High HPV viral load predicts worse prognosis in patients with cervical cancer treated with radiochemotherapy.

Abstract

Purpose: To evaluate the prognostic value of high-risk human papillomavirus (HR-HPV) viral load in long-term survival of cervical cancer (CC) patients.

Methods: Two hundred and twenty-nine CC patients from 2009 to 2013 who underwent radiochemotherapy (RCT) or plus hyperthermia (HT) were recruited. HPV type 16, 18, 58 DNA was detected by in situ hybridization (ISH) and either HR-HPV type with the highest intensive signals was chosen as the evaluating target. HPV viral load was evaluated by semiquantitative analysis for the intensity of ISH signal captured from the colonial cancer nests with the highest density of signal on section from each case. RNA scope was used to detect the HPV E6/E7 mRNA and P53/Rb mRNA expression. Immunohistochemistry (IHC) was used to detect P53/Rb protein expression.

Results: The number of patients with low and high HPV viral load was 152 (66.38%) and 77 (33.62%), respectively. 5-year Overall Survival (OS) of patients in the low and high HPV DNA group were 82.9 and 63.6%, respectively (p = .001). 5-year Local Relapse-Free Survival (LRFS) of patients in the low and high HPV DNA group were 80.3 and 62.3%, respectively (p = .004). Univariate and multivariate analyses also confirmed the higher risk death of high virus load group. HR-HPV oncogene mRNA expression was highly concert with HPV DNA. Radiation enhanced HPV E6/E7 mRNA and P53/Rb mRNA expressions and decreased P53/Rb protein expressions in tissue samples and cancer cell lines.

Conclusion: High initial viral load measured in cervical tumor nest was a strong independent prognostic factor that influenced poor survival in CC after RCT.