Diagnostic accuracy of cervical cancer screening and screening-triage strategies among women living with HIV-1 in Burkina Faso and South Africa: A cohort study.

<h4>Background</h4>Cervical cancer screening strategies using visual inspection or cytology may have suboptimal diagnostic accuracy for detection of precancer in women living with HIV (WLHIV). The optimal screen and screen-triage strategy, age to initiate, and frequency of screening for...

Full description

Bibliographic Details
Main Authors: Helen A Kelly, Admire Chikandiwa, Bernard Sawadogo, Clare Gilham, Pamela Michelow, Olga Goumbri Lompo, Tanvier Omar, Souleymane Zan, Precious Magooa, Michel Segondy, Nicolas Nagot, Nicolas Meda, Sinead Delany-Moretlwe, Philippe Mayaud, HARP Study Group
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-03-01
Series:PLoS Medicine
Online Access:https://doi.org/10.1371/journal.pmed.1003528
_version_ 1818835437940113408
author Helen A Kelly
Admire Chikandiwa
Bernard Sawadogo
Clare Gilham
Pamela Michelow
Olga Goumbri Lompo
Tanvier Omar
Souleymane Zan
Precious Magooa
Michel Segondy
Nicolas Nagot
Nicolas Meda
Sinead Delany-Moretlwe
Philippe Mayaud
HARP Study Group
author_facet Helen A Kelly
Admire Chikandiwa
Bernard Sawadogo
Clare Gilham
Pamela Michelow
Olga Goumbri Lompo
Tanvier Omar
Souleymane Zan
Precious Magooa
Michel Segondy
Nicolas Nagot
Nicolas Meda
Sinead Delany-Moretlwe
Philippe Mayaud
HARP Study Group
author_sort Helen A Kelly
collection DOAJ
description <h4>Background</h4>Cervical cancer screening strategies using visual inspection or cytology may have suboptimal diagnostic accuracy for detection of precancer in women living with HIV (WLHIV). The optimal screen and screen-triage strategy, age to initiate, and frequency of screening for WLHIV remain unclear. This study evaluated the sensitivity, specificity, and positive predictive value of different cervical cancer strategies in WLHIV in Africa.<h4>Methods and findings</h4>WLHIV aged 25-50 years attending HIV treatment centres in Burkina Faso (BF) and South Africa (SA) from 5 December 2011 to 30 October 2012 were enrolled in a prospective evaluation study of visual inspection using acetic acid (VIA) or visual inspection using Lugol's iodine (VILI), high-risk human papillomavirus DNA test (Hybrid Capture 2 [HC2] or careHPV), and cytology for histology-verified high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) at baseline and endline, a median 16 months later. Among 1,238 women (BF: 615; SA: 623), median age was 36 and 34 years (p < 0.001), 28.6% and 49.6% ever had prior cervical cancer screening (p < 0.001), and 69.9% and 64.2% were taking ART at enrolment (p = 0.045) in BF and SA, respectively. CIN2+ prevalence was 5.8% and 22.4% in BF and SA (p < 0.001), respectively. VIA had low sensitivity for CIN2+ (44.7%, 95% confidence interval [CI] 36.9%-52.7%) and CIN3+ (56.1%, 95% CI 43.3%-68.3%) in both countries, with specificity for ≤CIN1 of 78.7% (95% CI 76.0%-81.3%). HC2 had sensitivity of 88.8% (95% CI 82.9%-93.2%) for CIN2+ and 86.4% (95% CI 75.7%-93.6%) for CIN3+. Specificity for ≤CIN1 was 55.4% (95% CI 52.2%-58.6%), and screen positivity was 51.3%. Specificity was higher with a restricted genotype (HPV16/18/31/33/35/45/52/58) approach (73.5%, 95% CI 70.6%-76.2%), with lower screen positivity (33.7%), although there was lower sensitivity for CIN3+ (77.3%, 95% CI 65.3%-86.7%). In BF, HC2 was more sensitive for CIN2+/CIN3+ compared to VIA/VILI (relative sensitivity for CIN2+ = 1.72, 95% CI 1.28-2.32; CIN3+: 