Triage of HPV positivity in a high HIV prevalence setting: A prospective cohort study comparing visual triage methods and HPV genotype restriction in Botswana

Abstract

ObjectiveGuidelines for effective triage following positive primary high‐risk human papillomavirus (HPV) screening in low‐ and middle‐income countries with high human immunodeficiency virus (HIV)‐prevalence have not previously been established. In the present study, we evaluated the performance of three triage methods for positive HPV results in women living with HIV (WLHIV) and without HIV in Botswana.MethodsWe conducted baseline enrollment of a prospective cohort study from February 2021 to August 2022 in South‐East District, Botswana. Non‐pregnant women aged 25 or older with an intact cervix and no prior diagnosis of cervical cancer were systematically consented for enrollment, with enrichment of the cohort for WLHIV. Those who consented completed a questionnaire and then collected vaginal self‐samples for HPV testing. Primary HPV testing for 15 individual genotypes was conducted using Atila AmpFire® HPV assay. Those with positive HPV results returned for a triage visit where all underwent visual inspection with acetic acid (VIA), colposcopy, and biopsy. Triage strategies with VIA, colposcopy and 8‐type HPV genotype restriction (16/18/31/33/35/45/52/58), separately and in combination, were compared using histopathology as the gold standard in diagnosing cervical intraepithelial neoplasia (CIN) 2 or worse (CIN2+).ResultsAmong 2969 women enrolled, 1480 (50%) tested HPV positive. The cohort included 1478 (50%) WLHIV; 99% were virologically suppressed after a mean of 8 years on antiretroviral therapy. In total, 1269 (86%) women had histopathology data for analysis. Among WLHIV who tested positive for HPV, 131 (19%) of 688 had CIN2+ compared with 71 (12%) of 581 in women without HIV. Screening by 8‐type HPV genotype restriction was more sensitive as triage to detect CIN2+ in WLHIV 87.79% (95% CI: 80.92–92.85) and women without HIV 85.92% (95% CI: 75.62–93.03) when compared with VIA (WLHIV 62.31% [95% CI: 53.39–70.65], women without HIV 44.29% [95% CI: 32.41–56.66]) and colposcopy (WLHIV 70.77% [95% CI: 62.15–78.41], women without HIV 45.71% [95% CI: 33.74–58.06]). However, 8‐type HPV genotype restriction had low specificity in WLHIV of 30.88% (95% CI: 27.06–34.90) and women without HIV 37.06% (95% CI: 32.85–41.41). These results were similar when CIN3+ was used as the outcome. When combining 8‐type HPV genotype restriction with VIA as the triage strategy, there was improved specificity to detect CIN2+ in WLHIV of 81.65% (95% CI: 78.18–84.79) but dramatically reduced sensitivity of 56.15% (95% CI: 47.18–64.84).ConclusionsEight‐type HPV genotype restriction is a promising component of effective triage for HPV positivity. However, novel triage strategies in LMICs with high HIV prevalence may be needed to avoid the trade‐off between sensitivity and specificity with currently available options.Clinical trials registrationThis study is registered on Clinicaltrials.gov no. NCT04242823, https://clinicaltrials.gov/ct2/show/NCT04242823.

Feasibility and acceptability of an HPV self-testing strategy: lessons from a research context to assess for ability to implement into primary care at a national level in Botswana

“…Specimens were then kept refrigerated and transported to the research lab by research assistants once weekly. The specimens were tested using the AmpFire® HPV Assay (Atila BioSystems, Mountain View, California, USA) for 15 hHPV types (including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68) ( 29 ).…”

Editorial: Selected papers from the XXIV FIGO World Congress

“…In this issue, we are delighted to publish 12 papers that were invited following selection as outstanding abstracts from that Congress by FIGO's Scientific Programme Committee. All submitted full papers were independently peer reviewed by IJGO's Editorial Board, and the final selection covers a fascinating range of topics and geographical regions, including four papers from Europe, 1–4 two from Latin America, 5,6 three from Asia‐Oceania, 7–9 two from Africa–East Mediterranean, 10,11 and one from North America 12 . All papers in this special section will be free to read for a limited period following publication of the issue, and we hope that this will encourage a similarly wide breadth of readership.…”