New Insights into the Epidemiology of Vulvar Cancer: Systematic Literature Review for an Update of Incidence and Risk Factors

The aim of this review was an update of vulvar cancer incidence rates and trends and of all known and putative risk factors for the disease. The most recent incidence data were sought from official sources (WHO Cancer Incidence in Five Continents). To obtain an estimate of time trends in some areas, we compared data from Cancer Incidence in Five Continents with the few available studies that measured incidence using comparable methods. With respect to risk factors, a systematic PubMed search identified 1585 relevant articles published between 1980 and 2021. Abstracts and full texts were screened. Sixty-nine eligible original cohort and case-control studies were selected. Information was extracted using a PRISMA predesigned form. Nineteen risk factors, or risk factor categories, were investigated by two or more original studies. Solitary, unreplicated studies addressed the putative role of eight more factors. Recent advances have provided further evidence supporting the carcinogenic model centred on human papillomavirus infection with different defects of the immune function. Conversely, the model centred on the role of vulvar lichen sclerosus and the often associated differentiated vulvar intraepithelial neoplasia has continued to be epidemiologically understudied. More research on the association between these two conditions and vulvar cancer is a priority.

Vulvar Diseases that Required a Biopsy: A Retrospective Study

Introduction: The vulvar area may be affected by many noninfectious conditions with similar clinical appearance, requiring a cutaneous biopsy. Our goal was to characterize the noninfectious vulvar diseases that required a biopsy in a southwestern Europe Central Hospital during a 10-year period. Methods: A retrospective study of all the noninfectious vulvar diseases with histological confirmation diagnosed in our institution was conducted between January 1, 2008 and December 31, 2017. Results: The sample included a total of 323 biopsies from 317 patients, aged between 11 and 98 years (mean age of 54.2 years). A total of 36 vulvar diseases was identified. Neoplastic conditions were the most frequently found, particularly melanotic macules (22.3%). The most frequent malignant tumor was vulvar intraepithelial neoplasia (6.2%) and squamous cell carcinoma (5.6%). The most common dermatosis was lichen sclerosus (12.7%). Conclusion: Neoplasms were the most frequently diagnosed conditions affecting the vulvar area that required a biopsy. Ruling out malignancy was also the main reason to perform a biopsy. This study highlights the variety of noninfectious diseases that may affect the vulva and require a biopsy. Since vulvar diseases may be serious and carry high levels of patient distress a correct understanding of these conditions is crucial.

The Vulvar Cancer Risk in Differentiated Vulvar Intraepithelial Neoplasia: A Systematic Review

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.

Integrin αvβ6 as a Target for Tumor-Specific Imaging of Vulvar Squamous Cell Carcinoma and Adjacent Premalignant Lesions

Surgical removal of vulvar squamous cell carcinoma (VSCC) is associated with significant morbidity and high recurrence rates. This is at least partially related to the limited visual ability to distinguish (pre)malignant from normal vulvar tissue. Illumination of neoplastic tissue based on fluorescent tracers, known as fluorescence-guided surgery (FGS), could help resect involved tissue and decrease ancillary mutilation. To evaluate potential targets for FGS in VSCC, immunohistochemistry was performed on paraffin-embedded premalignant (high grade squamous intraepithelial lesion and differentiated vulvar intraepithelial neoplasia) and VSCC (human papillomavirus (HPV)-dependent and -independent) tissue sections with healthy vulvar skin as controls. Sections were stained for integrin αvβ6, CAIX, CD44v6, EGFR, EpCAM, FRα, MRP1, MUC1 and uPAR. The expression of each marker was quantified using digital image analysis. H-scores were calculated and percentages positive cells, expression pattern, and biomarker localization were assessed. In addition, tumor-to-background ratios were established, which were highest for (pre)malignant vulvar tissues stained for integrin αvβ6. In conclusion, integrin αvβ6 allowed for the most robust discrimination of VSCCs and adjacent premalignant lesions compared to surrounding healthy tissue in immunohistochemically stained tissue sections. The use of an αvβ6 targeted near-infrared fluorescent probe for FGS of vulvar (pre)malignancies should be evaluated in future studies.

