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

摘要:

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）。

Abstract:

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 and 2012, 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 andHPV16-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).