Vulvar Cancer

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

P2, N=70, Recruiting, Emory University | Not yet recruiting --> Recruiting

P2, N=125, Active, not recruiting, Tesaro, Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P2 | Trial completion date: Mar 2026 --> Apr 2027 | Trial primary completion date: Aug 2024 --> Aug 2025

P2, N=42, Not yet recruiting, AGO Research GmbH | Trial completion date: Jan 2029 --> Oct 2029

P1, N=18, Recruiting, The Affiliated Hospital of Qingdao University

P2, N=130, Recruiting, Duke University | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

In conclusion, VSCCs with CCND1 gain represent a prognostically adverse category among HPV-I/TP53mut tumors. All patients with VSCCs are potential candidates for targeted therapy.

P2, N=120, Completed, Olivia Newton-John Cancer Research Institute | Active, not recruiting --> Completed

All patients were alive without recurrence on most recent follow-up. Together, this overview of four additional tumors of MELTVR offers further insight into this rare and poorly understood disease.

P1/2, N=107, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Jun 2024 --> Dec 2025

P=N/A, N=60, Active, not recruiting, University of Alabama at Birmingham | Trial primary completion date: Jul 2024 --> Oct 2024

P1/2, N=66, Not yet recruiting, SCG Cell Therapy Pte. Ltd.

P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2033 --> May 2026 | Trial primary completion date: May 2033 --> May 2026

P2, N=818, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> May 2033 | Trial primary completion date: May 2026 --> May 2033

P=N/A, N=1295, Not yet recruiting, University of Aarhus

P2, N=41, Terminated, M.D. Anderson Cancer Center | N=77 --> 41 | Active, not recruiting --> Terminated; Project delays

P2, N=70, Not yet recruiting, Emory University