Elsevier

Journal of Clinical Virology

Volumes 99–100, February–March 2018, Pages 79-83
Journal of Clinical Virology

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

https://doi.org/10.1016/j.jcv.2018.01.006Get rights and content

Highlights

  • HPV16 and HPV18 E6 DNA loads increase with the grade of cervical lesions.

  • HPV18 viral load is less preformant than HPV16 viral load for idenfying CIN2+.

  • HPV16 viral load may be considered as a triage test in HPV16/HIV-coinfected women.

Abstract

Background

African women living with HIV (WLHIV) are at high risk of cervical cancer but rarely adequately screened. Better strategies enabling identification of WLHIV with high-grade cervical intraepithelial lesions (CIN2+) are required.

Objectives

To investigate the diagnostic value of HPV16 and HPV18 viral loads in a cohort of African WLHIV.

Design

HPV16 and HPV18 viral loads were determined by quantitation of the E6 gene DNA by real-time PCR in cervical specimens collected at baseline and endline (16 months) from 245 African WLHIV positive for HPV16 or/and HPV18. Cervical biopsies were graded using the histopathological CIN classification.

Results

Women with CIN2+ had higher viral load for HPV16 (p < 0.0001) or HPV18 (p = 0.03) than those without CIN2+. HPV16 viral load ≥3.59 log copies/1000 cells detected CIN2+ with sensitivity and specificity of 93.5% (95%CI: 81.7–98.3%) and 74.1% (95%CI: 66.3–80.6%), respectively, whereas HPV18 viral load ≥1.63 log copies/1000 cells detected CIN2+ with sensitivity and specificity of 59.1% (95%CI: 38.7–76.7%) and 66.9% (95%CI: 58.8–74.1%), respectively. A high baseline HPV16 viral load was significantly associated with persistence of, or progression to CIN2+ at endline; these findings were not observed for HPV18.

Conclusions

HPV16 viral load is a powerful marker of CIN2+ in African WLHIV. HPV18 viral load is of lower diagnostic value in this population.

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)

  • J.C. Gage et al.

    Effectiveness of a simple rapid human papillomavirus DNA test in rural Nigeria

    Int. J. Cancer

    (2012)
  • M. Segondy et al.

    Performance of careHPV for detecting high-grade cervical intraepithelial neoplasia among women living with HIV-1 in Burkina Faso and South Africa: HARP study

    Br. J. Cancer

    (2016)
  • C. Firnhaber et al.

    Validation of cervical cancer screening methods in HIV positive women from Johannesburg South Africa

    PLoS One

    (2013)
  • X. Carcopino et al.

    Determination of HPV type 16 and 18 viral load in cervical smears of women referred to colposcopy

    J. Med. Virol.

    (2006)
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