Vulvar Cancer

Furthermore, nuclear survivin expression is very low in normal vulvar squamous epithelium and increases to become abundant in vulvar invasive squamous cell carcinoma (ISCC), conferring resistance to apoptosis in vulvar carcinogenesis. In this review, we discuss in detail the impact of survivin signaling on gynecological cancers and provide insight on its therapeutic and diagnostic potential, existing research gaps, and areas for future research.

P=N/A, N=249, Recruiting, Canadian Cancer Trials Group | Not yet recruiting --> Recruiting

Tumors with p53 abnormal expression and absence of p16 showed a greater DOI. Our data suggest an association between PDL1 expression and increased inflammatory infiltrates in vulvar SCC.

P2, N=60, Not yet recruiting, MacroGenics

WLWH are at high risk of vulvar high-grade intraepithelial neoplasia and cancer, especially those with severe immunodepression. A careful inspection of vulva, perineum and anus, possibly with the aid of colposcopy, should become part of the surveillance protocol of HIV-infected women.

Pathologists without gynecologic subspecialty expertise benefited the most from a brief educational module, which fostered a better understanding and improved comfort level with the p16/p53 stain interpretation and tumor pathway designation in the diagnosis of vSCC. Some interpretative challenges remain, particularly in regard to select p53 patterns and high-risk HPV-in situ hybridization utilization, warranting additional research.

P=N/A, N=30, Recruiting, Queensland Centre for Gynaecological Cancer | Not yet recruiting --> Recruiting | Initiation date: Mar 2024 --> Jul 2024

P1, N=15, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed

P1, N=32, Active, not recruiting, Baylor College of Medicine | Trial primary completion date: Oct 2024 --> Oct 2025

P2, N=18, Recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Despite the retrospective nature and variations in immunohistochemistry reporting, our study provides valuable insights into patient outcomes, particularly in a demographically diverse population. Future research, like the STRIVE trial, may determine if implementation of p16 and p53 stratified management algorithm will improve outcomes for women with vulvar SCC (McAlpine, 2024).

P=N/A, N=0, Withdrawn, Travera Inc | N=630 --> 0 | Not yet recruiting --> Withdrawn

The study showed that brisk tumor-infiltrating lymphocytes and stromal tumor-infiltrating lymphocytes were a marker for disease progression, and for response to immunotherapy strategies. To validate these findings on a larger scale, further research is warranted through a multicenter study with a larger cohort and additional genetic and translational analysis.

P=N/A, N=40, Active, not recruiting, Istanbul University

Our results indicate that adenocarcinomas of intestinal-type, in distal vagina or vestibular vulva, might be a unique and single entity, probably originating from cloacogenic embryonic remnants and/or ectopic colorectal mucosae inclusions. An open question would be to explore the efficacy of systemic drugs prescribed in colorectal cancers, in VVAIts.

P=N/A, N=1295, Recruiting, University of Aarhus | Not yet recruiting --> Recruiting | Trial completion date: Dec 2032 --> Dec 2030 | Trial primary completion date: Dec 2029 --> Dec 2028

P2, N=85, Recruiting, Baylor College of Medicine

ET/HT can probably be used after ovarian neoplasms except for granulosa cell tumors, and with great caution after low-grade serous ovarian carcinoma and serous borderline ovarian tumors. ET/HT can be used with great caution in women after estrogen receptor (ER)/progesterone receptor (PR)-positive breast cancer and is probably allowed after ER/PR-negative breast cancer.

P=N/A, N=23, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting | N=75 --> 23

Overall, muSCC shows similar genomic alterations and TMB to HPV(–) vSCCs. CGP of inflammation-associated SCCs may be important to more fully inform therapeutic options and stratification in clinical trials.

