Digital Telecytology for Triage of HPV-Positive Women in Cameroon

Evaluation of Digital Cytology for the Triage of HPV-positive Women in a Same-day "Test-triage-treat" Cervical Cancer Screening Strategy in Cameroon

This study evaluates the diagnostic accuracy and feasibility of a same-day cervical cancer screening strategy using HPV self-sampling followed by digital telecytology triage among HPV-positive women in Cameroon. Women aged 30-49 years (or 25-49 years if HIV-positive) will undergo primary HPV testing using the GeneXpert system. HPV-positive women will be managed according to an extended HPV genotyping-based algorithm, including immediate treatment, telecytology triage, or follow-up. Histological assessment serves as the reference standard for the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Secondary objectives include evaluation of AI-assisted telecytology and visual inspection with acetic acid (VIA), as well as the acceptability of screening and treatment strategies among women and healthcare providers. The study aims to generate evidence to support scalable, WHO-recommended test-triage-treat approaches in low-resource settings

This study is a prospective, single-center diagnostic accuracy and feasibility study conducted at the Yaoundé University Hospital in Cameroon. It evaluates a same-day cervical cancer screening strategy based on primary HPV testing with self-sampling, followed by triage using extended HPV genotyping and digital telecytology among HPV-positive women, within a test-triage-treat approach.

Women aged 30 to 49 years, and HIV-positive women aged 25 to 49 years, will be invited to participate following community-based awareness activities and hospital-based recruitment. After providing written informed consent, participants will perform HPV self-sampling. Primary screening will be conducted using the GeneXpert system, which provides rapid detection and genotyping of oncogenic HPV types.

Management of HPV-positive women will follow a predefined algorithm based on extended HPV genotyping. Women positive for HPV type 16 will be considered for immediate treatment following clinical assessment. Women positive for HPV types 18, 45, 31, 33, 35, 52, or 58 will undergo same-day triage using digital telecytology. Women positive for HPV types 51, 59, 39, 56, 66, or 68 will be scheduled for follow-up without immediate treatment unless clinically indicated.

For triage procedures, all HPV-positive women will undergo visual inspection with acetic acid (VIA), cervical cytology, and endocervical sampling, with either a VIA-directed biopsy or a random biopsy of the transformation zone, as appropriate. Cytology slides will be prepared locally and digitized for remote interpretation by trained cytopathologists. Women with cytological abnormalities of atypical squamous cells of undetermined significance (ASC-US) or worse will be offered same-day treatment with thermal ablation. Histological assessment of endocervical samples and biopsies will serve as the reference standard for the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+).

Artificial intelligence-assisted telecytology and AI-assisted VIA will be evaluated as secondary diagnostic tools. These AI-based analyses will not be used for clinical decision-making but will be assessed retrospectively to determine their diagnostic performance and concordance with standard interpretation.

Eligible women diagnosed with CIN2+ will be offered treatment, if not already performed, primarily with thermal ablation, in accordance with World Health Organization eligibility criteria and local standards of care. Women with suspected invasive cancer will be referred for further diagnostic evaluation and appropriate management.

Participants who receive treatment will be followed by telephone at 4 to 6 weeks to assess adverse events and acceptability. All HPV-positive women will be invited for a follow-up visit at 12 months, including repeat HPV testing and additional examinations as clinically indicated. Acceptability of screening and treatment strategies will be assessed among participants and healthcare providers using standardized questionnaires.

The study aims to assess the diagnostic accuracy, feasibility, and acceptability of a scalable, same-day HPV-based cervical cancer screening strategy incorporating digital telecytology and artificial intelligence in a low-resource setting.

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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.