HIV Infections, HPV - Anogenital Human Papilloma Virus Infection
Conditions
Keywords
HIV infection, HPV infection, cervical cancer, screening algorithms, recurrence
Brief summary
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.
Interventions
DIAGNOSTIC_TESTHPV test with partial genotyping and VIA triage
HPV testing with the GenXpert platform VIA Biopsies of VIA+ lesions or random Treatment with thermal ablation of women with precancerous lesions
Sponsors
Institut de Recherche pour le Developpement
International Agency for Research on Cancer
Programme PAC-CI, Site ANRS-MIE de Côte d'Ivoire
University Hospital, Geneva
University of Bordeaux
ANRS, Emerging Infectious Diseases
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 49 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity of the triage options | Day 0 | Sensitivity of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard |
| Specificity of the triage options | Day 0 | Specificity of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positive and negative predictive value (PPV and NPV) of the triage options | Day 0 | PPV and NPV of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard |
| Positive and negative diagnostic likelihood ratio (DLR) of the triage options | Day 0 | Positive and negative DLR of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard |
| Acceptability and feasibility | Day 0 and Week 1 | Acceptability and feasibility of the self-sampling, of the different triage options and of the treatment cervical lesions |
| Prevalence of CIN2+ lesions | Day 0 | Prevalence of CIN2 lesions, overall and by sub-groups defined by age categories, current CD4-cell count, nadir CD4-cell count and treatment history |
| Prevalence of CIN3+ lesions | Day 0 | Prevalence of CIN3 lesions overall and by sub-groups defined by age categories, current CD4-cell count, nadir CD4-cell count and treatment history |
| Prevalence of cervical cancer | Day 0 | Prevalence of cervical cancer overall and by sub-groups defined by age categories, current CD4-cell count, nadir CD4-cell count and treatment history |
| Adverse events | Day 0 and Week 1 up to 24 weeks | Rate and nature of adverse events and protocol violations |
| Proportion of the women eligible to HPV screening who were actually screened and treated (if required) | Day 0 | Proportion of the women eligible for the study who were actually screened, treated (if required) |
| Evaluation of the micro-costing | Day 0 up to Week 26 | Evaluation of the micro-costing of the various components of the screening strategies |
| Evaluation of post-treatment HPV clearance | Week 24 and 48 post treatment | Evaluation of the HPV clearance at M6 and M12 after thermal-ablation |
| Evaluation of post-treatment cervical lesion | Week 48 post treatment | Evaluation of the proportion of CIN2 and CIN3 at M12 after treatment |
Countries
Burkina Faso, Cambodia, Côte d’Ivoire
Contacts
Primary ContactPierre Debeaudrap, PhD
Backup ContactApollinaire Horo, PhD
Outcome results
None listed