Screening Test Accuracy of Gynocular™, HR-HPV Testing, VIA for Detection of Cervical Neoplastic Lesions, in Women Living With HIV

• Conditions: Uterine Cervical Neoplasms; HIV/AIDS

• Registration Number: NCT03931083
• Lead Sponsor: University of Bern

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.

Study Timeline

• Study First Submitted: 2019-04-15
• Study First Submitted QC: 2019-04-24
• Study First Posted: 2019-04-30
• Study Start: 2019-05-08
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-30
• Last Update Posted: 2020-11-03
• Primary Completion: 2021-01-01
• Study Completion: 2022-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 450

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Test accuracy (sensitivity, specificity) of the Gynocular™ when used as stand-alone tests to detect CIN2+	6 months	To estimate the sensitivity and specificity of the Gynocular when used as a standalone tests to detect CIN2+ among WLHIV.
Test accuracy (sensitivity, specificity) of HR-HPV when used as stand-alone tests to detect CIN2+	6 months	To estimate the sensitivity and specificity of HR-HPV when used as a standalone tests to detect CIN2+ among WLHIV.
Test accuracy (sensitivity, specificity) of VIA when used as stand-alone tests to detect CIN2+	6 months	To estimate the sensitivity and specificity of VIA when used as a standalone tests to detect CIN2+ among WLHIV.

Secondary Outcome Measures

Name	Time	Method
Diagnostic test accuracy of the Gynocular™to detect CIN2+/HSIL: other estimates, stand alone	6 months	To determine other estimates of test accuracy of the Gynocular™ (including positive and negative predictive values, positive and negative likelihood ratios, false positive rate, false negative rate, number needed to screen and area under the ROC curve (AUC).
Diagnostic test accuracy of HR-HPV testing followed by Gynocular™ to detect CIN2+/HSIL: test combination	6 months	To determine estimates of test accuracy for combinations of screening tests, i.e. HR-HPV followed by Gynocular™
Diagnostic test accuracy of the Gynocular™ followed by HR-HPV testing to detect CIN2+/HSIL: test combination subgroup analyses	6 months	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
Diagnostic test accuracy VIA followed by Gynocular™ to detect CIN2+/HSIL: test combination	6 months	To determine estimates of test accuracy for combinations of screening tests, i.e. VIA followed by Gynocular™
Investigations to inform telemedicine capacity: Comparison of image quality	6 months	Description of image quality from static assessors, in terms of the assessors' ability to adequately evaluate the images.
Investigations to inform telemedicine capacity: use of static images	6 months	Proportion of correctly diagnosed CIN2+ through static images obtained by the Gynocular™.
Diagnostic test accuracy of HR-HPV testing followed by AI tool to detect CIN2+/HSIL: test combination	6 months	To determine estimates of test accuracy for combinations of screening tests, i.e. HR-HPV followed by AI tool
Diagnostic test accuracy of HR-HPV testing to detect CIN2+/HSIL: other estimates, stand alone	6 months	To determine other estimates of HR-HPV testing test accuracy (including positive and negative predictive values, positive and negative likelihood ratios, false positive rate, false negative rate, number needed to screen and area under the ROC curve (AUC).
Diagnostic test accuracy of VIA to detect CIN2+/HSIL: other estimates, stand alone	6 months	To determine other estimates of VIA test accuracy (including positive and negative predictive values, positive and negative likelihood ratios, false positive rate, false negative rate, number needed to screen and area under the ROC curve (AUC).
Diagnostic test accuracy of HR-HPV testing followed by Gynocular™ to detect CIN2+/HSIL: test combination - subgroup analyses	6 months	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
Diagnostic test accuracy of the Gynocular™ followed by HR-HPV testing to detect CIN2+/HSIL: test combination	6 months	To determine estimates of test accuracy for combinations of screening tests, i.e. Gynocular™ followed by HR-HPV
Diagnostic test accuracy of the Gynocular™ followed by VIA to detect CIN2+/HSIL: test combination	6 months	To determine estimates of test accuracy for combinations of screening tests, i.e. Gynocular™ followed by VIA
Diagnostic test accuracy of the HR-HPV followed by VIA to detect CIN2+/HSIL: test combination	6 months	To determine estimates of test accuracy for combinations of screening tests: HR-HPV followed by VIA.
Subgroup analyses for the diagnostic test accuracy of HR-HPV testing: stand alone test	6 months	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
Subgroup analyses for the diagnostic test accuracy of VIA, HR-HPV testing and Gynocular™: Combined tests	6 months	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
Investigation of Swede Score in WLHIV	6 months	Area under the receiver operating characteristic (ROC) curve for Swede score determined by Gynocular™ in WLHIV
Investigation of co-infections of premalignant and malignant disease (STIs/HR-HPV)	6 months	Descriptive analysis of the STI and HR-HPV type distribution associated with each stage of CIN, and when there is persistent disease in WLHIV.
Diagnostic test accuracy VIA followed by Gynocular™ to detect CIN2+/HSIL: test combination - subgroup analyses	6 months	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
Diagnostic test accuracy of the HR-HPV followed by VIA to detect CIN2+/HSIL: test combination - subgroup analyses	6 months	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
Diagnostic test accuracy of the VIA followed by HR-HPV to detect CIN2+/HSIL: test combination	6 months	To determine estimates of test accuracy for combinations of screening tests: VIA followed by HR-HPV.
Diagnostic test accuracy of the VIA followed by HR-HPV to detect CIN2+/HSIL: test combination subgroup analyses	6 months	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
Diagnostic test accuracy of the Gynocular™ followed by VIA to detect CIN2+/HSIL: test combination - subgroup analyses	6 months	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses
Subgroup analyses for the diagnostic test accuracy of Gynocular™: stand alone test	6 months	To investigate the effects of a age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses.
Investigation of Trichomonas vaginalis prevalence and persistence in association with menstrual hygiene practices	6 months	Descriptive analysis of the prevalence and persistence of Trichomonas vaginalis in association with vaginal and menstrual hygiene practices.
Subgroup analyses for the diagnostic test accuracy of VIA: stand alone test	6 months	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses.
Investigations to inform telemedicine capacity: ROC curve for Swede score	6 months	Area under the ROC for static image Swede score obtained by Gynocular™ in WLHIV.
Artificial Intelligence (AI) for improving the detection of precancerous cervical lesions: testing AI algorithm	6 months	Test accuracies of AI deep learning tool retrospectively using coded images obtained in the study through the Gynocular™ and smartphone.
Artificial Intelligence for improving the detection of precancerous cervical lesions: improve AI algorithm	6 months	Inform and improve AI deep learning tools to detect HSIL by using images or GIFs obtained in the study through the Gynocular™ and smartphone.
Diagnostic test accuracy of AI tool to detect CIN2+/HSIL: other estimates, stand alone	6 months	To estimate the sensitivity and specificity of HR-HPV when used as a standalone tests to detect CIN2+/HSIL among WLHIV.
Investigations to inform telemedicine capacity: Live versus static assessors	6 months	Cohen's kappa coefficient to assess agreement between live and static assessors.

Trial Locations

Locations (1)

Centre for Infectious Disease Research in Zambia; 🇿🇲 Lusaka, Zambia