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: Unknown

110 Participants Needed

Trial Summary

What is the purpose of this trial?

Almost half of all women will develop an HPV infection in their lifetime. While most infections are naturally asymptomatic or cleared by the immune system, some persist and can lead to the development of cervical, vulvar, or anal lesions and eventually cancer. Screening regimens for these lesions are currently only in place for the cervix through regular Pap tests. These Pap tests usually involve an examination of the vulva -however, no screening procedures exist for anal cancer for women. Several studies have suggested that women with existing gynecological lesions are more likely to develop anal lesions and anal cancer. Here the investigators propose a multi-center study which seeks to screen for and treat anal cancer in women over the age of 40 with vulvar lesions and a stable immune system. The investigators will achieve this through performing anal Pap smears on eligible women and conducting High Resolution Anoscopy (HRA) and appropriate treatment procedures on those with abnormal anal cells. With enough evidence, there may be an indication to establish regular anal cancer screening measures in this potentially underserved population. Hypothesis: The investigators hypothesize that at least 40% of women with vulvar cancer or VIN2/3 will have abnormal anal cytology. 35% of the population will be hrHPV DNA positive and 11% will additionally have AIN2/3. This prospective study may lay the groundwork for routine anal screening regimens in Ontario and help shift health policy to treat this population.

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 data supports the idea that Screening for Anal Cancer in Women with Vulvar Lesions is an effective treatment?

The available research shows that high-resolution anoscopy (HRA) is considered the best method for managing anal high-grade squamous intraepithelial lesions, which can prevent anal cancer. Although there are no specific guidelines or randomized trials for its use in women with vulvar lesions, HRA is widely used for screening in high-risk groups, such as those with HIV. This suggests that it could be effective for women with vulvar lesions as well. The research also indicates that HRA is becoming more popular for screening anal dysplasia, which supports its effectiveness as a treatment. ^{1 2 3 4 5}

What safety data exists for anal cancer screening methods?

The safety data for anal cancer screening methods, including high-resolution anoscopy (HRA) and anal Pap tests, is limited. There are no randomized controlled trials or established guidelines specifically for HRA. The understanding of these methods is largely adapted from cervical dysplasia research. HRA is considered the diagnostic standard for detecting anal dysplasia, especially in high-risk populations, but there is debate about the accuracy of these methods. The scarcity of trained providers is a noted barrier to widespread screening. ^{1 2 3 6 7}

Is high-resolution anoscopy a promising treatment for screening anal cancer in women with vulvar lesions?

High-resolution anoscopy (HRA) is a promising treatment for screening anal cancer in women with vulvar lesions because it helps detect precancerous changes early, especially in high-risk groups. It uses a special microscope to look closely at the anal area, which can help find and manage potential cancerous changes before they develop into cancer. ^{1 2 3 8 9}

Research Team

Danielle Vicus, MD

Principal Investigator

Odette Cancer Centre

Eligibility Criteria

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.

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

History of High-Resolution Anoscopy. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Patient Symptomatology in Anal Dysplasia. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

A Composite Cytology-Histology Endpoint Allows a More Accurate Estimate of Anal High-Grade Squamous Intraepithelial Lesion Prevalence. [2022]

4. England pubmed.ncbi.nlm.nih.gov

The acceptability of high resolution anoscopy examination in patients attending a tertiary referral centre. [2018]

5. United States 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. [2022]

6. Canada pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

The importance of anal cancer screening and high-resolution anoscopy to gastroenterology practice. [2021]

8. Greece pubmed.ncbi.nlm.nih.gov

An Update on the Current Role of High Resolution Anoscopy in Patients With Anal Dysplasia. [2019]

9. England 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. [2021]