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Recent Advances in Vulvar Cancer

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Epidemiology and Prevention".

Deadline for manuscript submissions: closed (15 November 2021) | Viewed by 72584

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Special Issue Editors

Prof. Mario Preti

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Guest Editor

Department of Surgical Sciences, University of Torino, Torino, Italy
Interests: vulvar intraepithelial neoplasia; vulvar cancer; cervical cancer screening; HPV

Dr. Denis Querleu

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Guest Editor

1. Department of Gynecologic Oncology, Agostino Gemelli University Hospital, 00168 Rome, Italy
2. Department of Obstetrics and Gynecology, University Hospital of Strasbourg, 67091 Strasbourg, France
Interests: gynecologic oncology; quality assurance; guidelines; laparoscopic surgery

Special Issue Information

Dear Colleagues,

Even though Vulvar Squamous Cell Carcinoma (VSCC) is a rare malignancy, representing 4% of all gynecological cancers, its incidence has been progressively increasing over the last few decades, particularly in women aged 50–60 years. Moreover, its incidence has increased in older patients, and no significant improvements in outcomes have been reported in decades.

At least two main pathways have been identified in VSCC oncogenesis. The first, which is more commonly found in younger women, has high-grade vulvar squamous intraepithelial neoplasia as a precursor and HPV infection in over 80% of cases. The second pathway arises within chronic dermatoses as lichen sclerosus and lichen planus, typical of older women, with differentiated VIN (dVIN) considered to be a transient pre-invasive lesion that rapidly progresses to an invasive malignancy. In addition, genomic alterations have different pathways, with p53 and HPV status having both prognostic and predictive value. Recently, researchers have identified a third subgroup with normal p53 expression, NOTCH1 and HRAS mutations (HPVneg/TP53wt VSCC), and an intermediate 5-year survival rate.

This Special Issue will focus on VSCC oncogenesis, its clinical and histopathological diagnosis, multimodal therapeutic approaches, adjuvant treatment, and tailored follow-up with psycho-sexuological support. The latest developments in the field of VSCC research, ranging from the tumor’s immune microenvironment to potential new approaches in advanced cases, will also be discussed.

Prof. Mario Preti
Prof. Denis Querleu
Guest Editors

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Keywords

vulvar cancer
epidemiology
genomic alteration
management
sentinel node
radiotherapy
chemotherapy
recurrent disease
prevention
quality of life

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Published Papers (14 papers)

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Editorial

Jump to: Research, Review, Other

3 pages, 177 KiB

Open AccessEditorial

Vulvar Cancer: Facing a Rare Disease

by Mario Preti and Denis Querleu

Cancers 2022, 14(6), 1581; https://doi.org/10.3390/cancers14061581 - 20 Mar 2022

Cited by 6 | Viewed by 2263

Abstract

“We must never be afraid to go too far, for truth lies beyond [...] Full article

(This article belongs to the Special Issue Recent Advances in Vulvar Cancer)

Research

Jump to: Editorial, Review, Other

14 pages, 1777 KiB

Open AccessArticle

Risk for Pelvic Metastasis and Role of Pelvic Lymphadenectomy in Node-Positive Vulvar Cancer-Results from the AGO-VOP.2 QS Vulva Study

by Linn Woelber, Monika Hampl, Christine zu Eulenburg, Katharina Prieske, Johanna Hambrecht, Sophie Fuerst, Ruediger Klapdor, Sabine Heublein, Paul Gass, Annika Rohner, Ulrich Canzler, Sven Becker, Mareike Bommert, Dirk Bauerschlag, Agnieszka Denecke, Lars Hanker, Ingo Runnebaumn, Dirk M. Forner, Fabienne Schochter, Maximilian Klar, Roxana Schwab, Melitta Koepke, Matthias Kalder, Peer Hantschmann, Dominik Ratiu, Dominik Denschlag, Willibald Schroeder, Benjamin Tuschy, Klaus Baumann, Alexander Mustea, Philipp Soergel, Holger Bronger, Gerd Bauerschmitz, Jens Kosse, Martin C. Koch, Atanas Ignatov, Jalid Sehouli, Christian Dannecker, Sven Mahner and Anna Jaeger Show full author list Hide full author list

