Comparison of human papillomavirus‐based cervical cancer screening strategies in Tanzania among women with and without HIV

Abstract

Cervical cancer is the most common female cancer in Eastern Africa, and the World Health Organization (WHO) recommends human papillomavirus (HPV)‐based screening as a key element to eliminate the disease. In this cross‐sectional study from Tanzania, we compared nine HPV‐based cervical cancer screening strategies, including HPV testing at standard cut‐off; HPV testing at increased viral load cut‐offs; HPV testing with partial/extended genotyping, and HPV testing with visual inspection with acetic acid (VIA). We pooled data collected during 2008 to 2009 and 2015 to 2017 from 6851 women aged 25 to 65. Cervical cytology samples were HPV tested with Hybrid Capture 2, and HPV positive samples were genotyped with INNO‐LiPA Extra II. Human immunodeficiency virus (HIV) testing and VIA were done according to local standards. We calculated sensitivity, specificity, positive and negative predictive value of screening strategies, with high‐grade cytological lesions as reference, separately for women with and without HIV. HPV testing at standard cut‐off (1.0 relative light units [RLU]) had highest sensitivity (HIV+: 97.8%; HIV−: 91.5%), but moderate specificity (HIV+: 68.1%; HIV−: 85.7%). Increasing the cut‐off for HPV positivity to higher viral loads (5.0/10.0 RLU) increased specificity (HIV+: 74.2%‐76.5%; HIV−: 89.5%‐91.2%), with modest sensitivity reductions (HIV+: 91.3%‐95.7%; HIV−: 83.5%‐87.8%). Limiting test positivity to HPV types 16/18/31/33/35/45/52/58 improved specificity while maintaining high sensitivity (HIV+: 90.2%; HIV−: 81.1%). Triage with VIA and/or partial genotyping for HPV16/18 or HPV16/18/45 had low sensitivities (≤65%). In conclusion, HPV testing alone, or HPV testing with extended genotyping or increased viral load cut‐offs, may improve cervical cancer screening in Sub‐Saharan Africa.

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

“…Kahesa et al. reported high sensitivity of 8‐type HPV genotype restriction in women with and without HIV (90% and 81%, respectively) but as in our study the specificity was low, with positive predictive values of only 30% and 20%, respectively 16 . Botha et al.…”

“…14 Kahesa et al reported high sensitivity of 8-type HPV genotype restriction in women with and without HIV (90% and 81%, respectively) but as in our study the specificity was low, with positive predictive values of only 30% and 20%, respectively. 16 Botha et al recently reported only 14% reduction in sensitivity of 7-type HPV genotype restriction to detect CIN2+ in WLHIV, using the same types as 8-type HPV genotype restriction except HPV35. 17 Our findings regarding the low sensitivity of visual triage methods are in-line with our prior findings 13 as well as a recent study from Papua New Guinea that reported a similar reduction in the sensitivity of HPV primary screening from 92% to 46% when triaged with VIA.…”

“…7,12,13 Alternative HPV triage strategies for LMICs are urgently needed. One such strategy that has been explored is limiting further triage or management to women positive for only the eight HPV genotypes most associated with cervical cancer (HPV 16,18,31,33,35,45,52,58). 14 Improved triage with an objective laboratory-based method such as this could improve the effectiveness of cervical screening programs in LMICs.…”

“…Participants were then instructed on HPV vaginal self-sampling and went to the health facility bathroom to collect their sample. Samples were transported to the Botswana Harvard Partnership Reference Laboratory in Gaborone and tested for 15 high-risk HPV types (16,18,31,33,35,39,45,51,52,53,56,58,59,66,68) using the AmpFire® HPV Assay (Atila BioSystems, Mountain View, California, USA) on high through-put PCR platforms already used in Botswana.…”

State of the science and future directions for research on HIV and cancer: Summary of a joint workshop sponsored by IARC and NCI

“…58,59 HPV infection and abnormal screening results are more common in with HIV, but it is not known whether cervical cancer risk, conditional on test results, differs by HIV status. In two recent studies, risks of high-grade cervical lesions (conditional on screening test results) were similar between women with and without HIV for all evaluated algorithms, prompting the question of whether the two populations could potentially be screened more similarly, 58,60 which could simplify implementation of screening in settings with high HIV prevalence.…”