TY - JOUR
T1 - Chromosomal profiles of high-grade cervical intraepithelial neoplasia relate to duration of preceding high-risk human papillomavirus infection
AU - Bierkens, M.
AU - Wilting, S.M.
AU - van Wieringen, W.N.
AU - van Kemenade, F.J.
AU - Bleeker, M.C.G.
AU - Jordanova, E.S.
AU - Bekker-Lettink, M.
AU - van de Wiel, M.
AU - Ylstra, B.
AU - Meijer, C.J.L.M.
AU - Snijders, P.J.F.
AU - Steenbergen, R.D.M.
PY - 2012
Y1 - 2012
N2 - High-grade cervical intraepithelial neoplasia (CIN2/3) represents a heterogeneous disease both with respect to clinical behavior and chromosomal aberrations detected. We hypothesized that the extent of chromosomal aberrations reflects the duration of their existence. Chromosomal profiles were determined of CIN3 of women with a known 5-year history of high-risk human papillomavirus virus (hrHPV) infection, in which duration of prior hrHPV infection was considered a proxy for duration of CIN3 existence. Eleven women had a <5 year preceding hrHPV infection (CIN3<5yrPHI) and 24 had a PHI lasting ≤yen;5 years (CIN3≤yen;5yrPHI). For comparison, six CIN3 adjacent to squamous cell carcinomas (CIN3-SCC), the corresponding SCCs, and six CIN1 were included. Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two clusters. One was characterized by a low number of chromosomal aberrations and included all CIN1, 81.8% of CIN3<5yrPHI and 33.3% of CIN3≤yen;5yrPHI. Samples in the second cluster, displaying multiple aberrations, included 18.2% of CIN3<5yrPHI, 66.7% CIN3≤yen;5yrPHI, all except one CIN3-SCC and all SCCs. The number of genomic aberrations increased according to lesion grade and also with longer duration of PHI. The increase in aberrations in CIN3≤yen;5yrPHI compared to <5yrPHI was highly significant (p = 0.001), suggesting that CIN3≤yen;5yrPHI represent more severe lesions. In conclusion, longer duration of preceding hrHPV infection is associated with an increased number of chromosomal aberrations. Hence, CIN3 with a longer duration of existence are likely more prone to have an increased short-term risk of cervical cancer. Copyright © 2011 UICC.
AB - High-grade cervical intraepithelial neoplasia (CIN2/3) represents a heterogeneous disease both with respect to clinical behavior and chromosomal aberrations detected. We hypothesized that the extent of chromosomal aberrations reflects the duration of their existence. Chromosomal profiles were determined of CIN3 of women with a known 5-year history of high-risk human papillomavirus virus (hrHPV) infection, in which duration of prior hrHPV infection was considered a proxy for duration of CIN3 existence. Eleven women had a <5 year preceding hrHPV infection (CIN3<5yrPHI) and 24 had a PHI lasting ≤yen;5 years (CIN3≤yen;5yrPHI). For comparison, six CIN3 adjacent to squamous cell carcinomas (CIN3-SCC), the corresponding SCCs, and six CIN1 were included. Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two clusters. One was characterized by a low number of chromosomal aberrations and included all CIN1, 81.8% of CIN3<5yrPHI and 33.3% of CIN3≤yen;5yrPHI. Samples in the second cluster, displaying multiple aberrations, included 18.2% of CIN3<5yrPHI, 66.7% CIN3≤yen;5yrPHI, all except one CIN3-SCC and all SCCs. The number of genomic aberrations increased according to lesion grade and also with longer duration of PHI. The increase in aberrations in CIN3≤yen;5yrPHI compared to <5yrPHI was highly significant (p = 0.001), suggesting that CIN3≤yen;5yrPHI represent more severe lesions. In conclusion, longer duration of preceding hrHPV infection is associated with an increased number of chromosomal aberrations. Hence, CIN3 with a longer duration of existence are likely more prone to have an increased short-term risk of cervical cancer. Copyright © 2011 UICC.
U2 - https://doi.org/10.1002/ijc.26496
DO - https://doi.org/10.1002/ijc.26496
M3 - Article
C2 - 22020762
SN - 0020-7136
VL - 131
SP - E579-E585
JO - International journal of cancer
JF - International journal of cancer
IS - 4
ER -