Cancers 2022, 14(2), 418; https://doi.org/10.3390/cancers14020418 - 14 Jan 2022

Cited by 3 | Viewed by 2496

Abstract

The need for pelvic treatment in patients with node-positive vulvar cancer (VSCC) and the value of pelvic lymphadenectomy (LAE) as a staging procedure to plan adjuvant radiotherapy (RT) is controversial. In this retrospective, multicenter analysis, 306 patients with primary node-positive VSCC treated at 33 gynecologic oncology centers in Germany between 2017 and 2019 were analyzed. All patients received surgical staging of the groins; nodal status was as follows: 23.9% (73/306) pN1a, 23.5% (72/306) pN1b, 20.4% (62/306) pN2a/b, and 31.9% (97/306) pN2c/pN3. A total of 35.6% (109/306) received pelvic LAE; pelvic nodal involvement was observed in 18.5%. None of the patients with nodal status pN1a or pN1b and pelvic LAE showed pelvic nodal involvement. Taking only patients with nodal status ≥pN2a into account, the rate of pelvic involvement was 25%. In total, adjuvant RT was applied in 64.4% (197/306). Only half of the pelvic node-positive (N+) patients received adjuvant RT to the pelvis (50%, 10/20 patients); 41.9% (122/291 patients) experienced recurrent disease or died. In patients with histologically-confirmed pelvic metastases after LAE, distant recurrences were most frequently observed (7/20 recurrences). Conclusions: A relevant risk regarding pelvic nodal involvement was observed from nodal status pN2a and higher. Our data support the omission of pelvic treatment in patients with nodal status pN1a and pN1b. Full article

(This article belongs to the Special Issue Recent Advances in Vulvar Cancer)

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15 pages, 598 KiB

Open AccessArticle

Perineural Invasion in Vulvar Squamous-Cell Carcinoma Is an Independent Risk Factor for Cancer-Specific Survival, but Not for Locoregional Recurrence: Results from a Single Tertiary Referral Center

by Leonardo Micheletti, Fulvio Borella, Mario Preti, Valentina Frau, Stefano Cosma, Sebastiana Privitera, Luca Bertero and Chiara Benedetto

Cancers 2022, 14(1), 124; https://doi.org/10.3390/cancers14010124 - 28 Dec 2021

Cited by 5 | Viewed by 2776

Abstract

The aims of this study were to assess the prevalence of perineural invasion (PNI) in vulvar squamous cell carcinoma (VSCC) and its prognostic role in locoregional recurrence (LRR) and cancer-specific survival (CSS). We performed a retrospective analysis of 223 consecutive stage IB–IIIC surgically treated VSCCs at S. Anna Hospital, University of Turin, from 2000 to 2019. We identified 133/223 (59.6%) patients with PNI-positive VSCCs. PNI was associated with aggressive biological features (i.e., advanced FIGO stage, larger tumor diameter, greater depth of invasion, a higher number of metastatic lymph nodes, and lymphovascular invasion) and shorter 5-year CSS (78% vs. 90%, log-rank p = 0.02) compared with PNI-negative VSCCs. Multivariate analysis showed that PNI (HR 2.99 CI 95% 1.17–7.63; p = 0.02) and the presence of tumor cells on pathological surgical margins (HR 3.13 CI 95% 1.37–7.13; p = 0.007) are independent prognostic factors for CSS. PNI does not appear to be related to LRR, but is an independent prognostic factor for worse survival outcomes. Future studies are necessary to explore the possible value of PNI in tailoring the choice of adjuvant treatment. Full article

(This article belongs to the Special Issue Recent Advances in Vulvar Cancer)

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19 pages, 1542 KiB

Open AccessArticle

The Vulvar Immunohistochemical Panel (VIP) Project: Molecular Profiles of Vulvar Squamous Cell Carcinoma

by Giorgia Garganese, Frediano Inzani, Simona Maria Fragomeni, Giulia Mantovani, Luigi Della Corte, Alessia Piermattei, Angela Santoro, Giuseppe Angelico, Luciano Giacò, Giacomo Corrado, Anna Fagotti, Gian Franco Zannoni and Giovanni Scambia

Cancers 2021, 13(24), 6373; https://doi.org/10.3390/cancers13246373 - 19 Dec 2021

Cited by 21 | Viewed by 3733

Abstract

Introduction: The study’s aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC). Methodology: A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N. Results: In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, p = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14–15.87, p = 0.03) and 2.68 (CI 95% = 1.0–7.19, p < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T diverged significantly in 18/41 (43.9%) cases. Conclusions: Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expression. Full article

(This article belongs to the Special Issue Recent Advances in Vulvar Cancer)

