Fifteen PEPFAR-supported clinics across 8 Nigerian states were selected based on geographic diversity (including urbanicity), level of care, ownership, and patient volume, to represent the diversity of care settings in Nigeria. Each site aims to recruit 100 WLWH aged 25–50.

The MoMent HIV+HCC adapted intervention will consist primarily of MMs supporting WLWH in testing for hrHPV. MMs will be responsible for recruiting and enrolling WLWH into the study, educating them about HPV and SC, transporting samples to the clinic/laboratory, returning testing results and facilitating treatment for WLWH who need follow up care. Details are described below.

hrHPV negative WLWH will be counselled to repeat the HPV test in 3 years and counselled that a negative result does not indicate future protection from HPV.

All WLWH who test positive for hrHPV 16/18/45/other will undergo visual inspection with acetic acid (VIA). Patients with acetowhite lesions after application of 3%–5% acetic acid per VIA protocol [31] will have these areas biopsied for diagnosis. Those who do not demonstrate acetowhite lesions on VIA (VIA-negative) will have 4 quadrant biopsies on the cervix along the squamocolumnar junction. For patients where the squamocolumnar junction is not fully visualized secondary to being in the endocervical canal, an endocervical curettage will be collected. If the patient qualifies for thermal ablation treatment, she will receive same-day treatment. However, if the lesion is ineligible for thermal ablation, the patient will be referred for excisional procedure for diagnosis and treatment. VIA, biopsies, and treatment will be performed by the clinic gynaecologist and biopsies will be sent to the state pathology laboratory.

All hrHPV WLWH treated per the protocol will repeat a self-test for HPV at 1 and 2 years from the time of treatment to determine clearance/persistence of hrHPV infection. If the WLWH is positive for hrHPV at 1- or 2-year post treatment, they will undergo VIA and biopsies and, based on the gynaecologist’s recommendation, repeat thermal ablation if eligible, or excisional treatment.

All test and treatment outcomes will be correlated with the CD4 count and viral load of the participants. As will be specified in consent forms, all left over aliquots from all cases of positive hrHPV, pathology blocks, and slides will be archived for future relevant studies. The HPV SC samples will also be available for full HPV genotyping.

We will use purposive sampling techniques to select 30 HIV+HCC MMs from among existing MMs in the 15 selected facilities. Two MMs will work at each site and share responsibility for 100 WLWH. MMs will provide counselling and support, encourage clients to uptake the CC screening, facilitate the screening process, return HPV results, and provide support services for necessary treatment. Selected MMs will demonstrate: (1) 4+ years’ experience as an MM, (2) sustained viral suppression, (3) good adherence to drugs and clinic appointments, (4) history of advocating for people living with HIV, (5) history of returning patient logs, and (6) experience with CC screening.

Two MMs, a senior MM and a junior MM, as defined by length of time working as an MM at that clinic, were selected for participation in the CHESS study. The senior MMs were invited to a two-day, interactive training. Training included an overview of the CHESS project and information on HPV, CC screening, and project-specific MM responsibilities. MMs conducted their own HPV SC test using the Evalyn Brush tool [32] (HPV results were returned privately to each participating MM). MMs completed pre- and post-training assessments and were required to demonstrate proficiency (>80% correct responses) across all topics or require retraining.

Senior MMs who participated in the in-person training returned to their clinic and trained the junior MMs using study-provided workbooks and materials. Further, an online refresher training was held 3 weeks prior to the start of study implementation to review all study elements with all MMs and clinic site managers.

We conducted a clinical training for gynaecologists and nurses who will treat WLWH who have hrHPV results. Clinicians were trained in performing cervical biopsies for documentation of histological grade of disease and conducting thermal ablation and LEEP. Trainees also worked through case presentations to assist with decision making during colposcopy and treatment.

Clinicians completed pre- and post-training surveys to assess skill improvement.

