Clinical trial NCT03931083: Screening Test Accuracy of Gynocular™, HR-HPV Testing, VIA for Detection of Cervical Neoplastic Lesions, in Women Living With HIV
Official title: Screening Test Accuracy of a Gynocular™, HR-HPV Testing, and VIA for Detection of Cervical Intraepithelial Neoplasia, Grade Two and Above, in Women Living With HIV in Lusaka, Zambia
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Uterine Cervical Neoplasms
HIV/AIDS
Lead sponsor: University of Bern
Sponsor class: OTHER
Collaborators: name: Centre for Infectious Disease Research in Zambia
name: Cervical Cancer Prevention Program in Zambia
name: International Agency for Research on Cancer
First posted: 2019-04-30
Enrollment: 450
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population includes women who are enrolled in the ART program at Kanyama Clinic, Lusaka, Zambia. Kanyama Clinic is situated on the western side of the central business district, 3km away from the town centre. It has a catchment population of 262,715. It has registered 52,658 people living with HIV, of which 40,650 have commenced treatment. In addition to ART services, the clinic has also been providing cervical cancer screening since October 2006. The clinic is well established in the application of cancer screening based on a "screen-and-treat" approach, where women undergo visual screening, followed by immediate treatment where possible. Since inception in 2006, the clinic has screened over 23,900 women for cervical cancer. Clinic nurses are trained to offer cervical cancer screening and treatment with cryotherapy or thermal coagulation and to refer suspicious cases for LEEP and further treatment.

Brief summary: Cervical cancer in HIV-positive women is largely preventable through regular screening. The World Health Organization (WHO) recommends cervical screening for HIV-positive women every three years. Currently the least costly method for screening and the most viable option for many countries is visual inspection after application of acetic acid (VIA). Alternative testing methods are HPV testing and assessment with a portable magnification device. The investigators plan to assess and compare the screening test accuracy of these screening tests in women living with HIV. All women will receive histopathology reference standard.

Detailed description: The simplest and least costly method for cervical cancer screening is visual inspection after application of acetic acid (VIA). However, the ability of this screening method to correctly identify precancerous lesions (sensitivity) and women free from these lesions (specificity) is limited. The investigators aim to identify alternative screening methods which maximize sensitivity and specificity, particularly in HIV-infected women in receiving care in Southern Africa. The investigators will evaluate the screening test accuracy of a new portable magnification device , the Gynocular™ with Swede score assessment, in women who are HIV-positive and eligible for cervical cancer screening. The investigators will assess the accuracy of the device when used as a stand alone test, as well as when used subsequent to positive VIA or HPV tests. The investigators will make comparisons with current screening practices (VIA alone), as well as, recommended screening practices (HPV testing). The investigators will enrol 450 HIV-positive women receiving care for HIV/AIDS at the Centre for Infectious Disease Research in Zambia, in Lusaka, Zambia. Consenting women will be screened with VIA, HPV testing and visual assessment with Gynocular™. All women undergo biopsy (reference standard) and receive treatment as indicated and in accordance with national guidelines.

Eligibility criteria: Inclusion Criteria:

1. HIV-infected women confirmed through medical records
2. Women residing within Lusaka district and plans to stay in this area for the next 6 months
3. Women between 18 and 65 years of age (age bracket as per Zambian guidelines for cervical cancer screening)
4. Able and willing to consent
5. Willing to undergo a pelvic examination and cancer screening
6. Has had sexual intercourse before
7. Agrees to have follow-up appointment in 6 months

Exclusion Criteria:

1. Women with a history of cervical cancer or previous hysterectomy (where the cervix was also removed)
2. Pregnant women or women who plan to get pregnant within the next 6 months
3. Women who have been vaccinated against HR-HPV