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15 pages, 2343 KiB

Open AccessArticle

Transcriptome Analysis in Vulvar Squamous Cell Cancer

by Katharina Prieske, Malik Alawi, Anna Jaeger, Maximilian Christian Wankner, Kathrin Eylmann, Susanne Reuter, Patrick Lebok, Eike Burandt, Niclas C. Blessin, Barbara Schmalfeldt, Leticia Oliveira-Ferrer, Simon A. Joosse and Linn Woelber

Cancers 2021, 13(24), 6372; https://doi.org/10.3390/cancers13246372 - 19 Dec 2021

Cited by 6 | Viewed by 3176

Abstract

To date, therapeutic strategies in vulvar squamous cell carcinoma (VSCC) are lacking molecular pathological information and targeted therapy hasn’t been approved in the treatment of VSCC, yet. Two etiological pathways are widely accepted: HPV induced vs. HPV independent, associated with chronic skin disease, often harboring TP53 mutations (mut). The aim of this analysis was to analyze the RNA expression patterns for subtype stratification on VSCC samples that can be integrated into the previously performed whole exome sequencing data for the detection of prognostic markers and potential therapeutic targets. We performed multiplex gene expression analysis (NanoString) with 770 genes in 24 prior next generation sequenced samples. An integrative data analysis was performed. Here, 98 genes were differentially expressed in TP53mut vs. HPV+ VSCC, in the TP53mut cohort, where 56 genes were upregulated and 42 were downregulated in comparison to the HPV+ tumors. Aberrant expression was primarily observed in cell cycle regulation, especially in HPV+ disease. Within the TP53mut group, a distinct cluster was identified that was correlated to a significantly worse overall survival (p = 0.017). The RNA expression profiles showed distinct patterns with regard to the known VSCC subtypes and could potentially enable further subclassification in the TP53mut groups Full article

(This article belongs to the Special Issue Recent Advances in Vulvar Cancer)

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16 pages, 1830 KiB

Open AccessArticle

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

by Bertine W. Huisman, Merve Cankat, Tjalling Bosse, Alexander L. Vahrmeijer, Robert Rissmann, Jacobus Burggraaf, Cornelis F. M. Sier and Mariette I. E. van Poelgeest

Cancers 2021, 13(23), 6006; https://doi.org/10.3390/cancers13236006 - 29 Nov 2021

Cited by 1 | Viewed by 2547

Abstract

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. Full article

(This article belongs to the Special Issue Recent Advances in Vulvar Cancer)

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10 pages, 3477 KiB

Open AccessArticle

Biomarker Expression in Multifocal Vulvar High-Grade Squamous Intraepithelial Lesions

by Nikki B. Thuijs, Willemijn A. M. Schonck, Linde L. J. Klaver, Guus Fons, Marc van Beurden, Renske D. M. Steenbergen and Maaike C. G. Bleeker

Cancers 2021, 13(22), 5646; https://doi.org/10.3390/cancers13225646 - 11 Nov 2021

Cited by 3 | Viewed by 2211

Abstract

In patients with high-grade squamous intraepithelial lesion (HSIL) of the vulva, the presence of multiple lesions, called multifocal HSIL, is common. The aim of this exploratory study was to investigate biomarker expression profiles in multifocal HSIL. In total, 27 lesions from 12 patients with high-risk human papillomavirus (HPV)-positive multifocal HSIL were tested for HPV genotype, expression of p16^INK4a and Ki-67, and DNA methylation of six genes. HPV16 was found most commonly in 21 (77.8%) HSILs. In two (16.4%) patients, HPV genotype differed between the lesions. All lesions demonstrated diffuse p16^INK4a staining, of which three (11.1%) were combined with patchy staining. One patient (8.3%) demonstrated markedly different DNA methylation levels between lesions. Generally, heterogeneity in methylation profiles was observed between different patients, even when other biomarkers showed similar expression. In conclusion, this study is the first to demonstrate heterogeneity of individual lesions in patients with multifocal HSIL. The studied biomarkers have the potential to refine prognostic and predictive diagnostics. Future prospective, longitudinal studies are needed to further explore the potential of a biomarker profile for management of patients with multifocal HSIL. Full article

(This article belongs to the Special Issue Recent Advances in Vulvar Cancer)

