Vulvar Cancer

Although the patient's age helped rule out d-VIN, similar cases in elderly patients may be occurring. Pathologists must be aware that reactive forms of untreated LS can mimic d-VIN, to avoid misdiagnosis.

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

P2, N=98, Recruiting, The Netherlands Cancer Institute | Not yet recruiting --> Recruiting

P=N/A, N=249, Not yet recruiting, Canadian Cancer Trials Group

P1/2, N=150, Active, not recruiting, Transgene | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

The incidence of detected HPV-independent VIN has substantially increased the last decade and the subsequent recurrence and vulvar cancer risks are high. Although HPV-independent VIN may present as a wide morphologic spectrum, surgical treatment should aim for negative resection margins followed by close surveillance, especially for p53 mutant lesions.

Close surveillance with a low threshold for additional biopsies is warranted. P53 and GATA3 IHC stains may be useful markers of disease outcome.

P=N/A, N=20, Terminated, British Columbia Cancer Agency | Unknown status --> Terminated; No funding

P2, N=24, Recruiting, Massachusetts General Hospital | Trial completion date: Jan 2026 --> Jan 2028 | Trial primary completion date: Dec 2024 --> Dec 2025

P=N/A, N=89, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Oct 2023

Worldwide, nine cases of malignancy were associated with HPV and four with EBV. Immunocompromised WHIMS patients appear to be particularly susceptible to developing early malignancy, mainly HPV-induced carcinomas, followed by EBV-related lymphomas.

These findings provide support for considering pembrolizumab in the treatment paradigm for this specific subset of cancer patients. https://www.crd.york.ac.uk/prospero/, identifier CRD42023391888.

P2, N=99, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

P=N/A, N=20, Enrolling by invitation, Sahlgrenska University Hospital, Sweden

P1, N=18, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2026

P1, N=40, Recruiting, Thomas Jefferson University | Trial completion date: Jun 2024 --> Jun 2026 | Trial primary completion date: May 2024 --> Dec 2025

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

AdCC-BGs constitute a convergent phenotype, whereby activation of MYB or MYBL1 can be driven by the MYB::NFIB fusion gene or MYBL1 rearrangements. Our observations further support the notion that AdCCs, irrespective of organ site, constitute a genotypic-phenotypic correlation. Assessment of MYB or MYBL1 rearrangements may be used as an ancillary marker for the diagnosis of AdCC-BGs.

PCR analysis using the Promega OncoMate® MSI Dx Analysis System with an investigational data interpretation software correlates with evaluation of MMR expression by IHC in 94% of cases, among the tumor types evaluated. MSI-high results reliably (100% in this sample) predict loss of MMR protein IHC staining, but occasional cases yield MSS results while having MMR loss by IHC.

P=N/A, N=30, Not yet recruiting, Queensland Centre for Gynaecological Cancer

P=N/A, N=10, Not yet recruiting, Tufts Medical Center | Initiation date: Dec 2023 --> May 2024

P=N/A, N=120, Recruiting, University Hospital Tuebingen | Initiation date: Jun 2023 --> Sep 2023

P2, N=112, Active, not recruiting, UNICANCER | Trial completion date: Oct 2024 --> Jan 2025

TRPS1 immunostain is often expressed in gynecologic carcinomas. Awareness of this phenomenon is crucial when evaluating challenging cases in which the differential diagnosis includes a malignancy of breast origin, to avoid misclassification of the primary site.

CK17, SOX2 and GATA3 can be useful in the diagnosis of vaVIN and its distinction from hyperplastic non-neoplastic vulvar lesions. Although CK17 has higher sensitivity, SOX2 and GATA3 are more specific, and the combination of all markers shows optimal diagnostic accuracy.

Compared to the final resections specimen, the three-tiered molecular classification of VSCC can be determined on pre-surgical biopsies with a high accuracy rate. This enables more precise surgical planning, prediction of the response to (chemo) radiation, selection of targeted therapies and planning of the optimal follow-up strategy for patients in the age of personalised medicine.

P=N/A, N=60, Active, not recruiting, Indiana University | Enrolling by invitation --> Active, not recruiting

ctDNA values were elevated in patients with vulvar cancer pre-RT/CRT but sustained reduction mid-way, and became undetectable at the end of treatment and in follow-up with a strong correlation with imaging. A mid-way ctDNA test identified future responders to RT/CRT and requires further investigation as a potential early biomarker of response. To our knowledge, these early promising results suggest that there is a role for ctDNA in the management of patients with vulvar cancer and warrants a larger cohort assessment in a prospective study.

Our findings contribute to the growing evidence that PD-L1 is expressed in the majority of invasive VSCCs, and thus may serve as an attractive therapeutic target. PD-L1 expression is higher in HPV-independent tumors, suggesting that this subtype may be more responsive to PD-L1 inhibitor therapy.

P1, N=32, Recruiting, HRYZ Biotech Co. | Not yet recruiting --> Recruiting

"These neoplasms have shown variable response to immunotherapy which appears to be influenced by genetic and protein expression profiles, including factors such as mismatch repair status, tumor mutational burden, and checkpoint ligand expression. In the present paper, an extensive review of PD-L1 expression in various gynecologic cancer types is discussed, providing a guide for their pathological assessment and reporting."

There were no MYBL1 or NFIB rearrangements and no MYB::NFIB fusions. Our findings corroborate that the histologic, immunohistochemical, and oncogenic background is similar between ACCs of the lower female genital tract and ACCs elsewhere, although the canonical MYB::NFIB fusion seems to be a less common finding in this location.

P=N/A, N=380, Terminated, University Of Otago Christchurch | Recruiting --> Terminated

P=N/A, N=10, Terminated, Centre Hospitalier Universitaire de Nice | N=30 --> 10 | Unknown status --> Terminated; significant results after inclusion of 10 patients

This article provided new insights into underlining VuM molecular regulation and potential signaling involved in immunotherapy, which would benefit the clinical practice and administration.

P=N/A, N=10000, Recruiting, New York Stem Cell Foundation Research Institute

HER2 testing by immunohistochemistry and in situ hybridisation is applicable to endometrial serous carcinomas to assess trastuzumab eligibility...Awareness of the variety and pitfalls of expression patterns for p16 and p53 in vulvar carcinomas is crucial for accurate designation. It is hoped that collaborative efforts in standardising and optimising biomarker testing for gynaecological tumours will contribute to evidence-based therapeutic decisions.

P1, N=100, Recruiting, TScan Therapeutics, Inc. | Initiation date: Nov 2023 --> Feb 2024

P2, N=198, Not yet recruiting, Yonsei University | Initiation date: Sep 2023 --> Jan 2024

P=N/A, N=75, Recruiting, City of Hope Medical Center | Initiation date: Dec 2023 --> Mar 2024

P=N/A, N=40, Recruiting, Memorial Sloan Kettering Cancer Center

P1/2, N=29, Suspended, University of Florida