title: The impact of human papillomavirus infection on the survival and treatment response of patients with esophageal cancers.
abstract: OBJECTIVE
  This study aimed to investigate the impact of human papillomavirus (HPV) infection on the prognosis and treatment response of esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  We examined the presence and subtypes of HPV in the tumors by polymerase chain reaction and sequencing in 150 ESCC patients. Their clinicopathological characteristics, treatment response and survival were further analyzed according to the presence of HPV infection.
  
  
  RESULTS
  Of 150 ESCC tumor samples, 27 (18.0%) were HPV-positive, of which 22 (81.5%) had HPV-16 infection. The risk of developing multifocal ESCC was not significantly different in the HPV-positive and HPV-negative groups (29.6% vs 28.5%, P = 0.90). In subgroup analysis, patients with HPV-16-positive advanced ESCC had a significantly better survival than those with HPV-negative ESCC (3-year survival: 55% vs 21%, log-rank P = 0.03). Cox proportional hazards model showed that the presence of HPV-16 was associated with a significant reduction in the mortality rate (hazard ratio 0.41, 95% CI 0.18-0.96). Patients with HPV-16 infection had better response to chemoradiotherapy (CRT) than those without HPV-16 infection (P = 0.026).
  
  
  CONCLUSIONS
  In patients with advanced ESCC, HPV-16-positive patients had a significantly favorable survival, especially those who received CRT. Larger scale studies are needed to determine the causal relationship.
authors.affiliation: Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan, China.
authors.forename: Wen-Lun
authors.initials: WL
authors.lastname: Wang
authors.affiliation: Department of Biological Science & Technology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan, China.
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan, China.
authors.forename: Ching-Tai
authors.initials: CT
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan, China.
authors.forename: Chi-Yang
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Oncology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan, China.
authors.forename: Jo-Lin
authors.initials: JL
authors.lastname: Lo
authors.affiliation: Department of Radiation Oncology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan, China.
authors.forename: Yao-Hung
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan, China.
authors.forename: Yao-Chun
authors.initials: YC
authors.lastname: Hsu
authors.affiliation: Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan, China.
authors.forename: Lein-Ray
authors.initials: LR
authors.lastname: Mo
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000628:therapy / Q000821:virology; D059248:Chemoradiotherapy; D004938:Esophageal Neoplasms / Q000401:mortality* / Q000628:therapy / Q000821:virology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000401:mortality* / Q000628:therapy / Q000821:virology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis
keywords: chemoradiotherapy; esophageal neoplasms; human papillomavirus; survival