Screening Study for Cervical Pre-cancer and Cancer Prevention in South African Women. (DiaVACCS)

Primary HPV Screening as an Indicator of Cervical Pre-invasive and Invasive Neoplasia in HIV-positive and -Negative Southern African Women

Nearly 8 000 new cervical cancer cases are diagnosed in South Africa per year; many are still undiagnosed and about 50% of diagnosed cases succumb per year. Although the current prevalence of pre-cancer cervical disease is largely unknown, data from local studies suggest regional differences and an increase in the prevalence of cytological abnormalities when compared with historical data. Low frequency in cytology screening is the primary factor attributable to development of invasive cervical cancer and almost one-third of all cervical cancer patients had previous negative cytology. Due to the low sensitivity of cytology it can be assumed that the true prevalence of pre-cancer disease is underestimated by all available data. One round of optimal cervical cytology will detect around 50% of existing pre-cancer cervical disease as identified and proven using colposcopy and directed biopsy. It is now widely accepted that primary screening with a human papilloma virus (HPV) test can improve the sensitivity of screening and that even a single round of HPV screening can rapidly reduce the incidence of invasive cervical cancer and related mortality within a few years.

South Africa has a high prevalence of HIV infection and a delay in or failure to initiate antiretroviral therapy (ART). These facts, together with the largely unscreened status of the female population and the high incidence of cervical cancer all suggest that HPV infection and precursors to cervical cancer are both unusually common among South African women. Accurate current knowledge of the performance of newer generation HPV based screening tests in HIV-infected and general female population are essential for cost-analysis and planning for national prevention and screening programs. This study will aim to demonstrate the feasibility and efficacy of new generation HPV deoxyribonucleic acid (DNA) based screening assays in a South African setting.

The investigators hypothesize that HPV testing followed by normal and special cytology tests will be a successful screening model for a South African population.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer; CIN2; High Grade Sil
• Intervention / Treatment: Other: Screening; Other: Colposcopy; Procedure: LLETZ

• Study Type: Observational
• Enrollment (Anticipated): 1500

Contacts and Locations

• Study Contact: Name: Greta Dreyer, PhD; Phone Number: +(27) 12 354 3900; Email: greta.dreyer@up.ac.za
• Study Contact Backup: Name: Cathy Visser, MSc; Phone Number: +(27) 12 354 3900; Email: cathy.visser@up.ac.za

Study Locations

• South Africa
  • Gauteng
    • Pretoria, Gauteng, South Africa
      • Recruiting
      • Steve Biko Academic Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

This is a multicentric study carried out in South Africa. Women with unknown HIV status will be recruited from the general population, and HIV positive women from adult antiretroviral treatment (ART) clinics.

Description

Inclusion Criteria:

• Informed consent accepted and signed
• Health seeking behaviour or request for a cervical cancer screening test
• Willing and able to receive test result by automated text message or clinic visit

Exclusion Criteria:

• Current pregnancy
• Hysterectomy
• Current or previous treatment for gynaecological cancer
• Hesitant or unable to undergo screening and treatment if indicated

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HIV pos; those who serologically tested positive for HIV	Other: Screening; Cervical specimen obtained using speculum examination and cervical collection bush.; Other: Colposcopy; Vaginal speculum examination followed by application of 2% acetic acid and lugol's iodine with inspection with colposcope and punch biopsies taken of abnormal areas.; Procedure: LLETZ; The above (see colposcopy) is followed by local anaesthetic with two dentist's ampoules of lignocaine and large loop excision using coagulation of the abnormal area (usually 2 x 3 x 1 cm).
HIV neg; those who serologically tested negative for HIV	Other: Screening; Cervical specimen obtained using speculum examination and cervical collection bush.; Other: Colposcopy; Vaginal speculum examination followed by application of 2% acetic acid and lugol's iodine with inspection with colposcope and punch biopsies taken of abnormal areas.; Procedure: LLETZ; The above (see colposcopy) is followed by local anaesthetic with two dentist's ampoules of lignocaine and large loop excision using coagulation of the abnormal area (usually 2 x 3 x 1 cm).
HIV unk; those with no available serological test for HIV	Other: Screening; Cervical specimen obtained using speculum examination and cervical collection bush.; Other: Colposcopy; Vaginal speculum examination followed by application of 2% acetic acid and lugol's iodine with inspection with colposcope and punch biopsies taken of abnormal areas.; Procedure: LLETZ; The above (see colposcopy) is followed by local anaesthetic with two dentist's ampoules of lignocaine and large loop excision using coagulation of the abnormal area (usually 2 x 3 x 1 cm).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of women with histologically proven cervical intraepithelial neoplasia grade 2+ (CIN2+) detected using HPV DNA analysis with partial genotyping as primary screen test followed by cervical cytology and immunocytochemistry as triage tests	Detected on histology biopsy at colposcopy after initial HPV screening with simultaneous cytology and immunocytochemistry testing

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of women with CIN2+ detected using HPV DNA analysis with partial genotyping that is associated with HPV types 16, 18, 16 and/or 18, only other high risk types	Detected on histology biopsy at colposcopy after initial HPV screening with simultaneous cytology and immunocytochemistry testing

Collaborators and Investigators

• Sponsor: University of Pretoria
• Collaborators: University of Stellenbosch
• Investigators: Principal Investigator: Greta D Dreyer, PhD, University of Pretoria

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Anticipated): December 1, 2038
• Study Completion (Anticipated): December 1, 2038

Study Registration Dates

• First Submitted: November 2, 2016
• First Submitted That Met QC Criteria: November 3, 2016
• First Posted (Estimate): November 4, 2016

Study Record Updates

• Last Update Posted (Actual): March 17, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: immunocytochemistry; cervical cancer; HPV testing; cervical screening; cancer prevention; cervical disease; cervical neoplasm; triage techniques
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms
• Other Study ID Numbers: DiaVACCS