1.18, 95% CI 0.94-1.49). Triage of HC2-positive women with VIA/VILI reduced the number of colposcopy referrals, but with loss in sensitivity for CIN2+ (58.1%) but not for CIN3+ (84.6%). In SA, cytology high-grade squamous intraepithelial lesion or greater (HSIL+) had best combination of sensitivity (CIN2+: 70.1%, 95% CI 61.3%-77.9%; CIN3+: 80.8%, 95% CI 67.5%-90.4%) and specificity (81.6%, 95% CI 77.6%-85.1%). HC2 had similar sensitivity for CIN3+ (83.0%, 95% CI 70.2%-91.9%) but lower specificity compared to HSIL+ (42.7%, 95% CI 38.4%-47.1%; relative specificity = 0.57, 95% CI 0.52-0.63), resulting in almost twice as many referrals. Compared to HC2, triage of HC2-positive women with HSIL+ resulted in a 40% reduction in colposcopy referrals but was associated with some loss in sensitivity. CIN2+ incidence over a median 16 months was highest among VIA baseline screen-negative women (2.2%, 95% CI 1.3%-3.7%) and women who were baseline double-negative with HC2 and VIA (2.1%, 95% CI 1.3%-3.5%) and lowest among HC2 baseline screen-negative women (0.5%, 95% CI 0.1%-1.8%). Limitations of our study are that WLHIV included in the study may not reflect a contemporary cohort of WLHIV initiating ART in the universal ART era and that we did not evaluate HPV tests available in study settings today.<h4>Conclusions</h4>In this cohort study among WLHIV in Africa, a human papillomavirus (HPV) test targeting 14 high-risk (HR) types had higher sensitivity to detect CIN2+ compared to visual inspection but had low specificity, although a restricted genotype approach targeting 8 HR types decreased the number of unnecessary colposcopy referrals. Cytology HSIL+ had optimal performance for CIN2+/CIN3+ detection in SA. Triage of HPV-positive women with HSIL+ maintained high specificity but with some loss in sensitivity compared to HC2 alone.
first_indexed 2024-12-19T02:50:42Z
format Article
id doaj.art-8bae79dbcf5a4fd3838bc9c871ea716e
institution Directory Open Access Journal
issn 1549-1277
1549-1676
language English
last_indexed 2024-12-19T02:50:42Z
publishDate 2021-03-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Medicine
spelling doaj.art-8bae79dbcf5a4fd3838bc9c871ea716e2022-12-21T20:38:39ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762021-03-01183e100352810.1371/journal.pmed.1003528Diagnostic accuracy of cervical cancer screening and screening-triage strategies among women living with HIV-1 in Burkina Faso and South Africa: A cohort study.Helen A KellyAdmire ChikandiwaBernard SawadogoClare GilhamPamela MichelowOlga Goumbri LompoTanvier OmarSouleymane ZanPrecious MagooaMichel SegondyNicolas NagotNicolas MedaSinead Delany-MoretlwePhilippe MayaudHARP Study Group<h4>Background</h4>Cervical cancer screening strategies using visual inspection or cytology may have suboptimal diagnostic accuracy for detection of precancer in women living with HIV (WLHIV). The optimal screen and screen-triage strategy, age to initiate, and frequency of screening for WLHIV remain unclear. This study evaluated the sensitivity, specificity, and positive predictive value of different cervical cancer strategies in WLHIV in Africa.