Poor Prognosis Associated With Human Papillomavirus ¦Á7?Genotypes in Cervical Carcinoma Cannot Be Explained?by Intrinsic Radiosensitivity

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• 作者：John S. Hall ; PhD^&lowast ; ; Rohan Iype ; MRes^&lowast ; ; Lucile S.C. Armenoult ; MSc^&lowast ; ; Janet Taylor ; PhD^&lowast ; ; ^&dagger ; ; Crispin J. Miller ; PhD^&dagger ; ; Susan Davidson ; MD^§ ; ; Silvia de Sanjose ; MD^¡¬ ; Xavier Bosch ; MD^¡¬ ; Peter L. Stern ; PhD^&Dagger ; ; Catharine M.L. West ; PhD^&lowast ; ; ^{Catharine.West@manchester.ac.uk}
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：2013
• 出版时间：1 April, 2013
• 年：2013
• 卷：85
• 期：5
• 页码：e223-e229
• 全文大小：538 K

文摘

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Purpose

To investigate the relationship between human papillomavirus (HPV) genotype and outcome after radiation therapy and intrinsic radiosensitivity.

Methods and Materials

HPV genotyping was performed on cervix biopsies by polymerase chain reaction using SPF-10 broad-spectrum primers, followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA₂₅) (version 1) (n=202). PapilloCheck and quantitative reverse transcription-polymerase chain reaction were used to genotype cervix cancer cell lines (n=16). Local progression-free survival after radiation therapy alone was assessed using log-rank and Cox proportionate hazard analyses. Intrinsic radiosensitivity was measured as surviving fraction at 2 Gy (SF2) using clonogenic assays.

Results

Of the 202 tumors, 107 (53.0 % ) were positive for HPV16, 29 (14.4 % ) for HPV18, 9 (4.5 % ) for HPV45, 23 (11.4 % ) for other HPV genotypes, and 22 (10.9 % ) were negative; 11 (5.5 % ) contained multiple genotypes, and 1 tumor was HPV X (0.5 % ). In 148 patients with outcome data, those with HPV¦Á9-positive tumors had better local progression-free survival compared with ¦Á7 patients in univariate (P<.004) and multivariate (hazard ratio 1.54, 95 % confidence interval 1.11-1.76, P=.021) analyses. There was no difference in the median SF2 of ¦Á9 and ¦Á7 cervical tumors (n=63). In the cell lines, 9 were ¦Á7 and 4 ¦Á9 positive and 3 negative. There was no difference in SF2 between ¦Á9 and ¦Á7 cell lines (n=14).

Conclusion

The reduced radioresponsiveness of ¦Á7 cervical tumors is not related to intrinsic radiosensitivity.