Early posttherapy clearance of human papillomavirus and treatment response in cervical carcinoma
Early posttherapy clearance of human papillomavirus and treatment response in cervical carcinoma
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DOI：
10.1002/cncr.33040
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发表时间：
2020-07-08
期刊：
影响因子：
6.2
通讯作者：
Grigsby, Perry W.
中科院分区：
文献类型：
--
作者：
Srivastava, Amar J.;Contreras, Jessika A.;Grigsby, Perry W.
背景在宫颈癌患者中，对于放化疗（CRT）后持续性人乳头瘤病毒（HPV）表达的意义知之甚少。本研究评价了治疗后早期HPV清除率与患者结局之间的相关性，并重点关注了治疗后正电子发射断层扫描（PET）成像的价值。方法纳入的患者在CRT后接受了提示高危HPV感染的治疗前检测和基于信使RNA（mRNA）的生殖器拭子的治疗后检测。根据HPV mRNA检测将治疗后应答分层为早期清除（EC）组（无mRNA）和持续表达（PE）组（可检测mRNA），基于治疗后中位数6周的评估。Kaplan-Meier方法用于比较结局，多变量分析用于确定结局的预测因素。结果97例患者中有72例（74.2%）发生EC。平均随访时间为25个月（范围，4-56个月），2年盆腔控制（76.9% vs 50.2%;P = 0.01）和总生存率（OS; 80.9% vs 52.2%;P <0.01）在EC患者中上级。在多变量分析中，EC预测生存率改善（死亡率风险比[HR]为0.46; 95%置信区间[CI]为0.21-0.96;P = 0.047），治疗后PET显示完全缓解（CR）也是如此（PET显示CR以下的HR为6.17; 95% CI为2.58-14.72;P <0.01）。在对治疗后PET CR患者的亚组分析中，HPV清除保留了预后意义（2年OS，EC为95.6%，PE为66.7%;P = 0.04），而没有PET CR的PE患者的生存率最差（35.9%;趋势P <0.01）。结论治疗后早期HPV清除与宫颈癌生存率的提高有关。在这6周的时间点评估HPV表达提供了治疗后PET成像以外的预后信息，并可能有助于风险分层和治疗升级的决策。
Background Among patients with cervical cancer, little is known about the significance of persistent human papillomavirus (HPV) expression after chemoradiation (CRT). This study evaluated associations between early posttreatment HPV clearance and patient outcomes with an added focus on the value of posttherapy positron emission tomography (PET) imaging. Methods Included patients underwent pretreatment testing indicating a high-risk HPV infection and posttreatment testing with a messenger RNA (mRNA)-based genital swab after CRT. Posttherapy responses were stratified on the basis of HPV mRNA detection into an early clearance (EC) group (no mRNA) and a persistent expression (PE) group (detectable mRNA) on the basis of an evaluation at a median of 6 weeks after therapy. The Kaplan-Meier method was used to compare outcomes, and multivariable analysis was used to identify predictors of outcomes. Results Seventy-two of the 97 eligible patients (74.2%) had EC. The mean follow-up time was 25 months (range, 4-56 months), and 2-year pelvic control (76.9% vs 50.2%;P = .01) and overall survival (OS; 80.9% vs 52.2%;P < .01) were superior among EC patients. In the multivariable analysis, EC predicted for improved survival (hazard ratio [HR] for mortality, 0.46; 95% confidence interval [CI], 0.21-0.96;P = .047), as did a complete response (CR) on posttherapy PET (HR for less than a CR on PET, 6.17; 95% CI, 2.58-14.72;P < .01). In a subset analysis of patients with a posttherapy PET CR, HPV clearance retained prognostic significance (2-year OS, 95.6% with EC vs 66.7% with PE;P = .04), whereas PE patients without a PET CR had the worst survival (35.9%;P < .01 for trend). Conclusions Early posttherapy clearance of HPV is associated with improved survival in cervical cancer. Evaluating HPV expression at this 6-week time point provides prognostic information beyond posttherapy PET imaging and may aid in risk stratification and decisions for treatment escalation.