<h4>Methods and findings</h4>WLHIV aged 25-50 years attending HIV treatment centres in Burkina Faso (BF) and South Africa (SA) from 5 December 2011 to 30 October 2012 were enrolled in a prospective evaluation study of visual inspection using acetic acid (VIA) or visual inspection using Lugol's iodine (VILI), high-risk human papillomavirus DNA test (Hybrid Capture 2 [HC2] or careHPV), and cytology for histology-verified high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) at baseline and endline, a median 16 months later. Among 1,238 women (BF: 615; SA: 623), median age was 36 and 34 years (p < 0.001), 28.6% and 49.6% ever had prior cervical cancer screening (p < 0.001), and 69.9% and 64.2% were taking ART at enrolment (p = 0.045) in BF and SA, respectively. CIN2+ prevalence was 5.8% and 22.4% in BF and SA (p < 0.001), respectively. VIA had low sensitivity for CIN2+ (44.7%, 95% confidence interval [CI] 36.9%-52.7%) and CIN3+ (56.1%, 95% CI 43.3%-68.3%) in both countries, with specificity for ≤CIN1 of 78.7% (95% CI 76.0%-81.3%). HC2 had sensitivity of 88.8% (95% CI 82.9%-93.2%) for CIN2+ and 86.4% (95% CI 75.7%-93.6%) for CIN3+. Specificity for ≤CIN1 was 55.4% (95% CI 52.2%-58.6%), and screen positivity was 51.3%. Specificity was higher with a restricted genotype (HPV16/18/31/33/35/45/52/58) approach (73.5%, 95% CI 70.6%-76.2%), with lower screen positivity (33.7%), although there was lower sensitivity for CIN3+ (77.3%, 95% CI 65.3%-86.7%). In BF, HC2 was more sensitive for CIN2+/CIN3+ compared to VIA/VILI (relative sensitivity for CIN2+ = 1.72, 95% CI 1.28-2.32; CIN3+: 1.18, 95% CI 0.94-1.49). Triage of HC2-positive women with VIA/VILI reduced the number of colposcopy referrals, but with loss in sensitivity for CIN2+ (58.1%) but not for CIN3+ (84.6%). In SA, cytology high-grade squamous intraepithelial lesion or greater (HSIL+) had best combination of sensitivity (CIN2+: 70.1%, 95% CI 61.3%-77.9%; CIN3+: 80.8%, 95% CI 67.5%-90.4%) and specificity (81.6%, 95% CI 77.6%-85.1%). HC2 had similar sensitivity for CIN3+ (83.0%, 95% CI 70.2%-91.9%) but lower specificity compared to HSIL+ (42.7%, 95% CI 38.4%-47.1%; relative specificity = 0.57, 95% CI 0.52-0.63), resulting in almost twice as many referrals. Compared to HC2, triage of HC2-positive women with HSIL+ resulted in a 40% reduction in colposcopy referrals but was associated with some loss in sensitivity. CIN2+ incidence over a median 16 months was highest among VIA baseline screen-negative women (2.2%, 95% CI 1.3%-3.7%) and women who were baseline double-negative with HC2 and VIA (2.1%, 95% CI 1.3%-3.5%) and lowest among HC2 baseline screen-negative women (0.5%, 95% CI 0.1%-1.8%). Limitations of our study are that WLHIV included in the study may not reflect a contemporary cohort of WLHIV initiating ART in the universal ART era and that we did not evaluate HPV tests available in study settings today.<h4>Conclusions</h4>In this cohort study among WLHIV in Africa, a human papillomavirus (HPV) test targeting 14 high-risk (HR) types had higher sensitivity to detect CIN2+ compared to visual inspection but had low specificity, although a restricted genotype approach targeting 8 HR types decreased the number of unnecessary colposcopy referrals. Cytology HSIL+ had optimal performance for CIN2+/CIN3+ detection in SA. Triage of HPV-positive women with HSIL+ maintained high specificity but with some loss in sensitivity compared to HC2 alone.https://doi.org/10.1371/journal.pmed.1003528
spellingShingle Helen A Kelly
Admire Chikandiwa
Bernard Sawadogo
Clare Gilham
Pamela Michelow
Olga Goumbri Lompo
Tanvier Omar
Souleymane Zan
Precious Magooa
Michel Segondy
Nicolas Nagot
Nicolas Meda
Sinead Delany-Moretlwe
Philippe Mayaud
HARP Study Group
Diagnostic accuracy of cervical cancer screening and screening-triage strategies among women living with HIV-1 in Burkina Faso and South Africa: A cohort study.
