Diagnostic value of human papillomavirus (HPV) 16 and HPV18 viral loads for the detection of high-grade cervical intraepithelial neoplasia (CIN2+) in a cohort of African women living with HIV
Section snippets
Background
Cervical cancer is the fourth most common cancer in women worldwide and the most common cancer and main cause of cancer mortality in women living in low income and developing countries, particularly in sub-Saharan Africa [[1], [2]]. Virtually all cases of cervical cancer result from a persistent infection with high-risk human papillomaviruses (HR-HPV), HPV16 and HPV18 being associated with over 70% invasive cervical cancer cases [3].
Women living with HIV (WLHIV) have an increased risk of
Objectives
The objective of the present study was to investigate the diagnostic value of HPV16 and HPV18 viral loads in a cohort of WLHIV enrolled in a prospective evaluation of cervical cancer screening approaches in sub-Saharan Africa.
Study population
The HARP (HPV in Africa Research partnership) study enrolled women with HIV-1 infection aged 15–49 in Ouagadougou, Burkina Faso, and Johannesburg, South Africa, for a prospective study over 18 months. The HARP study methodology has been described in detail elsewhere [[11], [25]]. In brief, at enrolment (baseline) and at the follow-up visit scheduled at month (M) 18 (endline) and that actually occurred at a median (IQR) 16 (15.5–16.8) months later, women benefited from cervical screening using
Results
Among the 1238 WLHIV enrolled in the HARP study who were tested for HPV detection and genotyping, 245 (19.8%) were positive for HPV16 or HPV18 at baseline and/or endline. These women had a median (IQR) age of 34 (30–41) years, had a median (IQR) CD4+ T-cell count of 417 (324–557) cells/μL, and 158 of them (64.5%) were on antiretroviral therapy (ART).
At baseline, 122 and 103 of these women were positive for HPV16 and HPV18, respectively, 25 of them being positive for both HPV16 and HPV18. At
Discussion
Results obtained in this study indicate that HPV16 viral load, as determined by quantitation of E6 DNA, could be a reliable marker of high-grade CIN (CIN2+). HPV16 viral load significantly increased with histological grades, and a threshold of 3.59 log DNA copies/1000 cells detected CIN2+ with a sensitivity and specificity of 93.5% and 74.1%, respectively, and a high negative predictive value (97.2%). Moreover, among the women initially <CIN2, a high HPV16 viral load at baseline was associated
Contributors
MND, PM and MS conceived and planned the study, JN performed the experiments, MS and HK analysed the data, TO, OGL and SD performed histological diagnosis and slide reviews, MS drafted the manuscript, all authors revised and approved the manuscript.
Funding
This study was funded by the National Agency for Research on AIDS and Viral Hepatitis (No. ANRS 12321). The HARP project has received funding from the European Commission (EC) 7th Framework Programme under grant agreement No. HEALTH-2010-F2-265396.
Competing interest
The authors have no conflicts of interest to disclose.
Ethical approval
Ethical clearance was obtained from the Ministry of Health of Burkina Faso, the University of Witwatersrand in Johannesburg, South Africa, and the London School of Hygiene & Tropical Medicine. Written informed consent was obtained at the screening visit and all women provided a second written informed consent at the enrolment visit for enrolment and follow-up over 18 months.
Acknowledgements
Other contributing members of the HARP study group included: A. Chikandiwa, E. Cutler, S. Delany-Moretlwe, D. A. Lewis, M.P. Magooa, V. Maseko, P. Michelow, B. Muzah, A. Puren (Johannesburg, South Africa); F. Djigma, J. Drabo, N. Meda, B. Sawadogo, J. Simporé, A. Yonli, S. Zan (Ouagadougou, Burkina Faso); V. Costes, N. Leventoux, N. Nagot, (Montpellier, France); and A. Devine, C. Gilham, L. Gibson, R. Legood, H.A. Weiss (London, UK).
We also thank the HARP International Scientific Advisory Group
References (29)
- et al.
Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials
Lancet
(2014) - et al.
A new HPV-DNA test for cervical screening in developing regions: a cross-sectional study of clinical accuracy in rural China
Lancet Oncol.
(2008) - et al.
Viral DNA load, physical status and E2/E6 ratio as markers to grade HPV16 positive women for high-grade cervical lesions
Gynecol. Oncol.
(2007) - et al.
Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012
Int. J. Cancer
(2015) - et al.
Cervical cancer in Africa
Cancer Epidemiol. Biomarkers Prev.
(2012) - et al.
Time trends of human papillomavirus types in invasive cervical cancer, from 1940 to 2007
Int. J. Cancer
(2014) - et al.
HIV human papillomavirus, and cervical neoplasia and cancer in the era of highly active antiretroviral therapy
Eur. J. Cancer Prev.
(2008) - et al.
Screening for cervical cancer in developing countries
Vaccine
(2006) - et al.
Accuracy of visual inspection with acetic acid and with Lugol’s iodine for cervical cancer screening: meta-analysis
J. Obstet. Gynaecol. Res.
(2015) - et al.
Determinants of cervical cancer screening accuracy for visual inspection with acetic acid (VIA) and Lugol’s iodine (VILI) performed by nurse and physician
PLoS One
(2017)