Screening for Anal Cancer in Women with Vulvar Lesions

(Vulvar-AIN Trial)

Overseen By Nithla Mohanathas, BSc

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Dr. Danielle Vicus

Must not be taking: Immunosuppressants

Disqualifiers: HIV positive, Previous hysterectomy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find effective ways to screen for anal cancer in women with existing vulvar lesions. Researchers will use anal Pap smears and may follow up with high-resolution anoscopy (a detailed exam of the anal area) if needed. The goal is to determine if regular screening for anal cancer could benefit women at higher risk due to their existing conditions. Women over 40 with vulvar lesions and a stable immune system might be suitable candidates for this trial. As an unphased trial, this study offers participants the opportunity to contribute to important research that could enhance cancer screening methods for at-risk women.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking immunosuppressant medication.

What prior data suggests that these screening methods are safe for women with vulvar lesions?

Research has shown that anal Pap smears are generally safe for patients. These tests resemble the cervical Pap tests familiar to many women from regular health check-ups. Studies have found that anal Pap tests are well-tolerated and usually don't cause serious side effects, serving as a safe first step in identifying abnormal anal cells.

Research also considers high-resolution anoscopy (HRA) safe. One study found that HRA effectively detects abnormal cell growth, crucial for cancer prevention. Participants in studies generally accept this screening method, with no major reports of negative effects. Overall, both the anal Pap smear and HRA are safe tools for detecting potential anal cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the effectiveness of using anal Pap smears to screen for anal cancer in women with vulvar lesions, potentially enhancing early detection. Unlike traditional methods that might skip anal screening altogether or rely solely on symptom-driven examinations, this approach proactively identifies abnormalities. Moreover, the trial examines how adding high-resolution anoscopy to negative Pap smears might improve diagnostic accuracy, offering a more thorough evaluation. This could lead to more personalized care and potentially better outcomes for patients at risk.

What evidence suggests that this trial's screening methods could be effective for detecting anal cancer in women with vulvar lesions?

Research has shown that anal Pap tests, similar to cervical Pap tests, effectively identify anal lesions. Studies indicate that these tests detect lesions with a sensitivity ranging from 47% to 90%, depending on the group tested. In this trial, all participants will undergo an anal Pap test. An abnormal result will lead to a referral for high-resolution anoscopy (HRA), regarded as the best method for detecting early signs of anal cancer in high-risk groups. Evidence suggests that treating high-grade lesions with HRA can reduce the risk of developing anal cancer. These screening methods aim to catch issues early and improve outcomes for women at risk. ^{4 6 7 8 9}

Who Is on the Research Team?

Danielle Vicus, MD

Principal Investigator

Odette Cancer Centre

Are You a Good Fit for This Trial?

This trial is for women aged 40 or older who have been previously diagnosed with high-grade vulvar dysplasia (VIN 2/3) or vulvar cancer. It aims to screen these individuals for anal cancer, as they may be at higher risk due to their existing conditions.

Inclusion Criteria

I am a woman aged 40 or older.

I have had a severe precancerous condition of the vulva.

Exclusion Criteria

I have had cancer before, but it wasn't skin, cervical, or vulvar cancer.

I am a woman currently on immunosuppressant medication.

I have had a hysterectomy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Screening and Diagnosis

All participants receive an anal Pap test. Those with abnormal results are referred to HRA clinic for further management, including potential biopsy and treatment.

4-6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after screening and treatment procedures.

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Screening anal Pap smear - High-resolution anoscopy
• Screening anal Pap smear - No high-resolution anoscopy

Trial Overview The study is testing the effectiveness of screening for anal cancer using anal Pap smears followed by High-resolution Anoscopy (HRA) in detecting abnormal cells. The goal is to potentially establish regular screening procedures for women with a history of gynecological lesions.

How Is the Trial Designed?

Group I: Screening anal Pap Smear - Positive Experimental Treatment 1 Intervention

All patients will receive an anal Pap test. Any patient with abnormal cytology on their Pap test will be referred to HRA clinic for management. This includes potential biopsy and treatment.

