Phase I of the DiaVACCS screening trial: Study design, methods, population demographics and baseline results
DOI:
https://doi.org/10.7196/SAMJ.2022.v112i7.16478Keywords:
DiaVACCS screening trialAbstract
Background. Human papillomavirus (HPV)-based primary screening guidelines are based on screening test performance and prevalence data generated in high-resource areas with low HIV infection rates. There is an urgent need for local data on infection and disease prevalence, as well as screening test performance, among both HIV-positive and HIV-negative South African (SA) women, in order to inform updated screening guidelines.
Objectives. This study describes the baseline characteristics of participants in the cross-sectional phase of the multicentric DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) screening trial. The objective was to determine the prevalence of positive screening and pre-invasive disease using different tests and strategies in the SA HIV-positive and HIV-negative population.
Methods. A total of 1 104 women aged 25 - 65 years and eligible for screening were included, 465 HIV positive and 639 HIV negative. Visual inspection and molecular and cytological screening tests were done on self-sampled and healthcare worker-collected specimens. All participants who screened positive and 49.1% of those who screened negative were invited for colposcopy and biopsy, and those qualifying for treatment were recalled for large loop excision of the transformation zone as part of the trial. The worst histology result for each participant was used, and for untested women, multiple imputation was used to estimate verification bias- adjusted histology values.
Results. Visual inspection was positive in 50.4% of HIV-positive v. 20.9% of HIV-negative women, cytology (atypical squamous cells of undetermined significance) in 39.9% v. 17.0%, and high-risk HPV DNA in 41.2% v. 19.6%. Overall, high-grade squamous intraepithelial lesion-positive cytology peaked in the age group 30 - 39 years at 16.7%. After adjustment for verification bias, histological diagnosis of cervical intraepithelial neoplasia (CIN)2+ was suspected in 44.7% v. 23.5% and CIN3+ in 23.3% v. 10.2% of HIV-positive and negative women, respectively. Invasive cancer was diagnosed in 15 women (1.95% of histological studies performed), and verification bias adjustment suggested 20 cases (1.8% of the study population).
Conclusion. The baseline findings from the DiaVACCS trial confirm a high prevalence of HPV-related cervical pathology in the SA HIV-negative screening population, showing a clear need to reach these women with a screening programme. Among HIV-positive women, prevalence values were almost doubled. The prevalence of existing invasive cervical cancer was 1 - 2% of all women. Further analysis of the performance of single and multiple screening tests between the two subgroups will contribute to the choice of the most effective strategies to identify women at risk of developing invasive cancer.
References
Bruni L, Albero G, Serrano B, et al.; ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). Human papillomavirus and related diseases in South Africa: Summary report 22 October 2021. https://hpvcentre.net/statistics/reports/ZAF.pdf?t=1632401549610 (accessed 2 February 2022).
Statistics South Africa. Mid-year population estimates 2021. Statistical release P0302. http://www.statssa. gov.za/publications/P0302/P03022021.pdf (accessed 2 February 2022).
