High-risk human papillomavirus infection associated with telomere elongation in patients with esophageal squamous cell carcinoma with poor prognosis

摘要

Telomere maintenance is crucial in carcinogenesis and tumor progression. The results of a previous study from the authors indicated that infection with high-risk human papillomavirus (HR-HPV) types 16, 18, and 58 was a risk factor for esophageal squamous cell carcinoma (ESCC) in the Shantou region of China. In the current study, the authors explored the association between HR-HPV infection, telomere length (TL), and DNA methylation and their significance in the prognosis of patients with ESCC. METHODS TL and DNA methylation were analyzed by real-time polymerase chain reaction and methylation-specific polymerase chain reaction in 70 cases of ESCC tumor (T) and paired nontumor (NT) tissues and 50 cases of normal esophagus (NE). The prognostic value of TL and DNA methylation in ESCC was analyzed. RESULTS TL gradually decreased from NE to NT to T tissue. TL in tumor tissue (T-TL) was found to be longer in tissue that was positive for HR-HPV compared with negative tissue and was found to be positively associated with viral load (Spearman correlation, 0.410; P=.037) and integration (represented by the ratio of HR-HPV E2 to E6/E7 genes; P=.01). The DNA methylation ratio of human telomerase reverse transcriptase was more prevalent with long (≥ 0.7) compared with short (< 0.7) T-TL and was positively correlated with T-TL (Spearman correlation, 0.318; P=.007) and HR-HPV integration (P=.036). Furthermore, Cox proportional hazards modeling revealed a high ratio of T-TL to NT-TL (≥ 0.80) as a factor of poor prognosis, independent of other clinicopathologic variables. CONCLUSIONS HR-HPV infection and integration related to telomere elongation and DNA methylation of human telomerase reverse transcriptase may be a potential biomarker of prognosis in patients with ESCC. Cancer 2014;120:2673-2683.