人乳头瘤病毒独立状态对局部晚期宫颈癌同步放化疗后手术病理反应及预后的影响

Human papillomavirus independent status on pathologic response and outcomes in locally advanced cervical cancer managed with chemoradiotherapy followed by surgery.

作者信息

Turco Luigi Carlo, Pedone Anchora Luigi, Fedele Camilla, Inzani Frediano, Piermattei Alessia, Martini Maurizio, Volpe Mariaconcetta, Marchetti Simona, Santangelo Rosaria, Bizzarri Nicolò, Cosentino Francesco, Vargiu Virginia, De Ninno Maria, Macchia Gabriella, Valentini Vincenzo, Zannoni Gianfranco, Scambia Giovanni, Ferrandina Gabriella

机构信息

Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy.

出版信息

Int J Gynecol Cancer. 2023 Apr 3;33(4):489-497. doi: 10.1136/ijgc-2022-003940.

DOI:10.1136/ijgc-2022-003940

PMID:36720505

Abstract

OBJECTIVE

While human papillomavirus (HPV) has been shown to play a significant role in cervical cancer carcinogenesis (HPV associated cases), a considerable percentage of cervical cancers occur independently of HPV status (HPV independent).

METHODS

In this retrospective study of 254 locally advanced cervical cancer patients treated with chemoradiotherapy and radical surgery, HPV genotypes were determined using the Anyplex II HPV28 kit that uses multiplex, real time polymerase chain reaction technology. The primary endpoints of this study were to evaluate the complete response to chemoradiotherapy (pathologic complete response), the presence of microscopic (3 mm, pathologic micro partial response, group 1) and macroscopic (>3 mm, pathologic macro partial response, group 2) residual carcinoma in the cervix, and the persistence of metastatic lymph nodes (group 3) in HPV independent cervical cancers. Secondary endpoints were evaluation of disease-free survival and overall survival.

RESULTS

Of 254 patients studied, 21 cases (8.3%) of cervical cancer were determined to be HPV independent. The percentage of pathologic complete response was found to be higher in the HPV associated group compared with the HPV independent group (p<0.001). In the HPV associated cervical cancer group, 5 year disease free survival was found to be 80.8% versus 59.9% in the HPV independent group (p=0.014). Overall survival was also higher in the HPV associated group (87.9%) compared with the HPV independent patients (69.4%) (p=0.023). In the multivariate analysis, the International Federation of Gynecology and Obstetrics (FIGO) stage and HPV genotypes maintained their relevant impact on pathologic complete response to chemoradiotherapy: FIGO stages IIIC1 and IIIC2 were associated with a 13-fold increased risk for the presence of metastatic lymph nodes compared with group 1 (p<0.001). HPV independent cervical cancers showed the highest risk for the development of macroscopic/stable disease (p=0.007), and persistence of metastatic lymph nodes (p=0.004) versus group 1, respectively.

CONCLUSIONS

This study showed that HPV status at diagnosis could be a relevant factor for clinical outcomes in locally advanced cervical cancer patients.

摘要

目的

虽然已证明人乳头瘤病毒（HPV）在宫颈癌致癌过程中起重要作用（HPV相关病例），但相当比例的宫颈癌独立于HPV状态发生（HPV非相关病例）。

方法

在这项对254例接受放化疗和根治性手术的局部晚期宫颈癌患者的回顾性研究中，使用采用多重实时聚合酶链反应技术的Anyplex II HPV28试剂盒测定HPV基因型。本研究的主要终点是评估放化疗的完全缓解（病理完全缓解）、宫颈微观（3毫米，病理微观部分缓解，第1组）和宏观（>3毫米，病理宏观部分缓解，第2组）残留癌的存在，以及HPV非相关宫颈癌中转移性淋巴结的持续存在（第3组）。次要终点是评估无病生存期和总生存期。

结果

在研究的254例患者中，21例（8.3%）宫颈癌被确定为HPV非相关。发现HPV相关组的病理完全缓解率高于HPV非相关组（p<0.001）。在HPV相关宫颈癌组中，5年无病生存率为80.8%，而HPV非相关组为59.9%（p=0.014）。HPV相关组的总生存率（87.9%）也高于HPV非相关患者（69.4%）（p=0.023）。在多变量分析中，国际妇产科联合会（FIGO）分期和HPV基因型对放化疗的病理完全缓解仍有相关影响：与第1组相比，FIGO分期IIIC1和IIIC2发生转移性淋巴结的风险增加13倍（p<0.001）。与第1组相比，HPV非相关宫颈癌发生宏观/稳定疾病（p=0.007）和转移性淋巴结持续存在（p=0.004）的风险最高。