Our study addresses critical diagnostic challenges related to p-16 testing, a key marker for HPV-associated cervical dysplasia. Our pathology team, with two Nigerians and one American pathologist, identified significant gaps in their ability to perform p-16 testing due to lack of essential supplies, such as the P-16 primary antibody and detection kits. Nigerian pathologists also do not have access to digital microscopes, which are crucial for remote consultations and quality control. To address these limitations, the study procured digital smartphone microscope adaptors, which will enhance diagnostic accuracy and facilitate second reviews by pathologists for quality assurance.

As part of our efforts to standardize diagnostic procedures, we convened a meeting with Nigerian pathologists, virologists, and an Emory pathologist to review the study schema, particularly the 4-quadrant biopsy collection process. This review was essential to ensure consistent collection techniques and reliable diagnostic outcomes. We also examined the indications for p-16 staining, ensuring it is appropriately applied to cases where HPV-related dysplasia is suspected, organized training on the use of GeneXpert for HPV testing and collaboratively worked on the distribution of HPV testing cartridges and transport medium. Furthermore, we standardized terminology used on treatment evaluation forms for vaginal biopsies, ensuring that all sites are aligned in documenting biopsy results and treatment evaluations accurately.

We established quarterly quality assurance conferences to maintain diagnostic consistency, especially in the interpretation of various levels of dysplasia. Our discussions with the virologists also focused on refining protocols for sample collection, storage, shipping, and necessary reagents to ensure sample integrity. These coordinated efforts aim to enhance local diagnostic capacity while adhering to rigorous quality control standards.

We will recruit 1500 consenting WLWH from 15 healthcare facilities (100 per facility) across eight states over a period of 18 months. A sampling frame of WLWH will be generated using a report run by the clinic staff of eligible women currently receiving care. Eligible WLWH will be contacted via telephone by the MM who will provide information about the study process. WLWH who are interested in participating will be invited to a community education meeting. Upon arrival at the community meeting, the MM will educate about HPV screening, enroll interested participants into the study and facilitate logistics for the self-screening process in a private location at the meeting site.

Eligibility inclusion criteria include:

Female gender

The decision to screen WLHIV age 25–50 years is based on WHO recommendation which recommends HPV screening from age 25 years up to 65 years when there are tools to manage such women. However, we chose to limit our screening to upper age of 50 years because neither VIA nor ablative treatment, which are our proposed triaging test and first line treatments respectively, are suitable for women in whom the transformation zone is not visible which is typical after menopause. WLWH will not be eligible if they are pregnant, have had a hysterectomy or are not able/willing to perform vaginal self-collection.

A sample size of 1500 WLWH was determined after considering a design effect of 1.2 (to adjust for cluster sampling) and then incorporating a dropout rate of 20%. A sample size of 1500 has 89% power to detect an absolute difference in proportions of 0.04 using a two -sided exact test with a significance level of 0.05. This calculation assumes that the population proportion under the null hypothesis (P0) is 0.79. This is based on previous research that identified the proportion of women that are willing to screen for CC [33, 34].

Each week, MMs will call eligible patients and invite them to a culturally appropriate education session on HPV screening and SC. The MM will also introduce the CHESS study and take names for women who are interested in enrolling.

The Site Coordinator will receive the list of interested women from the MM and, given resource limitations, will use a random number generator to select 10 women/month. The MM will contact the selected participants and arrange to meet them in the community, where they will consent and enroll the WLWH. Women not randomly selected will be offered alternative screening through standard of care (VIA). Upon enrollment, the participant will self-collect an HPV sample in a private space using the Evalyn Brush [32], aided by pictorial brochures and videos developed in English and the three most common Nigerian languages. MMs will transport the labelled samples securely to a laboratory for testing. The Evalyn Brush, whose accuracy is similar to clinician-collected samples [35] may be stored dry in the container it comes in at room temperature and remains stable up to 6 months. If a private collection space is not available, the MM and participant will make a plan for the return of the sample within 10 days of collection. HPV testing will be done on aliquots of samples using GeneXpert HPV platform to determine sample HPV positivity and intervention decisions. Laboratory processing of cervicovaginal samples entails pipetting 1 mL of each HPV sample into the GeneXpert HPV cartridge and then slotting the cartridge into the GeneXpert machine for processing.

