Testing the Feasibility of Different HPV Screening and Care Strategies for Women Living With HIV

CASCADE: A Feasibility Study of HPV Screening and Management Strategies Utilizing Extended Molecular HPV DNA Genotyping and HPV Viral Load in Women Living With HIV

The overall goal of this study is to inform the design and establish feasibility for a future clinical trial to determine the optimal management of women living with HIV (WLWH) with high-risk human papillomavirus (hrHPV) detected on HPV-based cervical cancer screening. WLWH have a higher diversity of anogenital HPV types causing cervical high-grade squamous intraepithelial lesions (hHSIL) and invasive cancer compared to women without HIV. While there is consensus that women testing positive for HPV 16 and/or 18 should be immediately managed and treated, optimal management strategies for women with other hrHPV types (non-16/18) are not well defined.

This prospective cohort study will enroll WLWH undergoing cervical cancer screening using primary HPV testing. Women will self-collect vaginal specimens for hrHPV testing using the Abbott Alinity m HPV assay, which provides extended HPV genotyping and a proxy for HPV viral load based on cycle threshold (CT) values. Women with hrHPV detected will return for further evaluation and treatment as indicated. A subset of women will return at Month 6 for repeat evaluation.

The study will evaluate feasibility for a future trial by examining recruitment, retention, return for evaluation, and completion of treatment. It will also explore management strategies for women with non-16/18 hrHPV based on extended genotyping and HPV viral load compared to standard of care approaches using visual inspection with acetic acid (VIA).

Study Overview

• Status: Not yet recruiting
• Conditions: Cervical Cancer; Human Immunodeficiency Virus (HIV); Human Papillomavirus (HPV); Cervical Intraepithelial Neoplasia (CIN); HPV Associated Cancers
• Intervention / Treatment: Diagnostic test: HPV DNA Testing (Abbott Alinity m HPV Assay); Procedure: Visual Inspection with Acetic Acid; Procedure: Cervical Histology (Biopsy Procedures); Procedure: Cervical Treatment (Thermal Ablation or LEEP/LLETZ)

• Study Type: Interventional
• Enrollment (Estimated): 750
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Caique Mello, MPH; Phone Number: 858-253-6394; Email: camello@health.ucsd.edu

Study Locations

• Botswana
  • South-East District
    • Gaborone, South-East District, Botswana
      • Botswana Harvard Health Partnership
      • Contact: Scott L Dryden-Peterson, MD, MSc; Phone Number: 617-732-8881; Email: sldrydenpeterson@bwh.harvard.edu
      • Principal Investigator: Scott L Dryden-Peterson, MD, MSc
      • Sub-Investigator: Rebecca G Luckett, MD, MPH
      • Sub-Investigator: Doreen Ramogola-Masire, MBBS, PhD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• HIV-1 infection, as documented by:

  1. any FDA-approved, licensed HIV rapid test performed in conjunction with screening (oral immunoblot, ELISA test kit, and confirmed by Western blot or other approved test), OR
  2. a physician's written record that documents HIV infection with supporting information on the participant's relevant medical history and/or current management of HIV infection, OR
  3. documentation of a prescription of an approved antiretroviral regimen by either possession of pill bottles or packages with prescriber's name or ARVs dispensed from an HIV clinical treatment program with participant identifiers affixed to the bottles or packages.
• Aged 25 or older.
• Ability to understand and the willingness to sign a written informed consent document by the participant or by the legal representative(s) of the participant.
• Have an intact cervix.

Exclusion Criteria:

• Current symptoms or concern for cervical cancer.
• History of cervical, vulvar, vaginal, perianal, anal cancer or oral cancer or current symptoms of cervical, vulvar, vaginal, perianal, anal cancer or oral cancer.
• Have undergone cervical hHSIL treatment in the past year.
• Have a history of hysterectomy with removal of the cervix.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including opportunistic infections of AIDS and/or genitourinary infections), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Any other medical condition or social situation that would put the participant, the study staff, or the study outcomes at risk, as determined by the site investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Primary HPV screen with management based on HPV types and VIA status; All women will self-collect a vaginal specimen for primary HPV testing to be evaluated on the Abbott Alinity m platform. WLWH who test hrHPV negative will exit the study. Women with hrHPV will return for speculum examination, cervical swab collection, VIA, and histology. Women with HPV 16/18 will undergo immediate treatment. Women with non-16/18 hrHPV will undergo immediate treatment only if cervical lesions are seen on VIA. Women who are not treated, but subsequently found to have cervical HSIL on histology, will return for cervical treatment. The choice of treatment modality (TA vs. LEEP/LLETZ) will be determined by the extent of cervical lesions seen on VIA. Women with extensive lesions will undergo LEEP/LLETZ treatment. All women who are enrolled (and therefore hrHPV positive) in the early months of the study will be asked to return for a visit 4-6 months later for repeat HPV testing and cervical histology.