Group II: Screening anal Pap Smear - Negative (75%) Experimental Treatment 1 Intervention

All patients will receive an anal Pap test. 75% of patients with a negative anal Pap will complete study with no further intervention.

Group III: Screening anal Pap Smear - Negative (25%) Experimental Treatment 1 Intervention

All patients will receive an anal Pap test. Remaining 25% of patients will proceed to high-resolution anoscopy (HRA) clinic to assess the negative predictive rate of HRA.

Who Is Running the Clinical Trial?

Dr. Danielle Vicus

Lead Sponsor

Trials

1

Recruited

110+

Published Research Related to This Trial

In a study of 605 high-risk men, the combined diagnostic approach of anal cytology and high-resolution anoscopy (HRA) significantly increased the detection of high-grade squamous intraepithelial lesions (HSIL), with a composite prevalence of 37.7% compared to 17.9% for cytology alone and 31.7% for histology alone.

The study found a clear trend where higher grades of HSIL were associated with increased prevalence of HPV16, suggesting that using a composite endpoint of cytology and histology could serve as an important biomarker for anal cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Composite Cytology-Histology Endpoint Allows a More Accurate Estimate of Anal High-Grade Squamous Intraepithelial Lesion Prevalence. Machalek, DA., Poynten, IM., Jin, F., et al.[2022]

The incidence of HPV-related anal squamous cell cancer (ASCC) is increasing, particularly among elderly women and young black men, highlighting the need for targeted screening in high-risk populations.

High-resolution anoscopy (HRA) is the gold standard for detecting premalignant lesions and ASCC, but a lack of trained providers limits its availability; ongoing studies like the ANCHOR study aim to assess the impact of treating high-grade lesions on ASCC incidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The importance of anal cancer screening and high-resolution anoscopy to gastroenterology practice. Bull-Henry, K., Morris, B., Buchwald, UK.[2021]

In a study of 27 women with a history of HPV-related vulvar and perianal high-grade lesions, 22% were found to have intra-anal high-grade squamous intra-epithelial lesions (HSIL), indicating a significant prevalence of these lesions in this high-risk group.

The findings suggest that screening for intra-anal lesions using high-resolution anoscopy (HRA) is important for women with a history of vulvar and perianal HSIL, as there is a clear link between HSIL and the risk of developing anal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening for intra-anal squamous intra-epithelial lesions in women with a history of human papillomavirus-related vulvar or perianal disease: results of a screening protocol. Leber, K., van Beurden, M., Zijlmans, HJ., et al.[2021]

High-resolution anoscopy with biopsy is an effective method for diagnosing high-grade anal neoplasia, particularly in men who have sex with men (MSM), with a study involving 125 participants showing significant differences in HPV infection rates between HIV-positive (91%) and HIV-negative (57%) individuals.

The sensitivity of anal cytology for detecting high-grade anal neoplasia varies by HIV status, with 87% sensitivity in HIV-positive MSM and only 55% in HIV-negative MSM; however, combining cytology with HPV testing significantly improves detection rates, especially in HIV-negative men.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance characteristics of anal cytology and human papillomavirus testing in patients with high-resolution anoscopy-guided biopsy of high-grade anal intraepithelial neoplasia. Berry, JM., Palefsky, JM., Jay, N., et al.[2022]

High-resolution anoscopy (HRA) is currently used for screening and managing anal squamous dysplasia, particularly in HIV-positive populations where the incidence is highest, but there are no randomized controlled trials or established guidelines for its use.

The understanding of anal dysplasia has evolved from studies on cervical dysplasia, highlighting the importance of human papillomavirus (HPV) in its development and the need for effective screening methods like HRA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

History of High-Resolution Anoscopy. Cho, SD., Groves, E., Lao, VV.[2020]

High Resolution Anoscopy (HRA) is a screening method used to detect anal intraepithelial neoplasia (AIN), a precancerous condition that can lead to anal squamous cell carcinoma (ASCC), particularly in immunocompromised patients.

