Evaluation of Triage Options After HPV Testing for Cervical Cancer Screening Among HIV-infected Women

Study Overview
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Brief Summary
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Cervical cancer is the most common cause of cancer and a leading cause of death among HIV-infected women living in resource-limited settings. Although screening for premalignant lesions is an effective way of reducing cervical cancer incidence, its uptake in low-resource settings to date is low. The use of HPV testing for primary screening is currently recommended by many guidelines - including the WHO guidelines for cervical cancer screening in resource-limited settings - because of its greater sensitivity and ease of use compared to other options. However, these WHO guidelines have both highlighted the need to conduct more research on appropriate HPV-based algorithms among HIV-infected women, as immunodeficiency may affect the screening performance. Indeed, HPV infections in HIV-infected women are very common, so there is a need for additional triage to identify women most at risk and there remains considerable uncertainty on the optimal option for such triage. Most of the evidence available comes from HIV-negative populations living in high-resource settings and is not necessarily relevant for low-resource contexts where the epidemiological background is different, women access late to screening and may not have follow up visits, where financial constraints are important and health service resources limited. Hence, the proposed project aims to provide evidence on the effectiveness and feasibility of HPV-based screening algorithms among HIV-infected women in low-resource settings. This multicenter cross-sectional study will include 3,000 HIV-infected women (30-49 years old) receiving HAART and followed in Abidjan (Ivory Coast), Bobo-Dioulasso (Burkina Faso) and Phnom Penh (Cambodia). After self-collection of cervico-vaginal samples, each participant will have an HPV test with partial genotyping primary using the Xpert HPV assay, a real-time PCR assay that provides the possibility of identifying 14 HR-HPV types within one hour. The Xpert HPV test has been chosen because of the wide availability of the Genexpert platform in HIV care centers from resource-limited settings. Furthermore, it can specifically detect HPV-16, 18 and 45, the most carcinogenic HPV types in both HIV-negative and HIV-positive women, separately from other high-risk HPV types. VIA will be another triage option either alone or combined to HPV DNA genotyping. In addition, participants treated for cervical lesion will be followed over 12 months to assess the risk of post-treatment lesions (CIN2+/HSIL) and to identify associated risk-factors.

Official Title
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Evaluation of Screening Algorithms Based on Self-collection and HPV Testing With Partial Genotyping for the Prevention of Cervical Cancer Among HIV-infected Women in Low-income Countries

Conditions
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HIV Infections, HPV - Anogenital Human Papilloma Virus Infection

Intervention / Treatment
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* Diagnostic Test: HPV test with partial genotyping and VIA triage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women HIV-1 infection Age 30 to 49 years In care for HIV infection, receiving or initiating antiretroviral therapy Written informed consent given Exclusion Criteria: HIV-2 infection Ongoing pregnancy (evidenced by self-report or clinical examination) Previous total hysterectomy Severe concomitant disease that, according to the investigators, may contraindicate or compromise participation to the study History of cervical cancer screening with treatment for precancerous lesions within the last 12 months Differed inclusion Ongoing heavy menstruation Immediate post-partum (<12 weeks post delivery) Sign of ongoing genital infection (e.g. mucopurulante discharge)

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Triage with different options<br>All women will have an HPV test, partial genotyping (16/18/45 versus other high-risk HPV [hr-HPV]) and VIA. The different options for triage that will be compared are: Participants hr-HVP+ and VIA+ participants selected for treatment; Participants HPV 16/18/45+ selected for treatment; Participant HPV 16/18/45+ and/or VIA+ selected for treatment; | Diagnostic Test: HPV test with partial genotyping and VIA triage<br>* HPV testing with the GenXpert platform VIA Biopsies of VIA+ lesions or random Treatment with thermal ablation of women with precancerous lesions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of the triage options | Sensitivity of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard | Day 0 | 
| Specificity of the triage options | Specificity of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard | Day 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and negative predictive value (PPV and NPV) of the triage options | PPV and NPV of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard | Day 0 | 
| Positive and negative diagnostic likelihood ratio (DLR) of the triage options | Positive and negative DLR of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard | Day 0 | 
| Acceptability and feasibility | Acceptability and feasibility of the self-sampling, of the different triage options and of the treatment cervical lesions | Day 0 and Week 1 | 
| Prevalence of CIN2+ lesions | Prevalence of CIN2 lesions, overall and by sub-groups defined by age categories, current CD4-cell count, nadir CD4-cell count and treatment history | Day 0 | 
| Prevalence of CIN3+ lesions | Prevalence of CIN3 lesions overall and by sub-groups defined by age categories, current CD4-cell count, nadir CD4-cell count and treatment history | Day 0 | 
| Prevalence of cervical cancer | Prevalence of cervical cancer overall and by sub-groups defined by age categories, current CD4-cell count, nadir CD4-cell count and treatment history | Day 0 | 
| Adverse events | Rate and nature of adverse events and protocol violations | Day 0 and Week 1 up to 24 weeks | 
| Proportion of the women eligible to HPV screening who were actually screened and treated (if required) | Proportion of the women eligible for the study who were actually screened, treated (if required) | Day 0 | 
| Evaluation of the micro-costing | Evaluation of the micro-costing of the various components of the screening strategies | Day 0 up to Week 26 | 
| Evaluation of post-treatment HPV clearance | Evaluation of the HPV clearance at M6 and M12 after thermal-ablation | Week 24 and 48 post treatment | 
| Evaluation of post-treatment cervical lesion | Evaluation of the proportion of CIN2 and CIN3 at M12 after treatment | Week 48 post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV infection, HPV infection, cervical cancer, screening algorithms, recurrence