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

Official title

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

Overview

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).

Interventions

• 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
• 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.
• 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 ter
• 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

Primary outcome measures

• Feasibility for a Future Clinical Trial [Time frame: From enrollment through Month 6 visit]
• Proportion Receiving Treatment Under Different Management Strategies [Time frame: Baseline through Month 6 visit]

Secondary outcome measures (3)

• hrHPV Prevalence and Genotype Distribution [Time frame: Screening]
• Alternative CT Value Cutoffs for Management [Time frame: Baseline through Month 6 visit]
• Rate of Invasive Cancer or CIN 3 Managed With No Treatment [Time frame: Baseline through Month 6 visit]

Eligibility criteria

Inclusion criteria

• HIV-1 infection, as documented by:

• 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
• 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
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Botswana · 1 center

• Botswana Harvard Health Partnership — Gaborone

Identifiers

NCT: NCT07576842 · 813535 · UG1CA275414 · UG1CA275416 · U24CA275417 · C2001P-CS3

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