Search Results (12)

Vulvar carcinoma is the fourth most common gynecological cancer, with squamous cell carcinoma being the most frequent type. Vulvar intraepithelial neoplasia (VIN) is a precursor lesion and is strongly associated with human papillomavirus (HPV) infection. This paper presents two patients in their sixth decade of life, the first diagnosed with VIN 3 (carcinoma in situ) and the second with stage IA keratinizing squamous cell carcinoma. Both patients had HPV infection; immunohistochemistry confirmed HPV-dependent VIN3 in the first case, while the second patient had a pre-existing HPV high-risk 53 infection. Both patients underwent partial vulvectomy, with the second also having bilateral inguinal–femoral lymph node dissection, which showed no lymph node invasion. The first patient had a histopathological result of VIN 3 with clear margins. The second patient underwent adjuvant radiotherapy following restaging pathology. Both are showing favorable postoperative progress. Conclusions. The early diagnosis of vulvar neoplasms enables less radical but effective surgeries, balancing oncologic control with quality of life. A multidisciplinary approach is essential for adjusting treatments, improving both clinical outcomes and patient well-being. Full article

Cutaneous squamous cell carcinoma (cSCC) is the second-most-prevalent malignancy in humans. A delayed diagnosis of cSCC leads to heightened invasiveness and positive surgical margins. Bowen’s disease (BD) represents an early form of cSCC and presents as a small erythematous, photo-distributed, psoriasiform plaque. Although certain dermoscopy features in BD are quite characteristic, histopathology remains the gold standard for diagnosis and provides a severity-scoring system that assists in guiding appropriate treatment strategies. The classification of precancerous lesions of the vulva and penis has undergone multifarious transformations due to variations in clinical and histopathological characteristics. Presently, erythroplasia of Queyrat is categorized as a clinical variant of penile intraepithelial neoplasia (PeIN). The diagnoses of vulvar intraepithelial neoplasia (VIN) and PeIN present significant challenges and typically necessitate one or more biopsies, potentially guided by dermoscopy. Aceto-white testing demonstrates a notably high negative predictive value for genital precancerous lesions. Histopathological examination represents the gold-standard diagnosis in VIN and PeIN, while p16 and p53 immunostainings alongside HPV testing provide crucial diagnostic clues. The histopathologic features, degree of differentiation, and associations with lichen planus, lichen sclerosus, and HPV guide the selection of conservative treatments or surgical excision. Full article

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

Introduction: Topical Imiquimod is an immune response modifier approved for the off-label use of vulvar intraepithelial neoplasia. We conducted this systematic review and meta-analysis to investigate the efficacy and safety of Imiquimod in treating cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV)-positive patients. Methods: The study was prospectively registered (CRD420222870) and involved a comprehensive systematic search of five medical databases on 10 October 2022. We included articles that assessed the use of Imiquimod in cervical dysplasia and HPV-positive patients. Pooled proportions, risk ratios (RRs), and corresponding 95% confidence intervals (CIs) were calculated using a random effects model to generate summary estimates. Statistical heterogeneity was assessed using I² tested by the Cochran Q tests. Results: Eight articles reported on 398 patients who received Imiquimod out of 672 patients. Among CIN-2–3 patients, we observed a pooled regression rate of 61% (CI: 0.46–0.75; I²: 77%). When compared, Imiquimod was inferior to conization (RR: 0.62; CI: 0.42–0.92; I²: 64%). The HPV clearance rate in women who completed Imiquimod treatment was 60% (CI: 0.31–0.81; I²: 57%). The majority of side effects reported were mild to moderate in severity. Conclusions: Our findings indicate that topical Imiquimod is safe and effective in reducing cervical intraepithelial neoplasia and promoting HPV clearance. However, it was found to be inferior compared to conization. Imiquimod could be considered a potential medication for high-grade CIN patients and should be incorporated into guidelines for treating cervical dysplasia. Full article

