Objective: To investigate the relationship between human papillomavirus (HPV) integration and prognosis of cervical cancer patients. Methods: The data of 82 patients with cervical cancer treated in the Radiotherapy Department of Peking Union Medical College Hospital from October 2004 to June 2012 were retrospectively analyzed.The patients were divided into poor prognosis group (recurrence or metastasis after surgery and adjuvant radiotherapy) and good prognosis group based on a propensity score matching strategy.The HPV integration of the two groups were detected by whole exome sequencing to determine whether the integration sites were located in the common fragile sites (CFSs). HPV integration and integration into CFSs were compared between the two groups. Results: Among the enrolled 82 patients, 37 were divided in poor survival group and 45 in good survival group. A total of 90 integration breakpoints were identified, 30 of them occurred in poor prognosis group and 60 occurred in good prognosis group. In the poor prognosis group, HPV integration occurred in 20 patients, 13 of them were inserted in CFSs of 11 patients, and the numbers in good prognosis group were 26, 17, 11, respectively. There were no significantly statistical differences in the number of HPV integration events (P=0.289), HPV integration patients (P=0.735), CFSs integration events (P=0.427), and CFSs integration patients (P=0.591) between the two groups. In poor prognosis group, more CFSs integration events occurred in patients with metastasis than those in patients with only local recurrence (9 vs 2, P=0.003). Conclusions: No significant differences are observed in HPV integration and HPV integration into CFSs between cervical cancer patients with different prognoses. HPV integration into CFSs may be associated with distant metastasis.
目的： 探讨人乳头瘤病毒(HPV)整合至人类基因组与宫颈癌患者预后的关系。 方法： 回顾性分析2004年10月至2012年6月在北京协和医院放疗科进行治疗的82例宫颈癌患者资料，通过倾向评分匹配策略，将宫颈癌患者分为预后差组(手术及辅助放疗后出现复发或转移)和预后好组。采用全外显子组测序法检测两组患者的HPV整合情况，明确其整合位点是否位于普通型脆性位点(CFSs)中。比较两组患者的HPV整合情况以及整合至CFSs的情况。 结果： 82例宫颈癌患者中，预后差组37例，预后好组45例。82例宫颈癌患者共发生90个HPV整合事件，其中预后差组30个，预后好组60个。在预后差组患者中，有20例发生HPV整合事件，HPV整合在CFSs中的事件共有13个，涉及11例患者。在预后好组患者中，有26例发生了HPV整合事件，HPV整合在CFSs中的事件共有17个，涉及11例患者。预后差组和预后好组间HPV整合事件数(P＝0.289)、HPV整合患者数(P＝0.735)、HPV整合至CFSs事件数(P＝0.427)以及HPV整合至CFSs患者数(P＝0.591)的差异均无统计学意义。在预后差组中，与仅局部复发患者相比，发生转移的患者发生了更多的CFSs整合事件(分别为9和2个，P＝0.003)。 结论： 预后差组和预后好组宫颈癌患者HPV整合情况及HPV整合至CFSs情况的差异无统计学意义。HPV整合至CFSs可能与肿瘤远处转移相关。.
Keywords: Cervical neoplasms; Common fragile sites; Human papilloma virus integration; Prognosis.