Verrucous carcinoma of vulva associated with lichen sclerosus and condyloma: case report

Vulvar Verrucous Carcinoma (VVC) is a rare lesion, with few described cases. It has low metastatic potential with high morbidity due to the necessity of extensive resections, although. Previously, VVC was considered a synonym to the Buschke-Lowenstein Tumor (BLT) or Giant Condyloma Acuminatum (GCA). Lichen Sclerosus (LS) is associated with Vulvar Intraepithelial Neoplasia (VIN) and Vulvar Squamous-cell carcinoma (SCC); association with VVC is also described. The case of a 60-year-old menopausal woman is reported; she had chronic itching and an extensive verrucous lesion in vulva, initially diagnosed and treated as condyloma acuminatum; there was recurrence as verrucous carcinoma associated to LS. Excision with margins was performed and clobetasol and imiquimod were used. Patient had complete remission with no further recurrences. Distinction between VVC and BLT can be difficult; current literature considers them different entities. Human papillomavirus (HPV) infection and the presence of LS play a controversial role in these injuries.

Focused Ultrasound Surgery Applications in Treating Vulvar Non-neoplastic Epithelial Disorders

: Vulvar intraepithelial neoplasia is a premalignant skin lesion of the vulva that often presents with severe vulvar pruritus, pain, and psychosexual disorders. The technology of non-invasive focused ultrasound surgery has improved over the years. Today its potential to treat these irritating diseases noninvasively is a relatively new area of clinical research interest. Increasing studies in China revealed that FUS treatment is effective and safe. This paper describes the preparation, technique, postoperative care, and results of this focused ultrasound surgery for treating vulvar non-neoplastic epithelial disease. Therefore it could be a future alternative treatment for benign vulvar diseases, replacing many invasive surgical treatments.

Vulvar intraepithelial neoplasia. Literature review

Vulvar intraepithelial neoplasia (VIN) is the proliferation of atypical basal cells in the vulvar epithelium. The global VIN incidence has recently doubled; its incidence among white women under 35 years of age has almost tripled with a tendency for further growth. Such an increase in the number of usual-type VIN cases in young women is primarily attributed to infection with highly oncogenic human papillomavirus. The second type of dysplasia, namely differentiated VIN, is usually found in older women and is associated with chronic dystrophic diseases of the vulva, most frequently with lichen sclerosus of the vulva. VIN diagnosis is quite challenging; no screening programs for this disorder have been developed so far. Patients with VIN practice self-treatment for a long time, which aggravates their condition and might trigger the development of vulvar cancer. Several treatment options are currently available; however, their efficacy worldwide is not high.

Cytomorphologic Features of Extramammary Paget’s Disease of The Vulva in a patient with history of Squamous Cell Carcinoma of The Cervix, Status Post Chemoradiation and Neoadjuvant Therapy. The Importance of Basic Principles

Introduction/Objective Extramammary Paget disease (EMPD) is a rare neoplasm commonly affects postmenopausal women. It usually presents in the anogenital area where apocrine sweat glands are abundant, most commonly in the vulva. The disease is characterized by slow grow and high local recurrence rates. Clinically, EMPD present as well demarcated erythematous lesion or plaques that may ulcerated. Microscopically, it shows a group of atypical cells with abundant clear cytoplasm and nuclear pleomorphism. Methods/Case Report Here in we present a 58-year-old female with history of vulvar intraepithelial neoplasia III (VIN III) status post wide local excision, and poorly differentiated squamous cell carcinoma status post radical hysterectomy and bilateral salpingo-oopherectomy and chemoradiation who presented for perineal pain, itching and discomfort. She also noticed skin changes on her left labia without bleeding or discharge. Punch biopsies of the vulva and periurethral areas revealed acanthosis of the epidermis with intraepidermal scattering of single or clusters of large cells with round/ovoid nuclei and abundant clear cytoplasm. The cells are positive for p16, CK19, CK7, PAX8 supporting the diagnosis of EMPD without evidence of dysplasia. The concurrent PAP smear shows hypercellular specimen composed of hyperchromatic fragments of tissue with high nuclear-to-cytoplasmic rations, and apoptotic bodies. The presence of intracytoplasmic mucin and the tridimensionality of the fragments supported the diagnosis of adenocarcinoma. The HPV testing was positive for HPV-16. Results (if a Case Study enter NA) N/A Conclusion This study compares the histological and cytomorphological features of EMPD with high-grade squamous intraepithelial lesion (HSIL), since the molecular pathways, precursor lesions, etiologic associations, staging, clinical treatment, and prognosis differ substantially and may have a significant clinical impact for the patient’s treatment.