Regarding the latter, some authors consider TP53/p53 aberration to be a diagnostic requirement for dVIN, although this is controversial, as discussed further herein. Also included in the spectrum of lesions that are considered in this review are possibly related HPV-independent, p53-wild type lesions that have historically been reported as "vulvar acanthosis with altered differentiation" (VAAD), "differentiated exophytic vulvar intraepithelial lesion" (DEVIL), "verruciform lichen simplex chronicus" (vLSC), and which more recently, have collectively been described as "verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN)" or "vulvar aberrant maturation (VAM)." In this review, we perform a comprehensive clinicopathologic review of putative precancerous lesions of HPV-independent squamous cell carcinomas of the vulva, with an emphasis on recent developments in terminology, practical diagnostic issues, biomarkers, and pathogenesis.

Like other rare cancers, vulvar cancer lags behind in the identification and optimization of precision medicine strategies. Molecular-based preclinical models and rationally designed clinical trials, incorporating high-quality translational studies, are urgently required. These trials will require international collaboration to ensure feasibility and improvement of outcomes for women diagnosed with this disease.

In summary, the combined use of p16 and p53 immunohistochemistry for subclassification of vulvar carcinomas is justified in daily practice. Molecular tests should be restricted to rare cases with ambiguous clinicopathologic or immunohistochemical features.

P=N/A, N=60, Recruiting, Indiana University | Active, not recruiting --> Recruiting | Trial completion date: Dec 2024 --> Mar 2025

P=N/A, N=60, Not yet recruiting, Northwestern University

Based on the findings in this study, suppressing PAI1 expression in VC cells appears to reduce their progression and tumorigenic potential. Therefore, PAI1 could possibly function as an oncogene in VC. GPER1 appears to be a suitable target for suppressing PAI1 in VC.

P=N/A, N=409, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2024 --> Apr 2026 | Trial primary completion date: Apr 2024 --> Apr 2026

P=N/A, N=1000, Active, not recruiting, Tempus AI | Recruiting --> Active, not recruiting

P1, N=15, Not yet recruiting, Karolinska University Hospital

An 87-year-old female presented with a recurrent vulvar lesion refractory to topical imiquimod and treated with multiple wide local excisions (WLE)...AAEMPD, a rare variant of EMPD, shares similar prognosis and behavior with the classic Paget disease. Recognition and accurate diagnosis of this subtype is crucial for optimal patient management, given distinct treatment strategies compared with other entities in the differential diagnosis.

It closely mirrors the morphology, immunohistochemistry, and biological behavior of its breast counterpart. Due to its slow progression and localized, encapsulated nature, the treatment approach for this carcinoma differs from other vulvar adenocarcinomas, aligning more with carcinoma in situ management similar to breast encapsulated papillary carcinoma.

P=N/A, N=33, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting

P=N/A, N=20, Recruiting, Wake Forest University Health Sciences | Trial primary completion date: Sep 2024 --> Feb 2025

Each group has different prognostic implications as well as response to treatment, thus reinforcing the need for this 3-tier molecular classification. This molecular subtyping can easily be done on vulvar biopsies using p16 and p53 immunohistochemistry stains to further improve risk prediction and individualized treatment decisions, leading to better patient outcomes.

P=N/A, N=249, Not yet recruiting, Canadian Cancer Trials Group | Initiation date: Aug 2024 --> Nov 2024

Vulvar melanoma is the third tumor to have been reported to harbor TRIM33::CSDE1 fusion. Detecting fusions may have a clinically significant impact in patients with advanced mucosal melanoma who have failed front-line immunotherapy.

P=N/A, N=10, Not yet recruiting, Tufts Medical Center | Trial completion date: Jun 2025 --> Jan 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=29, Recruiting, University of Florida | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2024 --> Jun 2025

SOX17 is a sensitive and specific marker for gynecologic origin in the tissues tested and may be a valuable adjunct to PAX8 and other commonly used markers to confirm endometrial or ovarian origin. SOX17 expression is lower in mucinous tumors, endocervical adenocarcinoma, high-grade neuroendocrine tumors, and undifferentiated/dedifferentiated endometrial carcinoma.

P=N/A, N=190, Not yet recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

P=N/A, N=33, Not yet recruiting, Washington University School of Medicine

P=N/A, N=55, Recruiting, CNAO National Center of Oncological Hadrontherapy | Phase classification: P2 --> P=N/A