HPV Screening With Triage by HPV Genotyping Versus Visual Inspection With Acetic Acid

NCT05385406 | Recruiting DMC

• 1 other identifier: AO_2021-00066
• Study Type: interventional
• Target: 5,500
• Locations: 1 country
• Sites: 2

Brief Summary

Cervical cancer is the leading cause of cancer death among women in sub-Saharan Africa, despite the existence of effective prevention and screening methods. Because vaccination rates against human papillomavirus (causing nearly all cervical cancers) are still insufficient in some low-resource countries, early detection and treatment of cervical lesions at risk of progressing to cancer are crucial components of cervical cancer control. Therefore, it is essential to find the most reliable and appropriate screening strategy in the context of low-resource countries in order to identify women in need of treatment and thus prevent the development of cervical cancer. The objective of our study is to compare two different methods of cervical cancer screening adapted to low-resource settings, in two study centers in Cameroon.

Conditions

Cervical Cancer

Keywords

cervical cancer; human papillomavirus; screening; genotyping

Outcome Measures

Primary Outcomes (1)

• Sensitivity of triage by HPV genotyping and VIA/VILI for cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) detection

  Sensitivity of triage by HPV genotyping and VIA/VILI for cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) detection at time of screening (first visit), considering histologic results (from cervical biopsy and/or endocervical brushing) as the gold-standard.

  2 years

Secondary Outcomes (9)

• Specificity, positive predictive value and negative predictive value of triage by HPV genotyping and VIA/VILI for cervical intraepithelial neoplasia

  2 years

• Percentage of participants who have correctly followed the screening, triage and treatment strategy in each study arm

  2 years

• Overtreatment rate in each screening group

  2.5 years

• Proportion of adverse events in each screening group

  2.5 years

• Participant characteristics associated with better prediction of CIN2+ for each screening group

  2 years

Study Arms (2)

Triage by genotyping

EXPERIMENTAL

The study intervention will consist in applying HPV genotyping as a triage method of HPV-positive women for cervical cancer screening. After primary screening with the Xpert HPV test, positive women will be sorted according to two groups of genotypes: group 1 (HPV types 16,18,45, 31, 33, 35, 52 and/or 58 obtained from channels 1, 2 and 3) and group 2 (HPV types 51, 59, 39,56, 66 and/or 68 obtained from channels 4 and 5). Women of group 1 will immediately treated, while those of group 2 will not receive immediate treatment and will be followed-up at 12 months. An exception will be made for participants with lesions suspicious of invasive cancer upon examination, which will be referred for further investigations regardless of the HPV type.

Diagnostic Test: HPV genotyping

Triage by visual inspection after application of acetic acid (VIA)

ACTIVE COMPARATOR

The control arm will consist in triage of HPV-positive women by VIA, as currently recommended by the WHO. Women with a positive VIA will be treated immediately, while VIA-negative women will not be treated and will be followed-up at 12 months.

Diagnostic Test: Visual inspection after application of acetic acid

Interventions

HPV genotyping DIAGNOSTIC_TEST

Genotyping will be obtained by the Xpert system which uses 5 color channels containing primers and probes for the detection of specific genotypes or pooled results as follows: i) HPV 16, ii) HPV 18/45 in pooled result, iii) HPV types 31, 33, 35 52, or 58, in pooled result, iv) HPV types 51 or 59, in pooled result, and v) HPV types 39, 56, 66 or 68 in pooled result.

Also known as: HPV GeneXpert

Triage by genotyping

Visual inspection after application of acetic acid DIAGNOSTIC_TEST

After application of acetic acid and Lugol's iodine, the cervix will be assessed using simplified "ABCD criteria" (A= acetowhite lesion within the transformation zone, B = spontaneous bleeding or upon slight touch, C (optional) = Lugol-positive coloring of acetowhite lesions, D = diameter \> 5mm of acetowhite lesion).

Also known as: VIA

Triage by visual inspection after application of acetic acid (VIA)

Eligibility Criteria

• Age: 25 Years - 49 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• HIV-negative women aged 30-49 and HIV-positive women aged 25-49 years old
• Ability to understand study procedures and accepting voluntarily to participate by signing an informed consent form (ICF).

You may not qualify if:

• Pregnancy at the time of screening
• Previous hysterectomy
• Known cervical cancer
• Symptoms of cervical cancer (e.g. metrorrhagia, known pelvic mass)
• Conditions that can interfere with visualization of the cervix
• Severe pre-existing medical conditions (e.g. advanced cancer, terminal renal failure)
• Women who are not able to comply with the study protocol.

Sponsors & Collaborators

• Prof. Patrick Petignat: lead
• University Hospital, Geneva: collaborator
• Bafoussam Regional Hospital, Cameroon: collaborator
• Dschang District Hospital, Cameroon: collaborator
• University of Dschang: collaborator

Study Sites (2)

Dschang Annex Regional Hospital

Dschang, Menoua, Cameroon

RECRUITING

Bafoussam Regional Hospital

Bafoussam, Mifi, Cameroon

NOT YET RECRUITING

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Patrick Petignat, PD

  University Hospital, Geneva

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patrick Petignat, PD

CONTACT

22 37 24 432; patrick.petignat@hcuge.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Allocation to the study arm will be concealed until primary HPV screening by the GeneXpert machine has been performed, in order to ensure that the health care provider enrolling the participant into the study and the participant herself have no a priori knowledge of group assignment. Detected HPV genotypes will only be revealed to the midwife executing the pelvic examination and treatment if the participant is randomized in the intervention arm (triage by genotyping), in order to know whether to treat the participant or not. If the participant is randomized in the control arm (triage by VIA), the midwife will be blinded to the exact HPV genotype channel(s) in order to avoid influence of treatment. The pathologist performing histological analysis (gold standard) will be blinded to the study arm and the on-site diagnosis.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: National multicentric open-label two-arm randomized controlled trial

Study Record Dates

• First Submitted: December 7, 2021
• First Posted: May 23, 2022
• Study Start: December 6, 2022
• Primary Completion: June 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: May 9, 2024

Record last verified: 2024-05

Locations

CA (2)