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

Summary

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).

Conditions

• Human Papillomavirus (HPV)
• HPV Associated Cancers
• Cervical Cancer
• Human Immunodeficiency Virus (HIV)
• Cervical Intraepithelial Neoplasia (CIN)

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. 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.

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.

Sponsors & Collaborators

• Frontier Science & Technology Research Foundation, Inc.

  collaborator INDUSTRY

• Botswana Harvard Health Partnership

  collaborator UNKNOWN

• Brigham and Women's Hospital

  collaborator OTHER

• Beth Israel Deaconess Medical Center

  collaborator OTHER

• H. Lee Moffitt Cancer Center and Research Institute

  collaborator OTHER

• University of North Carolina, Chapel Hill

  collaborator OTHER

• National Cancer Institute (NCI)

  collaborator NIH

• University of California, San Diego

  lead OTHER

Principal Investigators

• Timothy J Wilkin, MD, MPH · University of California, San Diego

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

25 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-06-01

Primary Completion

2027-06-01

Completion

2027-06-01

Countries

• Botswana