on a growing role, as long as it is carried out by expert sonographer. The management of this rare disease should be always performed by a multidisciplinary team in order to precisely stage the tumor and determine the most suitable treatment approach.
... Pruritus, soreness, dyspareunia, and anal discomfort are common symptoms and have a significant impact on quality of life and sexual well-being [1][2][3][4]. Untreated LS is associated with a 4-6.7% risk of developing vulvar squamous cell carcinoma (SCC) [5,6]. The LS-mediated pathway leads to vulvar intraepithelial neoplasia (VIN), a differentiated type that leads to keratinizing SCC. ...
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Lichen sclerosus (LS) is a chronic inflammatory disease that mainly affects the anogenital area, with a higher incidence in post-menopausal women. In the long term, it can lead to loss of vulvar architecture or progress to squamous cell carcinoma. The evidence-based treatment involves high-potency topical corticosteroids in long regimens. However, second-line treatments are not well-established, including laser therapy. This current study aims to assess the level of evidence supporting this therapy. We conducted a search for primary-level studies published before April 2023 through MEDLINE/PubMed, Embase, Web of Science, Scopus, and CENTRAL, with no restrictions on the publication language or date. The methodological quality and risk of bias of the included studies were evaluated using the updated Cochrane Collaboration’s tool for assessing risk of bias (RoB-2). Six studies (177 patients) met our eligibility criteria. Laser therapy was compared to topical corticosteroid treatment in five out of six studies. No significant histological differences were found, except for an increase in collagen production in the laser group. A greater reduction in itching, pain, and dyspareunia at 1 and 3 months of treatment in the laser group, as well as in the Skindex-29 at 6 months, was reported. Patient satisfaction was significantly higher among those who received laser therapy. Tolerability was excellent. No significant differences were observed in any of the previous aspects in the study compared to the placebo. In conclusion, there is not enough evidence to recommend laser therapy as a standalone treatment.
... Для уменьшения риска рецидива рака вульвы после хирургического лечения должны проводиться терапия, направленная на предупреждение прогрессирования склеротического лишая, и тщательное наблюдение за пациенткой с целью выявления местного рецидива заболевания на раннем этапе [17,[22][23][24][25]. Возвращаясь к нашим пациенткам, следует отметить, что они не получали терапию, направленную на подавление склеротического лишая, ни после первичного лечения, ни после 1-го рецидива болезни. ...
Article
Background . In recent years, there has been an increase in the incidence of vulvar precancer (lichen sclerosus), as well as vulvar cancer. Since this disorder is rare, treatment planning and therapy itself are often suboptimal, which results in a high recurrence rate. Treatment of patients with local recurrence is even more difficult. Improper therapy often leads to fatal outcomes. Aim . To develop an innovative therapeutic approach to local recurrent vulvar cancer that includes combination (intraarterial and systemic) chemotherapy and surgery. Materials and methods . This pilot study included two patients with a second episode of local recurrent vulvar cancer. The first patient was denied special treatment, whereas the second one was offered abdominoperineal resection of the rectum. At the first stage, the patients received combination chemotherapy; at the second stage, they had combination reconstructive surgeries. Results . Combination chemotherapy was highly effective as demonstrated by the reduction of the recurrent tumor to a resectable size. Combination and reconstructive surgeries allowed us to preform radical treatment and preserve functions of the adjacent organs. Conclusion . Combination treatment was highly effective in patients with local recurrent vulvar cancer, when the tumor was located near the urethra, vagina, and anus or invaded them. Combination chemotherapy ensured good tumor regression, while surgery gave hopes for a favorable outcome.
... Vulvar cancer can be derived from two pathways: one associated with vulvar dermatosis (lichen sclerosus or lichen planus) and one associated with HPV infection. According to the International Society for the Study of Vulvovaginal Diseases, the associated precursor lesions are differentiated vulvar intraepithelial neoplasia and vulvar high-grade squamous intraepithelial lesion, respectively [84,85]. Most vulvar cancers are associated with vulvar dermatosis, while most cases of vulvar intraepithelial neoplasia are associated with HPV infection. ...
