Screening Tests for Cervical and Anal Cancer in HIV Patients

(CAMPO-101 Trial)

Not currently recruiting at 8 trial locations

Overseen By Joel Palefsky, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must be taking: Antiretrovirals

Disqualifiers: Hysterectomy, Cancer history, Recent lesion treatment, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to identify the most effective screening tests for detecting high-grade squamous intraepithelial lesions (HSIL) in people living with HIV. HSIL represents abnormal tissue changes in the cervix or anus caused by HPV. Early detection is crucial, as treatment can prevent progression to cervical or anal cancer. Participants will undergo various procedures, including imaging techniques, swabs, and biopsies, to test for HPV and any lesions. The trial seeks individuals with a confirmed HIV diagnosis who have not recently received treatment for related lesions. As an unphased trial, it offers participants the chance to contribute to research that could enhance early detection methods for HSIL.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it does require documentation of antiretroviral therapy (ART) for HIV, so you may need to continue those medications.

What prior data suggests that these screening tests are safe for detecting HSIL in HIV patients?

Research has shown that the main procedures in this trial, high-resolution anoscopy and colposcopy, have been used safely in previous studies. High-resolution anoscopy plays a crucial role in certain screenings. Although sometimes labeled experimental, it has been widely used without major safety issues. Colposcopy is a common procedure for cervical cancer screening. Studies have found that these screenings, including colposcopy, are important and generally safe for people with HIV.

These procedures involve taking tissue samples and examining them closely, which can sometimes cause minor discomfort or bleeding. However, serious side effects are rare. Overall, past research suggests these procedures are well-tolerated and safe for screening and diagnosing conditions like high-grade squamous intraepithelial lesions (HSIL) linked to HPV. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores new ways to screen for cervical and anal cancer specifically in HIV patients. Unlike current screening methods that might miss early signs, this approach uses advanced imaging techniques and real-time testing for HPV, which could make detection faster and more accurate. The focus on high-resolution anoscopy and colposcopy, combined with the immediate analysis of biospecimens, aims to catch precancerous changes earlier, potentially leading to better outcomes. This trial could revolutionize how screenings are conducted, offering a tailored approach that addresses the unique needs of HIV patients.

What evidence suggests that this trial's tests could be effective for detecting HSIL in HIV patients?

In this trial, participants will undergo various screening methods to detect cervical and anal cancer early. Research has shown that high-resolution anoscopy, a detailed examination of the anal canal, can lower cancer risk by identifying serious lesions early in people with HIV. Similarly, colposcopy, a close examination of the cervix, helps detect abnormal changes related to HPV in people with HIV. Participants will also have biospecimen collection from the cervix or anus, aiding in accurately diagnosing these pre-cancerous changes. Using these methods together in the trial aims to improve early detection, leading to timely treatment and better outcomes for people with HIV. ^{6 7 8 9 10}

Who Is on the Research Team?

Joel Palefsky, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults over 21 with HIV who have not had a hysterectomy, are not pregnant or recently post-partum, and haven't been treated for related lesions in the last 18 months. They must understand the study and agree to participate, have an ECOG performance status of <=1 (or Karnofsky >=70%), documented HIV infection, and be on antiretroviral therapy.

Inclusion Criteria

Documentation of HIV-1 infection by means of any one of the following: Documentation of HIV diagnosis in the medical record by a licensed health care provider, Documentation of receipt of antiretroviral therapy (ART) by a licensed health care provider, HIV-1 ribonucleic acid (RNA) detection by a licensed HIV-1 RNA assay demonstrating > 1000 RNA copies/mL, Any locally licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot confirmation or HIV rapid multispot antibody differentiation assay, Age 21 years or older, Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky score >= 70%), Ability to understand and the willingness to sign a written informed consent document

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Assessment and Testing

Participants undergo collection of cervical images, cervical and anal swabs for real-time testing of high-risk HPV. Positive results lead to further diagnostic procedures such as colposcopy or high-resolution anoscopy.

1 month

2 visits (in-person)

Diagnosis and Treatment

Participants may receive a diagnosis and treatment based on test results. Those diagnosed with HSIL may undergo standard of care treatment or enroll in additional studies.

1 month

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with potential for additional studies.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Biopsy
• Biospecimen Collection - Anal
• Biospecimen Collection - Cervical
• Colposcopy
• High Resolution Anoscopy
• Imaging Technique

Trial Overview

The trial tests various screening methods like biopsies and imaging techniques to detect high-grade squamous intraepithelial lesions (HSIL) that could lead to cervical or anal cancer in people with HIV. It aims to identify which screenings work best for early detection.

