A new marker based on risk stratification of human papillomavirus DNA and tumor size to predict survival of locally advanced cervical cancer

Abstract

ObjectiveTo assess the prognostic value of human papillomavirus (HPV) viral load in locally advanced cervical carcinoma treated with radical concurrent chemoradiotherapy.MethodsFrom January 2012 to October 2013, a total of 246 locally advanced cervical carcinoma patients were included in this retrospective study. HPV DNA status was tested by Hybrid Capture 2 assay. Tumor size was measured on T2WI. All the patients in the study received concurrent cisplatin-based chemoradiotherapy with intensity-modulated radiotherapy and three-dimensional brachytherapy. Survival rate was calculated by the Kaplan-Meier method, and a log-rank test was used to compare the survival. Multivariate analysis employed the Cox regression model.ResultsThe median follow-up time was 52 months. The median value of HPV DNA was 163.13 relative light unit/cut-off (RLU/CO) (range 1.65–2162.62 RLU/CO). The 5-year overall survival, distant metastasis-free survival of patients in the low HPV DNA group (HPV DNA ≤ 163.13 RLU/CO) and the high HPV DNA group (HPV DNA > 163.13 RLU/CO) were 46.3 % vs 58.5 % (p = 0.009) and 65.9 % vs 75.6% (p = 0.003), respectively. Multivariate analysis showed that the HPV DNA, tumor size, and International Federation of Gynecology and Obstetrics (FIGO) stage were independent prognostic factors for overall survival and distant metastasis-free survival. We choose the tumor size and HPV DNA as the risk stratification factors to build a new prediction marker which can better predict overall survival for locally advanced cervical cancer than can the FIGO stage.ConclusionsHPV DNA may be a useful biomarker for locally advanced cervical cancer. Low HPV load predicts a worse survival. The new marker based on risk stratification by combining HPV DNA and tumor size is better associated with overall survival of locally advanced cervical cancer treated with concurrent chemoradiotherapy.

Molecular Markers to Predict Prognosis and Treatment Response in Uterine Cervical Cancer

“…Determining the predictive value of the HPV viral load was the objective of several studies. In locally advanced cervical cancer, a low HPV viral load was associated with an impaired distant metastasis free (DMFS) and overall survival (OS), while the combined analysis HPV viral load and tumor size were superior for predicting OS [70]. These findings are consistent with the findings by Kim et al, who reported worse disease-free survival (DFS) in 169 women with low HPV viral load treated with CRT [71].…”

Multicentre, randomised controlled trial of adjuvant chemotherapy in cervical cancer with residual human papilloma virus DNA following primary radiotherapy or chemoradiotherapy: a study protocol

“…It also has been reported that residual HPV DNA is clinically useful as a new marker to predict local recurrence after conization for cervical intraepithelial neoplasia14–18 and after RT for invasive cervical carcinoma 19–28. In the study conducted by the University of the Ryukyus in Japan, local recurrence rate was significantly higher in patients with persistent HPV than in patients cleared for HPV who were treated with RT (34% vs 7.1%).…”

TP53 mutants and non-HPV16/18 genotypes are poor prognostic factors for concurrent chemoradiotherapy in locally advanced cervical cancer

“…In addition to tumor volume, performance status, treatment received, and prognostic factors for locally advanced cervical cancers, such as age, race, stage, histological type, grade, lymph node enlargement, and location, are associated with poor outcomes 4 . Several studies have focused on the prognostic factors for patients receiving CCRT in locally advanced cervical cancer, and it has been reported that larger tumor size and high-risk HPV were correlated with prognosis 13 , 14 . However, most studies have targeted operable cases.…”