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

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

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.

Study Overview

• Status: Recruiting
• Conditions: HIV Infections; HPV - Anogenital Human Papilloma Virus Infection
• Intervention / Treatment: Diagnostic test: HPV test with partial genotyping and VIA triage

• Study Type: Interventional
• Enrollment (Anticipated): 3000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pierre Debeaudrap, PhD; Phone Number: +33 (0) 1 76 53 34 53; Email: pierre.debeaudrap@ird.fr
• Study Contact Backup: Name: Apollinaire Horo, PhD; Email: horoapollinaire@gmail.com

Study Locations

• Burkina Faso
  • Bobo-Dioulasso, Burkina Faso
    • Recruiting
    • HIV day care center
    • Contact: Armel Poda
• Cambodia
  • Phnom Penh, Cambodia
    • Recruiting
    • Calmette Hospital
    • Contact: Kim Sothea
• Côte D'Ivoire
  • Abidjan, Côte D'Ivoire
    • Enrolling by invitation
    • CEPREF

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 49 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SCREENING
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Triage with different options; 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; HPV testing with the GenXpert platform VIA Biopsies of VIA+ lesions or random Treatment with thermal ablation of women with precancerous lesions

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Collaborators: University Hospital, Geneva; University of Bordeaux; International Agency for Research on Cancer; Institut de Recherche pour le Developpement; Programme PAC-CI, Site ANRS-MIE de Côte d'Ivoire
• Investigators: Study Director: Pierre Debeaudrap, PhD, CEPED - UMR196; Study Director: Apollinaire Debeaudrap, PhD, PACCI - Ivory Coast

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2019
• Primary Completion (ANTICIPATED): September 1, 2022
• Study Completion (ANTICIPATED): September 1, 2022

Study Registration Dates

• First Submitted: September 3, 2018
• First Submitted That Met QC Criteria: December 27, 2018
• First Posted (ACTUAL): December 28, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 16, 2022
• Last Update Submitted That Met QC Criteria: February 15, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: recurrence; HIV infection, HPV infection, cervical cancer, screening algorithms
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Disease Attributes; DNA Virus Infections; Tumor Virus Infections; Neoplasms, Squamous Cell; HIV Infections; Uterine Cervical Neoplasms; Infections; Communicable Diseases; Papillomavirus Infections; Papilloma
• Other Study ID Numbers: ANRS12375 AIMA-CC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No