How Is the Trial Designed?

Group I: Imaging, biospecimen collection, anoscopy and/or colposcopy Experimental Treatment 6 Interventions

Patients undergo collection of cervical images (if applicable), 3 cervical anal swabs (if applicable) and 3 anal swabs for real-time testing of HPV or hrHPV over 90 minutes. Patients with a positive HPV or hrHPV test on undergo biopsies of visible lesions. Patients with a negative hrHPV test on their cervical swab may undergo a colposcopy. Patients with a positive hrHPV test on their anal swab undergo high-resolution anoscopy at a later visit within 1 month. Patients with a negative hrHPV on their anal swabs may undergo a high-resolution anoscopy and biopsies of visible lesions, and those with a positive anal cytology for LSIL or worse undergo a high-resolution anoscopy and biopsies within 1 month. Patients may be given a diagnosis and treatment at the second visit. Patients diagnosed with HSIL may undergo SOC treatment or enroll in additional studies when they are open to accrual

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

US-Latin American-Caribbean HIV/HPV-Cancer Prevention Clinical Trials Network (ULACNet)

Collaborator

Trials

2

Recruited

2,100+

Published Research Related to This Trial

In a study of 149 HIV-negative women attending a colposcopy clinic, 56.3% had anal HPV infections, indicating a high prevalence of HPV in the anal region, similar to the 53.7% prevalence found in cervical samples.

Although cytological abnormalities were relatively rare (10.8% in anal smears), the high concordance of HPV genotypes between anal and cervical samples suggests that HPV may pose a risk for future anal lesions, highlighting the need for thorough clinical examinations of the anal region.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anal human papillomavirus DNA in women at a colposcopy clinic. D'Hauwers, KW., Cornelissen, T., Depuydt, CE., et al.[2012]

In a study of HIV-infected women, hybrid capture II screening for cervical cancer precursor lesions demonstrated 100% sensitivity, meaning it correctly identified all cases of high-grade squamous intraepithelial lesions (HSIL), but had lower specificity at 52%.

Cytology screening, while less sensitive at 31.8%, had a much higher specificity of 95.5%, indicating it was better at correctly identifying women without HSIL, making it a more reliable test for ruling out disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Performance by cytology and hybrid capture II in screening for high-grade squamous intraepithelial lesions in women with HIV]. Raposo, LM., Velasque, L., Luz, PM., et al.[2022]

The National Cancer Institute has created a comprehensive database of nearly 100,000 digitized cervigram images and clinical data from 15,000 women to enhance the accuracy and training of colposcopy, addressing existing deficiencies in the practice.

Two web-accessible tools have been developed to facilitate expert evaluation of cervigram images and to allow for targeted retrieval of clinical data, which will support research and education in gynecologic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Digital tools for collecting data from cervigrams for research and training in colposcopy. Jeronimo, J., Long, LR., Neve, L., et al.[2019]

Molecular screening strategies, particularly those using HPV testing and FAM19A4/miR124-2 methylation, showed higher sensitivity (up to 83.1%) for detecting CIN3+ compared to traditional cytology screening, which had a sensitivity of only 59.3%.

While cytology had the highest specificity (91.6%), combining it with methylation did not significantly enhance performance; however, triaging high-risk HPV positive women with methylation improved specificity to 76.1% while maintaining acceptable sensitivity (72.9%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of molecular markers for cervical screening of women living with HIV in South Africa. Kremer, WW., van Zummeren, M., Breytenbach, E., et al.[2022]

High-resolution anoscopy (HRA) is generally well tolerated among HIV-infected patients, with 91.7% of surveyed patients reporting acceptable pain levels and all expressing willingness to return for a repeat procedure.

Factors such as pre-existing anal conditions, smoking history, and being female were associated with lower acceptability of HRA, indicating that certain patient characteristics may influence their experience and likelihood of returning for follow-up screenings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acceptability of high-resolution anoscopy for anal cancer screening in HIV-infected patients. Lam, JO., Barnell, GM., Merchant, M., et al.[2019]

Anal cancer rates are rising, especially among men who have sex with men and those with HIV, and it is linked to human papillomavirus (HPV), similar to cervical cancer.

High-resolution anoscopy (HRA) can be used for secondary prevention of anal cancer by identifying and treating high-grade anal intraepithelial neoplasia (HGAIN), but it presents unique challenges compared to cervical colposcopy, requiring significant training to master.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practising high-resolution anoscopy. Palefsky, JM.[2022]

Cytology testing for anal intraepithelial neoplasia (AIN) in HIV-positive patients shows high sensitivity (82%) for detecting high-grade AIN (HGAIN) when using a cutoff of any squamous intra-epithelial lesion (SIL), making it a potential triaging method.

