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).
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.
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.
Single group
HPV DNA Testing (Abbott Alinity m HPV Assay)
Diagnostic testWomen 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.
Visual Inspection with Acetic Acid
Procedure/SurgeryParticipants 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.
Cervical Histology (Biopsy Procedures)
Procedure/SurgeryCervical 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.
Cervical Treatment (Thermal Ablation or LEEP/LLETZ)
Procedure/SurgeryWomen 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.
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.
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.
hrHPV Prevalence and Genotype Distribution
To describe the hrHPV prevalence and HPV genotype distribution by clinical site.
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.
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).
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BotswanaClick on the lead sponsor to view all of their trials.
University of California, San Diego
Lead sponsor
Frontier Science & Technology Research Foundation, Inc.
Collaborator
Botswana Harvard Health Partnership
Collaborator
Brigham and Women's Hospital
Collaborator
Beth Israel Deaconess Medical Center
Collaborator
H. Lee Moffitt Cancer Center and Research Institute
Collaborator
University of North Carolina, Chapel Hill
Collaborator
National Cancer Institute (NCI)
Collaborator
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