Diagnostic test: HPV DNA Testing (Abbott Alinity m HPV Assay); Women will self-collect a vaginal specimen for primary HPV testing to be evaluated on the Abbott Alinity m platform. The Alinity m HR HPV assay is a qualitative, real-time polymerase chain reaction (PCR) assay for the detection of high-risk HPV DNA. The assay detects 14 hrHPV genotypes by targeting the conserved L1 region of HPV DNA and provides individual or group-level genotyping results, including separate readouts for HPV 16, HPV 18, and HPV 45, and grouped detection of other high-risk types. The assay also provides a proxy for HPV viral load as measured by the cycle threshold (CT) value for the type- or group-specific readout.; Procedure: Visual Inspection with Acetic Acid; Participants with hrHPV detected will undergo visual inspection with acetic acid (VIA) during a speculum examination. Standard acetic acid (3-5%) is applied to the cervix, and the provider will assess for the presence of cervical lesions, determine suitability for ablative treatment, and characterize the transformation zone (TZ1, TZ2, or TZ3). VIA findings will be used to guide participant management and treatment decisions.; Other Names: VIA; Procedure: Cervical Histology (Biopsy Procedures); Cervical histology specimens will be obtained from participants with hrHPV detected. Biopsies may include lesion-directed cervical punch biopsies, endo- and ectocervical soft-brush biopsies, or endocervical curettage (ECC). At least two biopsies will be obtained even if no lesions are seen. For participants undergoing LEEP/LLETZ, histology will be obtained through the excisional procedure. Cervical histology will be processed locally and interpreted according to the lower anogenital squamous terminology (LAST), including p16 testing where available to confirm morphologic-appearing CIN 2.; Procedure: Cervical Treatment (Thermal Ablation or LEEP/LLETZ); Women with HPV 16 and/or 18 will undergo immediate treatment. Women with non-16/18 hrHPV will undergo immediate treatment if cervical lesions are seen on VIA. Women who are not treated but are subsequently found to have cervical high-grade squamous intraepithelial lesions (hHSIL) on histology will return for cervical treatment. Treatment modality will be determined based on the extent of cervical lesions, with thermal ablation (TA) used for lesions appropriate for ablative therapy and LEEP/LLETZ used for more extensive lesions.; Other Names: LEEP; Thermal Ablation; LEEP/LLETZ; LLETZ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility for a Future Clinical Trial	To describe the feasibility for a future clinical trial testing various management strategies for women with non-16/18 hrHPV by examining the proportion of potentially eligible women agreeing to study participation, the timeliness and proportion of women receiving the HPV results, the proportion returning for baseline evaluation, and the proportion retained for the Month 6 visit.	From enrollment through Month 6 visit
Proportion Receiving Treatment Under Different Management Strategies	To estimate the proportion of women living with HIV (WLWH) with hrHPV infection and cervical high-grade squamous intraepithelial lesions (hHSIL) who receive treatment under three different management strategies: visual inspection with acetic acid (VIA) triage, genotype restriction alone, and genotype restriction plus HPV viral load.	Baseline through Month 6 visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hrHPV Prevalence and Genotype Distribution	To describe the hrHPV prevalence and HPV genotype distribution by clinical site.	Screening
Alternative CT Value Cutoffs for Management	To explore alternative Abbott Alinity m CT value cutoffs for non-16/18 hrHPV to determine which women are managed with cervical treatment.	Baseline through Month 6 visit
Rate of Invasive Cancer or CIN 3 Managed With No Treatment	To estimate the rate of invasive cancer or cervical intraepithelial neoplasia (CIN) 3 managed with no treatment for the various management strategies (i.e., VIA triage, genotype restriction, and genotype restriction with incorporation of HPV viral load).	Baseline through Month 6 visit

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: National Cancer Institute (NCI); Beth Israel Deaconess Medical Center; Brigham and Women's Hospital; University of North Carolina, Chapel Hill; H. Lee Moffitt Cancer Center and Research Institute; Frontier Science & Technology Research Foundation, Inc.; Botswana Harvard Health Partnership
• Investigators: Study Chair: Timothy J Wilkin, MD, MPH, University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: May 4, 2026
• First Submitted That Met QC Criteria: May 4, 2026
• First Posted (Actual): May 8, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Uterine Diseases; Genital Diseases, Female; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Genital Neoplasms, Female; Slow Virus Diseases; Precancerous Conditions; Uterine Cervical Diseases; Uterine Neoplasms; HIV Infections; Acquired Immunodeficiency Syndrome; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia; Health Services Administration; Organic Chemicals; Fatty Acids; Lipids; Surgical Procedures, Operative; Quality of Health Care; Acids, Acyclic; Carboxylic Acids; Fatty Acids, Volatile; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Urologic Surgical Procedures; Urogenital Surgical Procedures; Acetates; Urologic Surgical Procedures, Male; Prostatectomy; Acetic Acid; Watchful Waiting; Transurethral Resection of Prostate
• Other Study ID Numbers: 813535; U24CA275417 (U.S. NIH Grant/Contract); UG1CA275414 (U.S. NIH Grant/Contract); UG1CA275416 (U.S. NIH Grant/Contract); C2001P-CS3 (Other Identifier: National Cancer Institute)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No