C2001P-CS6: Testing the Feasibility of Different HPV Screening and Care Strategies for Women Living With HIV

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.

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.

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.

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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.

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.

• LEEP
• Thermal Ablation
• LEEP/LLETZ
• LLETZ

Number of participants providing informed consent divided by the number approached for consent.

Number of days from vaginal sample collection to clinic receipt of HPV test results.

Percentage of participants who provided a vaginal sample and received their HPV test results.

Number of participants returning for the baseline evaluation divided by the total number who provided a vaginal self-sample at enrollment.

Number of participants returning for the Month 6 visit divided by the number who completed the baseline visit more than 6 months before the end of the study.

Proportion of participants with hrHPV and histologically-confirmed cervical high-grade squamous intraepithelial lesions (HSIL) classified for treatment under each strategy: visual inspection with acetic acid (VIA), genotype restriction, and genotype restriction plus HPV viral load. The denominator includes estimated HSIL cases among participants who did not return for baseline evaluation. Results are reported separately for each strategy.

Proportion of participants with valid HPV results who test positive for any hrHPV, each Abbott Alinity m genotype channel, multiple channels, or hrHPV without HPV 16/18. Results are reported overall and by clinical enrollment unit.

Alternative Abbott Alinity m cycle threshold (CT) cutoffs, in PCR cycles, associated with cervical HSIL. Cutoffs are derived using receiver operating characteristic (ROC) analysis and reported by non-16/18 hrHPV channel. Central histology review is used when available.

Proportion of participants with cervical HSIL classified as positive using alternative CT cutoffs, reported by non-16/18 hrHPV channel among participants positive for that channel with interpretable histology.

Proportion of participants without cervical HSIL classified as negative using alternative CT cutoffs, reported by non-16/18 hrHPV channel among participants positive for that channel with interpretable histology.

Number of participants with CIN 3 or invasive cervical cancer classified for no treatment under each strategy divided by the total number with hrHPV. Strategies include VIA, genotype restriction, and genotype restriction plus HPV viral load. Estimates account for participants who did not return for baseline evaluation.