Article
This review analyzes the clinical associations between specific low genitourinary tract clinical circumstances in perimenopausal and postmenopausal women living with human immunodeficiency virus (WLHIV). Modern antiretroviral therapy (ART) improves survival and reduces opportunistic infections and HIV transmission. Despite appropriate ART, WLHIV may display menstrual dysfunction, risk of early menopause, vaginal microbiome alterations, vaginal dryness, dyspareunia, vasomotor symptoms and low sexual function as compared to women without the infection. They have increased risks of intraepithelial and invasive cervical, vaginal and vulvar cancers. The reduced immunity capacity may also increase the risk of urinary tract infections, side-effects or toxicity of ARTs, and opportunistic infections. Menstrual dysfunction and early menopause may contribute to the early onset of vascular atherosclerosis and plaque formation, and increased osteoporosis risks requiring specific early interventions. On the other hand, the association between being postmenopausal and having a low sexual function is significant and related to low adherence to ART. WLHIV deserve a specific approach to manage different low genitourinary risks and complications related to hormone dysfunction and early menopause.
... A consensus statement on the management of pre-invasive vulvar disease has been published already. 1 This consensus statement focuses on the management of VaIN. The statement was accepted when consensus of at least two thirds of experts was achieved. ...
Article
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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.
... According to European and international guidelines, non-HPV-related VSCC could be prevented by accurate diagnosis, treatment, and follow up of vulvar lichen sclerosus, lichen planus, and differentiated VIN [50,51]. Women with lichen sclerosus are at increased risk of VSCC especially if aged ≥70 years at baseline [52]. ...
Article
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(1) Objective: In many Western countries, survival from vulvar squamous cell carcinoma (VSCC) has been stagnating for decades or has increased insufficiently from a clinical perspective. In Italy, previous studies on cancer survival have not taken vulvar cancer into consideration or have pooled patients with vulvar and vaginal cancer. To bridge this knowledge gap, we report the trend in survival from vulvar cancer between 1990 and 2015. (2) Methods: Thirty-eight local cancer registries covering 49% of the national female population contributed the records of 6274 patients. Study endpoints included 1- and 2-year net survival (NS) calculated using the Pohar-Perme estimator and 5-year NS conditional on having survived two years (5|2-year CNS). The significance of survival trends was assessed with the Wald test on the coefficient of the period of diagnosis, entered as a continuous regressor in a Poisson regression model. (3) Results: The median patient age was stable at 76 years. One-year NS decreased from 83.9% in 1990–2001 to 81.9% in 2009–2015 and 2-year NS from 72.2% to 70.5%. Five|2-year CNS increased from 85.7% to 86.7%. These trends were not significant. In the age stratum 70–79 years, a weakly significant decrease in 2-year NS from 71.4% to 65.7% occurred. Multivariate analysis adjusting for age group at diagnosis and geographic area showed an excess risk of death at 5|2-years, of borderline significance, in 2003–2015 versus 1990–2002. (4) Conclusions: One- and 2-year NS and 5|2-year CNS showed no improvements. Current strategies for VSCC control need to be revised both in Italy and at the global level.
... The HPV-associated squamous intraepithelial lesions include vLSIL and vHSIL, whereas HPV-independent VIN includes dVIN, the more controversial differentiated exophytic vulvar intraepithelial lesion (DEVIL), and vulvar acanthosis with altered differentiation (VAAD). 3 Vulvar high-grade squamous intraepithelial lesions tend to occur in younger women, and it is associated with high-risk HPV infection, whereas dVIN typically affects older women and is associated with lichen sclerosus and possibly lichen planus. [3][4][5][6] The prevalence of HPV infection is higher than 80% in vHSIL. ...
... 3 Vulvar high-grade squamous intraepithelial lesions tend to occur in younger women, and it is associated with high-risk HPV infection, whereas dVIN typically affects older women and is associated with lichen sclerosus and possibly lichen planus. [3][4][5][6] The prevalence of HPV infection is higher than 80% in vHSIL. [7][8][9][10] However, the estimated prevalence of HPV infection in squamous cell carcinomas of the vulva ranges from 15% to 79%. ...
... Therefore, reintervention in case of positive margins is not recommended, but long-term surveillance is recommended. 3,4,13 The potential for recurrence and malignancy of vHSIL after treatment has a large variance, and risk factors are still poorly established. Our study aims to examine which clinical characteristics are associated with recurrence and progression to vulvar cancer in women with vHSIL. ...
Article
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.
... Instead, with the cervical screening programme ending at 65 years of age, women at significant risk of anal cancer are left with no surveillance nor education at the time they are most likely to develop anal pathology. Even most cervical and vulval cancer guidelines fail to include digital anal examination as part of routine follow-up [72][73][74][75][76][77]. An oversight given that the incidence rates for vaginal and vulval cancers have been shown to fall over successive years after a diagnosis of cervical HSIL [78]; thereby demonstrating the potential benefit of also including anal inspection in routine follow-up. ...