Current literature shows mixed results regarding the effectiveness of HRA in managing AIN, indicating a need for further randomized controlled trials to clarify its benefits compared to other screening techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Update on the Current Role of High Resolution Anoscopy in Patients With Anal Dysplasia. Gudur, A., Shanmuganandamurthy, D., Szep, Z., et al.[2019]

In a study of 91 high-risk patients undergoing high-resolution anoscopy (HRA), 30% were found to have high-grade dysplasia, highlighting the importance of screening in this population.

Patients presenting with anal pain or lesions were significantly more likely to have high-grade dysplasia, suggesting that these symptoms should prompt consideration for HRA screening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Symptomatology in Anal Dysplasia. Hicks, CW., Wick, EC., Leeds, IL., et al.[2015]

The anal Pap test, while showing potential for screening anal dysplasia in high-risk populations, lacks direct evidence supporting its effectiveness in reducing anal cancer morbidity or mortality, similar to the challenges faced by cervical Pap testing.

High-resolution anoscopy is now considered the diagnostic standard for evaluating abnormal anal cytology, but the variability in sensitivity (ranging from 26% to 69% in studies) highlights the need for further research to establish reliable screening protocols for anal cancer, especially in HIV-positive individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anal dysplasia screening: an evidence-based analysis. [2022]

A study involving 404 patients undergoing high resolution anoscopy (HRA) found that the median pain score was low (2 out of 10), indicating that the procedure is generally well-tolerated, although women reported higher pain levels than men.

Despite some experiencing higher pain, 76% of patients rated their satisfaction with the care received as a perfect 10, and 98% of women and 99% of men expressed willingness to undergo future HRA examinations, suggesting strong acceptability of the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The acceptability of high resolution anoscopy examination in patients attending a tertiary referral centre. De-Masi, A., Davis, E., Cuming, T., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11119426/

Deep Learning and High-Resolution Anoscopy High-resolution anoscopy (HRA) plays a central role in the detection and treatment of precursors of anal squamous cell carcinoma (ASCC).

2. ucsf.edu ucsf.edu/news/2022/06/423126/screening-and-removal-precancerous-lesions-prevents-anal-cancer

Screening and Removal of Precancerous Lesions Prevents ... With a median follow-up of nearly 26 months, nine cancer cases were diagnosed in the treatment arm while 21 cases were diagnosed in the ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666679022000015

Provider preferences for anal cancer prevention screening This study explores provider preferences regarding anal cancer screening indications, initiation age, tools, and referral threshold to high resolution anoscopy ...

4. targethiv.org targethiv.org/sites/default/files/RWNC2020/nrwc24-25512ImplementationofHRA-508.pdf

Implementation of High Resolution Anoscopy (HRA) Anal ... “Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring.” • “ ...

5. bhiva.org bhiva.org/file/633d66f07b37e/Screening-Women-for-Anal-Cancers-Guidance-for-Health-Care-Professionals.pdf

Screening Women for Anal Cancers: Guidance for Health ... ANAL CYTOLOGY AND HPV TESTING. High-resolution anoscopy (HRA) is considered the best screening method for very-high-risk groups (e.g., human immunodeficiency.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10524277/

Anal Cancer and Anal Cancer Screening - PMC This chapter provides an overview of the epidemiology and natural history of ASCC, as well as an overview of the available evidence on screening tools for anal ...

7. aetna.com aetna.com/cpb/medical/data/800_899/0808.html

High-Resolution Anoscopy - Medical Clinical Policy Bulletins Screening was considered to be highly acceptable by participants. The authors concluded that the high prevalence of high-risk-HPV and frequency of false ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01313104

Colposcopy and High Resolution Anoscopy in Screening ... Colposcopy and High Resolution Anoscopy in Screening For Anal Dysplasia in Patients With Cervical, Vaginal, or Vulvar Dysplasia or Cancer.

9. withpower.com withpower.com/trial/phase-uterine-cervical-neoplasms-1-2021-e4ef5

Screening for Anal Cancer in Women with Vulvar Lesions In a study of 91 high-risk patients undergoing high-resolution anoscopy (HRA), 30% were found to have high-grade dysplasia, highlighting the importance of ...