宫颈腺鳞癌人乳头瘤病毒基因型的分布、临床病理参数对预后的影响

Clinical implications of human papillomavirus genotype in cervical adeno-adenosquamous carcinoma

目的评估宫颈腺鳞癌患者中人乳头瘤病毒（HPV）基因型分布情况,并探讨HPV基因型分布、临床病理参数对宫颈腺鳞癌患者预后的影响。方法回顾性分析2005～2012年接受根治性宫颈癌切除术或放疗的FIGO分期Ⅰ、Ⅱ期的宫颈腺鳞癌患者。分析影响宫颈腺鳞癌患者预后的影响因素,并建立其预后模型。结果247例宫颈腺鳞癌患者纳入本次生存分析研究。247例患者HPV18和HPV16的阳性率分别为51.5%和36.2%。多元回归分析表明,年龄大于50岁、Ⅲ、Ⅳ期（FIGO分期）和HPV16阴性与肿瘤复发密切相关,而年龄大于50岁、Ⅲ、Ⅳ期（FIGO分期）、HPV16阴性和HPV58阳性是肿瘤相关生存率的预后因素。HPV16阳性与首次接受RT/CCRT患者预后较好密切相关（CSS：风险比0.41,95%可信区间0.21～0.78）。FIGOⅠ、Ⅱ期和HPV16阴性AD/ASC患者首次采用RH-PLND治疗后的CSS（P〈0.0001）明显好于首次采用RT/CCRT治疗的患者。结论年龄大于50岁、Ⅲ、Ⅳ期（FIGO分期）和HPV阴性是宫颈AD/ASC患者不良预后的因素。HPV16阴性患者首次治疗最好采用手术（如：Ⅲ、Ⅳ期宫颈癌根治性宫颈切除术和IVA期盆腔清扫术）。

Objective To evaluate the genotype distribution of human papillomavirus（HPV） and the correlations of HPV parameters and clinicopathological/treatment variables with prognosis in cervical adeno-adenosquamous carcinoma（AD/ASC）. Methods Consecutive patients, who received primary treatment for International Federation of Gynecology and Obstetrics（FIGO） stages Ⅰ, Ⅳ cervical AD/ASC between 2005 and2012, were retrospectively reviewed. Prognostic models were constructed and followed by internal validation with bootstrap resampling. Results A total of 247 AD/ASC patients were eligible for survival analysis. HPV18 was detected in 51.5% and HPV16 in 36.2% of the samples. Age 〉50 years, FIGO stages Ⅲ, Ⅳ and HPV16-negativity were significantly related to cancer relapse; and age 〉50 years, FIGO stages Ⅲ, Ⅳ,HPV16-negativity and HPV58-positivity were the significant predictors for cancer-specific survival（CSS） by multivariate analyses. HPV16-positivity was closely associated with good prognosis in those receiving primary radiotherapy or concurrent chemoradiation（RT/CCRT）（CSS： hazard ratio 0.41, 95% CI： 0.21-0.78）. Patients with FIGO stage Ⅰ, Ⅱ and HPV16-negative AD / ASC treated with primary RH-PLND had significantly better CSS than those treated with RT/CCRT（P〈0.001）. Conclusions Age 50 years, FIGO stages Ⅲ, Ⅳ and HPV16-negativity are significant poor prognostic factors in cervical AD/ASC. Patients with HPV16-negative tumour might be better treated with primary surgery（e.g. radical hysterectomy for stages Ⅰ, Ⅳ and pelvic exenteration for stage IVA）.