Translational Radiobiology Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.
Int J Radiat Oncol Biol Phys. 2013 Apr 1;85(5):e223-9. doi: 10.1016/j.ijrobp.2012.11.030. Epub 2013 Jan 17.
To investigate the relationship between human papillomavirus (HPV) genotype and outcome after radiation therapy and intrinsic radiosensitivity.
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.
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 HPVα9-positive tumors had better local progression-free survival compared with α7 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 α9 and α7 cervical tumors (n=63). In the cell lines, 9 were α7 and 4 α9 positive and 3 negative. There was no difference in SF2 between α9 and α7 cell lines (n=14).
The reduced radioresponsiveness of α7 cervical tumors is not related to intrinsic radiosensitivity.
研究人乳头瘤病毒(HPV)基因型与放射治疗后结局和内在放射敏感性之间的关系。
采用 SPF-10 广谱引物聚合酶链反应对宫颈活检进行 HPV 基因分型,随后进行脱氧核糖核酸酶免疫测定和反向杂交线探针分析(LiPA25)(版本 1)(n=202)基因分型。使用 PapilloCheck 和定量逆转录聚合酶链反应对宫颈癌细胞系(n=16)进行基因分型。使用对数秩和 Cox 比例风险分析评估单纯放射治疗后的局部无进展生存。使用集落形成测定法测量内在放射敏感性,即 2 Gy 时的存活分数(SF2)。
在 202 个肿瘤中,107 个(53.0%)HPV16 阳性,29 个(14.4%)HPV18 阳性,9 个(4.5%)HPV45 阳性,23 个(11.4%)其他 HPV 基因型阳性,22 个(10.9%)阴性;11 个(5.5%)包含多种基因型,1 个肿瘤 HPV X(0.5%)。在有结局数据的 148 例患者中,在单变量(P<.004)和多变量(危险比 1.54,95%置信区间 1.11-1.76,P=.021)分析中,HPVα9 阳性肿瘤患者的局部无进展生存优于α7 患者。α9 和α7 宫颈肿瘤的中位 SF2 无差异(n=63)。在细胞系中,9 个为α7 阳性,4 个为α9 阳性,3 个为阴性。α9 和α7 细胞系的 SF2 无差异(n=14)。
α7 宫颈肿瘤的放射反应性降低与内在放射敏感性无关。