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. 2014 Jan 10;9(1):e78995.
doi: 10.1371/journal.pone.0078995. eCollection 2014.

Physical status of human papillomavirus integration in cervical cancer is associated with treatment outcome of the patients treated with radiotherapy

Hye-Jin Shin  1 , Jungnam Joo  2 , Ji Hyun Yoon  3 , Chong Woo Yoo  4 , Joo-Young Kim  1
Affiliations

Physical status of human papillomavirus integration in cervical cancer is associated with treatment outcome of the patients treated with radiotherapy

Hye-Jin Shin et al. PLoS One. .

Erratum in

Abstract

Integration of human papillomavirus (HPV) DNA into the host genome is a critical aetiological event in the progression from normal cervix to intraepithelial neoplasm, and finally to invasive cervical cancer. However, there has been little work on how HPV integration status relates to treatment outcome for cervical carcinomas. In the current study, HPV E2 and E6 gene copy numbers were measured in 111 cervical cancer tissues using real-time QPCR. Integration patterns were divided into four groups: single copy-integrated with episomal components (group 1), single copy-integrated without episomal components (group 2), multicopy tandem repetition-integrated (group 3), and low HPV (group 4) groups. A relapse-predicting model was constructed using multivariable Cox proportional hazards model to classify patients into different risk groups for disease-free survival (DFS). The model was internally validated using bootstrap resampling. Oligonucleotide microarray analysis was performed to evaluate gene expression patterns in relation to the different integration groups. DFS rate was inferior in the order of the patients in group 4, group 2/3, and group 1. Multivariate analysis showed that histologic grade, clinical stage group, and integration pattern were significant prognostic factors for poor DFS. The current prognostic model accurately predicted the risk of relapse, with an area under the receiver operating characteristic curve (AUC) of 0.74 (bootstrap corrected, 0.71). In conclusion, these data suggest that HPV integration pattern is a potent prognostic factor for tailored treatment of cervical cancer.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Each Ct value of HPV E2 and E6 gene copies was measured in 111 cervical cancer patients using real-time QPCR.
The E2/E6 Ct ratios of the patients in each group are depicted as dots on the scatter plot. The horizontal bars represent the median value with interquartile range.
Figure 2
Figure 2. Disease-free survival rates of the patients by physical status of HPV DNA in cervical cancer.
Group 1; Single copy HPV integration with episomal components, Group 2; Single copy HPV integration without episomal components, Group 3; Multicopy tandem repeated integration, Group 4; low HPV.
Figure 3
Figure 3. Disease-free survival of the patients by three risk groups according to the predicted risk probability.
Figure 4
Figure 4. Heat map of the genes with significant linear trend from group1 to group4, increasing (a) and decreasing expression (b).
See this image and copyright information in PMC

References

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