Chromosomal gains and losses in human papillomavirus-associated neoplasia of the lower genital tract-A systematic review and meta-analysis

Lorenz K. Thomas, Justo Lorenzo Bermejo, Svetlana Vinokurova, Katrin Jensen, Mariska Bierkens, Renske Steenbergen, Marion Bergmann, Magnus von Knebel Doeberitz, Miriam Reuschenbach

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    49 Scopus citations

    Abstract

    Background Overexpression of the human papillomavirus (HPV) oncogenes E6 and E7 is necessary for the development of distinct lower genital tract cancers. However, secondary cellular genomic alterations are mandatory to promote progression of HPV-induced premalignant stages. We aimed at identifying the chromosomal regions most frequently gained and lost and the disease stage at which the latter occurs. These regions might be relevant for carcinogenesis and could serve as diagnostic markers to identify premalignant lesions with high progression risk towards invasive cancer. Methods We performed a systematic literature review and meta-analysis of studies listed in PubMed that analysed chromosomal copy number alterations by comparative genomic hybridisation (CGH) in HPV-positive and-negative cancers or premalignant lesions of the anogenital tract (cervix, anus, vagina, penis and vulva). Findings Data were extracted and analysed from 32 studies. The most common alterations in cervical squamous cell carcinoma (SCC) (12 studies, 293 samples) were gains at 3q with a rate of 0.55 (95% confidence interval (CI) 0.43-0.70), losses at 3p (0.36, 95%CI 0.27-0.48) and losses at 11q (0.33, 95%CI 0.26-0.43). Gains at 3q were particularly frequent in HPV16-positive cervical SCC (0.84, 95%CI 0.78-0.90). Also more than one quarter of high grade cervical intraepithelial neoplasia (CIN) harboured gains of 3q (0.27, 95%CI 0.20-0.36), but the rate in low grade CIN was low (0.02, 95%CI 0.00-0.09). For HPV-associated vulvar SCC (four studies, 30 samples) the same common alterations as in cervical SCC were reported. Studies on non-cervical and non-vulvar SCC and premalignant lesions of the lower genital tract are scarce. Interpretation 3q gains were most frequently found in HPV16-positive cervical SCC. The results suggest the selection of HPV-transformed cell clones harbouring 3q gains in high grade premalignant lesions, while alterations in low grade lesions are rare.

    Original languageEnglish (US)
    Pages (from-to)85-98
    Number of pages14
    JournalEuropean Journal of Cancer
    Volume50
    Issue number1
    DOIs
    StatePublished - Jan 1 2014

    Keywords

    • CGH
    • Cervical cancer
    • Chromosomal alterations
    • Genomic instability
    • Human papillomavirus

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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  • Cite this

    Thomas, L. K., Bermejo, J. L., Vinokurova, S., Jensen, K., Bierkens, M., Steenbergen, R., Bergmann, M., von Knebel Doeberitz, M., & Reuschenbach, M. (2014). Chromosomal gains and losses in human papillomavirus-associated neoplasia of the lower genital tract-A systematic review and meta-analysis. European Journal of Cancer, 50(1), 85-98. https://doi.org/10.1016/j.ejca.2013.08.022