Stelzle D, Tanaka LF, Lee KK, et al. Estimates of the global burden of cervical cancer associated with HIV. Lancet Glob Health 2021;9(2):e161-e169. https://doi.org/10.1016/S2214-109X(20)30459-9
Dreyer G. Clinical implications of the interaction between HPV and HIV infections. Best Pract Res Clin Obstet Gynaecol 2018;47:95-106. https://doi.org/10.1016/j.bpobgyn.2017.08.011
Looker KJ, Rönn MM, Brock PM, et al. Evidence of synergistic relationships between HIV and human papillomavirus (HPV): Systematic reviews and meta-analyses of longitudinal studies of HPV acquisition and clearance by HIV status, and of HIV acquisition by HPV status. J Int AIDS Soc 2018;21(6):e25110. https://doi.org/10.1002/jia2.25110
Zuma K, Shisana O, Rehle TM, et al. New insights into HIV epidemic in South Africa: Key findings from the National HIV Prevalence, Incidence and Behaviour Survey, 2012. Afr J AIDS Res 2016;15(1):67-75. https://doi.org/10.2989/16085906.2016.1153491
Liu G, Sharma M, Tan N, Barnabas RV. HIV-positive women have higher risk of human papilloma virus infection, precancerous lesions, and cervical cancer. AIDS 2018;32(6):795-808. https://doi.org/10.1097/ QAD.0000000000001765
Bogale AL, Belay NB, Medhin G, et al. Molecular epidemiology of human papillomavirus among HIV infected women in developing countries: Systematic review and meta-analysis. Virol J 2020;17:179. https:// doi.org/10.1186/s12985-020-01448-1
Van Aardt MC, Dreyer G, Pienaar HF, et al. Unique human papillomavirus-type distribution in South African women with invasive cervical cancer and the effect of human immunodeficiency virus infection. Int J Gynecol Cancer 2015;25(5):919-925. https://doi.org/10.1097/IGC.0000000000000422
Lekoane KMB, Kuupiel D, Mashamba-Thompson TP, Ginindza TG. The interplay of HIV and human papillomavirus-related cancers in sub-Saharan Africa: Scoping review. Syst Rev 2020;9(1):88. https://doi. org/10.1186/s13643-020-01354-1
Dhokotera T, Bohlius J, Spoerri A, et al. The burden of cancers associated with HIV in the South African public health sector, 2004 - 2014: A record linkage study. Infect Agents Cancer 2019;14:12. https://doi. org/10.1186/s13027-019-0228-7
DreyerG,BothaMH,SnymanLC,etal.Combiningcervicalcancerscreeningformotherswithschoolgirl vaccination during human papillomavirus (HPV) vaccine implementation in South Africa: Results from the VACCS1 and VACCS2 trials. Int J Gynecol Cancer 2022;32(5):592-598. https://doi.org/10.1136/ijgc- 2021-003079
Botha MH, van der Merwe FH, Snyman LC, Dreyer G. The vaccine and cervical cancer screen (VACCS) project: Acceptance of human papillomavirus vaccination in a school-based programme in two provinces of South Africa. S Afr Med J 2015;105(1):40-43. https://doi.org/10.7196/SAMJ.8419
Van Aardt MC, Dreyer G, Richter KL, Becker P. Human papilloma virus-type distribution in South African women without cytological abnormalities: A peri-urban study. South Afr J Gynaecol Oncol 2013;5(2):S21-S27. https://doi.org/10.1080/20742835.2013.11441218
National Department of Health, South Africa. Cervical cancer prevention and control policy 2017. https:// www.health.gov.za/wp-content/uploads/2021/07/cervical-cancer-policy.pdf (accessed 18 January 2022). 16. Wentzensen N, Walker J, Smith K, et al. A prospective study of risk-based colposcopy demonstrates
improved detection of cervical precancers. Am J Obstet Gynecol 2018;218(6):604.e1-604.e8. https://doi.
org/10.1016/j.ajog.2018.02.009
Katitas A. University of Virginia Library Research Data Services + Sciences. Getting started with multiple imputation in R. University of Virginia, 2019. https://data.library.virginia.edu/getting-started-with- multiple-imputation-in-r/ (accessed 3 February 2022).
BothaMH,DreyerG.GuidelinesforcervicalcancerscreeninginSouthAfrica.SouthAfrJGynaecolOncol 2017;9(1):8-12. https://journals.co.za/doi/pdf/10.10520/EJC-9584c6bc7 (accessed 1 June 2022).