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. Full article

Photodynamic therapy (PDT) is a valuable treatment method for vulvar intraepithelial neoplasia (VIN). It allows for the treatment of a multifocal disease with minimal tissue destruction. 5-Aminolevulinic acid (5-ALA) is the most commonly used prodrug, which is converted in the heme pathway to protoporphyrin IX (PpIX), an actual photosensitizer (PS). Unfortunately, not all patients treated with PDT undergo complete remission. The main cause of their failure is resistance to anticancer therapy. In many cancers, resistance to various anticancer treatments is correlated with increased activity of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1). Enhanced activity of drug pumps may also affect the effectiveness of therapy. To investigate whether multidrug resistance mechanisms underlie PDT resistance in VIN, porphyrins were isolated from sensitive and resistant vulvar cancer cells and their culture media. APE1 activity was measured, and survival assay after PDT combined with APE1 inhibitor was performed. Our results revealed that resistant cells accumulated and effluxed less porphyrins than sensitive cells, and in response to PDT, resistant cells increased APE1 activity. Moreover, PDT combined with inhibition of APE1 significantly decreased the survival of PDT-resistant cells. This means that resistance to PDT in vulvar cancer may be the result of alterations in the heme synthesis pathway. Moreover, increased APE1 activity may be essential for the repair of PDT-mediated DNA damage, and inhibition of APE1 activity may increase the efficacy of PDT. Full article

Background: Lichen sclerosus is the most common nonmalignant vulvar disease with morbidity in postmenopausal age. The first line of treatment is corticosteroid therapy. In case of insufficiency, tacrolimus or pimecrolimus can be provided. Photodynamic therapy (PDT) can be used as alternative way of treatment while symptoms recurrent despite other methods. Methods: the analyzed population of 182 women with diagnosis of lichen sclerosus treated using PDT was divided into three groups: patients with neoplastic disease or intraepithelial neoplasia; those with a positive family history of neoplastic disease; and a control group with no neoplastic disease and no familial history of neoplastic diseases. Results: Reduction of vulvar changes was assessed in the whole vulva in the groups as 21.9%, 21.2% and 21.8%, respectively. The most frequent symptom, itching, was reported to decrease in all groups, 39.3%, 35.5% and 42.5%, respectively. Improvement of quality of life was assessed in 91.3% of the whole group, stabilization of lichen sclerosus in 7.1% and progression in 1.6%. Conclusions: Photodynamic therapy gives positive results in most cases. Improvement after PDT is observed in objective vulvoscopic assessment and in subjective patients’ opinions. Neoplastic disease in the past can influence the effectiveness of PDT. Full article

Objective: To assess evidence on the efficacy of adjuvant human papillomavirus (HPV) vaccination in patients treated for HPV-related disease across different susceptible organ sites. Methods: A systematic review was conducted to identify studies addressing the efficacy of adjuvant HPV vaccination on reducing the risk of recurrence of HPV-related preinvasive diseases. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). Results: Sixteen studies were identified for the final analysis. Overall, 21,472 patients with cervical dysplasia were included: 4132 (19.2%) received the peri-operative HPV vaccine, while 17,340 (80.8%) underwent surgical treatment alone. The recurrences of CIN 1+ (OR 0.45, 95% CI 0.27 to 0.73; p = 0.001), CIN 2+ (OR 0.33, 95% CI 0.20 to 0.52; p < 0.0001), and CIN 3 (OR 0.28, 95% CI 0.13 to 0.59; p = 0.0009) were lower in the vaccinated than in unvaccinated group. Similarly, adjuvant vaccination reduced the risk of developing anal intraepithelial neoplasia (p = 0.005) and recurrent respiratory papillomatosis (p = 0.004). No differences in anogenital warts and vulvar intraepithelial neoplasia recurrence rate were observed comparing vaccinated and unvaccinated individuals. Conclusions: Adjuvant HPV vaccination is associated with a reduced risk of CIN recurrence, although there are limited data regarding its role in other HPV-related diseases. Further research is warranted to shed more light on the role of HPV vaccination as adjuvant therapy after primary treatment. Full article