Article
Full-text available
Simple Summary Anal cancer rates are on the rise, especially for women. Women with a background of genital dysplasia or cancer have been shown to be at a higher risk of anal cancer than the general population. Despite this, very little has been done to educate women of the increased risk and as a result women tend to present later with advanced disease. As anal cancer has a known precancerous precursor, there is potential for patients to receive preventative treatment prior to anal cancer development. Although, due to the rarity of the disease, there are currently no clinical guidelines for the prevention of anal cancer in women. There are likely to be missed opportunities in preventing anal cancer progression from treatable dysplastic precursor lesions. This review presents the current evidence supporting the screening, treatment, and surveillance of anal precancerous lesions in women with genital dysplasia or cancer. Abstract In developed countries the incidence of anal squamous cell carcinoma (SCC) has been rising; especially in women over the age of 60 years who present with more advanced disease stage than men. Historically, anal SCC screening has focused on people living with Human Immunodeficiency Virus (HIV) (PLWH) who are considered to be at the highest risk of anal SCC, and its precancerous lesion, anal squamous intraepithelial lesion (SIL). Despite this, women with vulval high-grade squamous epithelial lesions (HSIL) and SCCs have been shown to be as affected by anal HSIL and SCC as some PLWH. Nevertheless, there are no guidelines for the management of anal HSIL in this patient group. The ANCHOR trial demonstrated that treating anal HSIL significantly reduces the risk of anal SCC in PLWH, there is therefore an unmet requirement to clarify whether the screening and treatment of HSIL in women with a prior genital HSIL is also beneficial. This review presents the current evidence supporting the screening, treatment, and surveillance of anal HSIL in high-risk women with a previous history of genital HSIL and/or SCC.
... It is encountered in skin areas with abundant apocrine sweat glands and is characterized by the presence of cells with large pleomorphic nuclei that initially form in the lower layers of the epidermis, without invading the dermis, but as the disease progresses, they tend to involve the entire thickness of the epidermal layer. 1 Vulvar Paget disease (VPD) represents most extramammary lesions accounting for approximately 1% to 2% of all tumors of the female genital tract. [2][3][4] The estimated incidence in Europe is approximately 0.7 cases per 100,000 women, 4,5 Its diagnosis may be difficult and the most prominent symptoms include pruritus and local pain, while macroscopically the lesion is usually an asymmetrical, red, and white eczematoid pruritic lesions or as an erythematous plaque with typical white scaling on the vulva, which progressively expands with a slow rate. ...
... Radical surgery should not be used in the absence of invasive features as the disease tends to recur in more than one third of cases. 1,7,8 A recent randomized trial suggested that topical application of imiquimod may be an equally effective and safe alternative to surgical excision. 9 Given that multiple recurrences are rather frequent, regardless of the treatment modality that is used, 10 factors that contribute to their development should be thoroughly evaluated. ...
Article
Objectives: Vulvar Paget disease (VPD) is a benign disease with high recurrence rates. Standard treatment involves conservative surgery with wide local excision of the lesion. The purpose of the present study is to identify factors that increase the risk of relapse. Materials and Methods: We conducted a retrospective study and included patients treated with conservative surgery for noninvasive VPD. Cox regression analysis was carried out to assess the independent effect of age, presence of positive margins, tumor size greater than 4 cm, bilateral lesions, and compositive morbidity and pathology on recurrence free survival. Post hoc power analysis was performed with the G-power tool using an α error of 0.05. Results: Overall, 39 patients were included with a median age of 70 years (46-85 years). Of those, 19 patients relapsed within a median duration of 30.5 months (5-132 months). Twelve patients (63%) experienced at least a second relapse. The presence of composite comorbidity significantly affected the interval to recurrence (30.09 vs 71.80 months, p = .032). Univariate Cox regression analysis revealed that the presence of composite pathology features was indicative of a higher risk of recurrence (hazard ratio = −3.71, p = .024). The sample size did not allow for adequate power for this latter finding. Microscopically involved tumor margins and tumor size greater than 4 cm did not predict patients at risk of experiencing relapsing disease. Conclusions: Patients with noninvasive VPD experience high relapse rates. The presence of concurrent benign vulvar pathology may increase these rates, although larger sample sizes are needed to ascertain our findings.