StolerMH,WrightTCJr,ParvuV,YansonK,CooperCK,AndrewsJ.Stratifiedriskofhigh-gradecervical disease using Onclarity HPV extended genotyping in women, ≥25 years of age, with NILM cytology. Gynecol Oncol 2019;153(1):26-33. https://doi.org/10.1016/j.ygyno.2018.12.024
Iftner T, Becker S, Neis KJ, et al. Head-to-head comparison of the RNA-based Aptima human papillomavirus (HPV) assay and the DNA-Based Hybrid Capture 2 HPV test in a routine screening population of women aged 30 to 60 years in Germany. J Clin Microbiol 2015;53(8):2509-2516. https://doi. org/10.1128/JCM.01013-15
Kelly HA, Chikandiwa A, Sawadogo B, et al. 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 Med 2021;18(3):e1003528. https://doi.org/10.1371/journal.pmed.1003528
Richter K, Becker P, Horton A, Dreyer G. Age-specific prevalence of cervical human papillomavirus infection and cytological abnormalities in women in Gauteng Province, South Africa. S Afr Med J 2013;103(5):313-317. https://doi.org/10.7196/SAMJ.6514
Kuhn L, Wang C, Tsai WY, Wright TC, Denny L. Efficacy of human papillomavirus-based screen-and- treat for cervical cancer prevention among HIV-infected women. AIDS 2010;24(16):2553-2561. https://doi. org/10.1097/QAD.0b013e32833e163e
Wright TC Jr, Stoler MH, Behrens CM, Apple R, Derion T, Wright TL. The ATHENA human papillomavirus study: Design, methods, and baseline results. Am J Obstet Gynecol 2012;206(1):46.e1-46.e11. https://doi. org/10.1016/j.ajog.2011.07.024
Kitchener HC, Almonte M, Thomson C, et al. HPV testing in combination with liquid-based cytology in primary cervical screening (ARTISTIC): A randomised controlled trial. Lancet Oncol 2009;10(7):672-682. https://doi.org/10.1016/S1470-2045(09)70156-1
StolerMH,WrightTCJr,ParvuV,etal.TheOnclarityHumanPapillomavirusTrial:Design,methods,and baseline results. Gynecol Oncol 2018;149(3):498-505. https://doi.org/10.1016/j.ygyno.2018.04.007
Bonde J, Rebolj M, Ejegod DM, Preisler S, Lynge E, Rygaard C. HPV prevalence and genotype distribution in a population-based split-sample study of well-screened women using CLART HPV2 human papillomavirus genotype microarray system. BMC Infect Dis 2014;14:413. https://doi.org/10.1186/1471-2334-14-413
Li T, Wu Z, Jiang M, et al. Clinical performance of Onclarity HPV assay and Cobas HPV test in detection of cervical precancer and cancer in Chinese women. Gynecol Oncol 2020;157(1):202-208. https://doi. org/10.1016/j.ygyno.2020.01.011
Mbulawa ZZA, Somdyala NI, Mabunda SA, Williamson AL. High human papillomavirus prevalence among females attending high school in the Eastern Cape Province of South Africa. PLoS ONE 2021;16(6):e0253074. https://doi.org/10.1371/journal.pone.0253074
Taku O, Businge CB, Mdaka ML, et al. Human papillomavirus prevalence and risk factors among HIV- negative and HIV-positive women residing in rural Eastern Cape, South Africa. Int J Infect Dis 2020;95:176- 182. https://doi.org/10.1016/j.ijid.2020.02.051
CastlePE,VaralloJE,BertramMM,RatshaaB,KithekaM,RammipiK.High-riskhumanpapillomavirus prevalence in self-collected cervicovaginal specimens from human immunodeficiency virus (HIV)- negative women and women living with HIV living in Botswana. PLoS ONE 2020;15(2):e0229086. https:// doi.org/10.1371/journal.pone.0229086
Luckett R, Mogowa N, Li HJ, et al. Performance of two-stage cervical cancer screening with primary high-risk human papillomavirus testing in women living with human immunodeficiency virus. Obstet Gynecol 2019;134(4):840-849. https://doi.org/10.1097/AOG.0000000000003496
Preisler S, Rebolj M, Untermann A, et al. Prevalence of human papillomavirus in 5,072 consecutive cervical SurePath samples evaluated with the Roche cobas HPV real-time PCR assay. PLoS ONE 2013;8(3):e59765. https://doi.org/10.1371/journal.pone.0059765
Ogilvie GS, van Niekerk DJ, Krajden M, et al. A randomised controlled trial of human papillomavirus (HPV) testing for cervical cancer screening: Trial design and preliminary results (HPV FOCAL Trial). BMC Cancer 2010;10:111. https://doi.org/10.1186/1471-2407-10-111
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