PLoS Medicine
title Diagnostic accuracy of cervical cancer screening and screening-triage strategies among women living with HIV-1 in Burkina Faso and South Africa: A cohort study.
title_full Diagnostic accuracy of cervical cancer screening and screening-triage strategies among women living with HIV-1 in Burkina Faso and South Africa: A cohort study.
title_fullStr Diagnostic accuracy of cervical cancer screening and screening-triage strategies among women living with HIV-1 in Burkina Faso and South Africa: A cohort study.
title_full_unstemmed Diagnostic accuracy of cervical cancer screening and screening-triage strategies among women living with HIV-1 in Burkina Faso and South Africa: A cohort study.
title_short Diagnostic accuracy of cervical cancer screening and screening-triage strategies among women living with HIV-1 in Burkina Faso and South Africa: A cohort study.
title_sort diagnostic accuracy of cervical cancer screening and screening triage strategies among women living with hiv 1 in burkina faso and south africa a cohort study
url https://doi.org/10.1371/journal.pmed.1003528
work_keys_str_mv AT helenakelly diagnosticaccuracyofcervicalcancerscreeningandscreeningtriagestrategiesamongwomenlivingwithhiv1inburkinafasoandsouthafricaacohortstudy
AT admirechikandiwa diagnosticaccuracyofcervicalcancerscreeningandscreeningtriagestrategiesamongwomenlivingwithhiv1inburkinafasoandsouthafricaacohortstudy
AT bernardsawadogo diagnosticaccuracyofcervicalcancerscreeningandscreeningtriagestrategiesamongwomenlivingwithhiv1inburkinafasoandsouthafricaacohortstudy
AT claregilham diagnosticaccuracyofcervicalcancerscreeningandscreeningtriagestrategiesamongwomenlivingwithhiv1inburkinafasoandsouthafricaacohortstudy
AT pamelamichelow diagnosticaccuracyofcervicalcancerscreeningandscreeningtriagestrategiesamongwomenlivingwithhiv1inburkinafasoandsouthafricaacohortstudy
AT olgagoumbrilompo diagnosticaccuracyofcervicalcancerscreeningandscreeningtriagestrategiesamongwomenlivingwithhiv1inburkinafasoandsouthafricaacohortstudy
AT tanvieromar diagnosticaccuracyofcervicalcancerscreeningandscreeningtriagestrategiesamongwomenlivingwithhiv1inburkinafasoandsouthafricaacohortstudy
AT souleymanezan diagnosticaccuracyofcervicalcancerscreeningandscreeningtriagestrategiesamongwomenlivingwithhiv1inburkinafasoandsouthafricaacohortstudy
AT preciousmagooa diagnosticaccuracyofcervicalcancerscreeningandscreeningtriagestrategiesamongwomenlivingwithhiv1inburkinafasoandsouthafricaacohortstudy
AT michelsegondy diagnosticaccuracyofcervicalcancerscreeningandscreeningtriagestrategiesamongwomenlivingwithhiv1inburkinafasoandsouthafricaacohortstudy
AT nicolasnagot diagnosticaccuracyofcervicalcancerscreeningandscreeningtriagestrategiesamongwomenlivingwithhiv1inburkinafasoandsouthafricaacohortstudy
AT nicolasmeda diagnosticaccuracyofcervicalcancerscreeningandscreeningtriagestrategiesamongwomenlivingwithhiv1inburkinafasoandsouthafricaacohortstudy
AT sineaddelanymoretlwe diagnosticaccuracyofcervicalcancerscreeningandscreeningtriagestrategiesamongwomenlivingwithhiv1inburkinafasoandsouthafricaacohortstudy
AT philippemayaud diagnosticaccuracyofcervicalcancerscreeningandscreeningtriagestrategiesamongwomenlivingwithhiv1inburkinafasoandsouthafricaacohortstudy
AT harpstudygroup diagnosticaccuracyofcervicalcancerscreeningandscreeningtriagestrategiesamongwomenlivingwithhiv1inburkinafasoandsouthafricaacohortstudy