The MM will be responsible for returning test results to participants. For results indicating no presence of hrHPV, the MM will counsel the participant on the meaning of the results and encourage her to retest in 3 years. For results indicating the presence of hrHPV, the MM will work with the nurse at her clinic to facilitate further evaluation and treatment by a gynaecologist.

Study data will be managed in REDCap. Access to the password-protected database will be restricted to approved study team members. Data will be stored on institutionally certified, password-protected, and encrypted tablets, laptops, and external drives. Only approved study staff will receive data via secure file transfer platforms.

The study team collaboratively designed Case Report Forms (CRFs) for easy completion and data entry. Questions were tailored to support analysis and quality control. MMs will complete CRFs at various CHESS study stages, and clinical personnel will complete during or immediately after exams. All CRFs will be submitted to clinic-based data clerks within 48 h. Electronic data entry screens will replicate the CRFs. Site clinicians and data managers were trained in CRF completion and REDCap data entry during a virtual pre-study session with refreshers offered. Missing or anomalous data will be sent back to sites for clarification or resolution.

RE-AIM is a framework for planning and evaluating that assesses 5 dimensions: reach, efficacy, adoption, implementation, and maintenance [29, 30]. These dimensions occur at multiple levels including individual, clinic or organization and community and interact to determine health impact of the program. As shown in Table 1, we address relevant RE-AIM constructs for the study sample overall and by state.

Guided by the RE-AIM framework, we will use a convergent mixed-methods approach to implement a six-month, post-implementation assessment of reach, adoption, implementation, and fidelity. Quantitative and qualitive data will be collected in parallel and analyzed separately, then integrated during interpretation. Quantitative measures include numbers of women contacted, screened, and treated, numbers of MMs trained, and numbers of clinics that reach the optimal ratio (1:50) of MMs to WLWH. We chose this ratio on data from clinics in the six participating Nigerian states with input from experts in the field. The 1:50 ratio balances the needs of WLWH and the resource constraints faced by clinics/MM programs providing care. Data sources include site observations, clinical records, reports, training logs, and sample analysis. Quantitative outcome measures and data such as socio demographic/socioeconomic characteristics of participants will be analyzed using descriptive statistics and compared across states using the chi-squared test at the 5% level of significance.

To measure system flow, we will conduct rapid ethnography at a subset of 6 clinics (one per state) to assess daily clinical processes, recording observations in field notes. We will also follow 80 WLWH (10 per clinic) through the process, timing each step and noting barriers. Additionally, we will conduct virtual in-depth interviews (IDIs) with a clinical champion at each clinic (n = 15) and two focus groups (total n = 10–12) with HIV+HCC MMs to identify implementation barriers and facilitators. We will focus on MMs, who understand both systemic issues and the individual experiences of WLWH. Clinic champions will be asked to gather input from other staff before the IDIs to inform responses. Stakeholders will be informed they will participate in follow-up qualitative data collection at 18 months (Aim 3). IDIs and focus groups will be audio-recorded and transcribed, with a team member taking notes. Preliminary thematic analysis will be conducted to identify key barriers and facilitators to inform project adjustments.

Finally, we will capture project costs of adding the HCC components into the MoMent program as considerations for maintenance and sustainability. Measures will include costs for labor (clinical and laboratory staff and MMs), training and education, and clinical materials and supplies related to screening (e.g., Evalyn brush, GeneXpert Cartridge) and diagnosis (VIA consumables). Integrated findings will inform program refinement and support recommendations for scale-up and sustainability.

Aim 3

Conduct post-implementation process evaluation of barriers and enablers to program maintenance.

In the maintenance phase, we will evaluate how the intervention has become routine practice at 18 months post-implementation. We will again collect data from the same stakeholders identified for Aim 2. Stakeholders’ viewpoints and processes related to the RE-AIM construct of “maintenance” will be assessed via quantitative measures (Table 1), structured interviews (n = 15), focus groups (n = 10–12), and numbers of WLWH screened/treated during the maintenance period. Stakeholders will also identify barriers to maintenance, resources available to support and capacity to scale the intervention across Nigeria.