STRatIfication of Vulvar Squamous Cell Carcinoma by HPV and p53 Status to Guide Excision

NCT ID: NCT05576831

Last Updated: 2026-02-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 249 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-25
• Study Completion Date: 2031-11-25

Brief Summary

Vulvar cancer affects the external genitalia of women. This type of cancer is uncommon, arising mostly in older women and has been neglected in research and clinical trials. Over the recent years, investigators have learned that the most common type of vulvar cancer; vulvar squamous cell carcinoma (VSCC) develops from pre-cancerous lesions via different pathways. One pathway is associated with human papillomavirus (HPV) infection, and another is related to chronic inflammatory skin conditions (and not HPV). The VSCCs arising from these two principal pathways; HPV- associated (HPV A) and HPV-independent (HPV I), behave differently with different risks of recurrence, and different response to treatments. HPV-I VSCC are further defined by mutations in TP53 (Tumor Protein 53), which identify a group of patients with aggressive disease. Currently treatment is the same for all women with vulvar cancer, and consequently many women may be overtreated, and many women are not treated enough. Given evolving knowledge of this disease, this 'one size fits all' approach may no longer be appropriate. The investigators aim in this study is to see if personalizing surgical therapy for patients with vulvar cancer based on HPV and TP53 status will improve outcomes.

Detailed Description

Purpose:

The aim of this prospective study is to determine if implementation of HPV(p16) and p53 stratified management algorithms will improve outcomes for women with VSCC.

Hypothesis:

Primary:

Molecular stratification of VSCC, using margin status for both HPV and p53 pathology to direct surgical management, will improve clinical outcomes.

Patient Reported Outcomes (PRO) Hypothesis:

In women with HPV-associated (HPV-A) VSCC who undergo less radical surgery, treatment-related side effects will be reduced, health-related quality of life will be improved, and fear of cancer recurrence will not be increased, when compared to patients who undergoing standard surgery. PROs that are expected to be improved in this subgroup are: satisfaction with body image, frequency and enjoyment of sexual activity, urinary symptoms, and genital pain. In women with HPV-independent (HPV-I) VSCC, the expected PRO/HRQL (Health-related quality of life) trajectory is expected to remain unchanged in the intervention group compared to the observation group, and fear of recurrence will be decreased.

Justification:

Most VSCC guidelines today recommend tumour-free pathological margins of 8mm or more to adequately treat the primary tumour. These guidelines are based on retrospective data which did not stratify patients based on HPV or TP53 mutation status.

HPV-I VSCC: there is now data suggesting investigators are undertreating these patients and that surgical margins defined by proximity of invasive disease, presence of preinvasive disease and p53 IHC (Immunohistochemistry) status will guide the need for re-excision and optimize local disease control.

Goal in HPV-I VSCC = demonstrating re-excision to achieve clear margins will improve outcomes.

HPV-A VSCC: there is data supporting that investigators are likely overtreating these patients, and the absence of invasive disease at the resection margin will be sufficient without loss of local control and will improve patient reported outcomes.

Goal in HPV-A VSCC= demonstrating de-escalation of surgery is safe(and will improve QoL).

Objectives:

Primary Objective:

To determine if implementation of HPV and p53 stratified algorithms to guide surgical management will improve outcomes in patients with VSCC; based on 3-year local recurrence rates in both HPV-I and HPV-A disease

Secondary Objectives:

1. Determine the health economic impact (EQ-5D) of implementation of HPV and p53 stratified treatment algorithms

2. Determine the patient reported outcomes (EORTC QLQ (Quality of Life Questionnaire) -C30 and EORTC QLQ-VU34), patient decisional conflict, patient satisfaction /acceptance with HPV and p53 stratified care in VSCC

3. Determine the disease specific survival (DSS) and overall survival (OS) for HPV-I and HPV-A VSCC managed per algorithms

4. Determine the feasibility of implementation of routine p16 and p53 IHC reporting in VSCC pathology (proportion of patients who had p53 and p16 IHC successfully performed in an acceptable turnaround time ie >85% of patients within 21 days of surgery)

RESEARCH DESIGN:

The HPV-I arm of the study will be conducted as a phase II, randomised control trial and the HPV-A arm of the study will be a prospective trial.

STATISTICAL ANALYSIS:

The Kaplan-Meier method will be used to estimate 3-year rates of recurrence-free survival, vulvar cancer-specific survival, and overall survival and associated 95% confidence interval with the events defined as any recurrence or death for recurrence-free survival, death due to vulvar cancer for vulvar cancer-specific survival, and death due to any cause for overall survival. Women without the event observed at the time of analysis will be censored at the last follow-up.

Conditions

Vulvar Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HPV-A VSCC

Patients with HPV-A VSCC and margins that are negative for cancer but \<8mm (regardless of in-situ (HSIL) margin status) will be eligible for the de-escalation prospective study.

Group Type: NO_INTERVENTION

No interventions assigned to this group

HPV-I VSCC

If the margins are negative for cancer but \<8mm, or positive for Differentiated vulvar intraepithelial neoplasia (dVIN), and/or positive for p53 abnormality on IHC, these patients will be randomized (2:1) to further re-excision vs observation only.

Group Type: EXPERIMENTAL

Re-excision

Intervention Type: PROCEDURE

Re-excise (one take back only) Excise scar aiming for 1-2cm margin

Interventions

Re-excision

Re-excise (one take back only) Excise scar aiming for 1-2cm margin

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed primary diagnosis of vulvar squamous cell carcinoma
• Surgically staged FIGO (International Federation of Gynaecology and Obstetrics) I-II disease
• Margin status after primary surgery:

• HPV-I VSCC: margins are negative for cancer but <8mm, and/or positive for dVIN, and/or positive for p53 abnormality on IHC
• HPV-A VSCC: margins are negative for cancer but <8mm (regardless of in-situ (HSIL) margin status)
• Age ≥18 years old
• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate. A similar process must be followed for sites outside of Canada as per their respective cooperative group's procedures.

Exclusion Criteria

• Recurrent vulvar squamous cell carcinoma
• Non-squamous cell carcinoma histotypes
• FIGO stage III- IV disease
• Patients referred for adjuvant radiation for close margins
• Margins positive for cancer

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Gynecologic Cancer Initiative

OTHER

Sponsor Role: collaborator

Australia New Zealand Gynaecological Oncology Group

OTHER

Sponsor Role: collaborator

Canadian Cancer Trials Group

NETWORK

Sponsor Role: collaborator

British Columbia Cancer Agency

OTHER

Sponsor Role: lead

Responsible Party

Jessica McAlpine

Co-Division Head, Gynecologic Oncology Professor, Department of Obstetrics and Gynecology Gynecologic Tissue Bank Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amy Jamieson, MD

Role: PRINCIPAL_INVESTIGATOR

BC Cancer

Locations

BC Cancer - Vancouver Centre

Vancouver, British Columbia, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Amy Jamieson, MD

Role: CONTACT

Amy.Jamieson@vch.ca

604-875-4268

Jessica McAlpine, MD

Role: CONTACT

Jessica.Mcalpine@vch.ca

604-875-4268

Facility Contacts

Jessica McAlpine

Role: primary

Jessica.Mcalpine@vch.ca

604-875-4268

Other Identifiers

STRIVE

Identifier Type: -

Identifier Source: org_study_id