Screening Tests for Cervical and Anal Cancer in HIV Patients

(CAMPO-101 Trial)

Recruiting at5 trial locations

Overseen by Joel Palefsky, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of California, San Francisco

Must be taking: Antiretrovirals

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial uses quick tests to find abnormal tissue changes in the cervix or anus in men and women with HIV. These patients are at higher risk for HPV-related cancers. The tests help detect early signs of potential cancer so that further checks and treatments can be done if needed.

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 data supports the effectiveness of the treatment for screening cervical and anal cancer in HIV patients?

Research shows that using high-resolution anoscopy and biopsies can help accurately diagnose anal dysplasia in HIV patients. Additionally, molecular markers and hybrid capture techniques have been effective in screening for cervical cancer in women with HIV, offering high sensitivity in detecting precursor lesions. ^{1 2 3 4 5}

Is it safe to undergo colposcopy and high-resolution anoscopy for cancer screening?

Colposcopy and high-resolution anoscopy are generally safe procedures used to screen for cervical and anal cancer, respectively. While they may cause some discomfort, they are important for identifying precancerous lesions and preventing cancer progression. ^{6 7 8 9 10}

How does this treatment for cervical and anal cancer screening in HIV patients differ from other treatments?

This treatment is unique because it uses new biomarkers, originally developed for cervical cancer screening, to provide a targeted and easy-to-perform screening for anal dysplasia in HIV patients, which is not yet standardized. Unlike high-resolution imaging, which is not suitable for mass screening, these biomarkers offer a more accessible approach. ^{5 11 12 13 14}

Research Team

Joel Palefsky, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

Exclusion Criteria

Participants who have undergone hysterectomy, History of anal cancer, penile, vulvar, vaginal, or cervical cancer, Potential participants who received prior treatment of anal, cervical, penile, vaginal, or vulvar lesions within 18 months of study enrollment, Inability in the opinion of the study investigator of the participant to comply with study requirements, Participants who are pregnant (a urine pregnancy test will be provided to participants aged 60 years or less) or within 2 months being post-partum

Trial Timeline

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

Treatment Details

Interventions

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

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.

Participant Groups

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+

Suresh Gunasekaran

University of California, San Francisco

Chief Executive Officer since 2022

MBA from Southern Methodist University

Dr. Lukejohn Day

University of California, San Francisco

Chief Medical Officer

MD from Stanford University School of Medicine

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

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

Collaborator

Trials

2

Recruited

2,100+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

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]

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 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]

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]

References

1. United States 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? [2022]

2. England pubmed.ncbi.nlm.nih.gov

The use of molecular markers for cervical screening of women living with HIV in South Africa. [2022]

3. Brazil pubmed.ncbi.nlm.nih.gov

[Performance by cytology and hybrid capture II in screening for high-grade squamous intraepithelial lesions in women with HIV]. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Anal human papillomavirus DNA in women at a colposcopy clinic. [2012]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Use of human papillomavirus genotyping and biomarkers for targeted screening of anal dysplasia in human immunodeficiency virus-infected patients. [2022]

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

Digital tools for collecting data from cervigrams for research and training in colposcopy. [2019]

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

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

8. England pubmed.ncbi.nlm.nih.gov

Acceptability of high-resolution anoscopy for anal cancer screening in HIV-infected patients. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Treatment of Cervical Dysplasia by Clinicians Who Perform Colposcopy in German-speaking Countries - a Questionnaire-based Study. [2020]

10. Australia pubmed.ncbi.nlm.nih.gov

Practising high-resolution anoscopy. [2022]

11. United States 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. [2023]

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

High-resolution anoscopy: clinical features of anal intraepithelial neoplasia in HIV-positive men. [2013]

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

Screening for Squamous Cell Anal Cancer in HIV Positive Patients: A Five-Year Experience. [2019]

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

Elements of an anal dysplasia screening program. [2012]