... However, the classic surgical treatment produces high morbidity and recurrence rates [6]. This previously required extensive and repeated disfiguring surgeries to eradicate the lesions, while current treatment strategies aim to prevent progression to vulvar carcinoma, preserve normal anatomy, relieve symptoms, and maintain both quality of life and sexual function [7]. Medical treatment has therefore arisen as a treatment option for vulvar HSIL, particularly because it usually presents as multifocal lesions in young women [4]. ...
... Few studies have also evaluated the long-term effects of the response to imiquimod; one study [13] followed 24 patients included in the trial by van Seters [10] for a median of 7.2 years. The duration of follow-up is essential when comparing the reported recurrence rates: 6.8% at 6 months and up to 50% (14 th year of follow up) [7]. Research has also largely ignored the HPV genotypes in biopsy samples before and after imiquimod treatment or the association with pathologic response and recurrence in long-term follow-up, and has included only vulvar HSIL cases. ...
... The discrepancies in response rate likely reflect the different inclusion criteria. For example, the inclusion of vulvar HSIL/VIN 1 can increase the number of responses because vulvar LSIL is not considered a premalignant lesion [7]. Another issue may be the scarcity of patients and follow-up in these studies. ...
Article
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Objectives: Vulvar high-grade squamous intraepithelial lesion (vulvar HSIL) or vulvar intraepithelial neoplasia (VIN) is a premalignant condition that can progress to carcinoma. Imiquimod is a topical drug with high effectiveness and low morbidity. We aimed (1) to assess the long-term response to imiquimod in a cohort of patients with vulvar HSIL and (2) and to analyze the role of HPV determined in pre- and post-imiquimod treatment biopsies in the persistence or recurrence of vulvar HSIL. Design: Retrospective study between 2011 and 2022. Setting: Referrals from the primary care area of Baix Llobregat treated in the gynecology department of a university hospital in Barcelona, Spain. Population: 20 women with vulvar HSIL treated with imiquimod. Methods: The inclusion criteria were vulvar HSIL, vulvar HPV determination by pre- and post-treatment biopsy, acceptance of medical treatment, at least one follow-up and 4 weeks of treatment. Main outcome measures: Histological diagnosis of vulvar HSIL with pre- and post-imiquimod HPV determination. Response to treatment (complete, partial, no response, recurrence). Results: After imiquimod, 10 (50%) and 6 (30%) cases had complete and partial responses, respectively. Another 4 cases (20%) did not respond. Before treatment, 19 (95%) cases were positive for vulvar HPV (16 cases had HPV type 16). After treatment, 10 cases (50%) were positive for HPV (8 cases with HPV type 16): 2 cases (20%) with a complete response, 5 cases (83.3%) with a partial response and 3 cases (75%) with no response. Eight of the 10 HPV-negative cases (80%) post-treatment showed a complete response. HPV type 16 was present in 16 cases (84.2%) pre-treatment and in 8 cases (80%) post-treatment. Ten patients underwent additional treatments following a partial response, no response or recurrence. The 2 HIV and 3 immunosuppressed patients treated with imiquimod showed a partial response and required additional treatment. All these patients were HPV-positive pre- and post-treatment (100%). Response to imiquimod was associated with post-treatment vulvar HPV positivity (p = 0.03). The median time to a complete response in HPV-negative cases was 4.7 months versus 11.5 months in HPV-positive cases post-imiquimod treatment. Recurrence of vulvar HSIL was observed in 7 patients (35%), with a median time to recurrence of 19.7 months (range 3.2–32.7). Recurrence was experienced in 10% of cases with a complete response, in 4/6 (66.6%) cases with a partial response, and in 2/4 (50%) women with no response. Four of the 7 recurrent cases (57%) were infected with HIV or immunosuppressed. Six (85%) of the recurrent cases were HPV-positive post-treatment (all were HPV type 16). Four (30.7%) of the non-recurrent cases were HPV-positive post-treatment with imiquimod (p = 0.05), two of which were HPV type 16 (50%). Conclusions: Imiquimod effectively treats vulvar HSIL. Cases with a complete response showed less HPV positivity post-treatment than partial or non-response cases. Recurrences were more frequent in those with a partial or no response to imiquimod, and in immunosuppressed patients. In recurrent cases, 85% were HPV-positive post-treatment, while 30.7% of non-recurrent cases were HPV-positive. HPV positivity in the post-treatment biopsy suggests the need for stricter follow-up of patients.