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Linear viral load increase of a single HPV-type in women with multiple HPV infections predicts progression to cervical cancer.

Abstract

Persistent high-risk human papillomavirus (HPV) infection is strongly associated with development of high-grade cervical intraepithelial neoplasia or cancer (CIN3+). In single type infections, serial type-specific viral-load measurements predict the natural history of the infection. In infections with multiple HPV-types, the individual type-specific viral-load profile could distinguish progressing HPV-infections from regressing infections. A case-cohort natural history study was established using samples from untreated women with multiple HPV-infections who developed CIN3+ (n = 57) or cleared infections (n = 88). Enriched cell pellet from liquid based cytology samples were subjected to a clinically validated real-time qPCR-assay (18 HPV-types). Using serial type-specific viral-load measurements (≥3) we calculated HPV-specific slopes and coefficient of determination (R(2) ) by linear regression. For each woman slopes and R(2) were used to calculate which HPV-induced processes were ongoing (progression, regression, serial transient, transient). In transient infections with multiple HPV-types, each single HPV-type generated similar increasing (0.27copies/cell/day) and decreasing (-0.27copies/cell/day) viral-load slopes. In CIN3+, at least one of the HPV-types had a clonal progressive course (R(2)  ≥ 0.85; 0.0025copies/cell/day). In selected CIN3+ cases (n = 6), immunostaining detecting type-specific HPV 16, 31, 33, 58 and 67 RNA showed an even staining in clonal populations (CIN3+), whereas in transient virion-producing infections the RNA-staining was less in the basal layer compared to the upper layer where cells were ready to desquamate and release newly-formed virions. RNA-hybridization patterns matched the calculated ongoing processes measured by R(2) and slope in serial type-specific viral-load measurements preceding the biopsy. In women with multiple HPV-types, serial type-specific viral-load measurements predict the natural history of the different HPV-types and elucidates HPV-genotype attribution.

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  • Authors+Show Affiliations

    ,

    Department of Clinical and Molecular Pathology, AML, Sonic Healthcare, Antwerp, Belgium.

    ,

    Laboratory for Cell Biology and Histology, University of Antwerp, Antwerp, Belgium.

    ,

    Department of Clinical and Molecular Pathology, AML, Sonic Healthcare, Antwerp, Belgium. Intermediate Structure for Human Body Material, AML, Sonic Healthcare, Antwerp, Belgium.

    ,

    Department of Clinical and Molecular Pathology, AML, Sonic Healthcare, Antwerp, Belgium.

    ,

    Department of Clinical and Molecular Pathology, AML, Sonic Healthcare, Antwerp, Belgium.

    Department of Clinical and Molecular Pathology, AML, Sonic Healthcare, Antwerp, Belgium. Laboratory for Cell Biology and Histology, University of Antwerp, Antwerp, Belgium.

    Source

    International journal of cancer 139:9 2016 11 01 pg 2021-32

    MeSH

    Adult
    Cervical Intraepithelial Neoplasia
    Coinfection
    Disease Progression
    Female
    Humans
    Papillomaviridae
    Papillomavirus Infections
    RNA, Viral
    Uterine Cervical Neoplasms
    Viral Load

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    27339821

    Citation

    Depuydt, Christophe E., et al. "Linear Viral Load Increase of a Single HPV-type in Women With Multiple HPV Infections Predicts Progression to Cervical Cancer." International Journal of Cancer, vol. 139, no. 9, 2016, pp. 2021-32.
    Depuydt CE, Thys S, Beert J, et al. Linear viral load increase of a single HPV-type in women with multiple HPV infections predicts progression to cervical cancer. Int J Cancer. 2016;139(9):2021-32.
    Depuydt, C. E., Thys, S., Beert, J., Jonckheere, J., Salembier, G., & Bogers, J. J. (2016). Linear viral load increase of a single HPV-type in women with multiple HPV infections predicts progression to cervical cancer. International Journal of Cancer, 139(9), pp. 2021-32. doi:10.1002/ijc.30238.
    Depuydt CE, et al. Linear Viral Load Increase of a Single HPV-type in Women With Multiple HPV Infections Predicts Progression to Cervical Cancer. Int J Cancer. 2016 11 1;139(9):2021-32. PubMed PMID: 27339821.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Linear viral load increase of a single HPV-type in women with multiple HPV infections predicts progression to cervical cancer. AU - Depuydt,Christophe E, AU - Thys,Sofie, AU - Beert,Johan, AU - Jonckheere,Jef, AU - Salembier,Geert, AU - Bogers,Johannes J, Y1 - 2016/07/09/ PY - 2016/01/20/received PY - 2016/05/01/revised PY - 2016/06/06/accepted PY - 2016/6/25/entrez PY - 2016/6/25/pubmed PY - 2017/5/2/medline KW - cervical cancer screening KW - cervical intraepithelial neoplasia KW - clonal KW - liquid-based cytology leftover KW - real-time quantitative PCR KW - transient virion producing KW - viral doubling time SP - 2021 EP - 32 JF - International journal of cancer JO - Int. J. Cancer VL - 139 IS - 9 N2 - Persistent high-risk human papillomavirus (HPV) infection is strongly associated with development of high-grade cervical intraepithelial neoplasia or cancer (CIN3+). In single type infections, serial type-specific viral-load measurements predict the natural history of the infection. In infections with multiple HPV-types, the individual type-specific viral-load profile could distinguish progressing HPV-infections from regressing infections. A case-cohort natural history study was established using samples from untreated women with multiple HPV-infections who developed CIN3+ (n = 57) or cleared infections (n = 88). Enriched cell pellet from liquid based cytology samples were subjected to a clinically validated real-time qPCR-assay (18 HPV-types). Using serial type-specific viral-load measurements (≥3) we calculated HPV-specific slopes and coefficient of determination (R(2) ) by linear regression. For each woman slopes and R(2) were used to calculate which HPV-induced processes were ongoing (progression, regression, serial transient, transient). In transient infections with multiple HPV-types, each single HPV-type generated similar increasing (0.27copies/cell/day) and decreasing (-0.27copies/cell/day) viral-load slopes. In CIN3+, at least one of the HPV-types had a clonal progressive course (R(2)  ≥ 0.85; 0.0025copies/cell/day). In selected CIN3+ cases (n = 6), immunostaining detecting type-specific HPV 16, 31, 33, 58 and 67 RNA showed an even staining in clonal populations (CIN3+), whereas in transient virion-producing infections the RNA-staining was less in the basal layer compared to the upper layer where cells were ready to desquamate and release newly-formed virions. RNA-hybridization patterns matched the calculated ongoing processes measured by R(2) and slope in serial type-specific viral-load measurements preceding the biopsy. In women with multiple HPV-types, serial type-specific viral-load measurements predict the natural history of the different HPV-types and elucidates HPV-genotype attribution. SN - 1097-0215 UR - https://www.unboundmedicine.com/medline/citation/27339821/Linear_viral_load_increase_of_a_single_HPV-type_in_women_with_multiple_HPV_infections_predicts_progression_to_cervical_cancer L2 - https://doi.org/10.1002/ijc.30238 DB - PRIME DP - Unbound Medicine ER -