HR-HPV DNA detection has high sensitivity (91%) but very low specificity (27%), indicating it is not suitable for triaging AIN, while cytology with a cutoff of high-grade SIL (HSIL) offers better specificity (79%) and could be used for quality assurance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Accuracy of Anal Swab-Based Tests to Detect High-Grade Anal Intraepithelial Neoplasia in HIV-Infected Patients: A Systematic Review and Meta-analysis. Dias Gonçalves Lima, F., Viset, JD., Leeflang, MMG., et al.[2023]

In a five-year screening program involving 204 HIV patients, a significant 34% showed cytologic abnormalities for high-risk HPV, highlighting the importance of regular screening for early detection of squamous cell anal cancer (SCC).

The use of high-resolution video-proctoscopy (HR-VPS) proved effective, identifying 29% of patients with positive results, and the program successfully managed precancerous conditions without progression to cancer in treated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening for Squamous Cell Anal Cancer in HIV Positive Patients: A Five-Year Experience. Santorelli, C., Leo, CA., Hodgkinson, JD., et al.[2019]

HIV-infected men who have sex with men (MSM) are at a significantly higher risk for anal cancer and its precursor, high-grade anal intraepithelial neoplasia (HGAIN), compared to the general population.

Screening and treatment for HGAIN, similar to cervical cancer screening, could potentially prevent the development of anal cancer, but these screening programs are not yet standard practice and depend on community resources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elements of an anal dysplasia screening program. Jay, N.[2012]

In a study of 120 HIV-infected individuals, three biomarkers (HPV genotyping, E6/E7mRNA detection, and p16(INK4A)/Ki-67 immunostaining) were found to effectively identify anal dysplasia, potentially reducing the need for invasive procedures.

The combination of these biomarkers demonstrated a high sensitivity (0.93) for detecting high-risk HPV genotypes associated with dysplasia, suggesting they could improve screening compliance and patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of human papillomavirus genotyping and biomarkers for targeted screening of anal dysplasia in human immunodeficiency virus-infected patients. Dupin, C., Siproudhis, L., Henno, S., et al.[2022]

A survey of 160 gynecologists in Germany revealed that the majority perform an average of 2 cervical biopsies during colposcopy, but 94.5% do not use local anesthesia, which raises concerns about patient comfort and safety.

The most common treatment method for cervical precancerous cells is loop excision using an electrosurgical loop, but only 27.6% of physicians provide postoperative bleeding prophylaxis, indicating a need for improved standardization in clinical practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Cervical Dysplasia by Clinicians Who Perform Colposcopy in German-speaking Countries - a Questionnaire-based Study. Hilal, Z., Tempfer, CB., Rezniczek, GA.[2020]

In a study of 222 HIV-infected patients, anal Pap smears showed low sensitivity (61%) for detecting anal dysplasia, indicating they are not reliable enough to rule out the condition.

The study recommends using high-resolution anoscopy-guided biopsy as a complementary screening method for anal dysplasia, especially in high-risk patients, due to its higher specificity (97%) for detecting high-grade dysplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening anal dysplasia in HIV-infected patients: is there an agreement between anal pap smear and high-resolution anoscopy-guided biopsy? Nahas, CS., da Silva Filho, EV., Segurado, AA., et al.[2022]

A case study from the IMPROVE-COLPO study highlights that Dynamic Spectral Imaging (DSI) can improve the detection of cervical lesions that traditional colposcopy might miss, as seen in a patient with invasive squamous carcinoma despite initial negative findings.

The findings suggest that using DSI in conjunction with colposcopy can enhance the accuracy of cervical cancer screenings, emphasizing the importance of collecting multiple biopsies to ensure that no invasive cancers are overlooked.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How Colposcopy Misses Invasive Cervical Cancer: A Case Report from the IMPROVE-COLPO Study. Livingston, J., Papagiannakis, E.[2020]

In a study of 163 HIV+ men, high-resolution anoscopy showed that 55% of biopsies revealed anal intraepithelial neoplasia, with 22% showing high-grade lesions, indicating a significant prevalence of these conditions in this population.

Moderate to substantial agreement was found among dermatologists in identifying specific lesion features, with combinations of punctation, flat leukoplakia, and atypical vessels being the strongest predictors for high-grade anal intraepithelial neoplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution anoscopy: clinical features of anal intraepithelial neoplasia in HIV-positive men. Richel, O., Hallensleben, ND., Kreuter, A., et al.[2013]

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