Vulvar cancer is a rare gynaecological malignancy, accounting for 2–5% of cancers of the female genital tract. Squamous cell carcinoma is the most frequently occurring subtype and, historically, has been a disease of older post-menopausal women, occurring with a background of lichen sclerosus and other epithelial conditions of the vulvar skin that may be associated with well-differentiated vulvar intra-epithelial neoplasia (dVIN). An increase in human papillomavirus (HPV) infections worldwide has led to an increase in vulvar squamous carcinomas in younger women, resulting from HPV-associated high-grade vulvar squamous intra-epithelial lesions (vHSIL). Surgical resection is the gold standard for the treatment of vulvar cancer. However, as approximately 30% of patients present with locally advanced disease, which is either irresectable or will require radical surgical resection, possibly with a stoma, there has been a need to investigate alternative forms of treatment such as chemoradiation and targeted therapies, which may minimise the psychosexual morbidity of radical surgery. This review aims to provide an update on management strategies for women with advanced vulvar cancer. It is hoped that investigation of the molecular biologies of the two different pathways to vulvar squamous cell carcinoma (HPV-associated and non-HPV-associated) will lead to the development of targeted therapeutic agents. Full article

Differentiated vulvar intraepithelial neoplasia (dVIN) is the precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC). Given the rare incidence of dVIN, limited information on the exact cancer risk is available. We systematically reviewed the primary and recurrent VSCC risk in patients with dVIN, as well as the time to cancer development. A systematic search was performed up to July 2021 according to the PRISMA guidelines. Five reviewers independently screened articles on title, abstract and full text, followed by critical appraisal of selected articles using the Quality in Prognostic Studies (QUIPS) tool. Of the 455 screened articles, 7 were included for analysis. The absolute risk for primary VSCC in dVIN varied between 33 and 86%, with a median time to progression to VSCC of 9–23 months. The risk of developing recurrent VSCC in dVIN associated VSCC was 32–94%, with a median time to recurrence of 13–32 months. In conclusion, patients with dVIN have a high risk of developing primary and recurrent VSCC with a short time to cancer progression. Increased awareness, timely recognition, aggressive treatment and close follow-up of HPV-independent vulvar conditions including dVIN is therefore strongly recommended. Full article

Epigallocatechin-3-gallate (EGCG), the primary bioactive polyphenol in green tea, has been shown to inhibit the growth of human papilloma virus (HPV)-transformed keratinocytes. Here, we set out to examine the consequences of EGCG treatment on the growth of HPV18-immortalised foreskin keratinocytes (HFK-HPV18) and an authentic HPV18-positive vulvar intraepithelial neoplasia (VIN) clone, focusing on its ability to influence cell proliferation and differentiation and to impact on viral oncogene expression and virus replication. EGCG treatment was associated with degradation of the E6 and E7 oncoproteins and an upregulation of their associated tumour suppressor genes; consequently, keratinocyte proliferation was inhibited in both monolayer and organotypic raft culture. While EGCG exerted a profound effect on cell proliferation, it had little impact on keratinocyte differentiation. Expression of the late viral protein E4 was suppressed in the presence of EGCG, suggesting that EGCG was able to block productive viral replication in differentiating keratinocytes. Although EGCG did not alter the levels of E6 and E7 mRNA, it enhanced the turnover of the E6 and E7 proteins. The addition of MG132, a proteasome inhibitor, to EGCG-treated keratinocytes led to the accumulation of the E6/E7 proteins, showing that EGCG acts as an anti-viral, targeting the E6 and E7 proteins for proteasome-mediated degradation. Full article

Background: vulvar intraepithelial neoplasia is a non-invasive precursor lesion found in 50–70% of patients affected by vulvar squamous cell carcinoma. In the past, radical surgery was the standard treatment for vulvar intraepithelial neoplasia, however, considering the psychological and physical morbidities related to extensive surgery, several less aggressive treatment modalities have been proposed since the late 1970s. Photodynamic therapy is an effective and safe treatment for cutaneous non-melanoma skin cancer, with favorable cosmetic outcomes. Methods: in the present paper, the results of selected studies on photodynamic therapy in the treatment of vulvar intraepithelial neoplasia are reported and discussed. Results: Overall, complete histological response rates ranged between 20% and 67% and symptom response rates ranged between 52% and 89% according to different studies and case series. Conclusions: the real benefit of photodynamic therapy in the setting of vulvar intraepithelial neoplasia lies in its ability to treat multi-focal disease with minimal tissue destruction, preservation of vulvar anatomy and excellent cosmetic outcomes. These properties explain why photodynamic therapy is an attractive option for vulvar intraepithelial neoplasia treatment. Full article