Huang Lee-Wen, Chao Shiouh-Lirng, Hwang Jiann-Loung
Department of Obstetrics and Gynecology, Shin Kong Wu Ho-Su Memorial Hospital, No. 95 Wen Chang Road, Shih-Lin District, Taipei 111, Taiwan.
Cancer. 2004 Jan 15;100(2):327-34. doi: 10.1002/cncr.20003.
The aim of the current study was to explore the clinical implications and prognostic value of human papillomavirus (HPV) genotype in cervical carcinomas.
A total of 152 patients diagnosed with International Federation of Gynecology and Obstetrics Stage I-IV cervical carcinoma were studied between 1992-1999. HPV DNA status was assessed from paraffin-embedded, formaldehyde-fixed cervical carcinoma specimens by polymerase chain reaction-based methods using E7 type-specific and L1 modified general primers (MY11/GP6+ and GP5+/GP6+). The authors divided the patients into four groups: HPV-16-related, HPV-18-related, HPV-31-related, and HPV-58-related types. The relations with clinicopathologic data and overall survival were evaluated.
HPV DNA was detected in 98% of the tumor specimens and 28.9% of the tumor specimens contained multiple HPV types. The HPV-16-related types were detected more often in squamous cell carcinomas, whereas the HPV-18-related types were more prevalent in adenocarcinomas and adenosquamous carcinomas. In addition, Stage I-II diseases were found more frequently in the HPV-16-related group than in the other groups (P = 0.001). Otherwise, no significant correlation between the HPV genotype and other clinicopathologic parameters was found. After a median follow-up of 64.5 months, the 5-year survival rate was 92% in the HPV-31-related group compared with 70% in the HPV-16-related group, 69% in the HPV-18-related group, and 36% in the HPV-58-related group. The survival rates statistically differed among the four groups by log-rank test (P = 0.02). However, the presence of multiple HPV types was not associated with prognosis. After stratifying for clinical stage, multivariate analysis demonstrated that HPV genotype was an independent prognostic factor. Compared with the HPV-16-related group, the long-term mortality rate was 73 % lower in the HPV-31-related group (relative risk, 0.27; 95% confidence interval, 0.09-0.76; P = 0.013).
The presence of HPV-31-related types was an independent predictor of better survival in patients with cervical carcinoma. Therefore, HPV genotyping of cervical carcinomas may have profound implications for future patient management.
本研究旨在探讨人乳头瘤病毒（HPV）基因型在宫颈癌中的临床意义及预后价值。
1992年至1999年间，共对152例被诊断为国际妇产科联盟（FIGO）I-IV期宫颈癌的患者进行了研究。采用基于聚合酶链反应的方法，使用E7型特异性引物和L1改良通用引物（MY11/GP6+和GP5+/GP6+），从石蜡包埋、甲醛固定的宫颈癌标本中评估HPV DNA状态。作者将患者分为四组：HPV-16相关型、HPV-18相关型、HPV-31相关型和HPV-58相关型。评估其与临床病理数据及总生存期的关系。
98%的肿瘤标本中检测到HPV DNA，28.9%的肿瘤标本含有多种HPV类型。HPV-16相关型在鳞状细胞癌中更常被检测到，而HPV-18相关型在腺癌和腺鳞癌中更为普遍。此外，HPV-16相关组中I-II期疾病的发生率高于其他组（P = 0.001）。否则未发现HPV基因型与其他临床病理参数之间存在显著相关性。中位随访64.5个月后，HPV-31相关组的5年生存率为92%，而HPV-16相关组为70%，HPV-18相关组为69%，HPV-58相关组为36%。通过对数秩检验（P = 0.02），四组的生存率在统计学上存在差异。然而，多种HPV类型的存在与预后无关。在对临床分期进行分层后，多因素分析表明HPV基因型是一个独立的预后因素。与HPV-16相关组相比，HPV-31相关组的长期死亡率低73%（相对风险，0.27；95%置信区间，0.09-0.76；P = 0.013）。
HPV-31相关型的存在是宫颈癌患者生存较好的独立预测因素。因此，宫颈癌的HPV基因分型可能对未来患者的管理具有深远意义。