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Review

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16 pages, 8421 KiB

Open AccessReview

Early Diagnostics of Vulvar Intraepithelial Neoplasia

by Vesna Kesić, Pedro Vieira-Baptista and Colleen K. Stockdale

Cancers 2022, 14(7), 1822; https://doi.org/10.3390/cancers14071822 - 4 Apr 2022

Cited by 17 | Viewed by 28669

Abstract

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

(This article belongs to the Special Issue Recent Advances in Vulvar Cancer)

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36 pages, 648 KiB

Open AccessReview

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

by Lauro Bucchi, Margherita Pizzato, Stefano Rosso and Stefano Ferretti

Cancers 2022, 14(2), 389; https://doi.org/10.3390/cancers14020389 - 13 Jan 2022

Cited by 23 | Viewed by 4205

Abstract

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. Full article

(This article belongs to the Special Issue Recent Advances in Vulvar Cancer)

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12 pages, 2892 KiB

Open AccessReview

Management of Advanced Squamous Cell Carcinoma of the Vulva

by Linda J. Rogers

Cancers 2022, 14(1), 167; https://doi.org/10.3390/cancers14010167 - 30 Dec 2021

Cited by 9 | Viewed by 3777

Abstract

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

(This article belongs to the Special Issue Recent Advances in Vulvar Cancer)

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14 pages, 691 KiB

Open AccessReview

The Impact of Vulvar Cancer on Psychosocial and Sexual Functioning: A Literature Review

by Francesca Malandrone, Federica Bevilacqua, Mariagrazia Merola, Niccolò Gallio, Luca Ostacoli, Sara Carletto and Chiara Benedetto

Cancers 2022, 14(1), 63; https://doi.org/10.3390/cancers14010063 - 23 Dec 2021

Cited by 17 | Viewed by 4711

Abstract

Women who are diagnosed and treated for vulvar cancer are at higher risk of psychological distress, sexual dysfunction and dissatisfaction with partner relationships. The aim of this article is to provide a review of the psychological, relational and sexual issues experienced by women with vulvar cancer in order to highlight the importance of this issue and improve the quality of care offered to these patients. A review of the literature was performed using PubMed, CINAHL, PsycINFO, and the Cochrane Library. The results are presented as a narrative synthesis and highlight the massive impact of vulvar cancer: depressive and anxiety symptoms were more frequent in these women, and vulvar cancer may have a negative effect on sexuality from a physical, psychological and behavioural point of view. Factors that may negatively affect these women’s lives are shame, insecurity or difficulties in self-care and daily activities. This review highlights the psychosocial and psychosexual issues faced by women diagnosed and treated for vulvar cancer, although more studies are needed to better investigate this field of interest and to identify strategies to relieve their psychological distress. Care providers should implement an integrated care model to help women with vulvar cancer recognise and address their unmet needs. Full article

(This article belongs to the Special Issue Recent Advances in Vulvar Cancer)

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Other

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2 pages, 191 KiB

Open AccessReply

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

by Vesna Kesić, Pedro Vieira-Baptista and Colleen K. Stockdale

Cancers 2022, 14(20), 5088; https://doi.org/10.3390/cancers14205088 - 18 Oct 2022

Cited by 6 | Viewed by 980

Abstract

We thank you and your co-authors for the comment [...] Full article

(This article belongs to the Special Issue Recent Advances in Vulvar Cancer)

2 pages, 200 KiB

Open AccessComment

Comment on Kesić et al. Early Diagnostics of Vulvar Intraepithelial Neoplasia. Cancers 2022, 14, 1822

by Vincenzo De Giorgi, Elisabetta Magnaterra, Manfredi Magliulo, Flavia Silvestri, Federico Venturi, Biancamaria Zuccaro, Jacopo Colombo and Luciana Trane

Cancers 2022, 14(20), 5087; https://doi.org/10.3390/cancers14205087 - 18 Oct 2022

Cited by 1 | Viewed by 947

Abstract

We have read with great interest the paper by Kesić, V. et al. entitled “Early Diagnostics of Vulvar Intraepithelial Neoplasia” [...] Full article

(This article belongs to the Special Issue Recent Advances in Vulvar Cancer)

10 pages, 568 KiB

Open AccessSystematic Review

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

by Féline O. Voss, Nikki B. Thuijs, Ravi F. M. Vermeulen, Erica A. Wilthagen, Marc van Beurden and Maaike C. G. Bleeker

Cancers 2021, 13(24), 6170; https://doi.org/10.3390/cancers13246170 - 7 Dec 2021

Cited by 15 | Viewed by 4415

Abstract

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

(This article belongs to the Special Issue Recent Advances in Vulvar Cancer)

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