Primary outcomes:
measure: Test accuracy (sensitivity, specificity) of the Gynocular™ when used as stand-alone tests to detect CIN2+
timeFrame: 6 months
measure: Test accuracy (sensitivity, specificity) of HR-HPV when used as stand-alone tests to detect CIN2+
timeFrame: 6 months
measure: Test accuracy (sensitivity, specificity) of VIA when used as stand-alone tests to detect CIN2+
timeFrame: 6 months
Secondary outcomes:
measure: Diagnostic test accuracy of the Gynocular™to detect CIN2+/HSIL: other estimates, stand alone
timeFrame: 6 months
measure: Diagnostic test accuracy of HR-HPV testing to detect CIN2+/HSIL: other estimates, stand alone
timeFrame: 6 months
measure: Diagnostic test accuracy of VIA to detect CIN2+/HSIL: other estimates, stand alone
timeFrame: 6 months
measure: Diagnostic test accuracy of HR-HPV testing followed by Gynocular™ to detect CIN2+/HSIL: test combination
timeFrame: 6 months
measure: Diagnostic test accuracy of HR-HPV testing followed by Gynocular™ to detect CIN2+/HSIL: test combination - subgroup analyses
timeFrame: 6 months
measure: Diagnostic test accuracy of the Gynocular™ followed by HR-HPV testing to detect CIN2+/HSIL: test combination
timeFrame: 6 months
measure: Diagnostic test accuracy of the Gynocular™ followed by HR-HPV testing to detect CIN2+/HSIL: test combination subgroup analyses
timeFrame: 6 months
measure: Diagnostic test accuracy VIA followed by Gynocular™ to detect CIN2+/HSIL: test combination
timeFrame: 6 months
measure: Diagnostic test accuracy VIA followed by Gynocular™ to detect CIN2+/HSIL: test combination - subgroup analyses
timeFrame: 6 months
measure: Diagnostic test accuracy of the Gynocular™ followed by VIA to detect CIN2+/HSIL: test combination
timeFrame: 6 months
measure: Diagnostic test accuracy of the Gynocular™ followed by VIA to detect CIN2+/HSIL: test combination - subgroup analyses
timeFrame: 6 months
measure: Diagnostic test accuracy of the HR-HPV followed by VIA to detect CIN2+/HSIL: test combination
timeFrame: 6 months
measure: Diagnostic test accuracy of the HR-HPV followed by VIA to detect CIN2+/HSIL: test combination - subgroup analyses
timeFrame: 6 months
measure: Diagnostic test accuracy of the VIA followed by HR-HPV to detect CIN2+/HSIL: test combination
timeFrame: 6 months
measure: Diagnostic test accuracy of the VIA followed by HR-HPV to detect CIN2+/HSIL: test combination subgroup analyses
timeFrame: 6 months
measure: Subgroup analyses for the diagnostic test accuracy of Gynocular™: stand alone test
timeFrame: 6 months
measure: Subgroup analyses for the diagnostic test accuracy of VIA: stand alone test
timeFrame: 6 months
measure: Subgroup analyses for the diagnostic test accuracy of HR-HPV testing: stand alone test
timeFrame: 6 months
measure: Subgroup analyses for the diagnostic test accuracy of VIA, HR-HPV testing and Gynocular™: Combined tests
timeFrame: 6 months
measure: Investigation of Swede Score in WLHIV
timeFrame: 6 months
measure: Investigation of co-infections of premalignant and malignant disease (STIs/HR-HPV)
timeFrame: 6 months
measure: Investigation of Trichomonas vaginalis prevalence and persistence in association with menstrual hygiene practices
timeFrame: 6 months
measure: Investigations to inform telemedicine capacity: Comparison of image quality
timeFrame: 6 months
measure: Investigations to inform telemedicine capacity: use of static images
timeFrame: 6 months
measure: Investigations to inform telemedicine capacity: ROC curve for Swede score
timeFrame: 6 months
measure: Investigations to inform telemedicine capacity: Live versus static assessors
timeFrame: 6 months
measure: Artificial Intelligence (AI) for improving the detection of precancerous cervical lesions: testing AI algorithm
timeFrame: 6 months
measure: Artificial Intelligence for improving the detection of precancerous cervical lesions: improve AI algorithm
timeFrame: 6 months
measure: Diagnostic test accuracy of AI tool to detect CIN2+/HSIL: other estimates, stand alone
timeFrame: 6 months
measure: Diagnostic test accuracy of HR-HPV testing followed by AI tool to detect CIN2+/HSIL: test combination
timeFrame: 6 months
Other outcomes:
measure: Safety outcomes: For each adverse event found the investigators will calculate crude frequencies
timeFrame: 9 months
Locations:
city: Lusaka
country: Zambia
facility: Centre for Infectious Disease Research in Zambia
Study officials:
affiliation: julia.bohlius@ispm.unibe.ch
name: Julia Bohlius, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Taghavi K, Moono M, Mwanahamuntu M, Basu P, Limacher A, Tembo T, Kapesa H, Hamusonde K, Asangbeh S, Sznitman R, Low N, Manasyan A, Bohlius J. Screening test accuracy to improve detection of precancerous lesions of the cervix in women living with HIV: a study protocol. BMJ Open. 2020 Dec 18;10(12):e037955. doi: 10.1136/bmjopen-2020-037955.